匡达人 2511true 郭志鲲 2510true 董霖 2509true 孙玉昆 2508true 郑正炯 2507true 张家兴 2506true 汪垣,李载平 2505true 中国科学院上海生物化学研究所生物膜组 2504true 中医研究院医史文献研究室 2503true 吴本玠 2502true 丰耕毅 2501true 中国科学院上海生物化学研究所生物膜组 2500true 中国科学院上海生物化学研究所一室 2499true 2498true 许根俊,钱元任,施建平 2497true 杨福愉 2496true 申吾 2495true 冯佑民,顾嘉琍 2494true 吴剑侯 2493true 郑若玄 2492true 王世中 2491true 汪云九 2490true 杨常仁,忻纪厚,王庆诚 2489true 蔡浩然 2488true 秦文斌 2487true 罗超权,威正武 2486true 中国科学院上海生物化学研究所三室 2485true 郭爱克 2484true 中国科学院生物物理研究所一室二组 2483true 匡达人 2482true 袁静明 2481true 中国科学院上海生物化学研究所肿瘤组 2480true 施立明 2479true 朱尚权 2478true 童裳亮 2477true 蔡浩然 2476true 王身立,戴君惕 2475true 郭兴华,王清海 2474true 汪云九 2473true 曹敬和 2472true 何泽涌 2471true 龚祖埙 2470true 梁子钧,施永德 2469true 凌义和 2468true 中国科学院自动化所控制论组 2467true 杨福愉 2466true 陈慎 2465true 陈作义 2464true 韩澄源 2463true 沈煜民 2462true 方福德,吴冠芸 2461true 中国科学院北京自动化研究所控制论组 2460true 施玉樑 2459true 中国科学院上海生物化学研究所遗传工程组 2458true 孙玉昆 2457true 陈惟昌 2456true 施玉樑 2455true 陈连仲 2454true 涂光俦 2453true 朱尚权 2452true 范世藩 2451true 劳为德 2450true 陈诗书等 2449true 蒋英华 2448true 郑国璋 2447true 杨振玉,杨雄里 2446true 秦文斌 2445true 劳为德 2444true 童坦君,张昌颖 2443true 汤佩松 2442true 陈建文,静国忠 2441true 劳为德 2440true 李国栋 2439true 谢彦博 2438true 李国栋 2437true 蔡惠罗 2436true 李恩 2435true 林克椿 2434true 郑国锠 2433true 中国科学院上海生物化学研究所四室 2432true 杨福愉 2431true 王世真 2430true 中国科学院自动化研究所控制论组 2429true 中国科学院上海生物化学研究所四室 2428true 杨福愉 2427true 静国忠,陈建文 2426true 刘新垣,谌章群,陈常庆 2425true 翁元凯 2424true 涂光俦,阮长耿 2423true 冯佑民,鲁子贤,顾嘉琍 2422true 谌章群,刘新垣,陈常庆 2421true 王理开 2420true 朱仁华 2419true 刘育民 2418true 王书荣 2417true 朱尚权 2416true 陈德茂 2415true 陈德高 2414true 潘华 2413true 杨常仁 2412true 刁云程 2411true 张世荣 2410true 居乃琥 2409true 司马蕙兰,戚正武 2408true 陈润生 2407true 王书荣 2406true 甘景镐 2405true 张今,张德安,焦佐卿 2404true 尹明标,龚新昌,董永坤 2403true 许健生,高联佩 2402true 田佩珠 2401true 孟香琴,张仲纶 2400true 赵晜,魏西平 2399true 白迺彬 2398true 周虞灿 2397true 管汀鹭,程乃乾 2396true 许健生,高联佩 2395true 贝时璋 2394true 奚国良 2393true 王身立 2392true 黄秉宪,潘华 2391true 祁国荣,吴仁龙 2390true 童坦君 2389true 罗荣生 2388true 何泽涌 2387true 李树深 2386true 冯若 2385true 邹冈,华家柽,奚国良,吕植桢,易庆成 2384true 奥弗·瑞 2383true 陈惟昌,谢建周 2382true 施玉樑 2381true 何泽涌 2380true 王身立 2379true 陈执中 2378true 何泽涌 2377true 顾凡及 2376true 赵冠美 2375true 王曼霖 2374true 魏西平 2373true 唐海伦 2372true 陈惠黎,吴永麟 2371true 张德安,张今 2370true 曾广植 2369true 姜湧明 2368true 杨福愉 2367true 刘蓉 2366true 王培之 2365true 唐传业 2364true 周国平 2363true 刘为民 2362true 唐传业 2361true 王家槐 2360true 赵良仲 2359true 陆惠民,王今著 2358true 孙曼霁,周廷冲 2357true 孙册 2356true 王家槐 2355true 华庆新 2354true 王申五,吴冠芸 2353true 易健华 2352true 邹承鲁 2351true 徐京华 2350true 华庆新 2349true 黄惠慈 2348true 梅镇安 2347true 姚连生 2346true 温博贵 2345true 周金煦,胥彬 2344true 陈建华 2343true 李楠茜,赵晜,魏西平 2342true 严智强 2341true 施庆洛,鲁子贤 2340true 文重,周晴中 2339true 梅镇安 2338true 张玉瑛 2337true 李忠 2336true 孙册 2335true Thomas G．Ebrey 2334true 黄惠慈 2333true 张德安 2332true 郑秀龙 2331true 周新华 2330true 易健华,曾治义 2329true 喻致祥 2328true 王贵海 2327true 谢廷栋 2326true 王身立 2325true 赵似兰 2324true 顾凡及 2323true 厉朝龙 2322true 罗明典 2321true 甘景镐 2320true 郭爱克 2319true 陈丽筠 2318true 郭爱克 2317true 张建中,赵保路 2316true 聂玉生 2315true 施产甫 2314true 王志珍 2313true 施永德 2312true 李忠 2311true 施蕴渝,董名垂 2310true 陈兴 2309true 张人德,张惠珠 2308true 于秉治,西塚泰美 2307true 曾庆平 2306true 张翼伸 2305true 张伊平,祁国荣 2304true 顾凡及 2303true 黄芬 2302true 林克椿 2301true 吴越,张岱山 2300true 王志珍 2299true 赵保路,张建中 2298true 罗林儿,顾大明 2297true 刘秉慈 2296true 王志珍 2295true 庞素珍,沈恂 2294true 郑荣梁 2293true 何绍雄 2292true 苏渝生 2291true 王其武 2290true 阎脉绍 2289true 苏同进,易希璋 2288true 顾凡及 2287true 汪云九 2286true 黄熙泰,梁植权 2285true 王友京 2284true 沈建华 2283true 刘端 2282true 杨福愉 2281true 戚志红,陈常庆 2280true 施产甫 2279true 杨常仁,袁玉萍 2278true 方思明 2277true 姚国正,赵松年 2276true 潘卓华,汪云九 2275true 梅镇安 2274true 方福德 2273true 莫简 2272true 谭智群 2271true 陆选永,曾庆镒 2270true 吕昌祥 2269true 蔡体导 2268true 黄秉宪 2267true 姚国正 2266true 华庆新,王家槐 2265true 赵保路,张建中 2264true 汪淑华,朱应麒 2263true 傅亚珍 2262true 马永沂,秦永楠,朱鼎良 2261true 毕汝昌 2260true 许凯黎 2259true 严明标,李占荣 2258true 周新华 2257true 王家槐 2256true 郑荣梁 2255true 黄胜利,于树玉 2254true 寿天德 2253true 蒋汉英 2252true 徐秀璋,房月华 2251true 曲善乐 2250true 杨福愉,黄芬,王金凤 2249true 温元凯,程门燕 2248true 何绍雄 2247true 彭启明,张淑琴 2246true 杨福愉,黄芬,王金凤 2245true 梅尚筠,严定友 2244true 方福德,沈岩 2243true 杨雄里 2242true 施蕴渝,贠汝槐,王存新 2241true 梁金虎 2240true 邹冈 2239true 赵白 2238true 毕汝昌 2237true 纪极英 2236true 李庆国 2235true 黄仲贤 2234true 华庆新 2233true 朱长喜,宋鸿遇 2232true 李益新 2231true 黄仲贤 2230true 周玫,陈瑗 2229true 胡友纪,王世杰 2228true 李忠 2227true 徐友涵 2226true 范培昌 2225true 张少吾,孙其坚 2224true 蒋传葵,李文杰 2223true 王志珍 2222true 刘玮 2221true 徐友涵 2220true 芮海凤 2219true 杨福愉 2218true 冯佑民,张友尚 2217true 朱尚权,James D.Young 2216true 于维平,于树玉 2215true 陈国璋 2214true 李忠 2213true 范培昌 2212true 李家瑶 2211true 胡坤生 2210true 张明,陈慎 2209true 潘琼婧 2208true 彭银祥 2207true 张楚富 2206true 静国忠 2205true 党进军,孙志贤 2204true 范培昌 2203true 李在威,杨频 2202true 曾一鸥 2201true 周淑平,李瑛 2200true 方林求 2199true 邹光楣 2198true 唐家骏 2197true 于德山,汪云九 2196true 盂广震 2195true 唐向辉,屈贤铭 2194true 洪水根,胡友川 2193true 杨义力 2192true 祁鸣,薛京伦 2191true 杨文修 2190true 梁丽 2189true 黎先栋,王淑惠 2188true 甘纯玑,甘景镐 2187true 施建平 2186true 文重,乔英 2185true 王林发,王培之 2184true 曹锡清 2183true 傅亚珍 2182true 黄胜和 2181true 蔡体导 2180true 杜家纬 2179true 朱长喜 2178true 杨福愉 2177true 刘士新,关晓光 2176true 杨志安,庄弘,湛垦华 2175true 董素才,李建新,杨志铭 2174true 马凤森 2173true 黄建东,冷麟,王贤树 2172true 文重,黄震 2171true 王远亮 2170true +)是生物体内最重要的无机阳离子之一。引入适当的水溶性位移试剂(SR)，应用 ²³Na核磁共振波谱( ²³Na-NMR)技术，是研究活细胞中N⁺代谢的二条新途径。本文综述了活细胞中 ²³Na-SR-NMR研究的实验方法及其研究进展。]]> 赵明,卢耘 2169true 胡天喜 2168true 张今,张红缨 2167true 陈燕 2166true 方林求 2165true 陈瑗,周玫 2164true 杨福愉 2163true 2+结合的高亲和位，并据此提出了CaM活化靶酶的新模型。发现神经钙蛋白(CaN)为一种依赖CaM的磷酸酶和两种最强的CaM桔抗剂多肽Mastoparan和药物EBB。证明一些疾病同Ca²⁺、CaM有关。]]> 徐友涵,张遂坡 2162true 钟伟民,曹华 2161true 郑硕 2160true 曲善乐 2159true 耿建国,杨一峰,陈灏珠 2158true 马凤森 2157true 郭爱克 2156true 方雪,刁云程 2155true 汪云九 2154true 张孔华,徐成汤 2153true 韩刚毅 2152true 晏孝皋 2151true 邢蕴芳 2150true 6-甲基鸟嘌岭DNA是某些烷化剂直接或通过酶转化后与DNA反应生成的一种有致死、致突及致癌作用的产物。细胞内的O⁶-甲基鸟嘌呤DNA甲基转移酶能有效地去除这种损伤，即甲基基团从DNA鸟嘌呤第六位氧原子上特异地转移到受体蛋白的半胱氨酸的残基上，反应产物是S-甲基半胱氨酸。受体蛋白就是酶本身。O⁶-甲基乌嘌呤的修复过程所完成的是一种无错的修复，它可能与减少肿瘤的发生有关。]]> 曹恩华,王菊君 2149true 4溶菌酶、细胞色素c、胰蛋白酶以及胰岛素原等几个实例说明如何利用蛋白质晶体结构资料进行蛋白质工程设计。]]> 卢光莹 2148true 60src等也能使C-K活化。这提示，在细胞的癌变、增殖过程中，C-K很可能也发挥着重要的调控作用。]]> 于秉治 2147true 杨雨善 2146true 毕汝昌 2145true 易健华 2144true 朱鸣 2143true 黄玉明 2142true 肖悦梅 2141true 3)，胞内游离Ca²⁺浓度瞬间增高(Ca²⁺动员过程)，通过不同的蛋白激酶引起特定的生理效应。DG活化蛋白激酶-C，IP₃动员胞内Ca²⁺，它们通过二个相互独立而协同的过程调节细胞的代谢。]]> 徐友涵 2140true 伍嘉宁 2139true 陈汝琛,景毓庄 2138true 杨文修 2137true 李伟,吴旻 2136true 邢成 2135true 汤华,任中原 2134true 何绍雄 2133true 孔原,王先敏 2132true 2+依赖性蛋白激酶。它广泛传递多种细胞外信息通过细胞膜,调节细胞内许多依赖于Ca²⁺的代谢过程。无论是在细胞释放、溶解、膜运输、受体的增效与去敏、平滑肌的收缩,还是在调控细胞分化、增殖、癌变的过程中都起着关键性的作用。]]> 刘建军,崔肇春 2131true 李华儒 2130true 喻晶华,屈智超 2129true 戚正武 2128true 3受体的cDNA,并对受体的结构和功能进行了卓有成效的研究,为进一步阐明甾体激素受体的作用机制打下了基础。本文对这一进展进行了综述。]]> 杨义力 2127true 罗贵民 2126true 吴显荣,刘建卫 2125true 毛先枝,王子芳 2124true 王理开,徐晓利 2123true 3)和甘油二脂(DG)在信息传递中的作用,阐述了肌醇磷脂与神经信息跨突触传递的关系。]]> 李俊凤,吴奇久 2122true 4引起人们重视,它很有可能成为一种避孕疫苗。本文对这一方面作一介绍。]]> 王又明 2121true 周清 2120true 王曼莹,刘建华,黄汇丰 2119true 彭腾,刘宗定 2118true 刘杰 2117true 王汉中 2116true 华子千 2115true 侯宪玉,冯佑民 2114true 张遂坡,吴隽平,徐友涵 2113true 胡二丁,杨静 2112true 汪策 2111true 蹇敦龙,龙康侯 2110true 周宝宏 2109true 刘贵堂 2108true 杨文修,赵明利 2107true 汪乃兴 2106true 谢静平 2105true 程冠生 2104true 鲁先平,于树玉 2103true 张少吾 2102true 黄彦猷 2101true 梁逊,郭小丽 2100true 温元凯,戴亚,赵辉,孟庆涛 2099true 田志刚,朱迅 2098true 李庆国 2097true 孔原,冷麟 2096true 梅尚筠,海星元 2095true 叶明,周济兰,赵永芳 2094true 胡天喜 2093true 林政炯 2092true 王结义,宋后燕 2091true 吴炯 2090true ++K⁺)-ATPase属于生物膜的第二类质子泵(E₁E₂型),从生理角度它是胃酸分泌的质子泵。本文结合我们初步的研究结果:猪、大白鼠胃粘膜(H⁺+K⁺)-ATPase的纯化以及由消炎痛引起的急性胃粘膜病变与胃粘膜(H⁺+K⁺)-ATPase的关系等,对此酶在近十几年来它的纯化、结构、性质、催化机理,向胃腔分泌盐酸的功能及其调节和胃病变的分子机理等方面进行了简要的综述。]]> 左凤蓉,李生广,林治焕 2089true 刘启光,吴旻 2088true 马立伟,郭中和 2087true 倪行,贾玉珍,包建春 2086true +-ATPase)的性质进行了比较,说明它们的催化特性和泵质子功能。]]> 王延枝 2085true 孔原,冷麟,徐万祥 2084true 张林华,刘秉文 2083true 周宝宏 2082true 李凌松 2081true 陈丁丁 2080true 2+,Ni²⁺等多种金属离子的调节。]]> 魏群,吴国利 2079true 许凤浩,夏庆苏 2078true 姚文兵,胡卓逸 2077true 杨斌盛,杨频 2076true 缪金明,潘瑞彭 2075true 王书荣 2074true 翁元凯 2073true +/K⁺)-ATPase的一般分子性质。介绍神经元和脂肪细胞中两种不同分子形式(Na⁺/K⁺)-ATPase的分离鉴定和功能性质,以及(Na⁺/K⁺)-ATPase主要功能亚基一级序列和高级结构研究所取得的一些进展。]]> 谢静平 2072true 31P-NMR法因其共振谱线简单明了,灵敏度高,能无损伤地监控生物活组织内的与能量代谢密切相关的含磷化合物浓度的动态变化,而成为在生理条件下测定组织内部动力学参量的重要方法。本文通过介绍离体灌流标本和在体组织器官的 ³¹P-NMR的具体应用实例,集中反映了在这一领域研究的概况和新近的研究成果。]]> 沈行良,西川弘恭 2071true 韩贻仁 2070true 21蛋白的性质及ras P²¹与细胞增殖调控的关系。ras P²¹蛋白可能通过调节细胞增殖信号的传递、周期运行等一系列生化事件来实现其功能。]]> 陈禹保 2069true 32P标记等方法。同时还从理论上阐述了19聚体探针在生物实验使用中的合理性,并强调在检测基因的点突变时,设计人工合成的寡聚核苷酸探针应将点突变位点置于探针序列的中间为宜。在选择序列时,要注意避免发生G-T错配,这样有利于鉴别基因的点突变。]]> 史天良 2068true 陈瑗,周玫 2067true 徐宁志,邓国仁 2066true val比较时发现了某些共同的结构特点。tRNA-样结构的可能功能尚属推测。]]> 蒋秉坤,沈蓉,夏俊,赵学海 2065true 王克夷,冯佑民 2064true 姜淮春 2063true 董之海 2062true 景键,吴才宏 2061true 2是一个新近发现的调节代谢物。它广泛存在于植物体内,控制碳水化合物的合成和降解,参与光合代谢的精细调节和光合产物的分配,也调节植物的呼吸代谢。]]> 宋松泉 2060true 陈丁丁 2059true 许凤浩 2058true 彭腾,刘秉文 2057true 2+·CaM蛋白激酶相互区别而又紧密联系。C-激酶系通过催化多种蛋白特别是胰岛素受体,生长因子受体、钙调蛋白等生理活性蛋白的Ser/Thr残基磷酸化,以调节细胞代谢,分化、生长、增殖乃至癌变。]]> 乐志培 2056true 袁玉坤,张铣 2055true 黄一玲,姚志建 2054true 马凤森 2053true α链cDNA克隆建立以来,该领域研究已有很大突破,本文概要介绍了这方面的进展。]]> 朱迅,田志刚 2052true 潘琼婧 2051true 付四清,季文琴 2050true 刘望夷,王德宝 2049true 缪金明,潘瑞彭 2048true 郑硕 2047true 韩迎山 2046true 2^-_·密切相关。将SOD包入脂质体后不但可提高SOD进入细胞的量,还可选择性地将SOD导入到一定的器官中。SOD对某些自身免疫病、关节炎、化疗引起的骨髓损伤、阴茎海绵体硬结疼痛、放射病及放疗引起的副反应,以及肌肉疲劳等都有疗效。]]> 陈雨亭,郑荣梁 2045true 贺福初 2044true 韩刚毅 2043true 陈永青,刘坚 2042true 王书荣 2041true 陈世芝 2040true 刘德立 2039true 黄胜和,徐钤 2038true 张学军 2037true 何炬斌,焦炳华 2036true 刘鹏翰,梅尚筠 2035true 杨义力 2034true 朱美财 2033true 蒋达和 2032true 100酸性蛋白等分子发生变构作用的条件及其与学习记忆过程的关系。这些蛋白分子的变构作用既制约于条件刺激又决定于非条件刺激,两种刺激的结合就会实现较大的生物效应。这一规律表明,这些蛋白分子的变构作用是学习过程的基本机制。]]> 沈政 2031true 蒋秉坤 2030true 蔡仕英,马贤凯 2029true 奇云 2028true 毕汝昌,桂璐璐,楼美珍 2027true 吴明 2026true 顾涵英,冯佑民 2025true 陈泮藻,李振甲 2024true 龚守良,刘树铮 2023true 罗贵民,曹淑桂 2022true 徐惠 2021true 石颖,许根俊,鲁子贤 2020true 郝鸣鸿 2019true 谭景莹 2018true 阎哓霞 2017true 汪策,周宝宏 2016true 黎荣松,刘新垣 2015true 石秀凡,胡坤生 2014true 胡军 2013true 华庆新 2012true 付四清,宋后燕,程立 2011true 吴敏 2010true 郝军山 2009true 吉永华 2008true 宋任华 2007true 隋德新,马玉琏 2006true 韩晓亮,池芝盛,张世荣 2005true 张春霆 2004true 熊克勇,丁达明 2003true 蒋达和 2002true 茅力,练鸿振 2001true 李如生 2000true 胡卓逸,孙承琦 1999true 李成文 1998true +,K⁺-ATPase和Ca²⁺-ATPase活力下降,也有人认为Na⁺,K⁺-ATPase的活力没有变化。]]> 杨毅,陈晓明,冷麟 1997true 李齐,朱静和 1996true 卓肇文 1995true 王克夷 1994true 6-甲基鸟嘌呤-DNA甲基转移酶是细胞中一种重要的DNA损伤修复酶,它在抵御烷化剂所致的细胞突变和死亡中扮演重要的角色。本文综述近年来关于这个酶的研究进展,内容包括酶及其基因,酶与细胞突变,酶与肿瘤化疗的关系。]]> 章扬培,韩文智 1993true 范剑华,冯佑民 1992true 陈曦 1991true 李翠凤,尚克进,凌启阆 1990true 吴也凡,曾定 1989true 杨新林 1988true 徐梅,鲁子贤 1987true 毕汝昌,储乃明 1986true 范培昌 1985true 黄仲贤 1984true 张力,侯纬敏 1983true 陈德风,赵西林 1982true 武彩云,孙乐琴 1981true 徐科 1980true 许正平,王恩多 1979true 茹炳根,潘爱华,黄秉乾,张建业 1978true 马逸龙 1977true 王槐春 1976true 陈南岳 1975true 卢戈 1974true 王大成 1973true 唐建国 1972true 宋松泉,傅家瑞 1971true 彭勇,童坦君 1970true 柯杨 1969true 高静,吴馥梅 1968true 杨福愉 1967true 韩玉珉,申同健 1966true 王玉环,吴国利 1965true 史超,汪云九,姚国正 1964true 高奔,张少吾 1963true 韩金祥,王鲁泉,王美岭 1962true 隋德新,姜涌明 1961true 陈丁丁 1960true 刘望夷 1959true 马建农,戚正武 1958true 冯博 1957true 邓国仁 1956true 徐堤 1955true 沈珝琲 1954true 姜涌明,隋德新 1953true 马青平,张志文 1952true 商慧深,许政恺 1951true 吕志良,张惟杰 1950true 蒋达和 1949true 胡卓逸 1948true 王盛武,于秉治 1947true 徐荻,刘新垣 1946true 廖万国 1945true K_m具有相似性,但其一级结构不同。乙酰胆碱酯酶催化效率很高,其催化机制包括靠近、定向、一般酸碱催化及电荷接力系统等过程。乙酰胆碱酯酶在粗面内质网内合成,其代谢过程受某些因素的调节,在某些病理状态下酶活性发生改变。]]> 朱美财 1944true 涂长春,殷震 1943true 胡红雨,鲁子贤 1942true 姜琨,童坦君 1941true 沈波 1940true 张光毅,赵升皓 1939true 林炳承 1938true 岳国华,朱尚权 1937true 陆承荣,丰美福 1936true 2+结合后可以进一步与膜磷脂结合。这类蛋白质广泛存在于动物细胞,常常与质膜或内膜系统相联系。免疫化学证据和对其氨基酸顺序、cDNA序列分析表明,这是钙结合蛋白中一个包括多个成员、结构与功能相关的新家族。]]> 郭艳林 1935true 陈建敏,李春海 1934true 梁宋平 1933true 冯文科 1932true 杨能,张惟杰 1931true 罗贵民 1930true 徐明波,姚志建 1929true 党进军 1928true 文耕云,董燕麟 1927true 岳国华,朱尚权 1926true 景键 1925true 宗建超,倪爱国,刘福森 1924true 曹忠升,康华光,邹寿彬,周专 1923true 詹金彪 1922true 熊克勇 1921true 100是LDL受体的专一性配基,介导血中LDL-胆固醇(LDL-Ch)被外周组织细胞摄取和清除。载脂蛋白B基因遗传变异和apoB异常,血中LDL-Ch堆积,导致动脉粥样硬化发生是冠心病危险因素。]]> 许霖水 1920true 王丽辉,童坦君 1919true ^·₂,可以和超氧阴离子反应生成氧化性极强的超氧亚硝基阴离子(ONOO^-).NO·与一些重要生物功能有关,它是内皮细胞松弛因子,可使血管平滑肌松弛,防止血小板凝聚.细胞免疫活化和组织缺血再灌注也产生 NO·.它还和神经传导及光接受器的信号发射等有关.]]> 赵保路,陈惟昌 1918true 张灵芝,谭敦勇,周爱儒 1917true 董华玲,沈政 1916true 刘秀,陈宜张 1915true 孙立民,陈惟昌 1914true 朱扬明,韦钰 1913true 张人骥 1912true 王拥军 1911true 王军,贾弘禔 1910true 叶昕,甘人宝 1909true 贺福初,吴祖泽 1908true 沈先荣,韩玲 1907true -,K⁺和 Ca²⁺通道传导的改变并产生神经元抑制效应.近年 GABA_AR 基因及其表达的研究,已为不同的种属、不同脑区域和细胞类型中 GABA_AR 的亚基组成、生理功能及其对很多中枢神经系统药物反应的多样性提供了令人信服的依据,可以预见不久这方面深入的探索也必将为有关该受体的神经精神病发病的分子机理研究及其治疗性药物的设计提出新的线索.]]> 陈俊杰,程汉华 1906true 万晓余,吴淑华 1905true 石颖,许根俊,鲁子贤 1904true 于昕,周爱儒 1903true 方炳良,罗会元 1902true 张大军,皇甫永穆 1901true 薛沿宁,王会信,周廷冲 1900true 黄莹,余湢,胡坤生 1899true 郑宝胜,徐明波,姚志建 1898true 李俊凤,吴奇久 1897true 2+的内流,其释放呈两相性,对 ATP 有严格要求.Glu 的代谢异常和过量释放会对突触后受体造成滥刺激而导致神经毒性.研究对这种神经毒性的拮抗是目前神经科学的重要内容之一.Glu 连续荧光分析法为这类研究提供了一个有力手段.此法简便,易于在国内大多数实验室中进行.]]> 潘家祜 1896true 石颖,许根俊,鲁子贤 1895true 徐军,陈润生 1894true 来鲁华,骆兆文,徐筱杰 1893true 屠红旻,夏其昌 1892true 肖国芝,贾弘禔,张迺蘅 1891true 李俊凤,吴奇久 1890true 胡昌勤 1889true 郭军,张平城,白春礼 1888true 郭宇立,倪逸声 1887true 邵丽清,董仁杰 1886true 朱茂祥,吴国利 1885true 2+通道区分为不同亚型.]]> 徐幼芬,施玉樑 1884true 卑其新,程极济 1883true 李建义,童坦君 1882true 朱大栩 1881true +-ATPase 的结构、作用机制进行了深入的研究,证明这是一类新型质子泵,在进化的过程中与线粒体类型的 H⁺-ATPase 有密切的亲缘关系.]]> 王延枝,许献忠 1880true Zhang Wenfa 1879true Wang Yingjie and Xu Abing 1878true Lu Baisong and Huang Peitang 1877true Yu Yongtao and He Fuchu 1876true cis-active elements,such as the CATT(A/T) repeat sequence, GC-rioh sequence，CK-1, CK-2，kB specific sequence and inducible CsA-sensitive enhancer, which are all located in the 5'-untranscriptional region of the hGM-CSF gene.At the post-tanscriptional level,a 62bp AU-rich sequence located at 3'-untranslation region of the mRNA is related to the stability of hGM-CSF mRNA. These mechanisms can up or down regulate the production of hGM-CSF when the cells receive the singnals from the stimuli of cytokines and other stimulating factors.]]> Shen Baohe,Guo Donglin and Sun Naien 1875true Feng Ruo,Zhao Yiyun,Li Huamao and Wang Jin 1874true Mao Jianping and Sun Zhixian 1873true Hu Hongyu,Du Yucang and Lu Zixian 1872true Qi Jie,Lu Zhibin,Wang Yuhong and Li Wei 1871true Wang Fengjun,Huang Wenhua and Li Ao 1870true Liang Songping and Pan Xin 1869true Cheng Yuankai 1868true Zhang Li and Jia Hongti 1867true Chen Ming 1866true Bombyx mori nuclear polyhedrosis virus (BmNPV) as a expression vector.The expressed products involve in many fields such as pharmaceutics, medical diagnosis, vaccine production and biological control. The characteristics of BmNPV and its genome structure,characteristics of polyhedrin gene,construction of recombinant BmNPV and its expression in the silkworm larvae and cell line, and efficiency of production for the foreign gene products expressed in the silkworm-BmNPV system and application of the expressed product were described systematically in the review.]]> Zhang Yuqing 1865true ＋ gradient formed by V-ATPase serve an improtant function in endocytosis , exocvtosis, membrane traffic and transport systems of cells. In the families of H^＋-ATPases, increasing attention is being given to V-ATPase, about which much has been learned in recent years.]]> Cai Huiluo 1864true Li Zhou and Fan Qixiu 1863true 1R and D₅R mediating the activation of adenylyl cyclase through G protein (G_s) and (b) D₂R, D₃R, D₄R, inhibiting the activation of adenylyl cyclase through the G protein (G_i) . The gene structure, distribution of their mRNA in the brain and location on chroniosomes between the two classes of dopamine receptors were compared.]]> Xing Cheng 1862true Hu Kunsheng 1861true Luo Guimin 1860true et al in 1990. Apo J is a 70kD glycoprotein, comprised of two disulfide-linked subunits designated apo Ja (34-36kD) and apo Jβ(36-39kD) . The sequence of the 427 amino acid residues of apo J was deduced by the cDNA cloning and sequencing. The predicted a helical regions of apo J indicated that three of these could generate amphiphilic α helices, and may be lipid - bind domains in apo J . Apo J mRNA was expressed in relatively high levels in brain，ovary，testis and liver .Apo J is unique among previous characterized human apolipoproteins in its structure and tissue distribution. The function of apo J is thought to be involved in a variety of physiological processes, including bind and transport lipids. regulation of complement function and sperm maturation etc.]]> Liu Bingwen 1859true Ma Wenli and Xue Shepu 1858true Liang Hua and Ma Dalong 1857true Yang Yu and Yu Bingzhi 1856true in vitro, VEGF also stimulates angiogenesis and increases blood vessel permeability in vivo. Because its bioactivity has a direct bearing on the growth of solid tumors, the researches on VEGF have been payed a good deal of attention and made good progress.]]> Xiu Bo and Zhou Airu 1855true Gong Guosheng and Qian Liqing 1854true Wang Hemu and Wang Zhou 1853true Ling Mingsheng,Xu Mingbo and Ma Xiankai 1852true Xu Wei,Pan Dongri,XingLi and Tang Jinghua 1851true Liu Jie and Ma Dalong 1850true Qian Liqing,Gong Guosheng and Wu Shengmei 1849true 2+-dependent regulatory mechanisms between the crustacean and vertebrate striated muscles are different. The ratios of the thick to thin myofilament of vertebrate striated, crustacean fast and slow muscles are 1:2,1:3 and 1:6 respectively, as well as the myofilament arrangement also differ from one another.The molecular assembly of the crustacean thick myofilament composes of myosin and paramyosin are differ from that of the vertebrate striated muscle.The thin myofilament comprises actin, tropomyosin, and troponin. The molecular weight of troponin T is relatively high, and troponin C has only single Ca²⁺-binding site. The thin and thick myofilament regulatory mechanisms coexist in the crustacean striated muscle.]]> Chen Ming and Zhong Yongmei 1848true Liu Xiong and Yan Longfei 1847true Rhodopseudomonas viridis and Rhodopseudomonas sphaeroides have produced crystals and been analysed with 3Å resolution. Two-dimensional crystal can be formed in a series of membrane proteins and the information of three-dimensional structure may be obtained by electronmicroscopy and image reconstruction.]]> Zou Yuping 1846true Lu Xiaoyan 1845true Liu Dinggan 1844true Liu Xiaoqi and Cao Enhua 1843true Yan Shuizhong,Zhao Xiaohang and Wu Min 1842true Yang Zhen,D. A. ROBB and Ji Liangnian 1841true Sun Jianzhong and Wang Keyi 1840true Wang Ling,Wang Zhenyi and Qi Zhengwu 1839true Zhang Jinsong and Liu Wangyi 1838true Hu Meihao 1837true cis-acting DNA motifs and trans-acting proteins, which consist of nuclear factors. Four sequences involved in DNA sequence recognition have been determined as follows; zinc fingers : leucine-zippers; helix-turn-helix and helix-loop-helix motifs. Research from viral and animal systems turn to plant gene expression systems. Evidence has shown that the interaction of nuclear factors is the basis and pre-requisite for the regulation of gene expression.]]> Shao Hongbo and Chu Liye 1836true E.coli(Escherichia coli) has been widely used in expressing foreign genes, but different foreign genes may exhibit very different expression efficiencies. This article is the review of factors that influence expression of foreign genes in E.coli. and it will be helpful to know the information in this field, in order to take effective measures to improve expression efficiencies of foreign genes in E.coli.]]> Sui Guangchao and Hu Meihao 1835true Sun Congmei and Zhou Airu 1834true Ye Zucheng and Cai Yipeng 1833true in vitro mutadons. The individual antibody gene can then be affinity matured by emulating the process that occurs in B-cells in vivo .The affinity matured antibody fragments are selected for their ability to bind antigen after phage recovery. This novel recombinant DNA methods may replace the technology of using mice and hybridoma for the selection and production of antibodies.]]> Zhang Zhiwen and Zou Changjiang 1832true I difference.]]> Guo Yaojun and Guo Qiang 1831true 王克夷 1830true Lao Weide 1829true 2 of complex Ⅱ and cytochrome b₅₆₂ of complex Ⅲ was found. This kind of interactions may playsome roles in modulating the electron transfer from complex Ⅱ to complex Ⅲ. The maximum reconstitutive activity of lipid-deplited succinate-cytochrome c reductase with mixed phospholipids PC:CL:PE=2:2:1 were obtained. this means not only the lipid but also thier composition were important for regulating the enzyme activiy of respiratory chain.]]> Xu Jianxing 1828true Zhang Jinsong and Liu Wangyi 1827true Long Jianyin and Wang Huixin 1826true Pan Huazhen 1825true Geng Jieping,Qi Zhengwu and Chen Zhu 1824true Chen Ruihuan 1823true Yang Heping,Zhou Airu and Tang Jian 1822true Diao Yuncheng 1821true Zhang Jinzhu 1820true Xiong Shunbin,Tang Chaoyu and Xu Genjun 1819true Liu Cunren,He Fuchu and Wu Zuze 1818true Ni Juhua,Jia Hongti and Zhang Naiheng 1817true Li Tong and Wang Enduo 1816true Tu Zheng,Zhang Zhiwen and Liang Keshan 1815true Sun Zhirong 1814true Wang Shengqi 1813true Mao Junhao and Lu Zhiliang 1812true in vivo and in vitro studies to assess DNA damage and repair induced by various agents,such as physical factors,e.g. UV,radiation,chemical factors,e.g. oxidants, trichloro-ethylene, acrylamide,bleomycin,as well as ageing and smoking,in a variety of mammalian cell lines. A panorama of the development of the SCGE assay，the mechanism and the procedures of the method，and its potential applications in DNA damage and repair，biomonitoring，cancer therapy researches，etc. is given.]]> Qin Chunhua,Shen Jianying,Huang Shihe and Wang Guangzu 1811true 1 and NC₂ domains in which COL domain,a main peptide,has two cleavage sites sensitive to collagenase. Short as is its chain, type X collagen displays a very stable property，and its melting temperature is up to 47℃. The gene of type X collagen，unlike other interstitial collagens，is composed of three exons and two introns，and the entire COL domain is encoded by a large exon-exon₃ which condenses the gene information. Type X collagen plays an important role during endochondral ossification and seems to be related to matrix degradation，mineralization and/or vascular invasion. Distribution and quantity abnormalities of type X collagen were observed in some osteoarticular disorders，such as osteoarthritis and rachitis. The mutations of type X collagen gene coding for NC₁ domain make the mutant polypeptides difficultly associate with each other，impair supramolecular assembles and lead to its disfunction in growth cartilage， which appears to elicit given inheritable chondrodysplasias.]]> Bai Xiaowen,Lu Shemin and Bai Cai 1810true Chen Yuan and Zhou Mei 1809true Cao Lihuan and Zha Xiliang 1808true Hou Ping and Wu Min 1807true Shen Runnan and Li Shuben 1806true Guo Xu,Xue Jun,Zhang Yan and Lin Bingcheng 1805true Yu Jun,Wang Jun and Jia Hongti 1804true Lin Qishan and Liu Guoquan 1803true Liao Xiangru 1802true Du Hongyan and Wu Fumei 1801true Wang Lu and Ma Dalong 1800true Zeng Zhaohui and Zhang Zongyu 1799true Lai Luhua and Yang Yuting 1798true E.coli, which are located in the inner membrane,the outer membrane,the periplasmic space or the environment,have a structure containing the secretion signal on the N or C terminal.These two sorts of proteins elbow through the inner membrane with the help of two series of distinguishable protein factors and realize their final position by an unelucidated mechanism. The molecule containing its signal peptide on the N terminal is assisted by protein factors of the Sec family when rushing through the cytoplasma membrane. The leading peptide might be cut off in the process. ATP and the electrical potential supply the energy for the secretion. The molecule which has secretion signal on its C terminal is helped by the Hly family members to pass the inner and outer membrave at the same time while omitting the periplasmic space.]]> Yuan Yu and Gan Renbao 1797true Kang Yibin,Wu Xiaohui,Wei Yong and Chai Jianhua 1796true cis-acting elements,eg. the liver-specific-enhancer at the 5' upstream region and the positive or negative transcriptional factors such as ARP-1,HNF-4,RXRα,the apo A-Ⅰ gene is regulated to express specifically.]]> Yin Yinliang,Wang Keqin and Chen Baosheng 1795true Li Ji and Zhang Hongyuan 1794true Sun Ziyong,Zhou Song,Hu Jianzhong,Zhu Dexu,Chen Xiaohua and Zhu Longgeng 1793true Wang Huaichun 1792true Lu Yifan,Deng Jixian,Xiao Chengzu and Ma Qingjun 1791true Fan Peichang and Liu Jiaying 1790true Dong Jiaxin,Ren Yunfang and Shen Beifen 1789true Wang Shaoxiong,Dong Chen and Hua Zichun 1788true Mao Junhao and Lu Zhiliang 1787true 7-MT is one of the well known zinc-cluster protein which is suggested palying a crucial role in the zinc homeostasis. It is very possible that zinc occupies the central part in controlling the growth and development of organisrns by means of successive regulation of MT and zinc finger proteins. In addition，it was found that some of regulation protein binding to oncogene and human immunedeficiency virus also contains zinc finger amino acid sequence，that will open a new field to fight against cancer and aids diseases.]]> Huang Zhongxian,Gu Weiqiang and Hu Hongyu 1786true Qi Maosong and Li Chunying 1785true Guo Yanlin and Sun Daye 1784true Cheng Jieke 1783true Zhou Chen and Xu Qian 1782true Han Xing and LiGang 1781true E. coli in the early 1980s,the protein factors have been detected in many kinds of prokaryotes,and their regulatory functions have been found in sporulation, cell fission of bacteria, heterocyst cyto-differentiation, N₂ fixation and photosynthesis in cyanobacteria etc. The recent research progress in the field was reviewed.]]> Zhang Weiwen 1780true 34 family to find out their regulation functions in cell cycle and the relationship between them. Simultaneously,many regulation factors which are related with them have been found.All these factors interact to form a very complicated cascade regulation network.]]> Xu Jinlin and Xu Qin 1779true Tang Lixia and Shen Xun 1778true Pseudomonas aeruginosa exotoxin A(PE)contains three structure function domains. The amino-terminal domain Ⅰ is involved in binding to target cell-surface receptors through the active site Lys57.The central domain Ⅱ is responsible for the translocation of PE across membranes,Arg276 and Arg279 are the active key positions of the domain Ⅱ.The protease cleaves PE between Arg279 and Gly280 into 28 000 and 37 000 fragments. The carboxyl-terminal domain Ⅲ is located in 37 000 fragment which is directed by the REDLK sequence at the carboxyl end of domain Ⅲ to the endoplasmic reticulum and translocated to the cytosol, and then ADP-ribosylates the EF-2 (elongation factor 2) by binding NAD⁺ through the key site Glu553 to result in the inhibition of cell protein synthesis and death of target cells. It is a practical prospect that the recombinant immunotoxins are made by fusing DNA fragments encoding recognition proteins to the modified PE genes.]]> Du Shiyu 1777true halobacterium halobium.It serves the function of photochromic materials and light-driven proton pumps,with an extremely fast primary photo-isomeric process occurring within 430ps. On account of the fact that bacteriorhodopsin has a series of unique photoelectrical and optical properties such as differential responsivity to light intensity,high spatial resolution,high photosensitivity,high cycling,etc.,it has found many important applications in photoelectrical detection. visual simulation system, artificial neural network, nonlinear optics and optical information recording and processing. Depended on the techniques of ultrafast pulse laser, highly time-resolved spectroscopy and high speed sampling detection. studies on bacteri-orhodopsin' s photocycle, primary photo-iso-merization，excited state dynamics，lightdriven proton pump mechanism and other aspects have been successfully developed with many significant results.]]> Yao Baoli and Xu Dalun 1776true Wu Xuejun and Chai Jianhua 1775true Zhang Jianzhi and Chai Jianhua 1774true in vitro. completing homologous recombination and selection of recombinant viruses in yeast and in E. coli, and making recombinant viruses to produce polyhedra, have been developed in recent years to construct the recombinant baculoviruses rapidly and conveniently. These improved methods are. therefore. to be described.]]> Shi Xianzong and Chen Quhou 1773true Cui Xiaojiang,Liu Zhiqiao,Tian Yingchuan and Peng Xuexian 1772true Cao Shugui 1771true Li Mingyi and Jia Hongti 1770true Jiang Bingkun 1769true Zhang Jingwei and Zhao Yongfang 1768true Fu Tihui and Xie Zhirong 1767true Zeng Xiaodong,Wang Yunjiu and Qi Xianglin 1766true E.coli,in Saccharomyces cercoisiae or even in vitro. Owing to the greatly increasing frequency of positive recombinant virus,the stocks of positive recombinant virus are obtained easily. The advantages and disadvantages of each method are discussed.]]> Zhu Fanxiu,Wang Fushan and Qi Yipeng 1765true in situ without the requirement for additional parameters, such as labelled moleculars.With high sensitivity,the sequential reactions during adsorption or desorption can be monitored. So far, the applications are involved in biological binding analysis, kinetics, affinity measurement, immuno-distinguish, structure-actmty study and nucleic acid research, etc.]]> Wang Luo and Tao Zulai 1764true In situ PCR is a novel technique in the field of molecular biology.It combied advantages of both PCR and in situ hybnridiztion(ISH).Its origin, development and methodology are intoduced.Its application and prospect are also discribed briefly.]]> Ma Qi,Zhang Xiyuan and Xu Yaoxian 1763true Saccharomyces cerevisiae systems provide instructive suggestions to the mechanisms of replication initiation in eukaryotic systems and maneuvers with which the initiation are concerted with cell cycle. Many functions of protein factors involved in initiation of replication in eukaryotic cells are being clarified. And the cycle-dependent regulatory pattern is gaining experimental supports. Two regulation points in cell cycle for DNA replication initiation and the roles played by cyclins are mainly introduced. The relationship between carcinogenesis and the disturbance of replication-cycle is also discussed at appropriate point, which hints at the significance of initiation regulation.]]> Dou Yali and Tong Tanjun 1762true Zhang Qunzhou,Zhou Keyuan and Ling Guangxin 1761true Wang Xiangdong and Tong Tanjun 1760true in vivo. An unknown protein which interacts with certain target protein can also be found by using this method.Consequently, the DNA sequence encoding the unknown protein can be cloned,the key amino acids involved in the interaction can also be decided. Drawing protein linkage map is its another application. Being used in drug design, two-hybrid system will have a more practical value in future.]]> Huang Jiaxue,Ma Xiaojun and Liu Ting 1759true Zhang Hongying and Zhang Jin 1758true Yang Xuehui,Feng Weijian and Wen Jinkun 1757true Liu Chunyu,Zhang Chuming and Xia Jiahui 1756true Wu Xiaodong and Yang Shijie 1755true Chen Yan 1754true Zhou Chunshui and Zhen Yongsu 1753true 2+ homostasis, incurable destruction of enzyme system, block of energy production and so on, It is still at experimental stage to use antioxidants in AIDS therapy.]]> Wang Lanfang and Zheng Rongliang 1752true Ye Yuanjie 1751true Halobacterium halobium. Wild-type BR contains a single-chain polypeptide of 248 aminoacid residues and a retinal attached to Lys216 of the peptide via a schiff base, BR has the function of proton pump, Upon illumination, BR goes through a photocycle which is considered to be correlated with its proton pumping process. The good progress has been made in the studay of the structure and function of BR, but the path of photocycle and mechanism of proton pump are still not clear. The progress of the structure, photocycle and proton pump of BR in recent years are briefly introduced. And the four models of the path of photocycle which are in great argument are discussed in detail.]]> Jiang Qiuxing and Hu Kunsheng 1750true Wang Qiongqing and Feng Youmin 1749true Chen Huaiyang and Liu Wangyi 1748true Huang Changhui and Fu Jiliang 1747true Li Baoyuan and Wang Daishu 1746true Zhao Shanrong,Tang Yun and Chen Kaixian 1745true Liu Cunren and Zhang Hongwei 1744true Chen Jinwen,Sun Changkai and Huang Yuangui 1743true Zhou Yuegang 1742true Jin Ningyi and Yin Zhen 1741true Fang Rui,Qi Jie,Zhou Hui,Li Wei and Shen Jiacong 1740true 1 and itself. When cells are damaged by toxic agents that induce DNA breakages, PARP molecules will bind to DNA breakage and their catalytic activity is activated. Then they modify their acceptor protein and trigger a set of cascade reactions. Thus PARP is a possible molecular sensor and transducer to initiate the signal transferring path for reacting to damages of the cell. The information which they passed may decide the fate of a cell: repair or death.]]> Luo Ying,Sun Zhixian and Wu Zuze 1739true Wang Xue and Wang Haitao 1738true Sun Tao and Liu Xuefeng 1737true Lei Zhangheng,Pan Xinghua and Fu Jiliang 1736true Li Deling,Wang Huixin and Zhou Tingchong 1735true 2+-ATPase activity, thereby smooth muscle contraction. The actin-binding domain of calponin lies in 38 residues (145-182). Ser175 plays a critical role in the interaction of calponin with actin and the inhibition of the ATPase. It also binds to calmodulin in a Ca²⁺-dependent manner. The calmodulin-binding domain is between residue 52 and 144. Both binding and inhibition of the ATPase can be regulated by phosphorylation and dephosphorylation of calponin.]]> Tang Dachun,Xiang Jizhou and Lu Wentong 1734true Luo Chunyuan 1733true Zeng Yiqing and Sun Fangzhen 1732true Long Jianyin and Wang Huixin 1731true He Cheng,Lu Changlin and Ao Shizhou 1730true Zhang Ligang,Min Jimei and Zhang Lihe 1729true Wang Qingda and Lin Qishui 1728true Wang Qingding and Sun Manji 1727true In vitro genetics is a method for isolating and studying functional nucleic acid molecules in test-tubes based on their special phenotypes (e. g. binding properties, catalytic properties). In vitro genetic provides an effective, active method for determinating and artificial evolution of nucleic acid function sequences,so it was widely used in investigating the regulation of gene expression and biochemical reaction.The progress of in vitro genetic methods and applications in recent years is reviewed.]]> Shi Guoli and Chen Defeng 1726true 1 restriction point and G₁/S checkpoint. Furthermore, p21 gene can be regulated by wild type p53. p21 plays a role in p53 mediated G₁ arrest which is induced by DNA damage. Expression of p21 gene is 10～20 times higher in senescence cells than in proliferating cells. It begins to express when muscle cells start differentiation. These results demonstrate that p21 plays a major role in cell proliferation, differentiation and senescence.]]> Meng Xiangbing and Ye Changqing 1725true Zhou Anwu,Guo Jun and Du Yucang 1724true Zhou Le,Qian Jufen and Wang Jianchen 1723true Guo Xiangxue,Shi Dingji and Ru Binggen 1722true Zhang Mei and Zhu Zuoming 1721true Li Zaiquan and Liu Bingwen 1720true Peng Renwang,Guan Kaomei and Huang Xiuli 1719true in vitro.]]> Chen Ying,Huang Yongfen and Wang Qingyin 1718true Tang Jingrong and Sun Manji 1717true Lu Yi,Pan Huazhen and Xu Caimin 1716true Zhou Aiwu,Wu Haihong and Xu Xianxiu 1715true Jiao Xinfu and Shu Huying 1714true Jin Hong 1713true Cai Youqing 1712true +), and is a recently discovered second messenger. cADPR is active in mobilizing intracellular Ca²⁺ in invertebrate as well as mammalian cells. The mechanism of releasing Ca²⁺ from internal pool (s) has been studied. cADPR may bind its receptor, which in turn induces the release of Ca²⁺ from cADPRsensitive Ca²⁺ pool(s) through ryanodine receptor or ryanodine receptor-like mediated Ca²⁺ channel. In addition,a possible intracellular signal transduction pathway involving nitric oxide(NO)，cyclic guanylic acid(cGMP ) and cADPR has been suggested to exist in various cells.]]> Zhang Xiaohui and Zhu Peihong 1711true Dai Xuming,Pan Xinghua and Fu Jiliang 1710true E. coli. TRCF is a DNA binding protein with ATPase activity. In eukaryotes, some DNA repair proteins were found to be involved in transcription. For example, the largest subunit of general transcription factor TFⅡH, p89, is the encoding product of human excision repair gene ERCC-3 .And the excision repair gene RAD3 of yeast encodes the largest subunit of transcription factor b, p85.]]> Zhou Pingkun 1709true +.(2)Heat dissipation correlated with the thylakoid membrane energization and xanthophyll cycle. This mechanism exists in LHCⅡ，and responses quickly at relatively lower excess light stress (3) Heat dissipation via photosystem Ⅱ hetero-geneity and the turnover of D1 protein. This mechanism bases on the hypothesis that there are two kinds of photosystem Ⅱ.One is photosyn-thetic active with higher linear electron transport and higher fluorescence emission but lower heat dissipation. The other is photosynthetic inactive with lower linear electron transport, lower fluo-rescence' emission and higher heat dissipation. The latter is called dissipative PSⅡ .This dissipative PSⅡ can be reactive directly without protein synthesis or indirectly through D1 protein turnover process.]]> Li Xiaoping,Chen Yizhu and Guo Junyan 1708true Cai Youqing 1707true Liu Yongxue,He Fuchu and Wu Zuze 1706true Jiang Chuancang and Fan Leming 1705true Hui Hongxiang,Zhao Xiaoning,Jin Ming,Wang Chengji and Mo Jian 1704true Huang Wen and Wang Chunxin 1703true 2O₄^2- ) and MgATP are enough or only one is enough.]]> Huang Jingwei,Zhang Hongtu,Wan Huilin and CaiQirui 1702true in vivo. There are two hypotheses about the mechanism of enhancement: disrupting the peritrophic membrane (PM ) and facilitating the penetration of virions or increasing the attachment and fusion between the virion envelope and the midgut cell membrane. The proteins are encoded by virus. The first enhancin gene has been cloned and sequenced.Since enhancins can shorten the life-span of infected larvae and increased the effectiveness of biopesticides，it will stimulate the widespread application of viral pesticides.]]> Hu Wei,Li Lulin and Hong Huazhu 1701true Zhang Jingpu 1700true Yang Qisheng 1699true Yang Shaohua and Chen Junjie 1698true in vivo is also involved in regulating lipid metabolisms and hormone cycles. The present researches on the mechanisms of the modulation of cellular functions by DG, are mostly concentrating on its effects on cellular signalling transduction.]]> Sun Junhui and Zhu Peihong 1697true Liu Dongyuan and Fang Fude 1696true LIAN Dejun and XU Genjun 1695true WANG Die and LIN Qishui 1694true CHEN Zhengliang 1693true LIU Xiaoqiong and SHI Xianzong 1692true YU Wendou and ZHANG Jinzhu 1691true ZHAO Zhensheng,LI Hui,WU Mingzhong and ZHAN Jidong 1690true in vitro and in vivo, leading to cell cycle arrest associated with a dramatic decrease in the levels of cyclins and cyclin-dependent kinases(CDKs), and accompanied by an obvious increase of the expression of one of the cdk inhibitors, p21waf1/cip1. p21 waf1/cip1 protein(p21) can also mediate p53 dependent or p53-independent G1 arrest of many cell types, and plays an important role in PGA2-induced cell cycle arrest. Latest progress on the role of interaction of p21 and transcription factor E2F played in PGA2-mediated cell cycle arrest is reviewed.]]> DONG Weiren,PENG Biyou and LI Jin 1689true ZHU Bin and WANG Guoquan 1688true in vivo is thought to be due to their conversion into more reactive species, including hydroxyl radical, and probable ferryl iron species. The experimental material and theoretic result have shown that in addition to generation of hydroxyl radical, the ferryl iron species have been proposed to be involved when iron salts are mixed with hydrogen peroxide. The reactive intermediate of Fenton reagents is a nucleophilic adduct. The products profiles and reactivity for Fenton reagents are different from those for free hydroxyl radical and depend upon the transition metal, the ligand, the solvent matrix and substrate.]]> WANG Yuqiu and HE Xiwen 1687true trans-Golgi compartment participates in the biosynthesis of glycoconjugates. The long form on cell surface mediates cell-cell and cell-matrix interactions by binding to appropriate glycoside substrates on adjacent cell surfaces or in the extracellular matrix, including spermatogenesis, sperm-egg binding, early embryo cell adhesion, secondary trophoblast giant cell migration and neurite outgrowth, and functions as a signal-transducing receptor for extracellular oligosaccharide ligands to affect G protein signal cascades. Surface GalTase also delivers a growth inhibitory signal by modulating the ability of the EGF receptor to transduce EGF-dependent signals, and plays an important role during cell growth.]]> ZHANG Chunyu,DUAN Enkui,ZENG Guoqing and LIU Yixun 1686true LIU Aixiao and LIU Guoqin 1685true GUO Nini and WANG Enduo 1684true SHU Zhanyong and BI Ruchang 1683true PANG Zhanjun,CHEN Yuan and ZHOU Mei 1682true 5 M13mp2 DNA molecules can be detected. Besides, the kinetic rate constant of the reaction and the activation energy of deamination can be calculated.]]> CHEN Hong and LI Yumin 1681true 5-TR region of Epstein-Barr virus genome encodes a latent membrane protein (LMP-1). As the protein can transform B cells and plays a key role in the carcinogenesis of EB virus, so it has become the “hot spot” of studying for the diseases relavance to EB virus, such as nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkins disease etc, and also the molecular biology of EB virus. A series of achievements have been achieved, the progress in following aspects are reviewed: 1. the structure and expressing regulation of BNLF-1 gene; 2. the structure and biochemical function of LMP-1 protein; 3. the biological function of LMP-1; 4. looking forward to the future.]]> MA Xianyong,CAO Ya and YAO Kaitai 1680true ZENG Xianchun,JIANG Dahe,LI Wenxin and B.PERBAL 1679true In vivo, FKBP12 maintains a tight association with calcium release channel and forms a complex. This interaction plays important roles in modulating calcium release channels.]]> SUN Junhui and ZHU Peihong 1678true WANG Yutian,HU Jialu,CHEN Sumin and YANG Shengli 1677true LI Lin 1676true YU Ping,LIU Chuan and WANG Huixin 1675true LIAN Jun,CHEN Danmei,GUO Aike and CHEN Runsheng 1674true cis-elements and trans-factors are involved in this process. Based on the results of in vitro reconstitution transcription and the discovery of RNAPⅡ holoenzyme in yeast respectively, two models, step-wise assembly model and RNAPⅡ holoenzyme model, were proposed on the assembly of basal transcription initiation complex at promoters. Two related processes, antirepression and true activation, were supposed to be the molecular mechanism of the transcriptional activation.]]> YOU Zhongsheng and WANG Yuan 1673true REN Qinghu and TONG Tanjun 1672true MRP) was found in the study of the mechanism of multidrug resistance of cancer. The cognate gene is located on chromosome 16 at band P13∶3. Its mRNA encodes a member of the ATP-binding cassette transmemberance transporter superfa-mily with a mass of molecular 190 ku (p190). The MRP is mainly located on the plasma membrane and may play a role in the ATP dependent transport system. Further study indicates that apart from some kind of cancer cell lines, MRP overexpression was found in some blood malignancy, breast cancer, lung cancer and so on. The overexpression may be also related to the relapse of cancer.]]> BI Feng,ZHANG Xueyong and FAN Daiming 1671true ZHAO Kongshuang 1670true in vivo. The obtained clones provide valuable tools for investigation on the distribution and physiological roles of these receptor channels.]]> WANG Wen and XU Tianle 1669true in vitro, selenium has the regulatory role on HIV replication by inhibition of transcription factor NF-κB and HIV-1 long terminal repeat (LTR) promoter activity. These demonstrated a basis for the potential therapy use of Se to control disease process.]]> CHEN Chunying,ZHOU Jingyan and XU Huibi 1668true HUANG Fen 1667true HU Changqin 1666true TANG Weigang,GAN Renbao and WANG Keyi 1665true ZHU Guanshan,MIAO Weimin and JIAO Binghua 1664true WU Fumei,XU Xiaohong and QIANG Mei 1663true in vivo. The growth-promoting effects of insulin appear to be mediated by its own receptors, but in some cells, insulin appears to stimulate growth at high concentrations by activating insulin-like growth factor Ⅰ(IGF-Ⅰ) receptors. The post-receptor signal transduction consists of a series of receptor-associated tyrosine protein kinase activated intracellular protein phosphorylation and dephosphorylation reactions, such as the phosphorylation of insulin receptor substrate-1(IRS-1), Shc, Ras and phosphatidylinositol 3-kinase (PI3-K). It is supposed that some regions or sites on the insulin molecule may contribute more to the growth-promoting effects, and some preliminary evidences have come from the studies on several high mitogentic potent insulin analogues.]]> SHI Min and FENG Youmin 1662true ZHAO Ming,Yoneda Masahiko and Kimata Koji 1661true in vivo footprinting study.]]> JI Xinjun,LIU Depei and LIANG Zhiquan 1660true DU Guangwei,YUAN Jiangang and QIANG Boqin 1659true YANG Xiao,ZHANG Zhaoshan and HUANG Cuifen 1658true LU Yifan,DENG Jixian,XIAO Chengzu and MA Qingjun 1657true ZHAI Junhui,CUI Hong and YANG Ruifu 1656true Bombyx diapause hormone and pheromone biosynthesis activating neuropeptide, are encoded in a single gene.]]> XU Weihua 1655true SUN Yingqing,GUO Yan and RU Binggen 1654true E.coli is still the first choice of host when foreign gene is expressed. Heterologous proteins could be expressed directly in the cytoplasm, secreted into the periplasmic space or extracellular medium. Recent developments on E.coli expression system are covered, according to the possible destiny of foreign proteins.]]> LONG Jianyin and WANG Huixin 1653true 2+ can manipulate intracellular calcium concentation (［Ca²⁺］_i) by photolyzing specific photosensitive Ca²⁺ chelator in the cell to change its affinity with Ca²⁺. This technique is especially useful in elucidating the intracellular messenger role of Ca²⁺ in cell functions such as electrical excitability, muscle contraction and secretion, etc.]]> XU Jianhua,QU Anlian and KANG Huaguang 1652true LI Yong,LI Tong and WANG Enduo 1651true ＋-ATPase, MIP system and function of free radical reactions in the process are discussed. Finally, some important aspects for further investigation are suggested.]]> QIAN Zhongming,PU Yongmei and TANG Paklai 1650true DUAN Jubao and WANG Jiaxi 1649true ZHANG Man and ZHOU Airu 1648true TU Yizeng,CAI Minying and QU Xianming 1647true 2＋/Mg^2＋ nuclease,Ca^2＋/Mn^2＋ nuclease, DNaseγ, nuc58 and nuc40;The divalent cations independent nucleases mainly include DNaseⅡ and DNaseⅡ like nucleases.Moreover,the effect of nucleases on chromatin DNA degradation and the mechanism of this process were discussed.]]> DENG Youping and XIAO Peigen 1646true XIA Lu and QIU Guanying 1645true LU Liqun and QI Yipeng 1644true CHEN Zhong-Bin,WANG Sheng-Qi and SUN Zhi-Xian 1643true HE Hai-Qiong and WANG Jin-Fa 1642true ZHOU Zhi-Qi and LIU Qiang 1641true XIONG Ying 1640true ZHU Mei-Jun,WANG Xue-Chen,CHEN Jia and DU Min 1639true MAO Jian-Ping and SUN Zhi-Xian 1638true CHEN Ya-Li and LU Zu-Hong 1637true H) and light chain (V_L) are stabilized by an interchain disulfide bond. dsFv is more stable, an important biochemical feature for the preparation and handling of these proteins in clinical setting.]]> MAO Chun-Sheng,SONG Hong-Bin and WANG Hai-Tao 1636true －9 s. It therefore may open the door for the structure determination of membrane proteins and large complex and assembly as nucleosome core particle. The molecular weight of solution structure determined by NMR has beyond 35 000. Now the structural biology is marrying with the genomics to produce a new “big science”, the structural genomics, which will provide a large step towards the understanding of life in the postgenomic ear.]]> WANG Da-cheng 1635true in vivo or in vitro is positively correlated with their metastatic potential. Once stimulated by motile factor, tumor cells can promote their migration by themselves through chemotaxis and haptotaxis, the molecular mechanism of which is unclear at present yet.]]> JIANG Xin-nong and ZHOU Rou-li 1634true MA Wen-jian and CAO En-hua 1633true LIN Yong and WANG Zhong 1632true TONG Xin and SUN Zhi-xian 1631true in vitro synthesis of protein using cellular extracts has been a routine technique in molecular biology labs for twenty years. But it has seldom studied in our country. The characteristics including types, preparation, basics, functions and progress of cell-free systems are introduced. Its advantages and disadvantages are also discussed. It is beneficial for the application and understanding of the technique by our researchers in applied biochemistry and molecular biology assays.]]> WANG Jing-lin and GAO Pei-ji 1630true ＋/H^＋ exchangers (NHE) are vital transmembrane transporters involved in multiple cellular functions including the regulation of intracellular pH, the control of cell volume and ion transport. Five isoforms of Na^＋/H^＋ exchangers have been cloned and characterized to date; they constitute a new gene family of vertebrate transporters. And these isoforms are highly regulated by a remarkably wide variety of stimuli which can modulate their expression level and activity. Among the isoforms, the increased expression level and activity of human NHE-1 have been found to play a role in some critical diseases, such as tumor, hypertension and diabetes. Thus it may provide a new way of diagnosing and treating for these diseases by investigating on the transcription modulation of NHE-1 gene and the activity regulation of the exchanger.]]> HUANG Gui-jun and QIAN Gui-sheng 1629true YANG Jia-shu and RU Bing-gen 1628true ZHOU Wei,MIAO Wei-min and JIAO Bing-hua 1627true in vivo. The first-generation recombinant adenoviruses that lack E1 sequences have shown tremendous promise in animal and human models of gene therapy. Having some limitations at aspect of efficacy and safety,the adenovirus vectors are being gradually improved to resolve these problems. The developments of construction of adenovirus vectors in increasing the efficacy and safety was described.]]> LIU Xue-feng,ZHANG Lian-feng,WANG Li-hua and CAI You-yu 1626true 1, topoisomerase Ⅰ & Ⅱ, HMG I/Y, lamin B₁, and matrins.) and some tissue-specifically expressed proteins, including SATB₁ (special AT-rich binding protein 1) and osteocalcin gene promoter-binding factors. By the relationship with the nuclear matrix, these MAR-binding proteins can be classified in three groups, nuclear matrix-abundant composition, rare composition and non-nuclear matrix composition. Their interactions with MARs were compared and analyzed as well.]]> ZHOU Cong-zhao,QIAN Xin-guo and LI Zhen-gang 1625true LIU Bao-ying and WANG Hui-xin 1624true WANG De-an and XIA Jia-hui 1623true SUN Xue-guang and CAO En-hua 1622true － channels are found in all of cellular and subcellular membranes which have been determined. As housekeeper, they play vital roles in many different processes, such as regulation of cell volume, pH, resting membrane potential and excitability. Because the classical electrophysiological investigation has not been able to clearly charactarize a macroscopic Cl^－ current, as was done for Na^＋，K^＋ and Ca²⁺ current, Cl^－ channel are ignored for many years. The recent explosion in knowledge of Cl^－ channel is owing the technical using of single channel recording and molecular biology. The ionic permeation, selectivity, gating and pharmacological properties as well as the molecular clone and structure of background Cl^－ channels, the most widely existed Cl^－ channel in biomembranes, are reviewed.]]> ZHANG Guang-ping and SHI Yu-liang 1621true LU Xiao-feng,XIA Yu-xian and PEI Yan 1620true in situ hybridization, a new promising molecular cytogenetic technique, permits the simultaneous detection several specific nucleic acid sequences in interphase as well as metaphase by using cohybridization of probes labeled with serveral fluorescent labels or label combinations. It provids a simple, fast, and reliable means to assess genetic instability in cancer. This approach is being applied generally in physical mapping,mutation research, tumor pathology and prenatal dignosis.]]> YANG Ming-jie and CAO Jia 1619true CAO Ao-neng,LAI Lu-hua and TANG You-qi 1618true HE Ping and TANG Zhao-you 1617true ZHU Hao,SHI Nai,FAN Ying-xin and ZHOU Jun-mei 1616true LU Cun-fu,WANG Hong,JIAN Ling-cheng and KUANG Ting-yun 1615true ZHAI Da-yong and SHEN Li-ming 1614true MU Xiao-min and LIU Yi-xun 1613true LIU Liang,LAI Lu-hua and LI Chong-xi 1612true in vitro models of neuronal apoptosis have been developed, such as induced by nutrition deprivation, free radicals, glutamic acid, Ca²⁺ ,β-amyloid peptide etc. The detective technology of neuronal apoptosis is composed of testing the changes in enzymes and proteins which reflected neuronal damage, simultaneous morphological observation, and finally DNA electrophoresis etc, which could confirm the apoptosis.]]> ZHANG Ning-yuan,ZHU Li and GAO Jing 1611true PENG Rui,QIN Jun-chuan and SONG Xiao-ling 1610true LI Yong and WANG En-duo 1609true ZHENG Xiao-fei,WANG Sheng-qi and SUN Zhi-xian 1608true 2 or inositol-1,4,5-trisphosphate (IP₃)). All these implied that PH domain might play an important role in the interaction between the signaling molecules and help to form the signal transduction network.]]> WANG Ji-cun and YAO Li-bo 1607true LI Chong-hui 1606true in vivo to recognize and stabilize unfolded or partially folded polypeptides, and protect polypeptides from inappropriate intra- or interchain interaction. In some circumstances, the chaperones interact with native proteins and promote rearrangement of oligomeric complexes. Stemming from their ability to recognize and modulate the state of folding of polypeptides within cells, the molecular chaperones serve many functions including mediating mitochondrial protein translocation, regulating signal pathway and being involved in microtubule nucleation.]]> YU Jun,MA Kang-tao and ZHANG Nai-heng 1605true ZHANG Ping-bo,HONG Xi-jun and LIU Yan 1604true ZHANG Jian-bo and TIAN Geng-yuan 1603true ZHAI Da-yong and SHEN Li-ming 1602true ZHENG Li,LIU Chuan and WANG Hui-xin 1601true 2+ sensitivity in the transmitter release system is responsible to the synaptic block induced by BoNTs. Directly intracellular introducing of BoNTs shows BoNTs have no intracellularly cholinergic specificity and inhibit secretion from all types of cells. (2) Binding experiments indicate the binding of BoNTs includes an initial low-affinity step and a subsequent high-affinity step. The low-affinity receptors might be gangliosides, while the high-affinity receptor might be synaptotagmin, a synaptic vesicle membrane protein. (3) The intoxication of BoNTs is more appropriately described by a four-step process: binding to the preferential receptors, internalizing by the process of receptor-mediated endocytosis, membrane translocation and escaping endosomes by an acidification process, as well as selectively cleaving the proteins involved in exocytosis as an enzyme. The carboxyterminus and the aminoterminus of the heavy chain as well as the light chain play important roles in tissue targeting, internalization, and intracellular target modification respectively. The internalized light chain cleaves the proteins involved in the fusion of synaptic vesicles so that the exocytosis as well as the transmitter releases are inhibited.]]> SHI Yu-liang and HU Qian 1600true XU Zheng,SUO Zhi-yong,WEI Xian-wen and ZHU De-xu 1599true ZHANG Zhi-hong and WU Lu-ping 1598true 1 is thought to deform the catalytic sites to give binding change. When the crystal structure of the F₁-ATPase was eventually solved, direct evidences for rotation of subunits during catalysis of F₁-ATPase were provided.]]> ZHOU Jun-mei 1597true YANG Qi-sheng 1596true via the glycine amino nitrogen and methylenecarbonyl linkers. PNA can bind to complementary oligonucleotides by Watson-Crick base paring with high thermal stability and exhibit wide biological effects including modulating the function of DNA sequence specific binding protein and modulating the transcription and translation in vivo or in vitro. Many applications have been explored for PNA as a new kind of molecular biological tools. Despite its DNA(RNA)binding properties, recent progress has shown that PNA has potential for the development of gene-targeting pharmaceuticals.]]> LI Xiao-xu,ZHANG Liang-ren,ZHANG Li-he and CHEN Yao-zu 1595true 2+ requirements for half maximum activities. Both calpains have a large subunit and a small subunit, with molecular weights of 80 and 30 ku respectively. Large subunit is composed of 4 domains. Small subunit is composed of 2 domains. Recently, several tissue specific calpains were discovered, adding to the complexity of calpain system. Calpastatin is an endogenous suppressor of calpain, which can bind to activated calpain specifically and made them inactive. There are 5 domains in calpastatin, domain L and 4 repeated domains numbered 1 to 4 which are responsible for their inhibity effects. Calpain activity is restrictively regulated in living cells. Membrane attachment reaction can low the Ca²⁺ requirement of calpain to be activated. The negatively charged phosphate groups on the polar head of membrane phospholipids are inportment for that activation. Autolysis also can low the Ca²⁺ requirement of calpain.]]> Du Min,NAN Qing-xian and Zhu Mei-jun 1594true XU Jin-lin and XU Mo 1593true JIANG Zhi-hong and LI Bo-liang 1592true YUAN Yu-ren and XIA Zong-xiang 1591true XIAO Hua-sheng and CHEN Bin-fu 1590true WANG Ping and FENG You-Min 1589true WANG Cheng-Xing and CAO Ya 1588true JIANG Guo-Chun and YUAN Li-Zhen 1587true L,Bcl-X_S and Bcl-X_γ,are generated by alternative splicing.Bcl-X_L and Bcl-X_γ inhibit apoptosis. However,Bcl-X_S enhances apoptosis. Bcl-x plays a role in cell development,homeostatic balance, tumorigenesis and prognosis, which regulates apoptosis through interacting with Bcl-2, Bax, Bad and so on.]]> CHEN Yang-Chao and ZHOU Ke-Yuan 1586true JIN Zhao-Hui,LI Wei and PAN Hua-Zhen 1585true ZHU Hong-Bo and LUO Jian-Hong 1584true ZHOU Lu,LI Yue-Zhong and LI Jian 1583true CHEN Yuan and ZHOU Mei 1582true ZHANG Hao,WANG Quan-Li and MAO Bing-Zhi 1581true ZHANG Yu-Xiu and CHAI Tuan-Yao 1580true REN Jian-Guo,ZHOU Jun and DAI Yao-Ren 1579true CHEN Geng,ZHOU Jian-Xin and DONG Yan-Lin 1578true DENG Wen-Sheng,YANG Xi-Cai,PENG Yi and KANG Liang-Yi 1577true CAO Xue-Song 1576true FAN Zu-Sen and AO Shi-Zhou 1575true CHEN Wei-Jun,ZHAO Gui-Wen and GU Yue-Hua 1574true XIAO Hua-Sheng and HUANG Wen-Jin 1573true YANG Zheng,CAI Chen-Leng and SONG Yun-Chun 1572true TANG Gui-Lin and SU Xian-Shi 1571true HE Gen and MAI Kang-Sen 1570true YU Fang-Yuan and ZHOU Yuan-Guo 1569true 2+ influx and improve the function of GluRs, whereas dephosphorylation do on the contrary. The reversible phosphorylation of GluRs keep balance in normal conditions which play an important role in synaptic plasticity such as LTP, but it can enhance excitatory neuronal damage in pathological events such as ischemic brain damage when the balance lose.]]> GAO Can and ZHANG Guang-Yi 1568true ZHU Shun-Yi and LI Wen-Xin 1567true ZHU Xiong-Wei,WANG Yan-Zhi and WANG Huan 1566true Satschra,LIU Meng-Min and HE Fu-Chu 1565true in vivo. Recent studies have revealed the existence of a novel family of multicomponent receptors for GDNF family, composed of distinct glycosyl-phosphatidylinositol(GPI)-linked cell surface proteins and a shared transmembrane tyrosine kinase receptor, Ret.]]> DONG Min and HU Bing 1564true in situ hybridization and gene knock-out mice models in the study on the regulation of these neurotrophins and their receptors in the inner ear development. The application of exogenous neurotrophins has great clinical potential for the cure of hearing loss.]]> HU Bing and CHEN Xiang-Chuan 1563true ZHANG Zhi-Lei,GE Ji-Guang and GUO Xiao-Hui 1562true CHEN Xi 1561true neu/c-erbB-2 is a receptor tyrosine kinase. It's overexpressed in some adenocarcinomas, such as breast cancer and ovary cancer. It not only plays an important prognostic role, but also acts as a therapeutic target in breast cancer. Its function in signal tranduction is described. The protein engineering of antibodies against p185 and their application in cancer therapy is also discussed.]]> WANG Chen and LIU Jing 1560true YU Ting-Xi,ZHU Ying-Bao and TONG Tan-Jun 1559true Haemophilus influenzae, Saccharomyces cerevisiae, C.elegans, Drosophila melanogaster and human diseases.]]> HU Zhi-Yuan and HE Fu-Chu 1558true in vitro and in vivo. The satisfactory results were obtained from healing bone defects in many kinds of experimental animals with hOP-1.Recombinant hOP-1 has prospective clinical application.]]> WANG Jian,WU Hui-Lian and HAN Jin-Xiang 1557true 2+ receptor, is an important constituent of cellular signal transduction systems. In recent years, much progress has been made on the three-dimensional structure of calmodulin, this leads the scientists to understand the mechanisms of the activation of calmodulin by Ca²⁺ and the interaction between calmodulin and its target enzymes. A concise description is given on the 3D structures of Apo-calmodulin, Ca²⁺-calmodulin and the complex of calmodulin with its target peptides and antagonists.]]> MA Li-Geng,SUN Da-Ye and YAN Long-Fei 1556true zif268 codes for a transcription factor ZIF268. The expression pattern of zif268 in developing visual cortex is regulated. zif268 is highly expressed in adult visual cortex which experienced normal visual input. After visual deprivation, the expression level of zif268 is strongly down-regulated, while visual stimulation can significantly increase the expression level of zif268. The studies concerning the expression pattern of zif268 offer further insight into the physiological functions of zif268 in the mammalian visual system.]]> DING Pei,WEI Qing and WANG Yao 1555true L,MCL-1,CED-9,BAG-1,E1B-194 and A1 act as death repressors, whereas BAX, BAk, BCL-X_s and BAD promote cell death. These different functions were shown to be mediated by homodimerzation/heterodimerization of the various family members. Therefore a critical balance between molecules above may determine the fate of cells in reponse to apoptosis-inducing conditions.]]> LIU Tao-Wen 1554true MO Bi-Lan,LI Jiang and LIANG Song-Ping 1553true 2+ dependant proteolytic enzyme. MMPs expression is regulated strictly by growth factors, cytokines, and hormones at transcription level, by their natural activators and inhibitors at protein level. MMP participate various cells physiological and pathological process by degrading different ECM components.]]> ZHAO Yun-Ge,Orbit ANWAR and ZHU Cheng 1552true 15N,¹³C,²H labeling multidimensional NMR techniques, and this limit will probably be surpassed in the near future.]]> GAO Guang-Hua and WANG Da-Cheng 1551true YAN Bo-Xu,QI Fei,ZHANG Ying-Shu and GAO Pei-Ji 1550true SHEN Wen-Biao,XU Lang-Lai and YE Mao-Bing 1549true In vivo, the sugar conjugation of ecdysteroids by EGT causes suppression of host molting. The deletion of egt gene actually improves the pesticidal properties of the baculovirus. Insects infected by an egt-minus virus display reduce feeding and earlier death than those infected by wild-type virus. The recent advances in the studies of the egt gene and protein, EGT-catalyzed conjugation, EGT effects on host development and suvival as well as biological role of EGT are introduced.]]> YAN Qing-Sheng,OUYANG Xiao-Guang,LI Chong-Bi and PANG Yi 1548true CHEN Pei-Li,TONG Tan-Jun and ZHANG Zong-Yu 1547true 8(9)-double bond and 17-side chain of the substrate lanosterol are the key functional groups for the correct enzyme-substrate interaction and high catalytic turnover. The discussion about the structure-activity relationship (SAR) of two series inhibitors of the enzyme, substrate analogues and azole antifungals, provides the better basis for further high potent inhibitors design.]]> JI Hai-Tao,ZHANG Wan-Nian and ZHOU You-Jun 1546true H and POU_S) and variable linker between them. POU proteins interact with DNA by POU_H and POU_S. In aid of the domain flexibility and requirement of cofactors, POU proteins exhibit very complicated ability to bind and recognize DNA in function of regulator and transcription factors. In vertebrate and invertebrate, POU proteins take part in early embryogenesis, exert much regulation in cell lineage differentiation and neural development.]]> YANG Qi-Sheng and WU Min 1545true Drosophila to man. Wnt proteins, as well as other growth factors or signaling molecules, have the characteristics of secreted growth factors. As recently, a group of proteins in Frizzled (Fz) family have been identified as the putative receptors of Wnt family,several components are implicated in the downstream of Wnt/Fz signaling pathway, such as Dishevelled, GSK3 (glycogen synthase kinase 3), APC (adenomatous polyposis coli) and β-catenin.This signal transduction pathway plays a pivotal role not only in the formation and organization of developing organs, but also in biological tumorigenesis.]]> ZHUANG Li-Yan,GUO Ying-Lu and ZHANG Zhi-Wen 1544true ZHANG Qing-Shuo and WANG En-Duo 1543true in vivo may be to regulate the growth and to initiate implantation of blastocyst. LIF expression is under maternal control, which is influenced by steroid hormones and cytokines. Gp130, a signal transducer receptor component shared by the cytokines such as LIF, IL-6, OSM and CNTF,can convert the low affinity LIFRβ into a high affinity form, and its homodimerization (in the case of IL-6) or heterodimerization (in the case of LIF,OSM and CNTF) can activate tyrosine kinases, which further regulate expression of target genes by some kinds of pathway.]]> CAI Li-Quan,DUAN En-Kui and ZHU Cheng 1542true FENG Wen-Zheng,CAO Zhu-An and LIU Jin-Yuan 1541true XIE Fang,LIU Jun and ZHANG Yong-Lian 1540true in vitro, and very good results were shown. Some investigation have been done in vivo. These results demonstrate the potential clinical use of antisense nucleotides for hepadnavirus infection.]]> LIN Ru-Xian and WANG Sheng-Qi 1539true ZUO Wei and SHEN Zheng 1538true in vivo. Type ⅠB BMP receptor plays major roles in chondrogenesis, osteoblast differentiation and programmed cell death in vivo and in vitro. BMP receptor signaling molecules Smad1 and Smad5 are also cloned and characterized. They also play important roles in BMP receptor mediated function.]]> CHEN Di,YE Wei-Sheng and CAI Fang 1537true HU Hong-Yu and XU Gen-Jun 1536true DU Xin and TANG Jian-Guo 1535true ZHANG Xiao-Guang,YAO Li-Bo and SU Cheng-Zhi 1534true LI Hong-Jun,GUO Ying-Lu and ZHANG Zhi-Wen 1533true LI Wei-Zhong,WANG Ren-Xiao,LIN Da-Wei,MAO Feng-Lou,HAN Yu-Zhen and LAI Lu-Hua 1532true YANG Gen-Yan and ZHANG Yong-Lian 1531true GAO Bo and YIN Gui-Shan 1530true ZHOU Jun-Mei 1529true et al. The commonly used identification methods are amino acid analysis, protein sequence tags and peptide mass fingerprinting. The flow chat of proteome analysis is shown, and in particular the latest proteome technologies are summarized.]]> CHENG Hai-Ping and QIAN Xiao-Hong 1528true 2+ ions. They are heterodimeric proteins consisting of two highly homologous peptide chains linked by a single disulfide bridge. Each chain contains one Ca²⁺-binding site and an intrachain disulfide-bonding pattern similar to those of C-type carbohydrate recognition domain. The amino acid sequences of this family exhibit high homology amid them. The crystal structure of habu coagulation factors Ⅸ/Ⅹ-binding protein has been determined. It is an intertwined dimer with a central loop projecting into the adjoining chain. Excluding this loop, each chain has a fold similar to rat mannose-binding protein.]]> XU Xiao-Long and LIU Qing-Liang 1527true QIU Quan-Sheng 1526true E.coli employs a collection of Sec(secretion) proteins that catalyze the translocation of various polypeptides through the inner membrane. The targeting of periplamic proteins after the cleavage of signal peptide is commonly regarded as a default process, while the final destination of outer-membrane proteins needs the help of other factors and is well accepted as a periplasmic intermediate process.]]> GE Gao-Xiang and LIN Qi-Shui 1525true ZHANG Ru-Gang,WANG Xing-Wang and XIE Hong 1524true E.coli expression system and in vitro RNA replication system,it was demonstrated that the de novo synthesis of RNA could be catalyzed by NS5B,which resembles other viral RdRp.The biochemical properties and the mutation-function relationships of RdRp of HCV were comprehensively reviewed,and the potential of NS5B as an important new target for antiviral therapy was also discussed.]]> CHEN Zhong-Bin and WANG Sheng-Qi 1523true CHEN Jian,ZHANG Xiao-Qin and FU Ji-Liang 1522true + or Na⁺ flux. At present its rotary dynamics and torque-generating mechanisms were understood preliminarily.As a perfect research model for molecular rotary motor,the further study of flagellar motor would be very helpful for realizing the mechanisms of bioenergetic conversion and cell motility,thus its study is of widespread importance for biology.]]> DENG Guo-Hong,XU Qi-Wang,LIU Jun-Kang and CONG Yan-Guang 1521true 5 copies per genome. They can be divided into families and subfamilies according to the mutational or diagnostic sequence loci. SINEs are widespread in eukaryotic genomes and create additional sequence combinations through dispersal and exchange of genetic information. So, they are believed to be of major importance in creating genetic diversity, gene inactivity, new gene, and especially in gene expression and gene regulation. Almost all SINEs reported to date are derived from tRNAs, with the exception of the primate Alu and the rodent B1 families, which are derived from 7SL RNA. The tRNA-derived SINEs have a composite structure, with a region homologous to a tRNA, a middle tRNA-unrelated region, and a terminal AT-rich region. Each SINE contains an internal promoter for RNA polymerase Ⅲ and lacks open reading frames. “Master source gene model”, “multiple source gene model”, “transposon model (parasitism model)”, and “horizontal transfer model”have been postulated to explain the origin and evolution of SINEs. The observation of their molecular phylogeny was made with examples of salmons, whales and artiodactyls，hominoid primates，and western Palearctic water frogs. Their application to genetic profiles and antitumor technique was also introduced.]]> HAN De-Min,ZHOU Kai-Ya and WANG Yi-Quan 1520true FENG Bing,WANG De-Wen and HE Zuo-Yun 1519true 2VD₃ and TNF-α)regulate the expression of OPG/OCIF gene. The mechanisms by which OPG/OCIF inhibits bone resoption can be concluded that: 1) OPG/OCIF inhibits survival of osteoclasts and induces apoptosis of osteoclasts; 2) OPG/OCIF inhibits formation of osteoclasts.]]> HE Zhi-Yong,LI Ming-Feng,ZHANG Wei-Jie and WU Xiang-Fu 1518true LIU Ding-Gan 1517true Bacillus thuringiensis has been revealed to be three distinct domains. It has been found that different Cry toxins share similar structures. Domain Ⅰ, consisting of a bundle of α-helices in which a hydrophobic helix 5 is surrounded by 6～7 amphipathic helices, plays a unique role in pore formation. Domain Ⅱ, consisting of three antiparallel β-sheets with a loop at each apex, is responsible for receptor binding. Domain Ⅲ consists of two twisted, antiparallel β-sheets forming aβ-sandwich with a “jelly roll” topology, it might prevent the activated toxin from excessive degradation.]]> SHAO Zong-Ze,LIU Zi-Duo and YU Zi-Niu 1516true in vitro offers an efficient way for study on them. Now the focus is on the origin and location of NSCs in brains and their transplantation for therapy of CNS(central nerve system) diseases.]]> TANG Jiong,ZHAO Shou-Yuan and LI Chang-Ben 1515true 2+. It can also release Ca²⁺ through 2Na⁺/Ca²⁺ exchanger and mitochondrial permeablize transition pore. Therefore, the time-spatio characteristic of cytosolic calcium signal can be regulated and related cellular function can be affected by mitochondria. However, due to the limitation of technique used now, confused and contradictory results are often obtained and further exploration is needed.]]> CHEN Liang-Yi,ZOU Shou-Bin and KANG Hua-Guang 1514true JI Qing-Zhou,REN Hong-Wei,LI Ling-Yuan and RU Bing-Gen 1513true XU Hai-Ming,ZHANG Shen,LIU De-Pei and LIANG Zhi-Quan 1512true LIU Guo-Qi and WANG Hai-Tao 1511true in vitro and in vivo. The βⅡ-turn in the central tetrapeptide and the N-terminal tripeptide segment of decapeptide LHRH antagonists play an important role in receptor binding.]]> GAO Xing-Ming,TANG Yan-Chun and YE Yun-Hua 1510true 2O₂). The cloning of MAO A and B genes has demonstrated that the enzymes are made of different polypeptides. MAO A and B genes are located on the X-chromosome (Xp11.23) and consist of 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B exhibit distinct differences in the substrate selectivity and inhibitor sensitivity and play different role in the neurotrasmitter metabolism and behavior.]]> CHEN Jian-Feng and WANG En-Duo 1509true LIAO Shun-Yao and LU Cheng 1508true YAN Min-Jun and WANG Yun-Jiu 1507true ZHAO Chen-Yang and ZHENG Rong-Liang 1506true LUO Gui-Min 1505true In vitro evolution of enzymes use error-prone PCR , DNA shuffling and mutator stains. Many useful enzymes have been isolated following the artifical evolution.]]> DAI Ming-Hua,ZHU Ying-Min,JIANG Wei-Hong and ZHAO Guo-Ping 1504true CUI Da-Xiang,YAN Xiao-Jun,WANG Feng and SU Cheng-Zhi 1503true WANG Yuan-Liang,PAN Jun and CAI Shao-Xi 1502true KOU Ru-Qin,WANG Wei,LI Ling-Yuan and RU Bing-Gen 1501true LI Zhao-Yu,ZOU Wei and CUI Zhao-Chun 1500true ZHANG Ping and WANG Jin-Quan 1499true in vitro and in vivo. It has been used in transgenic mice to induce site-specific DNA recombination leading to gene expression or deletion/mutation not only in a tissue-specific or at a certain stage of development, by combining with inducible systems for controlling Cre expression or function, but also in temporally and spatially manner. These recombination-based strategies are likely to have a profound impact on study of gene function and the generation of animal models of human diseases.]]> ZHU Huan-Zhang and SHI Jing-Quan 1498true Aequorea victoria has emerged. It has been widely studied and used in biochemistry and cell biology. The protein emits green light (λ_max＝508 nm) when excited with ultraviolet (UV) or blue light (λ_max＝395 nm, minor peak at 479 nm). It is extremely useful as a marker for monitoring gene expression and as a tag in studying protein localization in organisms, intact cells and organelle. Mutagenesis and engineering of GFP fused into chimeric proteins are opening new prospect in physiological indicators, biosensors, photo-chemistry and production of luminescent fiber.]]> LIU Mo-Fang and WANG En-Duo 1497true in vitro assays. So they are thought to participate in the lipid transferring during biomembrane synthesis. Their purification, structure, gene expression and biological functions have been studied in various monocotyledonous and dicotyledonous plants. The latest studies found that they are secreted and located in the cell wall, and that it is suggested that plant LTPs are possibly related with cutin formation, defense reactions against phytopathogens and plant adaptation to various environmental stresses.]]> ZHANG Ming-Yong and LIANG Cheng-Ye 1496true XIONG Qing,WANG Bo-Chu and DUAN Chuan-Ren 1495true XU Bing-Sen and SHAO Jian-Zhong 1494true NI Rui,WU Xin-Nian,QI Xiang-Lin and WANG Yun-Jiu 1493true WANG Wen-Bing,ZHANG Zhi-Fang,HE Jia-Lu and Lü Hong-Sheng 1492true in vitro and in vivo as can low density lipoprotein(LDL), which causes many changes in HDL properties, such as peroxidation of polyunsaturated fatty acids, hydrolysis of phosphatidylcholine, apolipoprotein aggregation or degradation. HDL oxidative modification in vivo might be induced by arterial endothelial cells, macrophages and blood polymorphonuclears, monocytes. Ox-HDL might metabolize through scavenger receptors but not normal HDL receptors. Ox-HDL has many atherogenic roles. Vitamin E, C supplementation can inhibit HDL oxidation and may prevent the atherosclerosis.]]> FU Qiang and LIU Bing-Wen 1491true 1-ATPase and the bacterial flagellar motor. The molecular motors play an important role in the cell transport,DNA replication, transcription, and ATP synthesis.]]> WANG Hong-Bin and WANG Jin-Fa 1490true 2 to C₁，and ring closure of the product. GI gene has been cloned，sequenced and overexpressed in the homologous and heterogous hosts. GI whose properties have been improved by protein engineering may be one of the most important industrial enzymes of the future.]]> ZHU Guo-Ping,CHENG Yang,GONG Chun-Hong and XU Chong 1489true 121～206) are produced from a single VEGF gene by alternative splicing of the VEGF mRNA.The regulation of angiogenesis induced by VEGF and how to inhibit its effects arouse great interests.The function of VEGF in angiogenesis regulation was reviewed in several aspects.]]> XIAO Yang,JIAO Bing-Hua and MIAO Hui-Nan 1488true WEI Wen-Hui,SONG Yun-Chun and QIN Rui 1487true HUANG Xing-Xu and HUANG You-Guo 1486true FEN-1 gene contains two conserved regions and one PCNA binding region.]]> SHI Bin-Shan and YU Ying-Nian 1485true ZHU Guo-Ping,CHENG Yang,LIAO Jun and XU Chong 1484true Pichia pastoris has been utilized widely as a heterologous gene expression system recently. There are several advantages such as high productivity, stable inherity, secretable product, and mature fermentation techniques. The advances of vector types, vector elements(including promoter, selection marker and signal sequence), host strains, and the strategy for increasing integration copy number were reviewed.]]> OUYANG Li-Ming,ZHANG Hui-Zhan,ZHANG Si-Liang and LIU Zhi-Min 1483true LI Ai-Fen,CHEN Min and ZHOU Bai-Cheng 1482true 2+/calmodulin-dependent protein serine/threonine phosphatase, broadly distrbutes in various mammalian cells and involve into regulation of cellular function. It was known that CaN play a central role in T cell activation and is essential to transmitter release and synapic plasty. It is reported recently that CaN is likely a link of Ca²⁺ signal with cardiac hypertrophy. The advances in the molecular structure, enzymatic propertied, distribution and biological function of CaN were summrized.]]> FU Min-Gui and TANG Chao-Shu 1481true Escherichia coli 70S ribosome have been reconstructed. The picture of the ribosomal model are detailed, including the placement of the mRNA, the arrangement of the A-site and P-site tRNAs and the peptidytransferase within the interface gap as well as the path of nascent polypeptide chain, which results in a better understanding of the structure and function of ribosome as well as the translational process.]]> LIU Shu-Qun and LIU Ci-Quan 1480true XIE Tao,LIANG Wei-Ping and DING Da-Fu 1479true LI Min and CHEN Chang-Qing 1478true JIA Fan and ZHOU Yi-Feng 1477true ZHAO Jian-Hua,WANG Xiu-Qin,LIU Zhi-Hua and WU Min 1476true LIU Xin-Wen,TONG Tan-Jun and ZHANG Zong-Yu 1475true Caenorhabditis elegans is a very suitable model system for study of animal development. Based on the fixed cell lineage of Caenorhabditis elegans, many procedures involved in development, such as cell interaction, signal transduction mechanism, cell programmed death and multigene regulation of development, can be studied and clarified in the future.]]> FENG Liang and LIAO Xiang-Hua 1474true In vivo transfer the insulin gene to animals can improved control of the diabetes. New therapeutic approaches to diabetes which are based on gene technology and implications for future are summarized.]]> ZHANG Shu-Yun,GE Wei and QIAN Kai-Xian 1473true QIN Rui,WEI Wen-Hui and SONG Yun-Chun 1472true 2+ pathways with their related protein molecules such as PKC,CaM,CaMKⅡ,and Ras with their related protein molecules(such as Vav,Rap,Crk,C3G),cAMP,NF-κB pathways as well. Through the above mentioned four pathways and the cross-talk among them,extracellular signal molecules activate some protein kinases which regulate gene transcription and other related functions.It should be noted that phosphorylation plays a significant role in regulating the activity of protein kinases and transcript factors.]]> PANG Sa and GONG Xing-Guo 1471true ZHAO Jin-Rong,YAN Xiao-Jun and SU Cheng-Zhi 1470true XIONG Shi-Qin and ZHU Xi-Hua 1469true WEI Wan-Li and SUN Man-Ji 1468true YU Xue-Mei and GUO Shun-Xing 1467true ATP) which couple cell metabolism to electrical activity are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K⁺ channel (K_IR6.x) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/ K_IR6.x)₄. SUR and K_IR6.x genes come in pairs in chromosome. K_IR6.x subunit forms the electrical pore of the K_ATP channel and SUR endows the K_ATP channel with sensitivity to regulators such as sulfonylurea drugs, K⁺ channel-opening drugs, and Mg²⁺ nucleotides. The characterizations of K_ATP channel subtypes are determined by the combination of SUR and K_IR6.x subunits. The gates of K_ATP channels are ion-gated by ［ATP］_i and ［ADP］_i. Phosphatidylinositol phosphates (PIPs) antagonized ATP inhibition of K_ATP channels and cellular phosphotransfer cascades also involve in the regulation mechanism of ATP/ADP. K_ATP channels are inhibited by sulfonylurea complexes (SUs) and activated by K⁺ channel-opening drugs. G protein and protein kinase such as PKA, PKC, PKG also participate in the regulation of these channels. K_ATP channels play crucial roles in the secretion of insulin, preconditioning of cardiac myocytes and maintenance of blood vessel tone.]]> LIU Jie,JIANG Yong and ZHAO Ke-Sen 1466true q to stimulate PLC; activating G_i to restrain adenylyl cyclase and stimulate MAPK cascade; and activating G_12/13 to stimulate Rho cascade, etc.]]> MA Rui 1465true CHEN Chang-Po,MIN Ji-Mei and ZHANG Li-He 1464true LI Jian and WANG Zhi-Zhen 1463true MENG-Bin and WEN Bo-Gui 1462true CHEN Qi-Jun,WANG Xue-Chen and LIU Qiang 1461true cis-element for binding to transcription factor, thus leading to prevention of the endogenous gene expression. “Decoy” strategy was not only a novel strategy for gene therapy but also a powerful tool for the study endogenous gene regulation.]]> WANG Fu-Long,XU Xiang,LIANG Hua-Ping and LIU Xin 1460true RAO Heng-Yi and CHEN Lin 1459true lats gene (large tumor suppressor gene), first identified in Drosophila melanogaster, has its homologues in mouse and human. The function of lats is highly conserved from Drosophila to human. Its function includes: as a tumor suppressor gene, lats mutation will result in a tumor phenotype; phosphorylated Lats can bind to Cdc2 and regulate cell cycle; Lats may also be involved in size control mechanism via cell-cell communication. The study of lats function from Drosophila to human can provide a method to study gene functions in mammals using Drosophila as a model organism.]]> CHEN Wei-Li,DENG Ke-Jing,T. S. GREGORY and XU Tian 1458true PENG Hua-Zheng,PAN Jian-Wei and ZHU Mu-Yuan 1457true SONG Xin and CAO Ya 1456true XU Wei-Wen,LI Wen-Quan and MAO Yu-Min 1455true LIU Dong-Sheng and WANG Jin-Feng 1454true Lü Feng-Lin and HE Feng-Ci 1453true QIN Da-Nian 1452true LI Ping,XU Xiang-Min and YANG Xiong-Li 1451true C) remains unclear. But recently evidence is showing that PrP^C could specifically bind to Cu²⁺ and may transport Cu²⁺ to SOD1 by endocytosis from the plasma membrane via clathrin-coated pits so that taking part in copper metablism. Moreover, other evidence also shows that Cu²⁺ could enhance the reversibility of denatured PrP^Sc and may determine the difference of some PrP^Sc strains.]]> LI Ning and QIN Jun-Chuan 1450true ZHANG Su-Ping and LIANG Ai-Hua 1449true TAN Wen-Fu,XIAO Dong,WANG Jia-Long and DING Jian 1448true ZHANG Jian and DUAN En-Kui 1447true TAO Ye and ZHANG Jing-Pu 1446true SUN En-Jie,YAN Yu-Hua and XU Yun-Hua 1445true ＋-dependent and their sequences show a considerale degree of similarity and all are approximately the same size (～75 ku). All known eukaryotic DNA ligases are powered by ATP. DNA ligase Ⅰ is required for Okazaki frament joining and some repair pathways; DNA ligase Ⅱ appears to be a degradation product of ligase Ⅲ; DNA ligase Ⅲ has several isoforms, which are involved in repair and recombination of DNA.]]> ZHANG Bo and MENG Zi-Qiang 1444true st amino acid which is encoded by the UGA triplet in selenoproteins mRNA. Incorporation of selenocysteine in selenoproteins is rather complex but has been widely elucidated in prokaryotes. Four gene products (SELA, SELB, SELC, and SELD) and a specific stem-loop secondary structure which is termed selenocysteine insertion sequence (SECIS element) are required. However, the biosynthetic pathway of selenoproteins in eukaryotes may proceed by different routes in such aspects as the position and structure of SECIS element, specific elongation factors and other RNA-RNA or RNA-binding protein factors interactions. Observations also showed that translation of UGA as Sec in mammalian cells was an inefficient process and the regulation of the same UGA codon existing in an identical position in mRNA serves different functions (stop codon and Sec codon) might be involve in this process.]]> HUANG Zhi,XIANG Jun-Jian and GUO Bao-Jiang 1443true ZHANG Ling,LIN Cheng-Tao and WANG Heng 1442true ZHOU Zu-Ping and LIU Shu-Sen 1441true 373 and Ala³⁷⁴, a site different from the matrix metalloproteinases cleavage site, Asn³⁴¹～Phe³⁴². The discovery of aggrecanase and searching for its inhibitors will accelerate the development of therapeutic agents for arthritis.]]> LI Jing-Ya and YE Qi-Zhuang 1440true in vivo. As an antiapoptotic cytokine, BLyS provides survival signals by inducing up-regulation of Bcl-2. Transgenic mice overexpressing BLyS in lymphoid cells develops symptoms characteristic of systemic lupus erythaematosus (SLE).]]> WU Yi-Fan and ZHANG Shuang-Quan 1439true BI Zhi-Chu,H.T. TIEN and A.L. OTTOVA 1438true 1) are upstream kinases of IKK. MEKK₁ preferentially activates IKK-β,whereas NIK efficiently phosphorylates both IKK-α Ser176 and IKK-β. Through cascade reaction, IκBs are phosphorylated by IKK and dissociated from IκB- NF-κB complex, NF-κB dimer enter the nucleus and activate a series of genes.]]> WANG Yong and HUANG Wen-Hua 1437true HUANG Xin-Qiang and SONG Si-Yang 1436true i, voltage and cytokines on the modulating of gap junction are introduced. Gap junction is an information channel between the adjacent cells, with the function that delivering message and coordinating the actions of cell groups, but its formation and its function on the physical events need more research. The lower pH_i closes the gap junctional channel and it is explained by “particle-receptor” model. The increase of voltage downregulates the conductance of the channel. Cytokines regulate the permeability of gap junction by changing the synthesis and degradation of connexin, enhancing the phosphatizing the connexin.]]> YANG De-Hong,GAO Tian-Ming,CHEN Jian-Ting and JIN Da-Di 1435true GUO Shu-Zhen,TONG Tan-Jun and ZHANG Zong-Yu 1434true Ni Fu-Tai and Li Yong 1433true SONG Zhi-Gang and WANG De-Hua 1432true JIAO Hong-Li,YE Ping and ZHAO Bao-Lu 1431true FENG Xiao-Li 1430true ZHENG Xiao-Fei and SUN Zhi-Xian 1429true 2-terminal kinase), and inhibiting tumor cell growth. Moreover, the overexpression of TALL-1 in transgenic mice can result in severe B cell hyperplasia and autoimmune lupus-like disease. Therefore, TALL-1 functions as a potent regulatory factor in vivo and in vitro.]]> LIU Cun-Ren 1428true LUO Meng and JIA Ji-Zeng 1427true ZHANG Xiao-Guang,YAO Li-Bo and SU Cheng-Zhi 1426true Sun Ying and Sun Da-Ye 1425true 2＋ ,cGMP. Although great advances of signal transduction of reactive oxygen species has been taken in recent years，there are many important questions remained to be answer in future.]]> QIU Rong and ZHENG Rong-Liang 1424true HU Xiao-Yan,ZHOU Yan,YUAN Jian-Gang and QIANG Bo-Qin 1423true LIU Yao-Bo,WANG Jia-Zheng and FAN Ming 1422true Drosophila. Positional cloning work proceeded in mice recently has revealed that Lps encodes the Toll-like receptor 4 (TLR4) of mammals, which functions as the transmembrane component of LPS receptor complex. In contrast, TLR2, a receptor closely related to TLR4, makes no contribution to LPS induced signaling. The discovery of TLR4 has greatly promoted understanding on the LPS signal transduction pathway.]]> GONG Xiao-Wei and JIANG Yong 1421true WANG Liang-Hua,SI Yu-Hong and JIAO Bing-Hua 1420true HUANG Yue,LIU De-Pei and LIANG Zhi-Quan 1419true de novo ligand design and the rough docking for known chemical database screening for drug discovery. Their demands for the global minimization algorithms are different. New stochastic and deterministic global minimization algorithms that are suitable for docking problems are briefly reviewed. Those algorithms with potential smoothing techniques seem to be promising and are worth close noting.]]> LI Wei-Jiang 1418true ZHANG Yong,XU Jin-Lin,CHEN Chun and GU Jian-Xin 1417true OUYANG Li-Ming,ZHANG Si-Liang and LIU Zhi-Min 1416true E.coli.]]> ZHANG Ming 1415true Hox genes in mammals are the homogenetic genes of homeotic selector genes (HOM genes) in Drosophila. These genes include an encoding sequence of 183 bp, which encode a conservative protein domain of 61 amino acids. Both the nucleotide sequence of Hox gene and their position on the chromosomes are highly conservative. Hox genes are important in the regulation of spatial information during development, such as the differentiation of somites. Each somite acquires its own specialty according to its singular spatial position. Recent studies suggest that Hox genes not only influence embryonic development, but also have effects on the differentiation of adult reproductive system. They play an indispensable role in the establishment of uterine receptivity and the decidualization.]]> BAI Yu-Yan,FAN Heng-Yu and YANG Zeng-Ming 1414true LI Qi and HU Hong-Yu 1413true FAN Hong-Kuan,ZHOU Hui and LI Wei 1412true WAN Feng-Yi and HU Kun-Sheng 1411true ZHANG Wen-Li,YAN Qiu and ZHU Zheng-Mei 1410true In vivo and in vitro studies have shown that PACAP exhibits multiple activities especially a trophic activity during ontogenesis, notably in the adrenal medulla and the central nervous system. The biological effects of PACAP are mediated through three distinct receptor subtypes which exhibit differential affinities for PACAP and VIP. The PAC1 receptor, which shows high selectivity for PACAP, is coupled to several transduction systems. In contrast, VPAC1 and VPAC2, which bind with the same affinity for PACAP and VIP, are mainly coupled to the adenylyl cyclase pathway. In conclusion, PACAP is neuropeptide, and it functions as a hypothalamic hormone, neurohormone, neuromodulator, vasodilator, neurotransmitter or trophic factor in the brain and the various organs.]]> LI Xi-Long and ZHAO Xin-Xu 1409true LI Shi-Ying and LI Xiao-Hui 1408true in vivo.]]> ZHANG Han-Bo and DING Hua-Sun 1407true 9-tetrahydrocannabinoid ［(－)Δ⁹-THC］, a psycoactive derivative of marijuana. Fatty-acid amide hydrolase (FAAH), which is involved in hydrolyzing anandamide to arachidonic acid and ethanolamide, may quickly regulate level of anandamide in vivo.]]> LIU Wei-Min and DUAN En-Kui 1406true CHEN Wei-Chang,CHEN Zhi-Hua,QIU Hong-Xia and WANG Zi-Qiang 1405true TANG Li-Ling,WANG Yuan-Liang,PAN Jun,LU Xiao and CAI Shao-Xi 1404true LI Feng,GUAN Yong-Jun and CHEN Zhu-Chu 1403true 2^-_· in mitochondria. The role of mitochondria in anti-oxidant functions and cell apoptosis is discussed in terms of electron leak of respiratory chain, uncoupling of oxidative phosphorelation, mitochondrial pore, Box- or/and PTP-mediated release of cytochrome c from mitochondria and so on. The signaling act of ROS is emphasized in the regulation of cell apoptosis.]]> ZHAO Yun-Gang and XU Jian-Xing 1402true ZHANG Gui-Zhi,HUANG Gui-Jun and GUO Xian-Jian 1401true Saccharomyces cerevisiae genome sequencing, the gene disruption technique for systematic analysis meets the need of the functional genomics in yeast. It also enlighten the study on human functional genomics.]]> XU Zhi-Gang,HUO Ke-Ke and LI Yu-Yang 1400true XU Jun and TONG Jian 1399true XIE Jun,LIU Ci-Quan,HUANG Jing-Fei,SHI Xiu-Fan and SHAO Dan 1398true L inhibit cell apoptosis via mitochondrion while Bax, Bak and Bad induce apoptosis by means of regulation of mitochondrion.]]> CAI Xun,CHEN Guo-Qiang,CHEN Zhu and WANG Zhen-Yi 1397true LIU Jin,YUAN Jian-Gang and QIANG Bo-Qin 1396true FAN Heng-Yu,BAI Yu-Yan and YANG Zeng-Ming 1395true CHEN Ying,GE Yi-Qiang,LI Wen-Bin,ZHANG Li-Ming and SUN Yong-Ru 1394true TIE Guo-Dong,DUAN En-Kui and ZHAO Xing-Xu 1393true LIU Zhe,PENG Jing-Pian and ZHU Cheng 1392true in vivo directly; the other is to transfer objective genes to one proper kind of transplantable cells firstly, then graft the highest expressing cells to the target-cells in vivo. To realize the transfer of genes to cells, two measures are used in common: physical or chemical measure such as micro-infection et al and biochemical measure i.e. gene modified defective virus. Although there are some questions unresolved in this field, the clinical value of gene therapy of SCI in the future is depended.]]> ZHU Wei and SHI Jian 1391true WANG Ji-Cun,YAO Li-Bo and ZHAO Zhong-Liang 1390true LUO Ying,SUI Jian-Li and TIE Yi 1389true RTN (reticulon) is a gene family localized on the membrane of endoplasmic reticulum. Up to now RTN1,RTN2,RTN3,RTN4 in this family have been found. While further studies to dissect the concrete function of these genes in the protein secretary pathway and to identify the RTN1 as a marker of specificity of neuroendocrine secretion and its relation to the differentiation of neurons have been doing.]]> HUANG Xiao-Wei,YIN Bin,YUAN Jian-Gang and QIANG Bo-Qin 1388true + or Cl^－ channels, in addition to the knowledge of many kinds of long-chain peptides with the specificity on Na⁺ channels. According to the similarity of molecular structure and/or function, they have been classified into several groups. These short-chain scorpion peptides are playing more and more important role in studying the structure and function of K⁺ or Cl^－ channels. The advance of structure and function of short-chain scorpion peptides in recent years was briefly introduced.]]> CHEN Bing and JI Yong-Hua 1387true ZHU Yong-Hong and ZOU Quan-Ming 1386true XIN Hong,YAN Guang-Tao and CHEN Ban-Zao 1385true CHEN Jian-Ming and YU Ying-Nian 1384true LIN Jun and HUANG Jing-Fei 1383true INK4a/ARF gene locus on human chromosome 9p21, is one of the most frequent targets of inactivating mutations in the human tumors. Containing two different promoters, INK4a/ARF can encode two distinct proteins in alternative reading frames, p16^INK4a and p14^ARF (the mouse homologues is called p19^ARF). p16 is a recognized tumor suppressor that induces a G1 cell cycle arrest by inhibiting the phosphorylation of pRb by CDK4/6. While ARF inhibits oncoprotein MDM2, resulting in the stabilization of p53. These activities of ARF promote p53-mediated G1 and G2/M cell cycle arrests or apoptosis. So just like p16, the ARF protein also acts as a tumor suppressor.]]> PENG Li-Xia,ZHANG Wei,HE Da-Cheng and LIU Hui-Tu 1382true WENG Liang and FENG Yan 1381true p38α knockout mice, which is one member of MAPKs, is very typical in filtering noise from critical signals in signal transduction and translating phenotype into gene function. Looking back on the research of p38α knockout mice showed: the reasonable use of gene knockout technology, based on carefully designed and analyzed mutant mice, is very important for defining the function in vivo of important signal molecular and pushing forward the research of function gene.]]> WANG Feng-Yang,CHANG Zhi-Jie and CUI Yu-Dong 1380true in vitro.Combinatorial modify groups libraries offer the convience in the SELEX process,making the screening process fast, easy and high-throughput.Here the current designs and application of modified nucleotides for in SELEX process are reviewed, and expected to further the utility of this method in both practical and theoretical terms.]]> LIU Xiao,LI Chang-You and CHEN Yuan-Ding 1379true in vitro and in vivo and efficiently mediated the expression of interest genes. These results indicated that baculovirus could be developed as potential gene therapy vectors. The recent development and prospects on using baculoviruses as target gene delivered vectors in gene therapy is reviewed.]]> LIANG Chang-Yong,HU Zhi-Hong and CHEN Xin-Wen 1378true ZHANG Peng-Hua and CHEN Lan-Ying 1377true ZHU Shi-Guo and LI Gui-Yuan 1376true ZHANG Ling-Qiang and HE Fu-Chu 1375true PENG Li-Tao,JIANG Yue-Ming and YANG Shu-Zhen 1374true ZHANG Li-Sheng and CHEN Da-Yuan 1373true Drosophila's neural system. Due to the research on the formation and retrieval of memory, mushroom bodies might play an important role in the formation of long-term memory, and the signal transmission between the dorsal paired medial cells and the mushroom bodies might contribute a lot to the retrieval process of memory. Experiments in different paradigms on the flight-simulator have demonstrated the existence of some advanced functions of the mushroom bodies, so as to provide more evidences to the research on the integration of visual signals.]]> WEN Ai and LIU Li 1372true 2+ ions, to complete it's function. However, hairpin ribozyme can be considered as a distinct one that does not require metal ions as cofactors. In the genomic HDV ribozyme, a metal ion functions as a general base and a cytosine residue functions as a general acid.]]> WANG Jun-Feng,LIAO Xiang-Ru and FU Wei 1371true Arabidopsis, C.elegans and fungi. Latest study shows that 21～25 nt small interference RNA (siRNA) can mediate specific gene silencing in mammal cells. Being effective and highly specific, RNAi probably becomes a novel technique in knocking gene down and plays important roles in gene function study and gene therapy of diseases.]]> SUN Jian-Guo,LIAO Rong-Xia and CHEN Zheng-Tang 1370true ZHOU Qing-Jun,SHAO Jian-Zhong and XIANG Li-Xin 1369true DONG Hui,LI Yue-Zhong and HU Wei 1368true GUO Jian-Jun and GONG Xing-Guo 1367true XUE Wen,WANG Jin,HUANG Qi-Lai,ZHENG Wei-Juan and HUA Zi-Chun 1366true 2+ and phospholipid binding proteins. Annexins consist of a conserved C-terminal or core domain that confers Ca²⁺-dependent phospholipid binding and an N-terminal domain that is variable in sequences and length and responsible for the specific properties of each annexin. Annexin Ⅰ is one of the structurally related，calcium-dependent，phospholipid-binding proteins that have been implicated in diverse cellular roles, including anti-inflammatory, signal transduction, cell differentiation，membrane aggregation，inhibiting the activity of cytosolic phospholipase A2，calcium channels and interaction with cytoskeletal proteins.]]> ZHANG Li-Yong,ZHAO Xiao-Hang and WU Min 1365true In vitro molecular directed evolution, based on the combination of random mutagenesis, recombination and high throughput screening, is a new strategy of improving protein properties. With this technology, the properties of the target proteins, such as specificity, catalytic activity and affinity can be tuned without the knowledge of 3-D structure information and function mechanisms. Recently, the methodology originating from error prone PCR and DNA shuffling has been greatly developed by many new techniques. Here, based on the literature review and the experience of authors, the recent developments have been reviewed.]]> XU Hui-Fang,ZHANG Xian-En,ZHANG Yong-Mei and A.E.G.CASS 1364true YU Yue-Fei and Wen Bo-Gui 1363true LIU Zhu,ZHU Jian-Qing,ZHAO Jian,CHEN Dong-Hui and YANG Zhi-Rong 1362true 2+ influx through the voltage calcium channel by change of ATP/ADP ratio and other metabolic coupling factors. Hormones and neurotransmitters exert their regulation effects on insulin secretion through the signal transduction of heterotrimeric and monomeric G-protein. There are two regulatory steps on exocytosis, proximal regulatory step via the change of second messengers and distal one at the level of exocytosis machinery itself.]]> WU Zheng-Xing,LOU Xue-Lin,QU An-Lian,ZHOU Zhuan and XU Tao 1361true et al. The progress in study of Stat3 shows that Stat3 can be constantly activated in many kinds of tumor cell lines; constantly activated Stat3 can make cell malignant transformation happened and repress apoptosis. Study of Stat3 as an oncogene, sets an important basis for explanation of oncogenesis and screening the therapy medicine of many kinds of tumor.]]> WANG Feng-Yang and CHANG Zhi-Jie 1360true xylA（xylose isomerase gene） and pmi（phosphomannose isomerase gene） have been successfully used in plant transformation.]]> ZHAO Yan 1359true JIANG Hong,LUO Ying,ZHENG Xiao-Fei and SUN Zhi-Xian 1358true ZHANG Hui-Jing,CAI Shao-Xi and LU Xiao 1357true GU Zhi-Liang,ZHANG Yong,ZHU Da-Hai and LI Hui 1356true SHEN Li-Qun,XU Xiang,Lü Feng-Lin and LIANG Hua-Ping 1355true KE Ya and QIAN Zhong-Ming 1354true SONG Lun,LI Yan and SHEN Bei-Fen 1353true INK4a contributes to the maintenance of the pRb in its unphosphorylated or hypophosphorylated state, which in turn inhibits cell cycle progression. The expression of p16^INK4a is up-regulated by Ets and down-regulated by Bmi-1. Inactivation of p16^INK4a by deletion, mutation, methylation and aberrant splicing can lead to unlimited cell cycle progression and tumorization. Reasonably, p16^INK4a is now selected to treat some kind of tumors, but research in this field remains a long way to go.]]> GONG Zhen-Ming and FU Ji-Liang 1352true WU Long-Jun and XU Tian-Le 1351true JIA Shuai-Zheng,SUN Hong-Yan and WANG Quan-Li 1350true LI Jin-Song and CHEN Da-Yuan 1349true LIU Yu,ZHAO Xiao-Hang and WU Min 1348true GUO Bo,XIE Pei-Rong,ZOU Qiang and ZHENG Ping 1347true Drosophila, dsRNA has come to be a potent and efficacious inhibitor of gene activity in Drosophila. RNAi now promises to be a powerful reverse-genetic method to determine gene function in Drosophila.]]> XU Rong,CHEN Jun and DENG Ke-Jing 1346true 6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA repair protein that exist in cells and tissues from bacteria to mammalias. The function of the repair protein is to catalyzing and transfering the alkyl group from the O⁶ position of guanine of DNA to an internal cysteine residue of MGMT protein which repairs the lesion by reversion the guanine of DNA. Therefore the proper expression of MGMT is useful to repair O⁶-methylguanine-DNA adducts formed by the induction of alkyl agents. The amount and activity of MGMT are not only regulated by various factors at genetic level, but also associated with the directly effects of some drugs. It has important significance to regulate the activity of MGMT in the cells during the prevention of tumor-geneses and overcoming the drug resistance or marrow toxicity.]]> CHEN Wei-Ying and SHEN Zhong-Ying 1345true WANG Hong-Mei and ZHU Cheng 1344true in vitro. However, the Ca²⁺-triggered synaptic vesicle fusion with presynaptic plasma membrane can be regulated rapidly and tightly when the main SNARE intermediate is so stable. Some synaptic proteins, which regulate the accessibility of SNARE components by interacting with the individual SNARE proteins, might tightly control assembly of functional fusion machinery. Thus, the identification of regulators or molecular switches involved in the assembly of the fusion core complexes is critical for elucidating the molecular mechanisms underlying neurotransmitter release and synaptic plasticity.]]> WANG Yan-Ting,LU Pei-Hua and SHENG Zu-Hang 1343true Helicobacter pylori(Hp) causes gastritis and peptic ulcer disease of a human being, and is associated with certain types of gastric cancer. In recent years, much attention has been focuced on its moclecular mechanisms of H.pylori infection. As an important human pathogen, Hp genome has been sequenced. A detail summary of the literature, significant genome structure feature, gene expression regulation, and indentificaton of virulence factors is provided.]]> LIANG Jun,YUAN Zhi-Ming and LIANG Bu-Feng 1342true in vitro selection, were called deoxyribozymes or DNAzyme.Deoxyribozymes that exhibit RNA transesterification ,DNA transesterification,porphyrin metalation and peroxidase activities,DNA kinase activity and DNA ligase activity have recently been reported. Deoxyribozyme 10～23 might act as a sequence-specific RNA endoribonuclease in vitro,and could be used to inactivate target cellular RNA in vivo.]]> ZHAN Lin-Sheng,WANG Quan-Li and SUN Hong-Yan 1341true in vitro. The expression of some of them can be induced by many factors such as bacteria, fungi and other physical and chemical stimuli, others are constitutively expressed. According to the nucleotide sequences and their secondary-dimensional structures, nine families of peptide antibiotics have been identified in plants. These include thionins, defensins, so-called lipid transfer proteins, hevein- and knottin-like peptides, four cysteine-type, and the recently reported shepherdins, snakins and cyclotides. Recent advances concerning the classification, mode of action, biological properties and plant genetic engineering with some of peptides antibiotics are summarized in an attempt to promote the research and development in this field in China.]]> CHEN Yan,ZHAO Wen-Ming and TIAN Ying-Chuan 1340true 2 and is expressed predominately in vertebrate brain. NGB is a monomer composed of 151 amino acids, with high oxygen affinity. It is of ancient evolutionary origin. Hithertos, it has been proved to associate with oxygen storage, transport and neuron protection. NGB gene expression is mediated by at least 2 signal transduction pathways. The discovery of NGB provides a new direction for treating patients with strokes and other hypoxia-related diseases.]]> ZHAO Tong-Biao,CHANG Zhi-Jie and ZHAO Xin-Quan 1339true YANG Ying-Hua,MA Wen Ru,ZHENG Guo-Guang and WU Ke-Fu 1338true YANG Hong-Bo,YUAN Jian-Gang and PENG Xiao-Zhong 1337true C.elegans have mammalian equivalents, and represent elements of signaling pathways involved in uptake, which have been proposed to define two parallel and partially redundant pathways. The mutation of engulfment genes can change the process of apoptosis. The defections of phagocytosis can affect the body's normal immune response.]]> XU Ming-Yan and XU Xiao-Hu 1336true DMY gene in medaka is introduced and the significance of this affair is discussed. Studies about the existence of this gene in other fish species are also been introduced. Finally, direction for future research is suggested.]]> LIU Xu-Sheng,ZHANG Shu-Yi and LIANG Bing 1335true HE Zu-Ping,ZHNAG Hao-Jian,WANG Yun,WANG Jian-Jin and FENG Mei-Fu 1334true ZHAO Ming-Wei and WANG En-Duo 1333true CHEN Xiao-Wei and HU Zhi-An 1332true + channels, while activation of GalR2 leads to the stimulation of phospholipase C and intracellular Ca²⁺ mobilization. The distribution of the three galanin receptors in human, rats and mice have been investigated by Northern blot, RT-PCR and in situ hybridization. The different distribution of the galanin receptor indicates that galanin participates a broad range of physiological activities.]]> SUN Yan-Gang,HU Yi-Duo and YU Long-Chuan 1331true LI Ji-Xia and Zhou Ke-Yuan 1330true etc. Meanwhile, the molecular mechanisms and the problems of the anti-tumor genetic vaccines also attract the scientists in this field.]]> SHI Shu-Qun and PENG Jing-Pian 1329true + channel, Cl^- channel, Aquaporin 1 etc) and pumps (Ca²⁺ pumps) has led to the determination of 3D structures of a number of proteins responsible for selective transport of polar molecules and ions across biological membranes.In recent years several lines of evidence indicate that the lipids in the plasma membrane of animal cells are inhomogeneously distributed. Lipid rafts and caveolae are cholesterol-sphingolipid enriched microdomains. The characteristics of these domains, such as size, composition and dynamics were briefly reviewed in the present paper. A large number of signalling molecules are concentrated within these lipid microdomains, which has been proposed to function as signaling centers. Besides, the roles of lipid rafts in membrane transport were also discussed.]]> YANG Fu-Yu 1328true WU Ying and HE Rong-Qiao 1327true in vivo functions.]]> GONG Xiao-Wei and JIANG Yong 1326true YANG Cai-Xia,WEN Duan-Cheng,ZHANG Ke-Ying and CHEN Da-Yuan 1325true BI Chun-Ming,WEN Duan-Cheng and CHEN Da-Yuan 1324true 2 was the highest followed by PGE₂ in the site of blastocyst implantation. In addition, PGI₂ level was significantly higher at the implantation sites than inter-implantation sites. IP and PPARs are the G protein-coupled cell surface receptors that are linked to different cytoplasmic signaling pathways and the nuclear hormone receptors, respectively. IP is not expressed or undetectable at implantation sites, but PPARδ expression is very abundant. RXRs (the partner receptor for PPARs), PPARδ-RXRα heterodimer and PGI₂ synthase (COX-2/PGIS) are also abundant at implantation sites. Both PGI₂ agonist (cPGI) and PPARδ specific agonist can restore blastocyst implantation and decidualization in COX-2^－/－ mice. These data suggested that PGI₂ may play important roles in blastocyst implantation and decidualization by PPARδ activation.]]> HUO Li-Jun and YANG Zeng-Ming 1323true JIN Shun-Qian,WU Min and ZHAN Qi-Min 1322true CHANG Yan-Zhong,DUAN Xiang-Lin and QIAN Zhong-Ming 1321true 2+, Na⁺ and K⁺, and the receptors of acetylcholine, 5-hydroxy tryptamine, NMDA, vasopressin and neurotensin. Because of low molecular mass, diversity of structure and targets, high specifiticy and tissue selectivity of conotoxins, they have more advantages over other naturally occurring toxins. Conopeptides could be also used as tools in neuroscience or as therapeutic agents. The conopeptides characterized to date are estimated to represent only 0.1% of the total present in 500 known species of Conus, therefore many novel conotoxins remain to be elucidated and explored. Pharmaceutical companies are now utilizing Conus-derived peptides to develop novel medications for pain, epilepsy and other disorders.]]> WANG Cheng-Zhong,JIANG Hui and QI Zheng-Wu 1320true YI Ping,LIU Yi and ZHU Ying-Guo 1319true WU Long-Jun and XU Tian-Le 1318true WANG Jing-Qiang,YIN Jian-Ning and LIU Si-Qi 1317true JIANG Ying,XU Lang-Lai and HE Fu-Chu 1316true Drosophila, with uniquely powerful molecular genetics, has been a competent model to research human neurodegenerative disease. Screening the genes of Drosophila could not only define the molecular pathway that underlies the neurodegenerative process, but also provide valuable drug targets by consequently studying the control genes and gene products. All of these will uncover the novel means of preventing and curing human neurodegenerative disease.]]> WEN Ai and LIU Li 1315true LI Zhi-Jie and ZHANG Yi 1314true YE Mao,CHEN Yue-Lei and MING Zhen-Huan 1313true in vitro and in vivo experiments show the transformation suppressor activity of caveolin-1, indicating that caveolin-1 may provide a necessary brake in signal transduction. The targeted disruption of caveolin-1 in mice results in impaired nitric oxide and calcium signaling in the cardiovascular system, and displays thickening of alveolar septa caused by uncontrolled endothelial cell proliferation. Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. Caveolin-2-null phenotypes are identical to the ones that have been reported for caveolin-1-null mice in lung function. Caveolin-3 is a component of the dystrophin complex, and might be relevant to Duchennes and other muscular dystrophies. The loss of caveolin-3 expression in mice is sufficient to induce a molecular program leading to cardiac myocyte hypertrophy and cardiomyopathy.]]> LIANG Xu-Fang and HUANG Fen 1312true CAO Hui,LU Pei-Hua and SHENG Zu-Hang 1311true FAN Heng-Yu,HUO Li-Jun and SUN Qing-Yuan 1310true ZHANG Ya-Hui,LI Jia and ZHOU Zhong-Liang 1309true SUN Xiao-Yang and WANG Yan-Ling 1308true WEI Min and ZENG Xian-Lu 1307true ZHENG Mei-Zhen and JIANG Jian-Wei 1306true LIN Hai-Yan,WANG Hong-Mei and ZHU Cheng 1305true YU Yong,XIAO Geng-Fu,LI Min,ZHAN Rui and ZHANG Wen-Tao 1304true LIU Chun-Yan,SUN Hai-Jing,LU Jun and HUANG Bai-Qu 1303true LI Hong and SU Ben-Li 1302true LIU Wen-Guang,WANG Hong-Zhen and ZENG Xian-Lu 1301true E.coli to eukaryote and human. Defects in human mismatch repair genes cause genome instability and hereditary nonpolyposis colon cancer (HNPCC) and others tumors. MutS in E.coli MMR system can specifically recognize mispaired or unpaired base and has been developed into powerful tools for detecting gene mutations and polymorphisms.]]> BI Li-Jun,ZHOU Ya-Feng,DENG Jiao-Yu,ZHANG Xian-En and ZHANG Cheng-Gang 1300true Vibrio cholerae in recent years are reviewed. The gene ctxAB encoding cholera toxin CT is not a native component of Vibrio cholerae genome, while it originally comes from a bacteriophage CTXΦ. CTXΦ can specifically infect Vibrio cholerae and integrate into its genome, forming a prophage; while it can also secrete CTXΦ under the induction of the environmental factors.RS1 and CTX gene elements not only closely located in chromosome position, but also closely related functionally. RS1 element can also transform into a filamentous phage RS1Φ, secrete and transfer horizontally. VPI comes from VPIΦ,which can transmit between Vibrio cholerae strains, and it is the bridge for Vibrio cholerae to acquire CTX gene element. Two gene regions VSP-Ⅰ and VSP-Ⅱ closely related to pandemicity of the Vibrio cholerae were identified recently. The relationship between pathogenicity and pandemicity is discussed.]]> WANG Hong-Min,MA Wen-Li and ZHENG Wen-Ling 1299true Sleeping Beauty (SB), a member of the Tc1/mariner superfamily of transposable elements, is the only active DNA transposon system from vertebrate. The research progresses of SB in recent years are reviewed and some modifications are proposed to improve the performance of SB as a genetic manipulating system.]]> DING Sheng and WU Xiao-Hui 1298true YE Dan,PAN Jian-Wei,LIAO Ming-Juan,ZHANG Zhi-He and ZHU Mu-Yuan 1297true CHEN Lan,XU Cai-Min,YUAN Jian-Gang and PAN Hua-Zhen 1296true ZHOU Hou-De,LI Xiao-Ling and LI Gui-Yuan 1295true LIANG Wei,WANG Ya-Qin and DAVALIAN DARIUSH 1294true Arabidopsis, tomato and barley. VIGS vectors have been used to study function of genes involved in the signal transduction of N-mediated or Pto-mediated resistance, anti-virus mechanism, and plant development and metabolism. With the determination of complete genome sequences or expressed sequence tags, VIGS has recently emerged as a powerful method for identification of gene functions in plants.]]> TAO Xiao-Rong,ZHOU Xue-Ping,CUI Xiao-Feng and QIAN Ya-Juan 1293true WANG Ying and ZHAO Xiao-Hang 1292true ZHOU Yi-Ran and SONG Jian-Guo 1291true 12 and methionine biosynthesis in bacteria. The recent discovery of natural riboswitches, especially its property that precisely controlling basic metabolic pathways via binding to certain ligands with high affinity and specificity, inspires scientists to notice its potential application in medical research. The progress on the riboswitches, its characteristics, the function mechanism as well as the thinking and research trend triggered by its finding were introduced.]]> LUO Ying-Feng and CHEN Yue-Lei 1290true ZHANG Hao-Jian,MIAO Zhen-Chuan,WANG Yun and FENG Mei-Fu 1289true PAN Ping-Yue,LU Pei-Hua and SHENG Zu-Hang 1288true WANG Wei,ZHU Huan-Zhang and XUE Jing-Lun 1287true WANG Xiao-Jia,GATHERINE W.H.ZHANG,WANG Ming and GEORGE F. GAO 1286true SHI Zhi and FU Li-Wu 1285true WANG Jia-Huai 1284true + channel which can be closed by acidosis.]]> WU Long-Jun and XU Tian-Le 1283true TANG Chao-Ke,YI Guang-Hui,RUAN Chang-Geng and YANG Yong-Zong 1282true JIA Jie and JIN You-Xin 1281true YU Pan-Pan,XU Xiao-Ming and LU Pei-Hua 1280true SUN Dao-Chun,BO Xiao-Chen and WANG Sheng-Qi 1279true WANG Ai-Xia,CHEN Jie and LIU Hong-Lin 1278true DUAN Ming-Xing,HE Hong-Xuan and ZHANG Qiang-Zhe 1277true ZHOU Qing-Jun,HU Ruo-Zhen,SHAO Jian-Zhong and XIANG Li-Xin 1276true DU Mei-Jun,LIU De-Pei and LIANG Chih-Chuan 1275true 2 can interact with G protein-coupled receptor IP on the surface of cell membrane and nuclear receptor PPARs. Recently it was found that PGE₂ receptors localized not only on the cell membrane but also on the envelope of the nucleus. There exists difference in the signaling pathway and in regulation mechanism between nuclear receptor and membrane receptors.]]> CHEN Ying,LUAN Li-Ming and YANG Zeng-Ming 1274true C, and pathological, PrP^Sc, forms. According to the “protein only” hypothesis, disease results from infection with the misfolded prion form of the protein, or by inherited mutations in the PrP gene which apparently increase the propensity of the protein to misfold. The result is one of a number of devastating neurological diseases, which are inevitably fatal and are characteristed by spongiform changes in the brain. Hence prion diseases are also known as transmissable spongiform encephalopathies (TSEs). New advances in prion research were reviewed focusing on the structural characteristics of the PrP protein. Putative mechanisms for the conversion between PrP^C and PrP^Sc, and the factors thought to influence this change, are described. Progress in determining the physiological function of the PrP protein and prospects for diagnosis and treatment are discussed.]]> ZHOU Jun-Mei 1273true etc. It is becoming a new research field to investigate the structure-activity relationship of ORL1 receptor and its ligands in recent years. Now, the studies on NC fragments, agonists, partial agonists, and antagonists that were found in the course of investigating the structure-activity relationship of nociceptin are reviewed.]]> CHEN Yong,CHANG Min and WANG Rui 1272true WANG Jin-Xing and ZHAO Xiao-Fan 1271true C.elegans insulin-like peptide resembles that of human insulin and the peptide interacts with human insulin receptor. Other members of insulin super-family adopt the “insulin fold” mostly. The structural study of insulin-insulin receptor complex, that of C.elegans and other invertebrate insulin-like peptide, insulin fibril study and protein disulfide isomerase (PDI) assistant proinsulin folding study will be new topics in future to get insight into folding, binding, stability, evolution and fibrillation of insulin in detail.]]> HUA Qing-Xin 1270true WU Ke-Fu,MA Xiao-Tong and SONG Yu-Hua 1269true JIANG Tai-Jiao,XUE Yan-Hong and XU Tao 1268true JIANG Zu-Yun,YUAN Yi-Jun,MING Zhen-Huan and ZHANG Ming 1267true WANG Jing-Xue,ZHANG Xing-Tang,JIANG Xiao-Hong,LI Yun-Cai,HUANG Ya-Bin and DU Zu-Liang 1266true YUAN Yu-Hua,WANG Xue-Qian,GENG Yun-Qi and CHEN Qi-Min 1265true LI Xiao-Jun and QIN Jun-Chuan 1264true in vivo patch clamp is to recoding electrophysiological signal of neurons in vivo by whole cell techniques, which is useful approach in physical and pharmacological research. A blind patch-clamp technique in the intact brain is usually adopted. Now a new visual method are reported and termed as two-photon targeted patching, which uses two-photon imaging to guide in vivo whole-cell recordings to individual, genetically labeled cortical neurons, so that subset of neurons are specially focused. Here both two methods were simply reviewed.]]> YANG Sheng,ZHOU Wen-Xia and ZHANG Yong-Xiang 1263true PcG family is a group of the most important genes that related to system development. HPC2 protein which is encoded by a critical PcG gene, hpc2, associates with other PcG proteins, such as HPH, BMI-1 as well as RING1 and constitutes HPC/HPH PcG complex to maintain the repressed state of homeotic gene, so that it can regulate the body development, cellular proliferation and directional differentiation. Furthermore, HPC2 has also been found to interact with some other proteins, suggesting that HPC2 may possess some other functions. Therefore, further study of hpc2 is not only helpful to the understanding of the mechanism of biological action of PcG proteins and expanding of the knowledge on the regulation of gene expression, but also beneficial to the discovery of potential relationship between PcG family and other signal transduction pathways for better understanding of the cellular signal transduction network.]]> TANG Jing,LIU Jing-Hua and JIANG Yong 1262true SUN Yu-Lin and ZHAO Xiao-Hang 1261true LIU Hua-Ying and LI Gui-Yuan 1260true ZHANG Yi and SHUM Daisy Kwok-Yan 1259true YU Guo-Hua,LIU Si-Guo and CHENG Guo-Xiang 1258true LI Wei and JIN You-Xin 1257true Lǚ Jian-Xin,JIN Long-Jin and MING Zhen-Huan 1256true REN Li-Chen and DING Ming-Xiao 1255true WANG Xiao-Fei,YU Pan-Pan and LU Pei-Hua 1254true LI Xue-Bin,XIE Zhuang and SHI Fang-Xiong 1253true Zhang Ying-Jiu and YANMIN YANG 1252true GUO Peng,ZHANG Li-Qiang and JING Guo-Zhong 1251true Methanosarcina barkeri (M.barkeri) methylamine methyltransferases. It comes from the sense decoding of the UAG amber stop codon. It has specific pyrrolysyl-tRNA synthetase and tRNA^Pyl. tRNA^Pyl has noncanonical secondary structure. M.barkeri has two routes: direct and indirect routes to synthesize pyrrolysyl-tRNA^Pyl. The special structure in the mRNA and other unknown mechanisms may control the decoding of UAG as pyrrolysine or termination signal. Pyrrolysine was compared with the 21st amino acid: selenocysteine.]]> LING Chen and WANG En-Duo 1250true QIAN Yun-Xia and QIAN Kai-Xian 1249true RENé BARTZ,JOHNK ZEHMER and PINGSHENG LIU 1248true FAN Yi-Jun,OUYANG Ke-Qing,WANG Gui-Xue and HU Ying-He 1247true XU Jia,LIU Zhi-Feng and JIANG Yong 1246true FENG Xue-Chao and MA Tong-Hui 1245true LIN Fang,GU Zhen-Lun and QIN Zheng-Hong 1244true HUANG Sheng-He and XU Qian 1243true Caenorhabditis elegans, their use in mammalian cells has been hampered by toxic effect induced by long dsRNA. However, since 2003, several RNAi libraries that can be used in mammalian cells have been established and used for functional genetic screening. As a simple, effective, large scale and high-throughput screening technique in functional genomics, RNAi library can be used in functional genetic screening, drug target discovery and validation, disease gene discovery and many other areas.]]> CHENG Xiao-Xing,JIAN Rui,DENG Shao-Li and JIANG Jing 1242true WANG Chun-Yu,JIA Zhan-Sheng and HAN Hua 1241true HE Hong-Xia,MA Peng-Da,YANG Mei-ying and WANG Xing-Zhi 1240true CUI Xiao-Feng and ZHOU Xue-Ping 1239true WU Song-Feng,ZHU Yun-Ping and HE Fu-Chu 1238true RAO En-Yu and ZHAO Yong 1237true YUAN Cai,LIU Shan and HUANG Ming-Dong 1236true ZHOU Xian-Ju,YUAN Chun-Yan,YANG Xu-Ke and GUO Ai-Ke 1235true YANG Jun,CAI Shao-Xi and ZOU Quan-Ming 1234true ZHANG Jie and ZHANG Shuang-Quan 1233true MA Rui-Xin,GENG Mei-Yu and LI Jin-Ping 1232true WU Xi and ZHANG Shuang-Quan 1231true XIAO Ying,LI Bing and JIANG Jin-Chang 1230true WU Chun-Xiao,SHI Tai-Ping and MA Da-Long 1229true ZHANG Song-Ling and TANG Hong 1228true ZHANG Fa-Yun,YANG Zhen-Wei,LI Guo-Ming and LIANG Wei 1227true WENQING XU and DAVID KIMELMAN 1226true ZHOU Hai-Yan and CHEN Sheng-Di 1225true SUN Li-Guang,SUN Zu-Yue,GONG Shou-Liang and ZHAO Yong 1224true ZHANG Chun-Qing,CHEN Xiao-Wei and HU Zhi-An 1223true 2006/9/15 0:00:00 WANG Hai-Kun and HAN Dai-Shu 1222true Staphylococcus aureus and a series of SrtA inhibitors have been identified for providing the basis for further development of potent inhibitors.]]> 2006/9/15 0:00:00 LUO Li-Xin and SHI Zhou-Ming 1221true 2006/9/15 0:00:00 LUO Xiang-Jian and CAO Ya 1220true 2006/8/14 0:00:00 Tang Bin-Zhi,QIN Hao-Jie,FU Qiang and QU Yi 1219true kai gene cluster and three Kai proteins KaiA, KaiB and KaiC, which the kai genes encode. The interactions among the Kai proteins modulate the phosphorylation state of KaiC, which generates circadian rhythm. The KaiC phosphorylation cycle constitutes the pacemaker of the cyanobacterial circadian rhythm. And signal transduction into and out of the clock core could occur via histidine protein kinase-based phosphorylation relays.]]> 2006/8/14 0:00:00 Lin Shao-Yuan and Li Shu-Bin 1218true 2006/8/14 0:00:00 Sun Jin-Hua,WU Ming-Fu,XING Ming-Wei,JIN Miao and WANG Jun-Wei 1217true 2006/7/17 0:00:00 CHEN Chang,HUANG Bo,HAN Pei-Wei and DUAN Shao-Jin 1216true 2006/7/17 0:00:00 LI Chun-Hua,MA Xiao-Hui,CHEN Wei-Zu and WANG Cun-Xin 1215true 2006/7/17 0:00:00 ZHANG Rui-Ping and ZHANG Zhao-Shan 1214true 2006/6/14 0:00:00 Feng Chen,Tian Zhi-Gang and Zhang Jian 1213true 2006/6/14 0:00:00 TIAN Xiao-Qing and FANG Jing-Yuan 1212true Bacillus anthracis in different cell and animal models are reviewed, and the principles of choosing animal models of anthrax are discussed. In order to analyze the different results of experiments in different models, the pathogenesis of Bacillus anthracis and the researching progress of anthrax vaccines and drugs are also simply introduced.]]> 2006/6/14 0:00:00 Dong Da-Yong,Xu Jun-Jie and Chen Wei 1211true 2006/5/12 0:00:00 Tang Hui-Ru and Wang Yu-Lan 1210true Leu(UUR) and tRNA^Lys. Recently, it was reported that mitochondrial tRNAs harboring one of those encephalomyopathies related mutations, such as A8344G, A3243G, T3271C etc., lacked the normal taurine-containing modification at their anticodon wobble positions. Wobble modification deficiencies of mutant mitochondrial tRNAs were found from cybrid cells, as well as from patient tissues. Molecular surgery experiments showed that the wobble modification is essential for the interaction between the anticodon in tRNA and the codon in mRNA. Furthermore, the enzyme that is responsible for the formation of the modification was identified and characterized. These studies strongly suggested a key molecular factor responsible for the inherited mitochondrial encephalomyopathies and could potentially lead to the development of a gene therapy for these diseases.]]> 2006/5/12 0:00:00 HAO Rui and WANG En-Duo 1209true 2006/5/12 0:00:00 Wang Qing,Zhu Tian-Hui,Zhang Ming and Chen Di 1208true in vivo imaging. A brief introduction of photoacoustic imaging mechanisms is gives, and the imaging methods, the image reconstruction algorithm and the potential biomedical applications of photoacoustic tomography are reveiewed.]]> 2006/5/12 0:00:00 GU Huai-Min,YANG Si-Hua and XIANG Liang-Zhong 1207true SOC1, FT and LFY, the multiple flowering regulatory pathways control the flowering finely under the variable environmental condition and physiological condition.]]> ZHANG Su-Zhi and ZUO Jian-Ru 1206true LU Li-Li,XIAO Min,ZHAO Han,WANG Peng and QIAN Xin-Min 1205true in vitro or in vivo. In addition, soluble oligomers of α-synuclein might be even more toxic than the insoluble fibrils found in degenerative diseases. So it is significant to investigate factors affectingα-synuclein aggregation, especially their accurate effects on the aggregation process.]]> JIN Ling and YANG Hui 1204true in vitro evolution process termed SELEX (systematic evolution of ligands by exponential enrichment). The unique advantages of high-throughput screening technique and aptamers in precise recognition as well as easiness to synthesis and modification bring aptamers a bright prospect in analytical chemistry, biology and medicine research. The recent advances in the SELEX technique and aptamers are reviewed.]]> SHAO Ning-Sheng,LI Shao-Hua and HUANG Yan-Ping 1203true WANG Xia,LI Ping,ZHOU Yuan-Guo and CHEN Xing-Yun 1202true 2+-ATPase of sarcoplasmic reticulum is a Ca²⁺ pump that plays a key role in regulating cytosol calcium concentration in muscle cells. It undergoes a sequential conformational transition during the transport process. According to the classical E1/E2 theory, in the E1 state the binding sites have high affinity and open to the cytoplasm, whereas in the E2 state the binding sites have low affinity and face the luminal side. Crystal structures of several states during the reaction cycle of Ca²⁺-ATPase have been solved recently, including a Ca²⁺-bound form (E1-2Ca²⁺), a Ca²⁺-unbound form stabilized by a potent inhibitor thapsigargin (TG) (E2-TG), an ATP-bound form (E1-ATP), an E1-P-ADP state, and an E2-Pi state. The details of these crystal structures and the relationship between structure and function of Ca²⁺-ATPase during reaction cycle were summarized, and the issues to be addressed in future research were raised.]]> WEI Ri-Sheng,WANG Pei-Rong and YIN Chang-Cheng 1201true LIU Xiang-Jun,ZHANG Ling-Qiang,LIU Xiao-Lin and HE Fu-Chu 1200true QIAN Zhong-Ming,WANG Qin,XU You-Jia and KE Ya 1199true YANG Hong-Qi and CHEN Sheng-Di 1198true ZHOU Jian-Ying and SHI Yu-Liang 1197true SU Hua and HANG Hai-Ying 1196true LI Feng,Yang Fang,XIAO Zhi-Qiang and CHEN Zhu-Chu 1195true GUO Wei-Rui and YIN JAMES Q 1194true 2006/12/15 0:00:00 YANG Kai and WANG Chen 1193true Gadd45a, a p53 and BRCA1-regulated growth arrest and DNA damage gene, plays important roles in suppressing cell transformation and tumor malignancy. Gadd45a maintains the genomic stability through inhibiting the cell growth and promoting the DNA repair etc, by which it suppresses the tumor development. Additionally, Gadd45a is involved in some important signaling pathway, contributing to its function in tumor suppressing.]]> 2006/12/15 0:00:00 JI Jun-Fang,WU Min and ZHAN Qi-Min 1192true 2006/12/15 0:00:00 ZHAO Mei and HAN Wei 1191true 1190true 2006/11/17 0:00:00 LIU Chang,QIAO Wen-Tao,WANG Chen and GENG Yun-Qi 1189true trans-acting. Cis-acting eQTL is located on the same genomic region of the regulated gene, meaning the variation of mRNA level could be due to the polymorphism in the gene itself. Trans-acting eQTL is located on other genomic region, meaning other gene controls the variation of mRNA level. The integration of eQTL results, gene function annotation and statistic analysis will not only more precisely identify candidate genes controlling complex traits and the expression of related genes, but also construct regulatory networks for these complex traits.]]> 2006/11/17 0:00:00 LIU Xiu-Yan,XIE Zheng-Miao and CHEN Hui-Zhe 1188true 2006/10/18 0:00:00 LI Gui-Yuan,LIU Hua-Ying,ZHOU Ming,ZHOU Hou-De and LI Xiao-Ling 1187true 2006/10/18 0:00:00 MA Hua-Mou,XIE Fu-Hua and ZHOU Ke-Yuan 1186true 2007/7/13 0:00:00 GE Jian-Ning and SHAO Feng 1185true 2007/5/9 0:00:00 YANG Ning,LIU Hui-Tu and ZHANG Wei 1184true 2007/6/11 0:00:00 HUANG Xin,ZHU Ling-Ling and FAN Ming 1183true 2007/9/17 0:00:00 SONG Yi and SUN Zhi-Xian 1182true PDCD10 (programmed cell death 10, alias, “TF-1 cell apoptosis related gene 15, TFAR15”), cloned by means of cDNA-representational differences analysis, had been initially identified associated with cell apoptosis. Recent research suggested mutations within the PDCD10 gene or deletion were responsible for cerebral cavernous malformations, and PDCD10 was the third CCM gene. On the other hand, other research demonstrated that PDCD10 was strictly modulated and up regulated in many kinds of tumors, which implicated that PDCD10 participated in tumorous signal transduction. The recent research confirmed that PDCD10 interacts with MST4, a member of Ste20-related kinases, and the interaction promoted cell proliferation and transformation via modulation of the ERK-MARK pathway. In conclusion, all these demonstrate that PDCD10 has many biological effects, which suggests that it is a novel player in vascular morphogenesis and/or remodeling, as well as tumorigenesis and cancer progression.]]> 2007/8/13 0:00:00 MA Xi,ZHAO Hong-Shan and MA Da-Long 1181true de novo sequencing combined with similarity search and searching against nucleotide acid databases such as EST or genome databases. Several mature or newly developed methods and techniques were summarized, and the problems and strategies discussed here would be helpful for the related researches.]]> 2007/5/25 0:00:00 MA Jie,WU Song-Feng and ZHU Yun-Ping 1180true 2007/8/13 0:00:00 SUN Jin-Hua,CHENG Han-Hua and ZHOU Rong-Jia 1179true 2007/5/21 0:00:00 CHEN Qing,PAN Qiu-Wei,CAI Rong and QIAN Cheng 1178true 2007/6/7 0:00:00 LIU Hua-Ying,PENG Shu-Ping,ZHOU Ming and LI Gui-Yuan 1177true 2007/4/6 0:00:00 WANG Xiao-Jia and WANG Ming 1176true LMNA gene which encodes nuclear lamin A/C. The mutation activates a cryptic splice site within exon 11 of LMNA, resulting in a 50-amino acid in-frame deletion in prelamin A. However, it is not clear how the mutation in a structural protein under the nuclear envelope could give rise to premature aging phenotypes. Recent studies showed that various abnormalities have been found in nuclear structures and functions of HGPS cells, mainly including progerin accumulation and nuclear morphology abnormalities, altered nuclear mechanical properties, changes of histone methylation patterns and epigenetic control, gene misregulation, p53 signalling activation, and increased genomic instability. Two hypotheses recently emerged in the explanation of the pathogenic mechanisms contributing to HGPS. No effective clinical intervention has been developed so far for HGPS. Several fascinating therapeutic strategies have recently been provided, such as farnesyltransferase inhibitors, antisense oligonucleotides and RNA interference. HGPS has been considered to be a model for studying the mechanisms responsible for normal aging. This study will help to elucidate the physiological functions of lamin A and nuclear envelope, together with their roles in normal aging process and diseases.]]> 2007/6/7 0:00:00 ZENG Tao,LIU Xin-Guang and ZHOU Zhong-Jun 1175true 2007/6/25 0:00:00 GONG Xiao-Wei and JIANG Yong 1174true 2007/5/15 0:00:00 ZHU Bin and WANG En-Duo 1173true 2007/5/11 0:00:00 ZENG Yan-Li and LAN Xiao-Peng 1172true 2007/5/15 0:00:00 ZHANG Song,HUANG Bo,XIA Xue-Feng and SUN Zhi-Rong 1171true 2007/4/6 0:00:00 TANG Li-Ling,LI Da-Jun and WANG Yuan-Liang 1170true 2007/4/17 0:00:00 ZHONG Tian-Yu,LIU Jing-Hua and JIANG Yong 1169true 2007/3/20 0:00:00 HAN Qiu-Ju,ZHANG Cai,ZHANG Jian and TIAN Zhi-Gang 1168true + T cell biology and the interplay between innate and adaptive immunity for almost two decades. Recent studies have defined a previously unknown subset of the CD4⁺ T cell effectors, the Th17 lineage. The uncover on the differentiation of IL-17-producing effector T cells from naive T cell precursors provides insights into mechanisms by which signals from cells of the innate immune system guide alternative pathways of Th1, Th2 or Th17 development. Th17 lineage has an important role in autoimmune and inflammatory diseases. This promises to change our understanding on the immune regulation, immune pathogenesis and host defense. The identification, differentiation and immune function of the new subsets of Th cells, Th17 cells will be reviewed.]]> 2007/3/9 0:00:00 LIU Guang-Wei and ZHAO Yong 1167true Science represents the first unbiased systematic mutational analysis of human genome at any disease states after the completion of The Human Genome Project. It was tentatively discussed how to take advantage of the candidate cancer genes found in this study in discovery of novel targets of therapeutic drugs. In addition, the penitential values of the candidate cancer genes in identification of patients at high risk of cancer, and in renewing classification of tumors based on underlying molecular mechanisms are introduced.]]> 2007/2/12 0:00:00 TIAN Ze-Jun and GUO Ning 1166true 2007/2/13 0:00:00 SUI Shao-Hui,WANG Jing-Lan,CAI Yun and QIAN Xiao-Hong 1165true 2007/2/6 0:00:00 DAI Chun-Ling and FU Li-Wu 1164true 2007/1/17 0:00:00 CHEN Di and XING Fei-Yue 1163true 2+) sensor that exists in all eukaryotes. As it has no enzymatic activity, CaM transmits the Ca²⁺ signal by interacting with CaM-binding proteins (CaMBPs) to function in cellular regulation. In recent years, it has been found that CaM not only signals in the presence of Ca²⁺, it can also directly bind to target proteins as ApoCaM. Ca²⁺-independent CaM-binding proteins (ApoCaMBPs) is also an important way to elucidate the mechanism of CaM functions. Recent progresses in studies on animal and plant ApoCaMBPs were summarized. ApoCaM differs from Ca²⁺-CaM in its tertiary structure. It binds target proteins differently, utilizing different binding motifs such as the IQ motif, noncontiguous binding sites and others. The ApoCaMBPs are a diverse group of proteins including enzymes, transcription activators, as well as cytoskeletal and other membrane proteins, including receptors and ion channels. The overall picture that emerges is that CaM cycles between its Ca²⁺-bound and Ca²⁺-free states and in each state binds to different proteins and performs essential functions. Although much of the research focus has been on the roles of Ca²⁺-CaM binding proteins, the roles of ApoCaMBPs are equally vital but less well understood. Researches on ApoCaM and its binding proteins will make us understand the variety of CaM signaling pathway.]]> 2007/2/12 0:00:00 WEI Hui-Yan,GUO Zhen-Qing and CUI Su-Juan 1162true +- and Ca²⁺-channel activity. The research data to demonstrate that TSN inhibits K⁺-channel and facilitates L-type Ca²⁺-channel are summarized, and the mechanism of action of TSN is discussed.]]> 2007/1/18 0:00:00 SHI Yu-Liang and WANG Wen-Ping 1161true 2007/1/15 0:00:00 DI Xin and RAO Heng-Yi 1160true 2007/1/15 0:00:00 WENG Xie-Chuan,ZHENG Jian-Quan,PENG Shuang-Qing and LI Jin 1159true 2007/1/15 0:00:00 SUN Li-Wen,TANG Syao-Wei and HU Ying-He 1158true LRRC4, a novel member of LRR (leucine-rich repeat) superfamily, is cloned by expressed sequence tag (EST)-mediated positional cloning strategy combined with 5′-RACE technology. Normal expression of LRRC4 is highly specific for brain, whereas absent or significantly down-regulated in primary tumors including glioma, meningioma and pituitary adenoma. LRRC4 is a functional gene in neural development and axon growth, and associated with glioma grade progression. LRRC4 expression is gradually reduced, even absent accompany with glioma grade increase. Absent expression of LRRC4 is involved in the late event of malignant glioma progression.The reexpression of LRRC4 can decrease a series of growth factors/neurotrophic factors (IGF, EGF, PDGF, CNTF, bFGF,GDNF and BDNF) or receptors gene expression to regulate RTK-mediated many signaling transduction pathway, such as K-Ras/c-Raf/ERK/MAPK, PI-3K/AKT/NF-κB, p70S6/PKC, STAT3 and JNK2/c-Jun/mp53, which block U251 cells in late phase of G1 to inhibit glioma cells proliferation and invasion. This inhibitory effect of LRRC4 is dependent on its LRR domain. LRRC4 induces glioma cells to differentiate into astrocyte-like cells more than apoptosis.]]> 2007/9/11 0:00:00 Wu Ming-Hua,LI Xiao-Ling and LI Gui-Yuan 1157true 2007/9/11 0:00:00 NIE Jing,TIAN Chun-Yan and HE Fu-Chu 1156true 2007/7/16 0:00:00 ZHANG Yi-Ling,WEI Xu-Bin,CAI Rong and QIAN Cheng 1155true 2007/6/29 0:00:00 Lv Cong-Ying,ZHAO Gang-Bin and Lv Guan-Ting 1154true INK4a/Rb pathway and HMGA proteins play a very important role. Recent studies have shown that SAHF may suppress the expression of some E2F-target genes, thereby making the cell keep in a stable senescent state. The discovery of SAHF has provided a new biomarker for the research of cellular senescence, and it also gives us a molecular explanation for the stability of the senescent state.]]> 2007/11/14 0:00:00 Li Qian,MA Li-Wei,ZHANG Zong-Yu and Tong Tan-Jun 1153true 2007/6/6 0:00:00 HUANG Chen,WU Ming-Hua and LI Gui-Yuan 1152true 2+ release from the ER.]]> 2007/8/2 0:00:00 GUAN Li-Ying,XU Cai-Min and PAN Hua-Zhen 1151true 2007/7/11 0:00:00 WANG Lin and ZHENG Guo-Guang 1150true 2007/5/25 0:00:00 LIU Mo－Fang,JIANG Shuai and WANG En-Duo 1149true 2007/6/29 0:00:00 YANG Zhi,WEI Xu-Bin,CAI Rong and QIAN Cheng 1148true cis-regulatory element (for example, ESE, ISS and ESS) and trans-regulatory factors (such as SRp55, SC35, SF2/ASF and PTB). Recent progresses demonstrate that many genes associated with gliomas, including those encoding tumor suppressors or promoters, enzymes, receptors and ion channels are subject to regulation by alternative pre-mRNA splicing. Therefore, studying the alternative pre-mRNA splicing in gliomas will be of benefit to understanding the molecular basis of gliomas and identifying new targets potentially useful for early diagnose as well as therapy of gliomas.]]> 2007/4/28 0:00:00 PENG Zheng-Yu,ZHANG Wei,CHEN Xian-Hua and XU Ping 1147true 2008/9/23 0:00:00 QIN Yan 1146true 2008/6/19 0:00:00 WANG Hai-Zhen,WANG Ying and LIU Ding-Gan 1145true 2008/4/17 0:00:00 ZHU Chuan-Dong and LI Xiao-Jun 1144true ccdAB system interacts with the catalytic GyrA subunit of gyrase to inhibit the DNA replication. RelE toxin in the relBE system assists the RNA cleavage at the ribosome A site with a high coden specificity. PemK toxin in the pemIK system and MazF toxin in the mazEF system are identified as endoribonucleases, which cleave the cellular mRNA in a sequence-specific manner to interfere with mRNA function and inhibit the protein synthesis. This review summarizes the mechanism of the toxin in TA system and evaluates the applications of TA system in the future.]]> 2008/4/17 0:00:00 WANG Xiao-Lei,ZHAO Long-Xuan and ZHANG Jun-Jie 1143true 2008/4/17 0:00:00 ZHOU Guo-Qiang,CHEN Chun-Ying,LI Yu-Feng,LI Wei,GAO Yu-Xi and ZHAO Yu-Liang 1142true 2008/6/12 0:00:00 ZHOU Xiao-Long and WANG En-Duo 1141true in vivo. With the development of protease research and the application of protease proteomics, substrate degradomes of a protease may therefore represent an important tool for the research of TMPRSS3 function and its molecular mechanism.]]> 2008/4/17 0:00:00 GE Sheng-Lei,YI Yan and XIE Ding-Hua 1140true 2008/6/12 0:00:00 LIU Da-Fei,LIU Chun-Guo,LIU Ming and LIU Da-Cheng 1139true 2008/3/18 0:00:00 LU Li-Li,XIAO Min,ZHAO Han,XU Xiao-Dong and WANG Feng－Shan 1138true 2008/4/17 0:00:00 ZHU Qi,LI Xiao-Yong and JIANG Xing-Hong 1137true 2008/4/16 0:00:00 WANG Jiu-Ju,BI Hong-Yan,WEI Tong-Qi and WENG Xu-Chu 1136true 2+. GTP also counteracted 6-OHDA-induced nitric oxide increase and over-expression of nNOS and iNOS, and decreased the level of protein bound 3-Nitro-tyrosine (3-NT). Using PD rat model injected by 6-OHDA, the effect of GTP were investigated on animal model. Results showed that GTP attenuated the injury in a dose and time dependent manner. Pretreatment of the animals with GTP decreased ROS and NO production, thiobarituric acid reactive substances content, nitrite/nitrate concentration, and protein bound 3-Nitro-tyrosine (3-NT) in brain homogenate of midbrain and striatum in a concentration and time dependent manner. NOS participated in the neuron death induced by 6-OHDA and it was found that the pretreatment with GTP could decrease the protein level of nNOS and iNOS. More neurons survived and less cells suffered apoptosis in the substantia nigra pars compacta (SNc) of GTP treated animal brain. These results suggest that oral administration of GTP increases the antioxidant level in the brain and protects the brain against cell death caused by 6-OHDA. The experimental results of present study support the neuroprotection of GTP and provided new strategy of preventing and curing Parkinson's diseases by ROS-NO pathway.]]> 2008/7/25 0:00:00 ZHAO Bao-Lu 1135true 2007/12/19 0:00:00 LIU Jia,QU Cun-Ye,MA Lei-Na,SHI Wen-Fang and QIAN Qi-Jun 1134true E. coli as a model system, the recent progresses and the possible rules underlying E. coli DNA replication, repair and recombination have been analyzed. As it is believed that the researches on E. coli DNA replication, repair and recombination may be capable of providing clues to the eukaryotic research based on the universal conservations of the critical proteins in the pathways.]]> 2008/5/29 0:00:00 QIU Jie-Fang and PAN Xue-Feng 1133true 2008/4/16 0:00:00 XU Xue-Qing and LAI Ren 1132true 2008/2/3 0:00:00 CHEN Yan 1131true ebp50 gene have been found in both primary breast tumors and breast cancer cell lines. EBP50 suppresses the breast cancer cell proliferation via its interaction with many tumor suppressor protein including PTEN, SYK, MERLIN, etc. Here the molecular structure of EBP50, signal pathway regulated by EBP50, and the relationship between breast cancer development and EBP50 are discussed.]]> 2007/12/19 0:00:00 Zheng Jun-Fang and He Jun-Qi 1130true 2008/2/19 0:00:00 MA Hong-Hui,FANG Cun-Lei and ZENG Ping-Yao 1129true 2008/2/3 0:00:00 ZHANG Xue-Zhi,SHAN Chang-Liang,YE Li-Hong and Zhang Xiao-Dong 1128true kip1 is an important negatively regulator of cell cycle progression and plays a central role in the pathogenesis of a member of tumors including breast cancer. In breast cancer cells, the level of p27^kip1 expression usually decreases during tumor development and progression, in addition, cytoplasm　mislocalization of p27^kip1 has been reported, but less is known about the exact molecular mechanisms. Studies have indicated that phosphorylation is the key regulation way, several signal transduction pathways are involved in the regulation of the expression and distribution of p27^kip1. To further understand the mechanism, the disparity of the interacting protein profiling between tumor cells and normal cells must be identified first. Including cyclins, cyclin-depend kinases, CRM1, jab1, SKP2, p27^kip1 has various interacting molecules. There are also several interacting molecules especially for breast cancer cells. It seems that different protein profiling cause the different expression and intracellular distribution in different cell cycle phase. So, disparity of the p27^kip1 protein profiling may be the main mechanism of its down-expression and mislocalization in breast cancer cells.]]> 2008/4/16 0:00:00 HE Wei-Wei,GUAN Xiao-Xiang and CHEN Long-Bang 1127true 2007/12/19 0:00:00 HU Shi-Jun and YANG Zeng-Ming 1126true 2007/11/22 0:00:00 WANG Zhen and LIU Qing-Ying 1125true 2007/12/11 0:00:00 GUAN Na,XU Yan-Ning,ZHANG Qing-Hua and LEI Lei 1124true 2008/2/3 0:00:00 LI Xian-An,ZHANG Ying-Jiu,CHANG Ming,WANG Dan-Ping,LIU Tao and HU Lin-Sen 1123true Saccharomyces cerevisiae. Yeast has been validated as a model organism to investigate mechanisms of apoptosis. Recently, yeast has also been used as a model to study apoptosis-related disease, such as Huntington's disease and Parkinson's disease. The feasibility, the advantages and the perspectives of yeast model for apoptosis research are reviewed.]]> 2007/10/23 0:00:00 JIANG Qiao,LIN Lin and WANG Tian-Hong 1122true 2007/10/19 0:00:00 qiuxiaoyan and LI Yue-Min 1121true 2007/9/18 0:00:00 Hu Yan-Wei and Tang Chao-Ke 1120true 2007/10/15 0:00:00 Cui Ying-yu 1119true 2008/2/3 0:00:00 FENG Jun-Tao and HU Cheng-Ping 1118true 2007/9/11 0:00:00 FU Qing-Ying and GAO Yu-Qi 1117true via activating certain transcription factors which are capable of up-regulating NKG2 promoters' activity. Meanwhile, epigenetic mechanisms including DNA methylation and histone posttranslational modifications are also critical to expression of NKG2 receptors and their ligands and may control the clonally distribution of some NK cell receptors. Investigating the epigenetic mechanisms of NK cell receptors and their ligands might helpful to the rational design of therapy against infection, inflammation, cancer or autoimmune diseases.]]> 2007/8/20 0:00:00 ZHOU Zhi-Xia and ZHANG Cai 1116true 2007/12/19 0:00:00 TANG Sheng-Qiu,JIANG Qing-Yan,ZHANG Yong-Liang,ZHU Xiao-Tong,SHU Gang,GAO Ping and DONG Xiao-Ying 1115true 2008/1/16 0:00:00 ZHANG Wen-Ling,ZHOU Yan-Hong,XIAO Lan,FAN Song-Qing,ZENG Zhao-Yang,LI Xiao-Ling,WU Ming-Hua and liguiyuan 1114true 2007/11/8 0:00:00 YANG Na,HOU Qiao-Ming,NAN Jie and SU Xiao-Dong 1113true 2007/8/14 0:00:00 XING Shao-Chen and CLARKE JIHONG LIU 1112true 2008/9/22 0:00:00 XU Yan-min,GUO Yan-He,LIU Li,CAI Rong and QIAN Cheng 1111true 2008/8/19 0:00:00 YOU Hong-Jie,YAN Shao-Fei and DING Wei 1110true 2008/9/16 0:00:00 ZHANG Bao-Quan,GUO Zhen-Hui,FANG Wei and lU Feng-Lin 1109true 2008/9/2 0:00:00 LI Yang,WANG De-Chun and HU Zhi-An 1108true in vivo, and methyl-arginine is demethylated by “arginine demethylase”. Here, the most recent progresses in the methylation studies of histone arginine were summarized.]]> 2008/5/21 0:00:00 CHENG Zhi-Kui,GUO Qian-Ping and WU Hui-Jian 1107true 2008/6/19 0:00:00 GUI Lang,WANG Bing,LI Fu-Hua and XIANG Jian-Hai 1106true 2008/6/3 0:00:00 WANG Qing-Yun,YI Hui,LIU Lai-Fu and MENG Da-Zhi 1105true Anthozoa species have been subjected to a series of in vitro molecular evolution, resulting in various emission spectra ranging from 570 nm to 655 nm and thus providing powerful tools for cellular imaging or even body imaging. This article briefly reviewed the optical properties, structures and mutagenesis of RFPs and their applications.]]> 2008/5/27 0:00:00 FAN Jin-Yu,CUI Zong-Qiang and ZHANG Xian-En 1104true 2008/9/16 0:00:00 HUANG Qing-Lei and JIAO Ren-Jie 1103true 2008/3/7 0:00:00 HOU Zhao-Hua,ZHANG Jian and TIAN Zhi-Gang 1102true 2008/6/19 0:00:00 ZHAO Pu,ZHENG Yu-Shu,QIAO Chuan-Ling,JIA Bei-Bei and LIU Xing-You 1101true 2009/5/14 0:00:00 HE Shan,ZHANG Ling-Qiang and HE Fu-Chu 1100true 2009/4/13 0:00:00 MA Ning and GAO Xu 1099true 2009/4/15 0:00:00 ZHAO Juan,MAO Ying-Jie and GU Zhi-Yuan 1098true 2009/5/19 0:00:00 CHEN Hong-Wei,CHEN Jin-Can,CHEN Nai-Sheng,HUANG Jin-Ling,WANG Jun-Dong and HUANG Ming-Dong 1097true in vitro reprogrammed from nonembryonic cells and tissues have captured great attentions in both scientific community and general public. Somatic reprogramming, dedifferentiation and the resource of pluripotent stem cells become the research hot points of stem cells and developmental biology. Person-, patient- and disease-specific iPS cells could be very useful in regenerative medicine and drug discovery, etc. iPS cell history, the several key steps in generating iPS cells (including approaches to gene delivery, combined uses of defined factors and small molecules to induce somatic cells into iPS cells, and choice of somatic cell types), patient- and disease-specific iPS cells, in vivo and in vitro differentiation of iPS cells, and the possibility of genetic modification-free iPS cells were discussed.]]> 2009/4/15 0:00:00 SHEN Hong-Fen,YAO Zhi-Fang,XIAO Gao-Fang,JIA Jun-Shuang,XIAO Dong and YAO Kai-Tai 1096true 2009/4/24 0:00:00 LV Jin and WANG Xi-Liang 1095true 2009/6/5 0:00:00 SUN Yu-Lin,LIU Fei and ZHAO Xiao-Hang 1094true in vitro. And ESCs could differentiate into the hematopoietic cell fate. Therefore ESCs may provide an alternative for hematopoietic stem cell transplantation and blood cells transfusion. Furthermore, ESCs differentiation could also provide a powerful model system to better understand the hematopoietic development and the mechanism involved. The current status for efforts to differentiate ESCs into hematopoietic lineages were reviewed.]]> 2009/3/26 0:00:00 YANG Chao,XI Jia-Fei,YUE Wen and PEI Xue-Tao 1093true 2009/3/11 0:00:00 MENG Fan-Yi,MAI Kang-Sen,MA Hong-Ming and ZHANG Wen-Bing 1092true 2009/3/3 0:00:00 LI Wei,TIAN Xue-Jun,LIU Li and QIAN Cheng 1091true 2009/2/23 0:00:00 CHEN Jie,CHAI Bao-Feng and LIANG Ai－Hua 1090true 2008/10/21 0:00:00 XUAN Bin and ZHANG Da-Ren 1089true 2009/1/10 0:00:00 LI Ning,WU Song-Feng,ZHU Yun-Ping and YANG Xiao-Ming 1088true 2009/3/11 0:00:00 LI Bu-Hong,XIE Shu-Sen,HUANG Zheng and WILSON Brian C 1087true PKHD1( polycystic kidney and hepatic disease 1), the causal gene of human autosomal recessive polycystic kidney disease(ARPKD), is located on chromosome 6p12.2 and covers a genomic region of ～500 kb. PKHD1 is among the largest human genes, with a minimum of 86 exons from which multiple transcripts may be generated by alternative splicing. The longest continuous open reading frame consists of 12 222 bp, encoding a 4 074 amino acid protein, designated as fibrocystin/polyductin(FPC). FPC is predicted to be a receptor like protein, with single transmembrane domain and a short cytoplasmic tail. The expression of mouse FPC can be detected in various duct-containing organs. In mouse embryogenesis, FPC appears in developing neural tube, bronchi, and the primordial gut as early as the day of E9.5. In fetal human kidneys, high level of FPC expression is present in ureteric bud and its expression continues throughout the process of renal tubuobranching. In adult human kidneys, FPC mainly expresses in the epithelia of renal collecting ducts. FPC is subcellularly localized to the primary cilia and concentrated on the basal bodies in renal epithelial cells. The detail function of FPC is still unrevealed, most recent studies demonstrate that FPC, as a receptor, may transduce cell signal by interacting with a trp superfamily TRPP2 (PKD2), which is a causal gene for ADPKD, and mediate intracellular calcium homeostasis to regulate differentiation, proliferation, migration and polarity of various duct/tubular epithelia, in turn, to modulate the formation of all physiologic ducts, tubules and tracts.]]> 2009/2/23 0:00:00 FU Yu-Long and WU Guan-Qing 1086true 2009/5/14 0:00:00 ZHOU Kai and HE Hong-Xuan 1085true in vitro infection models. Recent years, primary hepatocytes from Tupaia belangeri has been substituted for primary human hepatocytes and upon induction of differentiation in vitro. A human hepatoma cell line named HepaRG has been found to be susceptible for HBV infection too. The two cell models enabled researchers to obtain a number of important discoveries for HBV entry. This article are focusing on these discoveries, including the domains of HBV surface proteins involved in HBV entry, potential HBV receptor candidates and the questions to be resolved in future years.]]> 2008/10/29 0:00:00 WANG Xue-Jun and WANG Sheng-Qi 1084true 2008/11/18 0:00:00 SHEN Zhi-Yong,LI Zhi-Feng,HANG Xing-Yi and ZHANG Cheng-Gang 1083true 2008/10/29 0:00:00 ZHANG Jie,LIU Qiong-Ming,XU Dan-Ke and HE Fu-Chu 1082true 2008/12/17 0:00:00 HE Ran and WANG En-Duo 1081true 2008/12/22 0:00:00 HOU Guo-Qiang and LI Dong-Feng 1080true 2008/11/18 0:00:00 LI Yang,CHEN Fang and HU Zhi-An 1079true 2+. The target gene products of CREB involve broad physiological processes such as cell proliferation and survival, carbohydrate and lipid metabolism, steroid synthesis, and learning and memory. The newly-identified transducer of regulated CREB activity (TORC) controls transcription and expression of many CREB target genes by undergoing nucleo-cytoplasmic shuttling. Salt-inducible kinase (SIK) is a group of serine/threonine protein kinase including SIK1, SIK2 and SIK3. These kinases indirectly modulate CREB target gene transcription and expression by affecting TORC phosphorylation and their subsequent distribution between nucleus and cytoplasm. In certain organs and tissues, SIK (SIK1) is also one of the target genes for CREB. Thus, a complete negative feedback regulatory circuit may be formed between SIK and TORC-CREB complex. To date, the latter has been identified in several organs and tissues such as pancreatic β-cell, the liver, adrenal cortex and skeletal muscle where they regulate β-cell survival, hepatic glyconeogenesis, steroid synthesis, and mitochondrial biogenesis and fatty acid oxidation in the skeletal muscle. The feedback regulation of TORC-CREB complex by SIK and its implications in pathogenesis of hypertension and diabetes mellitus are focused on.]]> 2008/8/21 0:00:00 LIU Yu,LI Jing,JIN Da-Qing and TANG Xiang-Dong 1078true 2008/9/16 0:00:00 OUYANG Yu-Mei 1077true 2008/10/6 0:00:00 LI Tian-Zhu and XIANG Ben-Qiong 1076true 2008/8/20 0:00:00 FAN Shi-Cai and ZHANG Xue-Gong 1075true 2008/9/16 0:00:00 PANG Jian-Hui,REN Chang-Hong,LI Zhi-Feng,LIU Hu-Qi and ZHANG Chang-Gang 1074true in vivo while some experimental models have been established which reviewed as follows.]]> 2008/8/1 0:00:00 ZOU Su-Qi,YIN Wu,YANG Yu-Peng,CHEN Lin and HU Bing 1073true 2008/10/29 0:00:00 LIU Zhong-Yang,LI Dong,ZHU Yun-Ping and HE Fu-Chu 1072true 2008/9/15 0:00:00 WANG Jin-Ye,CAI Rong and LUO Ben-Yan 1071true 2009/8/7 0:00:00 LIU Xiu-Li,ZHOU Wei and ZENG Shao-Qun 1070true 2009/7/27 0:00:00 SUN Bing and HAN Dai-Shu 1069true in vivo pharmacology and toxicology, a complete understanding of the mechanism and biological function of ABCG2 will be important for understanding its normal physiology as well as potentially for the development of novel chemotherapeutic treatment strategies. The discovery, the biochemistry, the normal physiology and the current insight of human ABCG2 were introduced.]]> 2009/6/12 0:00:00 WANG Ying-Ze,DUAN Xiang-Lin,LI Yong-Fu and LIANG Xing-Jie 1068true 2009/9/7 0:00:00 SI Xiao-Yu and LUO Ying 1067true et al, manifesting either in one specific area or by the asymmetry of one area; the functional image studies revealed that development dyslexia showed activity abnormal in most regions that proved to display structure abnormality; studies of brain functional connectivity demonstrates that the abnormality of development dyslexia happened not only in the connection between front-back part in one cerebral hemisphere, but also in the connection between the two hemispheres. In addition, some studies indicate Chinese development dyslexia has different brain mechanisms compared to that of alphabetic languages. These findings provide valuable insight for future developmental cerebral mechanisms research and for the expansion of Chinese development dyslexia research.]]> 2009/6/11 0:00:00 YANG Yang,BI Hong-Yan and WANG Jiu-Ju 1066true 2009/6/12 0:00:00 LIU Mei,YANG Pei-Hui and CAI Ji-Ye 1065true Agrobacterium tumefaciens can transfer a DNA fragment (T-DNA) from its Ti plasmid to host plant and integrate the T-DNA fragment into host cell nuclear genome. Agrobacterium-mediated T-DNA transfer is the most widely used genetic transformation method for plant. The T-DNA is delivered in the form of single-stranded T-DNA-protein complex (T-complex) by the polar-located Agrobacterium type Ⅳ secretion system (T4SS) to the host cell. T4SS is ancestrally related to bacterial conjugation machines and still used by many plasmids as conjugation channel. Moreover, T4SS is also the secretion channel that used by many human bacterial pathogens to inject the effector proteins to host cells, thus contributing directly to the bacterial pathogenicity. Therefore, in addition to the technical application as a gene vector to create transgenic plants, Agrobacterium-mediated T-DNA transfer also provides a fascinating model system to study the intercellular transfer of macromolecules. The study on the molecular mechanism of T-DNA transfer arouses extensive interest and progresses rapidly in recent years. Here the recent advances in research on T-complex formation and T-complex transfer in Agrobacterium cell are reviewed.]]> 2009/6/12 0:00:00 GUO Min-Liang,GAO Dian-Kun and JIN Ying-Shan 1064true 2009/5/25 0:00:00 QI Fei-Fei,HE Fu-Chu and JIANG Ying 1063true 2009/5/19 0:00:00 JIANG Zhi-Wen,LIU Xin-Guang and ZHOU Zhong-Jun 1062true M. tuberculosis, the RD-1 locus is 9.5 kb and spanning open reading frames Rv3871 to Rv3879c encoding 9 different proteins separately. The RD-1 locus is missing in all bacillus Calmette-Guerin (BCG) strains, and is one of the key virulence factor in M. tuberculosis. The RD-1 locus participates in a new secreting system named ESX-1, which can facilitate the secretion of some special proteins. The two important proteins encoded by the RD-1 locus named CFP-10 and ESAT-6 can form a tight 1∶1 complex, and has been shown to be coordinately secreted and lead to a strong T cell response, which suggests that these two proteins may act as ideal target antigens in diagnosis and prevention of tuberculosis (TB).]]> 2009/5/14 0:00:00 LI Hao,XU Jun-Jie and CHEN Wei 1061true 2009/4/15 0:00:00 KANG Cong-Min,WANG Da-Wei,LV Ying-Tao and ZHANG Yuan-Yuan 1060true via in-depth study. And this has an important role in promoting the development of molecular biology and other related life sciences. This article summarizes some representative anti-aging small molecules of the past decade or two and focuses on their molecular mechanisms.]]> 2010/5/27 0:00:00 GAO Ling-Yun,LI Guo-Dong and TONG Tan-Jun 1059true 2010/6/10 0:00:00 ZHAI Kan,WU Zhi-Yin and YU Dian-Ke 1058true 2010/5/27 0:00:00 CHEN Xiao-Dan and SONG Xin 1057true 2010/5/20 0:00:00 LIU Xing,SHI He-Xin and WANG Chen 1056true 2010/5/12 0:00:00 HUANG Wen-Tao,GUO Xiang-Qian,DAI Jia-Pei and CHEN Run-Sheng 1055true 2010/5/12 0:00:00 WANG Xi,WANG Xiao-Wo,WANG Li-Kun,FENG Zhi-Xing and ZHANG Xue-Gong 1054true 2010/4/20 0:00:00 SUN Ye-Ping and GAO Fu 1053true 2010/5/27 0:00:00 LI Qian,PAN Cong and LEI Ming 1052true 2010/4/20 0:00:00 WEI Chu-Guang,LI Yong-Hui,HAN Jin,WANG Hui-Ying and SUI Nan 1051true 2010/3/23 0:00:00 WANG Xiao-Jia 1050true 2010/3/23 0:00:00 XU Shu-Jun and LIU Gui-Lan 1049true 2010/3/30 0:00:00 LIANG Xiao-Huan and YANG Zeng-Ming 1048true Mas-related G protein-coupled receptors (Mrgs, also called Sensory neuron-specific G protein-coupled receptors or SNSRs), was found in 2001. Interestingly, the mRNAs of Mrgs are expressed predominantly, if not exclusively, in non-overlapping subsets of nonpeptidergic neurons in dorsal root (DRG) and trigeminal ganglia (TG). This specific expression pattern implies significance in physiological and pharmaceutical sciences of pain processing. Study of Mrgs is a new field and will help us to understand the mechanism of pain and nociceptor development. It would also contribute to develop a new analgesic with less central side-effects. The present article summarizes the research progress about Mrgs and provides useful information, such as classification, distribution, expressing regulation and the possible functions in neural circuit and nociception.]]> 2010/2/23 0:00:00 DAI Fei-Hong and HONG Yan-Guo 1047true O-glycosylated glycoproteins found in mucous secretions and as transmembrane glycoproteins of the cell surface with the glycan exposed to the external environment. In mucins, O-glycans are covalently α-linked via an N-acetylgalactosamine(GalNAc) moiety to serine or threonine, and the structures are named mucin-type O-glycans. Mucin-type O-glycans are initiated by UDP-GalNAc∶ polypeptide N-acetylgalactosaminyltransferases, which enzymatic mechanism and structural features have been a hot topic of glycosyltransferases research. Mucin-type O-glycans of cancer cells are often changed, both in structure and in quantity, developing several cancer-associated glycans, such as T and Tn antigens. These structural changes can alter the function of the cancer cells, and its antigenic and adhesive properties, as well as its potential to invade and metastasize. These cancer-associated glycans can be exploited to tumor diagnosis, and in the development of anti-tumor drug or vaccine.]]> 2010/3/9 0:00:00 LIU Chun-Liang and WU Shi-Liang 1046true 2010/3/9 0:00:00 WANG Yi-Fan,YU Wan-Cong,ZHOU Feng-Juan and XUE Zhao-Hui 1045true via the ubiquitin pathway by SCF^βTRCP ligase.]]> 2009/12/22 0:00:00 CAO Chun-Ming and SUN Zhen-Xiao 1044true 2009/12/15 0:00:00 CHEN Hong-Xiu,ZHANG Xiao-Ying,CHEN Chen,ZHAO Jian-Le,HAN Shui-Zhong,LI Yin-Qian and LIU Xiao-Qiang 1043true 2010/1/26 0:00:00 DU Xia,YUAN Hong and XING Xiao-Wei 1042true 2009/11/25 0:00:00 SUN Li,LIU Dian-Bo,YANG Yu-Dong,XING Ya-Ling,CHEN Xiao-Juan and Chen Zhong-Bin 1041true 2009/12/23 0:00:00 WANG Bo and FU Xiao-Lan 1040true 2009/11/30 0:00:00 ZHAO Guang-Ju,LU Zhong-Qiu and YAO Yong-Ming 1039true 2009/10/28 0:00:00 CAI Tan-Xi,LIU Ping-Sheng,YANG Fu-Quan and YANG Fu-Yu 1038true 2009/9/18 0:00:00 ZHU Xiao-Mei,YAO Yong-Ming and SHENG Zhi-Yong 1037true in vitro is a major restriction for the clinical treatment. Human embryonic stem cells (hESCs) may become an alternative source of endothelial progenitor cells because of their high proliferation capability and in vitro pluripotency. Although, there are many challenges for differentiating hESCs to endothelial progenitor cells in vitro. Current understanding of this subject from recent discoveries in this field was summarized. Future work will be needed to translate these in vitro findings to clinical applications.]]> 2009/9/16 0:00:00 WU Qiong,XI Jia-Fei,LI Ya-Li and PEI Xue-Tao 1036true et al. in 2002. It can regulate gene expression by binding directly to small metabolites without the aid of protein molecules. Compared to normal protein-mediated regulation, riboswitch responds to metabolites more rapidly and sensitively. Its discovery opens a new world for RNA research. The recent advances in riboswitch researches were summarized, including crystal structure determination, mechanism and dynamics study, biosensor and antibacterial drug design. Topp et al. successfully reprogrammed E. coli to detect, follow, and precisely localize to a completely new chemical signal by using a synthetic riboswitch. This work provided new ideas for synthetic biology and artificial biology network. The advances in riboswitch 3D structure determination, reaction mechanism and dynamics provide useful information for rational drug design towards new generation of riboswitch-targeting antibacterials.]]> 2009/6/8 0:00:00 HE Shan and LAI Lu-Hua 1035true 2009/9/7 0:00:00 LI An-An,RAO Xiao-Ping,WU Rui-Qi and XU Fu-Qiang 1034true in vivo. Calcineurindependent signals are transduced to the nucleus by nuclear factor of activated T-cells (NFAT) transcription factors that undergo nuclear translocation upon dephosphorylation and promote transcriptional activation of target genes. The recent researches have revealed that RCAN1 modulating catalytic activity of calcineurin can function as an endogenous backfeed inhibitor during the calcineurin-NFAT signalling pathway. RCANs have now been implicated in several pathological conditions including Alzheimer’s disease, down syndrome and cardiac hypertrophy. In addition, the RCAN family is a rational, functional name for RCAN gene and it is proposed in 2007. It is, therefore, necessary to review the RCAN gene, RCANs and the roles of RCANs in a wide variety of diseases especially including Alzheimer’s disease. It is suggested that regulation of RCAN expression may be a new target on neurodegeneration disease.]]> 2009/9/7 0:00:00 TU Ling-Hui,LIU Hai-Peng and LUO Jing 1033true 2009/11/24 0:00:00 LI Hong-Mei,WAN Xiao-Rong and HE Sheng-Gen 1032true 2010/6/23 0:00:00 XIONG Ying,GONG Xiao-Wei and JIANG Yong 1031true +-dependent deacetylase enzymes. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. The research progress of sirtuin and its relationship with aging were summarized.]]> 2010/6/28 0:00:00 PENG Qi,CHEN Wei-Chun and LIU Xin-Guang 1030true via tandem mass spectra. De novo peptide sequencing approach is database independent, which is a distinct advantage compared to database searching approach, so it can be used to analyze the data of new organisms or unsequenced organisms. De novo peptide sequencing problem is briefly described at first, and then the state-of-the-art of this problem is introduced from different aspects, which include the strategies with their advantages and disadvantages, frequently used algorithms and tools, criteria for algorithm assessment, and frequently used datasets for algorithm comparison. At last, the characteristics of some algorithms are summarized and some possible improvements of de novo peptide sequencing algorithm design are proposed.]]> 2010/7/14 0:00:00 SUN Han-Chang,ZHANG Ji-Yang,LIU Hui,ZHANG Wei,XU Chang-Ming,MA Hai-Bin,ZHU Yun-Ping and XIE Hong-Wei 1029true 2010/7/14 0:00:00 LIU Guo-Qing,Baiyinbaoligao and XING Yong-Qiang 1028true 2+)-activated chloride channels play fundamental roles in numerous physiological processes including transepithelial ion/fluid secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization, etc. Despite their physiological importance，the molecular identity of CaCC has not fully invested till now. Here the newly discovered CaCCs molecular basis TMEM16A was reviewed in the respects of the identification processes, gene structure and functions, ion channel's electrophysiological characters, related diseases, pharmocoligical functions and other current hot issues in the fields. The developmental trends of this field were discussed.]]> 2010/6/17 0:00:00 CHEN Ya-Fei,LI Ting,AN Hai-Long,YU Hui,ZHANG Su-Hua,HAN Ying-Rong,ZHANG Yu-Hong,GUO Peng and ZHAN Yong 1027true 2010/9/13 0:00:00 Huang Hao-Ran,Zhao Liang and Ding Yan-Qing 1026true 2010/7/14 0:00:00 LI Ling,CHENG Shi-Jun,LEI Xu and YAO De-Zhong 1025true 2010/7/20 0:00:00 ZHU Fei-Zhou and XIA Kun 1024true 2010/6/17 0:00:00 XU Yang and ZHAO Xiao-Hang 1023true 2010/7/14 0:00:00 WANG Tao,ZHONG Xiu-Li,MEI Xu-Rong and ZHANG Yan-Qing 1022true 2011/4/28 0:00:00 CHEN Wu-Jun,YIN Kai,ZHAO Guo-Jun and TANG Chao-Ke 1021true 2011/5/16 0:00:00 ZHANG Jing,LI Yan-Hua and PEI Xue-Tao 1020true 2011/4/2 0:00:00 LIU Zhen,HE Zhen,MA Wei-Lie and ZHANG Zhi-Zhen 1019true 2011/4/28 0:00:00 CHEN Xin and WANG En-Duo 1018true 2010/12/31 0:00:00 WANG Jing,LI Xiao-Li,XING Guo-Gang and WAN You 1017true 2011/3/29 0:00:00 GONG Ming-Liang,XUAN Yu-Ming and FU Xiao-Lan 1016true 2011/3/8 0:00:00 LUO Xiang-Jian and CAO Ya 1015true 2011/3/8 0:00:00 CHEN Ji-Wu,ZUO Qiu-Hong,JI Lei and LI Xiao-Tao 1014true 2010/12/27 0:00:00 LI Gun and PANG Xiao-Feng 1013true 2011/2/24 0:00:00 YE Hua,LIU Wei,YU Chao-Hui,LI You-Ming and JIANG Ying 1012true 2011/3/8 0:00:00 LI Yang,TANG Jia,FU Zi-Ying and CHEN Qi-Cai 1011true 2011/1/13 0:00:00 ZHANG Wei,ZHANG Ji-Yang,LIU Hui,SUN Han-Chang,XU Chang-Ming,MA Hai-Bin,ZHU Yun-Ping and XIE Hong-Wei 1010true 2010/12/27 0:00:00 ZHANG Yan-Jun,JIANG Jia-Huan,XIE Jing,YANG Li and SUNG KL Paul 1009true 2010/12/27 0:00:00 ZHANG Yu-Xiu,LIU Jin-Guang,CHAI Tuan-Yao and JIN Ling 1008true 2+ release channels, mediate Ca²⁺ release from intracellular stores in the sarcoplasmic reticulum and play essential roles in some excitable cells such as cardiac and skeletal cells. Cyclic adenosine diphosphate ribose (cADPR) and FK 506 binding proteins(FKBP) are tightly associated with RyR in these cells. A summary on latest research progress in RyR and some channel modulators for RyR2 was given based on authors′ research.]]> 2011/1/28 0:00:00 LI Yu-Ming and JI Guang-Ju 1007true 2010/11/5 0:00:00 QI Ting-Ting,LIN Lin,LIU Yun and JIANG Yong 1006true 2010/11/10 0:00:00 LIU Tie-Jun,XU Peng,YU Qian and YAO De-Zhong 1005true 2+ and 2-oxoglutarate dependent histone lysine demethylase and belongs to a family of JmjC domain-containing proteins. PHF8 also contains a plant homeodomain (PHD) finger motif in its N-terminus, which involves in transcriptional regulation. PHF8 can demethylate H3K9me2/1, H4K20me1 and H3K27me2 with JmjC domain, and also act as a transcriptional coactivator through binding to H3K4me3 via PHD finger. PHF8 regulates expression of rRNA and many protein-coding genes involved in neural development such as JARID1C. Mutations in human PHF8 which are defective in histone demethylase activity can cause inherited X-linked mental retardation(XLMR) and cleft lip/cleft palate. These researches suggested that PHF8 is an important regulator of neural development, which deepens the understanding of histone methylation with gene expression and provides novel clues to understanding of XLMR.]]> 2010/10/19 0:00:00 GUO Xiao-Qiang,SHEN Yong-Qing,LIU Bei,CHANG Yan-Zhong and DUAN Xiang-Lin 1004true Salmonella enterica, as well as the ubiquitin-like modification in Mycobacterium tuberculosis, were also introduced.]]> 2010/10/12 0:00:00 TAN Yong-Cong,WANG Qi-Jun,ZHAO Guo-Ping and YAO Yu-Feng 1003true 2010/8/24 0:00:00 LV Ling-Na,TANG Tie-Shan and GUO Cai-Xia 1002true in vivo. In mammals, nearly 41 Kelch proteins have been reported and proved to mediate the protein-protein interactions, protein degradation, and gene expression and signal transmission and so on. It was proposed that the crystal structure of Kelch domain of Keap 1 could be a preferable model for researching Kelch proteins in mammals. And it was also divided these mammal Kelch proteins into three groups according to their domain organizations and paid much attention to summarize their known function in vivo.]]> 2010/10/12 0:00:00 XIAO Feng,SONG Hong-Tao and WEI Qun 1001true 2010/9/13 0:00:00 FU Yu-Hua,ZHOU Xiu－Mei,XU Feng－Qing and QIAN Qi－Jun 1000true 2010/8/3 0:00:00 LIN Yan,QIAN Zhong-Ming and KE Ya 999true 2010/8/24 0:00:00 ZHANG Jia-Zhen,TAN Jin-Yin,ZUO Xiao,LI Bin,LV Zhao-Xia,ZHAO Rui-Pu and WAN Ya-Kun 998true DRD3 (the dopamine receptor D3 gene) and LINGO1 (the Leucine-rich repeat-and lg domain-containing NOGO receptor-interacting protein 1 gene) have been reported recently. The genetics of essential tremor will be summarized.]]> 2010/8/17 0:00:00 LIANG Hui,GUO Yi and DENG Hao 997true 2010/8/24 0:00:00 LIU Wei and XIE Hong-Wei 996true 2010/11/18 0:00:00 ZHANG Jun-Jie,ZHOU Ke-Yuan and Cai Chun 995true 2010/6/10 0:00:00 WANG Jin-Lan,WANG Lu-Shan,LIU Wei-Feng,CHEN Guan-Jun and GAO Pei-Ji 994true 2011/5/27 0:00:00 ZHOU Xiao-Jiang,HU Yuan and LIU Ping 993true Mycobacterium tuberculosis. With the help of accessory factors, Dop, PafA and Mpa, Pup covalently linked to the Lys ε-NH₂ in the target proteins and mediated the target protein degradation through the proteasome. The discovery of Pup-proteasome system revealed a novel mechanism of prokaryotic protein degradation, which is involved essential physiological function including the intermediary metabolism, information pathway, detoxification/virulence, cell wall and cell membrane formation and so on. Disruption of Pup-proteasome system can suppress the pathogenicity of Mycobacterium tuberculosis. Therefore it is regarded as the new therapeutic target for tuberculosis. In the present paper, the progress in the study on mechanism and function of Pup-proteasome system is reviewed.]]> 2011/4/2 0:00:00 WANG Chun-Jun,LIN Jin and ZHANG Jun-Jie 992true 2011/6/16 0:00:00 XING Ya-Ling,ZHENG Yang,WANG Kai,CHEN Xiao-Juan and CHEN Zhong-bin 991true Caenorhabditis elegans on a microfluidic platform for the past ten years. The related progress for biomedical purpose of Caenorhabditis elegans was reviewed. In particular, advances on microfluidic-based researches have been focused. The automated immobilization, behaviors, development, neurology, drug screening and gene screening of Caenorhabditis elegans were summarized. The prospects for the applications of microfluidic device are also discussed.]]> 2011/5/16 0:00:00 YANG Jian-Ping,YANG Fan,LI Xin-Chun,YU Yan-Yan and CHEN Zuan-Guang 990true 2011/5/16 0:00:00 CHEN Yong-Xiang and ZHU Li-Qi 989true 2011/4/11 0:00:00 HAN Yong-Feng,YANG Qian,ZHANG Sheng-Wei,SUN Da-Ye and SUN Ying 988true 2012/2/9 0:00:00 MO Wei-Chuan,LIU Ying and HE Rong-Qiao 987true 2011/9/21 0:00:00 LIU Hui,ZHUANG Zi-Heng,GUAN Ji-Hong and ZHOU Shui-Geng 986true 2012/2/21 0:00:00 ZHU Xin,MA Qing-Quan,DONG Na and SHAN An-Shan 985true 2011/12/31 0:00:00 YANG Li,XIAO Ling and CHEN Lin-Xi 984true Mycobacterium tuberculosis has been a serious threat to human health globally．All genetic events occurring in the genome evolution play an important role in all aspects such as M． tuberculosis's biological properties, pathogenicity and drug resistance．This review will summarize the origins and genomic features of M．tuberculosis, and discuss the current progress about its genome evolution．]]> 2012/2/8 0:00:00 WAN Bao-Shan,ZHANG Qiu-Fen,ZHOU Ai-Ping,ZHAO Guo-Ping and YAO Yu-Feng 983true 2012/3/1 0:00:00 ZHONG Yao-Gang,QIN Yan-Nan,SUN Shi-Sheng,CHEN Wen-Tian and LI Zheng 982true 2011/11/23 0:00:00 CHEN Ji-Wu,ZHENG Li-Na,WANG Bang-Zheng and LI Xiao-Tao 981true 2011/10/24 0:00:00 WEN Chong-Wei,NING De-Gang,LIU Rui-Jiang and ZHANG Ye-Wang 980true 2011/9/21 0:00:00 ZHU Li-Ping,LI Zhi-Feng,HAN Kui,LI Shu-Guang and LI Yue-Zhong 979true 2012/1/18 0:00:00 ZHAO Peng-Cheng,LV Yong-Gang,ZOU Yang,ZHANG Xiao-Mei,CHEN Guo-Bao and YANG Li 978true 2011/12/20 0:00:00 LIU Zhi-Lei,SUN Wei,HE Fu-Chu,CONG Xian-Ling and JIANG Ying 977true + and consequently ATP, culminating in cell dysfunction or necrosis. This cellular suicide mechanism has been implicated in the pathomechanism of atherosclerosis, myocardial ischemia, diabetes, and diabetes-associated cardiovascular dysfunction. Interestingly, several new and unexpected regulators of PARP1 activation have been found, including kinases, polyamines, caffeine metabolites, theophyline, and tetracycline antibiotics. The intracellular Ca²⁺ and NF-κB also participate in the regulatory mechanism. This review summarizes the biological function and general principle of targeted PARP, the possible pathomechanism of atherosclerosis, and the latest progress of PARP1-regulated atherosclerosis, which will make great strides in the study of atherosclerosis.]]> 2011/10/24 0:00:00 HUO Qing-Wei,LI Dong-Feng and LONG Cheng 976true 10⁸/d), thus possesses many advantages over the conventional technologies. FACS based screening method greatly improves our ability in handling large protein libraries and has tremendous potential in various fields such as metagenomics and directed evolution. Herein, recent progress of FACS based enzymatic screening method has been reviewed, with an emphasis on its applications in enzyme directed evolution.]]> 2011/9/30 0:00:00 MA Fu-Qiang,FENG Yan and YANG Guang-Yu 975true 2011/9/7 0:00:00 ZHANG Xiu-Hong and YANG Zeng-Ming 974true 2011/10/10 0:00:00 XU Gang,WU Ming-Hua and LI Gui-Yuan 973true 2011/9/27 0:00:00 LU Qian,CHEN Wu-Jun,YIN Kai,ZHAO Guo-Jun and TNAG Chao-Ke 972true 2012/2/20 0:00:00 LV Jing,SUN Hong-Lei,HE Hao and FU Peng-Cheng 971true 2012/2/20 0:00:00 LIU Hai-Yan 970true via X-ray single crystal diffraction technique, for which high quality membrane protein crystals are required. However, due to its amphipathicity, the membrane proteins are hard to crystallize, resulting in difficulties in the structural determination. In recent years, some methods (such as in surfo methods and in cubo methods) have been developed specifically for crystallizing membrane proteins. The progresses on crystallization methodology of membrane proteins are reviewed, and the prospective in this field are also discussed.]]> 2011/7/29 0:00:00 HU Yan-Ting,ZHANG Chen-Yan,MA Xiao-Liang and YIN Da-Chuan 969true in vitro selection and can be produced in large scale by chemical synthesis or prokaryotic expression. The smaller molecular size confers its higher tissue penetrativity and faster circulation clearance. Affibody has a higher physical and chemical stability than antibody. In addition, affibody can be cross-liked with or fusion co-expressed with reporter molecules such as fluorescent protein, biotin and so on. This class of engineered affinity proteins has been used in detection, separation, and purification of target proteins and, might be extensively applied in experimental diagnosis, molecular imaging and targeted therapeutics in the future.]]> 2011/8/24 0:00:00 LI Shuang and HAO Zhi-Ming 968true +/NADH ratio and regulating the level of nicotinamide. Similar mechanism also exist among Caenorhabditis elegans and Drosophila melanogasters. SIRT1 protein level increases in response to CR in mammals, leading to an increase in PNC1/Nampt expression, which favors the synthesis of NAD⁺ from NAM, potentially acting as a major mechanism to drop the leash of SIRT1 inhibition. NO up-regulates SIRT1 and mitochondrial biogenesis. Cellular and organism's senescence may be influenced through the deacetylation of histone, p53, NES1, FOXO by SIRT1, indicating sirtuin and its homologous analogues play important roles in aging process and lifespan extension under CR in different organisms.]]> 2011/9/21 0:00:00 LIU Bin,CHEN Wei-Chun,LIU Xin-Guang and ZHOU Zhong-Jun 967true 2011/7/29 0:00:00 LING Hong-Yan,HU Bi,FENG Shui-Dong,LIAO Duan-Fang and WEN Ge-Bo 966true Leu(UUR) A3243G are associated with hearing impairment and other clinical symptoms, while other tRNA mutations including tRNA^Ser(UCN) T7511C only produce the phenotype of hearing loss. These tRNA mutations are the primary factors for the development of hearing loss. On the other hand, other tRNA mutations such as tRNA^Thr G15927A act in synergy with the primary tRNA mutations, modulating the phenotypic manifestation. The mutations alter the secondary structures of tRNAs, impair translation and decrease the ATP production. Consequently, mitochondrial dysfunctions caused by these tRNA mutations lead to hearing loss. It this review we summarize the deafness-associated mitochondrial tRNA mutations and discuss the pathophysiology of these mitochondrial tRNA mutations.]]> 2011/8/24 0:00:00 ZHENG Jing,ZHENG Bin-Jiao,FANG Fang,ZHU Yi,LV Jian-Xin and GUAN Min-Xin 965true 2011/6/30 0:00:00 GUO Xiao-Qiang,SHEN Yong-Qing,GUO Zhen-Qing,CHANG Yan-Zhong and DUAN Xiang-Lin 964true TP53 gene, which encodes p53 protein, is a hotspot of all time in molecular oncology. p53 suppresses tumor initiation and progression through its regulation of many downstream genes. Recent studies have revealed that microRNAs (miRNAs) interact with the p53 pathway and form a complex regulatory network. On one hand, p53 promotes cell cycle arrest and induces cell apoptosis and senescence to suppress tumorigenesis by regulating the transcription and post-transcriptional maturation of multiple miRNAs. On the other hand, many miRNAs fine-tune the p53 pathway through regulation of TP53 and its upstream regulators or downstream effectors. The miR-34s family, directly transactivated by p53 represents a large number of p53-regulated miRNAs. They exert their tumor suppressing function via targeted inhibition of multiple key molecules in the p53 pathway. Furthermore, miR-34s enhance p53 activity through a feedback loop by inhibiting silent information regulator 1(SIRT 1). Investigation on the interaction between miRNAs and p53 is essential to fully understand the underline mechanisms of p53 tumor suppressing action.]]> 2013/2/28 2:15:03 GONG Zhao-Jian,HUANG Hong-Bin,XU Ke,LIANG Fang,LI Xiao-Ling,XIONG Wei,ZENG Zhao-Yang and LI Gui-Yuan 963true 2013/2/28 2:24:06 LIU Xiao-Yan,LU Qian,CHEN Wu-Jun and TANG Chao-Ke 962true 2013/2/28 2:32:05 SUN Lei,ZHANG Lin and LIU Hui 961true 2013/2/28 2:41:50 WU Qiu-Yan and DENG-Yuan 960true 2013/3/25 0:00:00 XIE Da-Fei,LI Peng,LI Fei,BO Xiao-Chen and WANG Sheng-Qi 959true 2013/3/25 0:00:00 LI Kai-Yun,FU Qiu-Fang and FU Xiao-Lan 958true 2013/3/25 0:00:00 LI Yu-Zhen and LIU Xiu-Hua 957true 2011/9/30 0:00:00 REN Da-Hai,CUI Ming-Yang,XIA Yi-Qiu and YOU Zheng 956true 2011/11/23 0:00:00 GUO Xiao-Fang,CHEN Pan,LI Xia-Yu,LI Xiao-Ling and LI Gui-Yuan 955true 2012/5/18 0:00:00 LI Jing,LIN Zhu-Mei and ZHU Li-Qi 954true 2012/3/1 0:00:00 PANG Yong-Qi,WANG Gao-Qi,WANG Xu-Chu,CHEN Jia and WANG Xue-Chen 953true 2013/9/16 0:00:00 WANG Cheng-Yu and WANG Xiao-Jia 952true 2013/9/16 0:00:00 ZHANG Yao-Hua,LIN Zhu-Mei and ZHU Li-Qi 951true 2013/9/16 0:00:00 YUAN Ting-Ting and CUI Su-Juan 950true 2013/8/21 0:00:00 FANG Rui,CHANG Fei,SUN Zhao-Lin,LI Ning and MENG Qing-Yong 949true in vitro using stem/progenitor cells. But enucleation remains one of the critical rate-limiting steps. Even though reticulocytes could be produced in vitro, the low efficiency should be concerned. To uncover the molecular mechanism of erythroblast enucleation will facilitate ex vivo production of functional erythrocytes. This review summarizes three prevalent enucleation mechanisms, including apoptosis, asymmetric cytokinesis and vesicle trafficking, discusses proteins and microRNAs playing important role in the process, and evaluates the prospects for ex vivo production of red blood cells.]]> 2013/8/21 0:00:00 FANG Fang,XIE Xiao-Yan,YUE Wen and PEI Xue-Tao 948true 2013/8/21 0:00:00 LIANG Zhi-Bin,LIANG Chen,GENG Yun-Qi and QIAO Wen-Tao 947true 2013/8/21 0:00:00 LIU Ru-Tao,WANG Shi-Wei and LIU Jing 946true 2013/6/20 0:00:00 MIAO Xin-Yu,LIU Yu and LI Chun-Lin 945true 2013/6/20 0:00:00 CAI Zhao-Lin,XIAO Peng and LONG Cheng 944true 2013/6/20 0:00:00 TANG Yan-Yan,CHEN Wu-Jun,LU Qian and TANG Chao-Ke 943true 2013/5/22 0:00:00 YANG Xing-Xing,WANG Kai,CHEN Xiao-Juan,XING Ya-Ling and CHEN Zhong-Bin 942true 2013/5/22 0:00:00 ZHAO Guo-Jun and TANG Chao-Ke 941true 2013/4/22 0:00:00 ZHANG Kun,WANG Le-Heng,CHI Hao,BU De-Chao,YUAN Zuo-Fei,LIU Chao,FAN Sheng-Bo,CHEN Hai-Feng,ZENG Wen-Feng,LUO Hai-Tao,SUN Rui-Xiang,HE Si-Min,XIE Lu and ZHAO Yi 940true 2013/4/22 0:00:00 ZHANG Cheng-Pu,LI Ning,MA Jie,WU Song-Feng and ZHU Yun-Ping 939true 2013/3/22 0:00:00 CHEN Ji-Wu,WANG Bang-Zheng,GAO Xiu-Xia and ZHANG Yuan-Yuan 938true 2013/3/22 0:00:00 YANG Yan and TANG Zong-Xiang 937true 2013/3/26 0:00:00 LIANG Fang,XU Ke,GONG Zhao-Jian,LI Qiao,MA Jian,XIONG Wei,ZENG Zhao-Yang and LI Gui-Yuan 936true 2013/2/26 11:38:53 XIA Heng-Chuan,ZHANG Chun-Xia,FENG Fan,YUAN Yi,ZHOU Yang,LIU Xiao-Yong,ZHU Ke-Ming,YAO Qin and CHEN Ke-Ping 935true via the combination to their target genes. Lipids of diets, especially the essential fatty acids, can involve in the biology processes, such as cancer resistance and inflammation remission, via the regulation of miRNAs.]]> 2013/2/26 2:34:36 NAN Xue-Mei,WANG Jia-Qi,CHEN Hai-Yan and HU Han 934true 2013/2/27 3:09:07 MING Xuan and JIANG Song-Min 933true 2013/2/27 3:26:23 ZHENG Yang,XING Ya-Ling,CHEN Xiao-Juan,YANG Xing-Xing,WANG Kai and CHEN Zhong-Bin 932true 2013/2/27 3:34:14 LI Chun-Lu,ZHU Ning,LI Yong-Hui,MENG Xiao-Lu,GAO Jun and SUI Nan 931true 2013/2/27 3:42:07 XIE Zhao-Hui,ZENG Qiang-Cheng,SHEN Liang and WANG Ji-You 930true 2013/12/20 0:00:00 XIAO Ling,LI Lan-Fang and CHEN Lin-Xi 929true CD25 regulatory T cells (Treg cells) play crucial roles in the maintenance of self-immune tolerance. Decreased numbers or functional deficiency of Treg cells result in development of a variety of autoimmune diseases like multiple sclerosis and typeⅠ diabetes. Moreover, Treg cells have been implicated in inflammation and transplantation settings. Two types of Treg cells including thymic-derived natural Treg (nTreg) and peripheral induced Treg (iTreg) cells have been identified based on their distinct developmental origin. nTreg cells are derived in the thymus and express high level of Forkhead transcription factor Foxp3, nTreg cells exhibit the suppressive function mainly in a cell-cell contact manner. nTreg cells develop in two steps largely shaped by TCR, co-stimulatory and cytokines in the thymus. In the present manuscript, we will mainly summarize recent advances regarding molecular and cellular regulation of nTreg development and differentiation.]]> 2013/12/20 0:00:00 CHEN Hui and ZHAO Yong 928true 2013/12/20 0:00:00 ZHOU Chao-Ping and LI Xin-Hui 927true 2013/12/20 0:00:00 LU Ya-Li,SUN Ai-Hua,HE Fu-Chu and JIANG Ying 926true de novo oocytes derived from FGSCs, but also found that if the FGSCs were delivered back into adult ovaries, they were capable of generating functional eggs produced healthy offsprings. However, some groups repeated or designed experiments carefully, but they did not get the same or even opposite results. Recently, some researchers announced that they had purified FGSCs from ovaries of reproductive-age women, which could produce functional oocytes in vivo and in vitro, but the fertilization competency of these oocytes still need to be clarified. Therefore, this paper reviews the study history of mammalian FGSCs, the long-standing controversy as well as prospects for the future use of these FGSCs.]]> 2013/11/22 0:00:00 CHEN Zhong-Liang and YANG Shi-Hua 925true 2013/11/22 0:00:00 LIU Hong-De,LUO Kun,MA Xin,ZHAI Jin-Cheng,XIE Jian-Ming,SUN Xiao and WAN Ya-Kun 924true 2013/11/22 0:00:00 CHEN Jia-Jun,TIAN Ming-Xiu,LI Xing-An and HU Lin-Sen 923true 2014/9/22 0:00:00 LI Xing-Yu and GAO Can 922true 2014/9/22 0:00:00 DING Liang,NI Yan-Hong,HU Qin-Gang and HOU Ya-Yi 921true 2014/9/22 0:00:00 GE Miao-Miao and CAI Chun 920true 2014/9/22 0:00:00 STOYANOV Stoyan B.,LENTZ Soren L.,VALDES-HERRERA Jose P.,KRASTEV Nikolai S. and KRASTEV Dimo S. 919true etc. The outcome of ENCODE project and subsequent studies have revealed that only a small portion of human genome encodes proteins, while the vast majority are transcribed as non-coding RNA (ncRNA). Long non-coding RNA (lncRNA) is commonly defined as an RNA molecule which is larger than 200 nucleotides (nt) and not translated into proteins. Growing evidences have suggested that lncRNAs can regulate gene expression at various levels including epigenetic regulation, transcriptional regulation and post-transcriptional regulation, and are involved in a wide variety of biological processes, such as cell proliferation, differentiation and apoptosis. In this review, we highlight the recent advances of how lncRNAs function in the epigenetic regulation.]]> 2014/8/18 0:00:00 CHEN Yu-Ning and XIONG Xing-Dong 918true 2014/8/18 0:00:00 LIU Yun,LI Jin-Mei,TAN Ting and JIANG Yong 917true 2014/8/18 0:00:00 LI Xiao-Fan,CHEN Chun-Ying,ZHAO Yun-Hui and YUAN Xiao-Yan 916true 2014/8/18 0:00:00 ZHU Xiao-Qian,SONG Yao-Wu and BI Hong-Yan 915true 2014/7/19 0:00:00 XIE Zhen-Hua and WU Yao-Jiong 914true via its basal surface. Cancer stem cell is a small subset of stem-like cells which have the capacity for self-renewal and asymmetric cell division. They play an important role in cancer initiation and progression. In rencent years, some researches reveal that EMT, which is closely related tumor metastasis, can generate tumour cells with propreties of stem cells. We review here recent observations correlated with the mechanism of it and its significance to clinical therapy.]]> 2014/7/19 0:00:00 YU Shuai-Shuai,MA Xiao-Juan,LIN Bi-Hua,LI Ji-Xia and ZHOU Ke-Yuan 913true 2014/7/19 0:00:00 LU Yi-Ming,QU Wu-Bin and ZHANG Cheng-Gang 912true 2014/7/19 0:00:00 LIU Feng-Yin,SHEN Yu-Dong,SUN Yuan-Ming,WANG Hong,LEI Hong-Tao,YANG Jin-Yi and XU Zhen-Lin 911true 2014/6/18 0:00:00 LI Wei,SU Ze-Hong,YANG Jie and HE Shu-Ya 910true 2014/6/18 0:00:00 ZHANG Xiao-Mei,LV Yong-Gang,XU Zhi-Ling and YANG Li 909true 2014/6/18 0:00:00 XU Na,FU Zi-Ying and CHEN Qi-Cai 908true per se from other phosphorylated amino acids, such as isomerism, chemical lability etc, it hydrolyzes easily during traditional handling methods. Due to the current progress in biochemistry and molecular biology, investigators have established innovative preparation, isolation and characterization strategies for phosphohistidine ad hoc. Therefore, the field begins to rapidly develop. Based on their chemical structures, this article analyzes the main physical and chemical properties as well as their reactivity of two phosphohistidine isomers, followed by the noval chemical biology tools and the main biological progresses.]]> 2014/5/22 0:00:00 WANG Zhi-Peng,CHEN Chen-Chen,WANG Tian,WANG Miao and LI Yi-Ming 907true 2014/5/22 0:00:00 LI Jin-Feng,XIE Di,HE Ping-Ping,TANG Yan-Yan,TU Yu-Lin and YIN Kai 906true 2014/5/22 0:00:00 XIE Zhao-Hui 905true 2014/5/22 0:00:00 ZHU Feng,MA Li-Wei and TONG Tan-Jun 904true 2014/4/22 0:00:00 OU YANG Xin-Ping,ZHANG Min,HE Ping-Ping,TANG Yan-Yan,LI Yuan and TANG Chao-Ke 903true 2014/4/22 0:00:00 YU Zheng-Yuan,SONG Ya-Li,GONG Zhao-Jian,ZENG Zhao-Yang,LU Jian-Hong,LI Xiao-Ling,XIONG Wei and LI Gui-Yuan 902true 2014/4/22 0:00:00 FU Xiao-Zhen,LI Hong-Yan,ZHANG Ye-Jun,QU Chao,ZHONG Guang-Ying,LIU Jing and ZOU Wei 901true 2014/4/22 0:00:00 ZHAO Chun-Xia,CUI Ying-Yu and CHEN Yi-Han 900true 2014/2/21 0:00:00 XU Zi-Xiang,ZHENG Ping and SUN Ji-Bin 899true 2014/2/21 0:00:00 LIU Wei and XIE Hong-Wei 898true 2014/2/21 0:00:00 CHEN Yu-Han,ZHANG Ling-Qiang and HE Fu-Chu 897true 2014/2/21 0:00:00 SHENG Jing-Hao and XU Zheng-Ping 896true 2014/12/19 0:00:00 LIU Pei-Bin,YE Zi-Lu,CAI Tan-Xi,DAI Shao-Jun and YANG Fu-Quan 895true via choline transporters is essential for ACh re-synthesis. Three types of transporters have been implicated in choline transporter family: high-affinity, Na⁺-dependent choline transporters (CHTs); intermediate-affinity, Na -independent choline transporter-like proteins (CTLs) and polyspecific organic cation transporters (OCTs) with low affinity for choline. It has been shown that abnormal choline transporters are involved in a number of neurodegenerative disorders, including AD. The article aims to summarize the physiological role of choline transporter in the cholinergic system and pathological alterations in AD, providing new insight into the therapeutic treatment of AD.]]> 2014/12/19 0:00:00 DENG Li,WANG Jin-Zhao,YANG Li and LONG Cheng 894true 2014/12/19 0:00:00 ZHANG Yun-Long and QU Shao-Gang 893true 2014/12/19 0:00:00 DAI A-Hui and SUN Wen-Jun 892true in vitro fertilization and embryo culture, embryo transfer and pregnancy management, thus "test-tube monkey", and all have been efficiently completed. The establishment and development of the current gene editing technology, ZFN (zinc-finger nucleases), TALEN (transcription activator-like effector nucleases) and CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/Cas9), create great chances for production of genetically modified macaques. Scientists in China have successfully developed transgenic macaques with overexpression of green fluorescence protein gene and gene mutagenesis in macaques. With the breakthrough and development of various technologies, combined with abundant experimental macaque resources, avoiding various reproductive physiological obstructions of macaques, China is expected to become an appropriate international base in application of genetic engineering macaques.]]> 2014/11/21 0:00:00 MA Yun-Han and YANG Shi-Hua 891true 2014/11/21 0:00:00 XU Yue and LIN Wen-Juan 890true 2014/11/21 0:00:00 FAN Sheng-Bo,WU Yan-Jie,YANG Bing,CHI Hao,MENG Jia-Ming,LU Shan,ZHANG Kun,WU Long,SUN Rui-Xiang,DONG Meng-Qiu and HE Si-Min 889true in vivo technically difficult. It can be of great significance to reconstruct bionic microenvironment in vitro for further revealing the functions of osteocyte. The systematic introduction of structural, biochemical and mechanical microenvironment surrounding osteocyte was presented here, and the recent technologies for simulation of bionic microenvironment in vitro were also reviewed. This review will provide a useful reference for researchers who are interested in osteology, tissue engineering and regenerative medicine.]]> 2014/11/21 0:00:00 REN Li,XU Hui-Yun,QIAN Ai-Rong and SHANG Peng 888true 2015/8/18 0:00:00 DING Su-Ping, LIU Li-Li, HUANG Ting, WANG Ying, YAN Ming-Li and YUAN Zhi-Dong 887true e.g., nanometer spatial resolution, picoNewton force sensitivity, label-free, can work in aqueous conditions), atomic force microscopy(AFM) has become an important instrument in cell biology. AFM can not only visualize the ultra-microstructures on the surface of living cells, but also can quantify the cellular mechanical properties (such as Young's modulus) by indenting technique, opening the doors to in situ explore the dynamical physiological activities and mechanical behaviors of single living cells at the nanoscale. In the past decades, researchers have carried out extensive investigations in imaging the cellular ultra-microstructures and measuring the cellular mechanical properties using AFM, yielding novel insights into our understanding of cellular physiological activities and providing a new idea to solve the related issues in the field of biomedicine. The AFM's own performances have also been steadily improved, which further promote its applications in biology. In this paper, based on our own research in investigating the killing effects of targeted cancer drugs at the nanoscale using AFM, the principle of AFM imaging and measuring the cellular mechanical properties was presented, the progress in visualizing the cellular ultra-microstructures and quantifying the cellular mechanical properties using AFM was summarized, the challenges facing AFM single-cell assay and its future directions were discussed.]]> 2015/8/18 0:00:00 LI Mi, LIU Lian-Qing, XI Ning and WANG Yue-Chao 886true 2015/8/18 0:00:00 JIA Li-Yan, LONG Jian-Gang and LIU Jian-Kang 885true 2015/8/18 0:00:00 CAO Jian-Gang, LI Lan-Fang and CHEN Lin-Xi 884true 2015/8/18 0:00:00 WANG Tao and LI Zhi-Wei 883true 2015/7/20 0:00:00 WU Jian-Peng, LIU Xiao-Li, ZHANG Huan, ZHANG Yi-Fan, LUO Yan-E and FAN Hai-Ming 882true 2015/7/20 0:00:00 ZHANG Jing-Jing, YOU Yong, LI Yi, GUI Qing-Jun, FENG Ju-Ling and YIN Kai 881true etc, showing its essential role in the normal development of the embryo. Recent studies have exhibited that GDF11 significantly improves brain cognition, reverses myocardial hypertrophy and improves the metabolism of skeletal muscle, proposing a wide range of biological effects and its potential in clinical application as a senescence-reversing agent. However, a most recent research obtained opposite results. In this review we will introduce the up-to-date knowledge of GDF11, concerning its discovery and research history, structure, expression regulation, signal transduction pathways and functions in order to provide ideas for future research.]]> 2015/7/20 0:00:00 LI Qian and HAO Zhi-Ming 880true etc. Studying the interactions between G-quadruplex and ligands, such as Telomestatin, TMPyP4, BRACO-19, RHPS4, contributes to understand the roles of G-quadruplex and the corresponding mechanisms in biological processes. The research relies on a variety of analytical methods. Biochemical methods includes DMS footprinting, EMSA and DNA polymerase stop assay, and spectroscopy methods, such as circular dichroism, fluorescence spectrum, fluorescence resonance energy transfer, nuclear magnetic resonance and X-ray crystal diffraction. In addition, surface plasma resonance, electrospray ionization mass spectrometry and capillary electrophoresis are also included. This paper reviews the ligands targeting G-quadruplex and methods mentioned above for characterizing G-quadruplex's structures and interactions with ligands.]]> 2015/7/20 0:00:00 WEI Qiang, QU Feng and GONG Rui 879true 2015/6/23 0:00:00 MA Kun, WANG Yu-Juan and WANG Jun-Feng 878true 2015/6/23 0:00:00 HUANG Yuan-Yu and LIANG Zi-Cai 877true COL1A1 or COL1A2 genes that encode the proa1 and proa2. Recessively inherited forms of OI are rare and are caused by mutations in many different genes, which related with post-transcriptional modification, defects of collagen's chaperons and C-propeptide cleavage enzyme, osteoblast/osteocyte differentiation and transcript factor, Ca²⁺ channel as well as Wnt signaling molecules. The pathogenic genes and mechanisms to dominant and recessive OI are useful for gene detection and individual therapy of OI patients.]]> 2015/6/23 0:00:00 LU Yan-Qin, REN Xiu-Zhi, WANG Yan-Zhou and HAN Jin-Xiang 876true i.e., freeze-frame, passively viewing, motion aftereffect, and fMRI adaption) to investigate implied motion. The role of attention and awareness in implied motion and the memory representation of implied motion are key issues in previous studies. Researchers also focus on the various activated brain regions engaged in implied motion, including medial temporal cortical areas (MT/MST), superior temporal sulcus, and mirrorneuron system. Future studies are needed to further explore the cognitive and neural mechanisms of implied motion in order to clarify whether motion and form processing in human visual system, especially the neural network for motion from form, are dissociated or integrated.]]> 2015/6/23 0:00:00 LI Kai-Yun, XU Li-Hui, XUAN Yu-Ming and FU Xiao-Lan 875true etc. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is activated by oxidative stress and regulates the expression of a variety of antioxidant enzymes and proteins that exert cytoprotective effects against oxidative stress. Numerous studies have addressed the role of Nrf2 against oxidative stress. Further, recent findings concerning that Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with anti-inflammatory, anti-apoptotic and nerve growth factor signaling in AD. In addition, activation of the Nrf2 pathway may have the effect of anti-amyloidogenic and reduces the levels of phosphorylated tau. Recently all new anti-AD drugs focused on a single target have failed, so researchers put forward that activation of Nrf2 may be a good treatment for AD through simultaneous modulation of numerous pathways involved in AD pathogenesis. Here in this review we summarize the research status of Nrf2 in AD.]]> 2015/6/23 0:00:00 CAO Hui-Min and YU Gang 874true 2015/6/23 0:00:00 ZHANG Xiao-Han and GUO Jun 873true 2015/5/21 0:00:00 LU Jian-Hong and LIU Ling-Zhi 872true 2+-dependent neurotransmitter release. In this review, we highlight the recent advances in the function of each domain of Cpx and the mechanisms of interacting with other vesicle exocytosis associated proteins such as SNARE complex and synaptotagmin.]]> 2015/5/21 0:00:00 LI Xiao-Hong, GONG Ji-Hong, LIN XianGuang and YANG Xiao-Fei 871true 2015/5/21 0:00:00 WU Qing, ZHOU Hai-Meng and LI Xu-Hui 870true 2015/5/21 0:00:00 HE Hong-Hui, ZENG Nan, LIAO Ran and MA Hui 869true cis-trans isomerase that recognizes pThr/pSer-Pro in proteins, relevant to the pathogenesis of Alzheimer′s disease (AD). Pin1 regulates the structures and functions of some molecules that are related to AD, inhibits the main AD pathological characteristics such as neurofibrillary tangles (NFTs), senile plaques (SPs), and cerebral amyloid angiopathy (CAA), promotes the differentiation of neural progenitor cells (NPCs) to neurons, and to some extent prevents the occurrence and development of AD. Meanwhile, Pin1 dysfunction in vivo may be involved in the pathogenesis of AD. Nevertheless, whether Pin1 could be a therapeutic target for the prevention and treatment of AD still needs to be verified clinically. Considering of the poor efficacy of AD medicines that target each single molecule in brain, the "combined multiple-target medicine" focusing on Pin1 and other related molecules may be a therapeutic strategy for AD in the future.]]> 2015/5/22 0:00:00 HOU Hai, WANG Jing-Zhang and LI Xue-Mei 868true 1c is generated by the irreversible, non-enzymatic glycation reactions on the α-amino groups of N-terminal residue Val1 in one or both beta subunits of tetrameric Hb. Due to the direct correlation of HbA_1c with ambient glycemic concentration over a prolonged period of time, HbA_1c could be useful in assessing diabetic control for the long-term, and is also an important predictor of potential risks to diabetes complications. Therefore, ADA and WHO recommended HbA_1c with a diagnostic cut point of ≥ 6.5% as a new diagnostic criterion for diabetes in 2010 and 2011, respectively. In this review, we summarize: (1) the standardization of HbA_1c from the global IFCC reference method and designated comparison methods in the United States, Japan and Sweden; (2) the basic principles of HbA_1c detection methods commonly used in clinic including affinity chromatography, immunoassay and enzymatic analysis, and their application limitations; (3) the development of POC technology for HbA_1c measurement.]]> 2015/5/22 0:00:00 ZHOU Wen-Juan, WU Yun-Xiang and YI Jun 867true 2015/4/24 0:00:00 LV Xiao-Qing, LI Lei, CHEN Hong-Mei, CHEN Peng and LIU Jing 866true 2+ activated potassium channel (BK) is the only ion channel which is regulated by intracellular Ca²⁺ and membrane potential in the cell membrane. Recently the structure of BK determined by cryo-electron microscopy (cryo-EM) shed the first light on the assembly of the whole channel, as well as the crystal structure of the cytosolic domain by x-ray single crystal diffraction. In addition, these 3D structures corroborate many close interactions among these domains during channel gating. More recently, great advancements have been made in the research on functional regulation and gating kinetics simulation of BK channels, these contribute to understand the gating mechanism of the BK channel and the pathophysiological basis of BK-related ion channel diseases.]]> 2015/4/24 0:00:00 WANG Yan-Ting, GUO Xi-Ying, HUANG Zhi-Gang and WANG Sheng 865true 2015/4/24 0:00:00 SHI Le, LONG Jian-Gang and LIU Jian-Kang 864true 2015/4/24 0:00:00 XUAN Bin and PENG Su-Hao 863true 2015/3/24 0:00:00 MENG Fan-Hui, JIANG Xu-Kai, LIU Lin, ZHANG Huai-Qiang, GAO Pei-Ji and WANG Lu-Shan 862true 2015/3/24 0:00:00 SU Tao, SONG Dan, LI Ting, WANG Xing-Hua and HE Rong-Qiao 861true in vitro with only these three proteins, in addition to ATP and an appropriate inorganic buffer. Molecular studies have shown that KaiA promotes the self-phosphorylation of KaiC, whereas KaiB antagonize KaiA's role and induce the de-phosphorylation of KaiC. An unsolved question is how KaiB interacts with KaiC exactly, including the binding site of KaiB on KaiC, the oligomerization form of KaiB, and the exact modulating mechanism of KaiB. Here, we reviewed the most recent progress on the KaiB-KaiC interaction mechanism, including our preliminary results on the KaiB-KaiC interaction, and provided a possible molecular mechanism of the molecular oscillator. We hope this review will provide a timely perspective on the study of this model system.]]> 2015/3/24 0:00:00 LIU Song and LIU Sen 860true 2015/3/24 0:00:00 LI Yu-Wei, WANG Yu-Min, ZHANG Xue-Ying, XUE Dan, KUANG Biao, PAN Xu-Ya, JING Yi-Zhou, LI Xiao-Ling, ZHOU Ming, XIONG Wei, ZENG Zhao-Yang and LI Gui-Yuan 859true in vitro. Aptamers are widespread recognition, easy to modification and good stability, they are called chemical antibodies. As novel target molecules studied in recent years, aptamers have been used in targeted drug delivery. This review described several aptamer targeted drug delivery systems, such as aptamer-drugs, aptamer-liposomes, aptamer-polymer micelles, aptamer-polymeric nanoparticles, aptamer-metal particles and aptamer-branched polymer drug delivery systems. The existing problems and shortcomings of the research hotspots in the current study were also reviewed.]]> 2015/3/24 0:00:00 ZHANG Yue, XING Shi-Ge, WANG Zhen, KANG Qing-He, LING Yun, YAO Mei-Yi, HE Yan-Ping, JIN Yong and CHU Xiao-Gang 858true 2015/3/24 0:00:00 LIU Guang-Hua, DENG Li and PENG Li-Fei 857true 2015/3/24 0:00:00 GUO Hai-Qiang, LIU Tong-Yang, JIA Shu-Ting and LUO Ying 856true 2015/2/5 0:00:00 SUN Rui-Xiang, LUO Lan, CHI Hao, LIU Chao and HE Si-Min 855true 2015/2/5 0:00:00 LI JIE, CHU Yan-Shuo, CHENG Liang, WANG Ya-Dong and KONG Lei-Lei 854true in vivo and in vitro methods have been developed for the efficient evolutionary effects, especially in high mutation rate and rapidly high-throughput screening capabilities. Some of the methods have only recently been applied for general use and are just beginning to find greater application. In this review, we summarize some of the new methods for mutant libraries generation, including random evolution, semi-rational evolution and rational evolution. And current state-of-the-art screening techniques in protein directed evolution are also reviewed. Advancements are discussed with respect to the state of the art in diversity generation and high-throughput screening capabilities. Meanwhile, limitations and remaining challenges are also pronounced.]]> 2015/2/5 0:00:00 WANG Xiao-Yue, WANG Bai-Yun, WANG Zhi-Wen, CHEN Tao and ZHAO Xue-Ming 853true 2015/2/5 0:00:00 ZUO Ru-Juan and YANG Zeng-Ming 852true 2015/2/5 0:00:00 YANG Min and HAN Yu-Zhen 851true 2015/2/6 0:00:00 CAO Zhi and WANG Wei-Dong 850true in vivo. One category of proteins, called chaperones, help other proteins to fold correctly. Chaperones can recognize and stabilize other instable protein to assist its folding. Recent studies showed that, the ring-shaped chaperone GroEL can repetitively unfolding kinetically trapped protein folding intermediate, giving the intermediate another chance to refold, thus increases its overall folding rate. The detailed mechanism of GroEL assisted folding is still under controversy. In this review, we briefly summarize the recent progress in the study of the latter mechanism.]]> 2015/2/6 0:00:00 YAO Ling, LIN Zong and FU Zheng-Wei 849true 2015/1/19 0:00:00 SUN Han, FENG Lei-Yu and CHEN Yin-Guang 848true 2015/1/19 0:00:00 MA Chong, YANG Dong, JIANG Ying, ZHONG Ru-Gang and HE Fu-Chu 847true 2015/1/19 0:00:00 ZHANG He, ZHANG Shi-Meng and ZHOU Ping-Kun 846true 2015/1/19 0:00:00 LI Qi, QI Yue, TIAN Mo-Qian, ZHANG Kan and LIU Xun 845true 2015/1/19 0:00:00 YANG Xiao-Na, ZHANG Hong-Xing, LIU He and CAO Jun-Li 844true 2015/1/19 0:00:00 WANG Jiu-Ju, WANG Peng-Fei, QUAN Wen-Xiang, TIAN Ju, LIU Jin and DONG Wen-Tian 843true 2015/12/18 0:00:00 CHEN Xi-Xi and SU Tao 842true 2015/12/18 0:00:00 SUN Peng, LIU Miao, FENG Li-Xing and LIU Xuan 841true 2015/12/18 0:00:00 CHEN Wu, MO Wei and WANG Lai-You 840true 2015/12/18 0:00:00 LI Zhan-Xing and ZHU Li-Qi 839true etc, which indicate the high complexity and diversity in cancer progression. Tumor heterogeneity is a great challenge of cancer treatment, and is also an important research field of tumorigenesis. In this paper, we reviewed the biological features of tumor heterogeneity and possible mechanisms of its occurrence, and gave our considerations on how to design more effective personalized treatment that aims tumor heterogeneity in the era of "precision medicine".]]> 2015/10/20 0:00:00 TU Chao-Feng, QI Peng, LI Xia-Yu, MO Yong-Zhen, LI Xiao-Ling, XIONG Wei, ZENG Zhao-Yang and LI Gui-Yuan 838true 2015/10/20 0:00:00 LIU Lian, ZHANG Shao-Wu, MENG Jia and CHEN Run-Sheng 837true 2015/10/20 0:00:00 XIAN Jin-Hua, HAN Bu-Xin and LIU Ping-Ping 836true Drosophila midgut has emerged as a useful model to study the homeostasis maintained by resident intestinal stem cells (ISCs) and their progeny, creating an active research field with prolific publications. In this study, we make a summing up of relevant researches of the mechanisms on the proliferation and differentiation of ISCs, meanwhile, we look far ahead into the prospect in this field, which make the theoretical base of the research for gut homeostasis in Drosophila.]]> 2015/10/20 0:00:00 LIU Qiang and JIN Li-Hua 835true via target gene expression. The relevant literatures concerning the role of the Nrf2 and its pathway in protecting against hepatic injury were summarized and we will discuss the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases.]]> 2015/10/20 0:00:00 LV Xiao-Mei and MA Li-Jie 834true 2016/9/18 0:00:00 LIU Xiao-Ya and GAO Can 833true 2016/9/18 0:00:00 ZHANG Xing, LIAO Yu-Heng, TONG Hui-Min, ZHANG Lei, ZHANG Sheng-Li and REN Gang 832true 2016/9/18 0:00:00 CI Ya-Li, XU Cai-Min and SHI Lei 831true 2016/9/18 0:00:00 LI Ye and ZHANG Lei-Liang 830true 2016/9/18 0:00:00 ZHENG Qing-Yun, WANG Tao, PAN Man, LI Yi-Ming and TIAN Chang-Lin 829true FMR1) and abnormal methylation of CpG island on its upstream, then leading to the reduction or deficiency of its protein product fragile X mental retardation protein (FMRP). Both FMRP and miRNA have transcriptional repression activity, and FMRP was related to miRNA regulation pathway in the biochemical and genetic. In addition, more and more studies showed that miRNA regulation pathway plays a role in the synthesis and translation regulation of miRNA. In this review, the role of miRNA in the pathogenesis and treatment of FXS. Thus in this paper, we described the functions of miRNA and its interaction with the fragile X protein family members, laying the foundation for understanding the nosogenesis of FXS at the level of miRNA.]]> 2016/9/18 0:00:00 TIAN Shuai and MA Yun 828true 2016/8/5 0:00:00 DONG Xiao-Meng, GAO Jing, SUN Qin, WANG Xiao-Yan, SHI Li-Min, GAO Run-Chi, ZHAO Min and ZHAO San-Jun 827true e.g. fluorescein, quantum dots, green fluorescent protein, etc.) and then detected via the fluorescent signal. However, simultaneous analysis of multiple parameters in a single cell is always challenging because of the overlap in fluorescent spectrum. In addition, the linear range of the fluorescence method is relatively narrow, making difficulty for accurate quantification, especially when comparing signals with considerable difference. To meet these challenges, a new method based on inductively coupled plasma mass spectrometry (ICP-MS) has emerged for single cell analysis. Intracellular elements can be determined directly by ICP-MS at a single cell level. In combination with labeling techniques(e.g. element labeling of an antibody), biomolecules in single cells can also be determined via elements analysis by ICP-MS. This paper summaries both the ICP-MS-based methodology and selected applications in immunoassay, disease detection, drug screen, and nanoanalysis at a single cell level. A prospective of this method and its applications is also discussed.]]> 2016/8/5 0:00:00 SHI Jun-Wen, ZHANG Xin-Ying, LI Liang, FENG Wei-Yue, WANG Hai-Fang and WANG Meng 826true 2016/8/5 0:00:00 CHEN Yu, ZHANG Huai-Qiang, ZHAO Yue, GAO Pei-Ji and WANG Lu-Shan 825true 2016/8/5 0:00:00 JI Ling-Ling and PENG Hua-Mao 824true 2016/7/18 0:00:00 ZHAO Ming, XIE Hao, HU Zhi-Di, WANG Jia-Cheng and DING Xian-Feng 823true 2016/7/18 0:00:00 JIANG Yu, DING Yi, LI Wen-Qing, LU Zhong, ZHANG Jian, YANG Xiao-Yi and WANG Li-Hua 822true 2016/7/18 0:00:00 GUO Yu-Sheng, ZHANG Ru-Yi, JIA Shu-Ting and LUO Ying 821true 2016/7/18 0:00:00 FENG Xiao-Dong, MA Jie, CHANG Cheng, BAI Ming-Ze, ZHU Yun-Ping and SHU Kun-Xian 820true 2016/6/21 0:00:00 YAN Meng-Jie, HOU Yun-Hua, LV Shan-Shan and ZHONG Yao-Hua 819true 2016/6/21 0:00:00 ZENG Wen-Feng, ZHANG Yang, LIU Ming-Qi, WU Jian-Qiang, ZHANG Xiao-Jin, YANG Hao, LIU Chao, CHI Hao, ZHANG Kun, SUN Rui-Xiang, YANG Peng-Yuan and HE Si-Min 818true 2016/6/21 0:00:00 XIAO Zhong-Lin, YANG Qing, ZHANG Jian and FAN Xiu-Jun 817true 2016/5/20 0:00:00 JIA Yan, SUN Ying-Jie, HE Cong-Fen, TANG Shuang-Yan and ZHU En-Guang 816true Helicobacter pylori (H. pylori) uses glycan to adhere the host mucosa, which leads to the increase of sialyl-Lewis^x level. Further up-regulation of the H. pylori colonization induces sustained inflammation in stomach. In the process of chronic atrophic gastritis and intestinal metaplasia, sialyl-Tn antigen showed a significant up-regulation. Moreover, in GC, the abnormal protein glycosylation emerges in serum and tissue from GC patients as well as GC cell lines, such as down-regulation of core fucosylated N-glycan and up-regulation of β1, 6-GlcNAc branched N-glycan were discovered. It also shows that the altered glycosylation of adhesin contributes to the development of GC. This review summarizes the recent progress of protein glycosylation in GC and the important functions of glycosylation in the carcinogenesis and development. Finally, the application values of the alterations of glycosylation, such as potential biomarker for early diagnosis and drug target designing were discussed.]]> 2016/5/20 0:00:00 SHU Jian, YU Han-Jie, LIU Xia-Wei, ZHANG Dan-Dan and LI Zheng 815true Kcnq1/Cdkn1c, Igf2r/Airn, Prader-Willi (PWS)/Angelman (AS), Snurf/Snrpn, Dlk1-Dio3, H19/Igf2, and overview the functional role of antisense lncRNAs (Kcnq1ot1t1, Airn and Ube3a-ATS), intergenic lncRNAs (H19, IPW and MEG3), and enhancer lncRNAs (IG-DMR eRNAs) to understand the diverse mechanisms being employed by them in cis and (/or) trans to regulate the parent-of-origin-specific expression of target genes. A better understanding of these downstream mechanisms will help to improve our general understanding of the function of ncRNAs throughout the genome.]]> 2016/5/20 0:00:00 YANG Wen-Zhi, ZHANG Cui, WANG Guan-Nan, LI Dong-Jie and LI Shi-Jie 814true 2016/5/20 0:00:00 LI Yuan, LUO Zhi-Gang, GUAN Nai-Yang, YIN Xiao-Yao, WANG Bing, BO Xiao-Chen and LI Fei 813true 2016/3/21 0:00:00 ZHANG Hong-Jie 812true in vitro and in vivo. What's more, a combination of mTOR inhibitors and other anti-cancer drugs provide superior effectiveness, giving new hopes to patients suffering from adrenal tumors. This review summarizes recent advances in understanding the roles of mTOR signal pathway in the pathogenesis and progression of adrenal tumors.]]> 2016/3/21 0:00:00 XU Mei-Nian, HU Wei-Lie, AO Chun-Ping, WU Yu-Kun, BAI Xiao-Chun, LIU Jun and LI Ming 811true 2016/3/21 0:00:00 LIAN Yu, LI Xia-Yu, TANG Yan-Yan, YANG Li-Ting, LI Xiao-Ling, XIONG Wei, LI Gui-Yuan and ZENG Zhao-Yang 810true 2016/2/19 0:00:00 WANG Jiang-Hua, TIAN Guo-Hong and HE Shi-Gang 809true 2016/2/19 0:00:00 AN Peng-Yuan, WANG Qin-Wen and XU Shu-Jun 808true 2016/2/19 0:00:00 LI Min-Min, XIONG Yu-Ting, QING Guang-Yan and SUN Tao-Lei 807true 2016/2/19 0:00:00 BAI Jie-Yun, WANG Kuan-Quan and ZHANG Heng-Gui 806true 2016/1/19 0:00:00 LIU Wei, SUN Zhi-Qiang and XIE Hong-Wei 805true 2016/1/19 0:00:00 DU Hao-Qi, YU Han-Jie, JIA Li-Yuan and LI Zheng 804true 2016/1/19 0:00:00 YU Xiao-Ting, YANG Zhong-Bo, WANG Xin-Yan, TANG Ming-Jie, WANG Zhan-Zhong and WANG Hua-Bin 803true 2016/1/19 0:00:00 ZHOU Na-Na, WANG Lu-Shan, GONG Wei-Li, ZHAO Yue and ZHANG Huai-Qiang 802true in vivo could be regulated by the external magnetic field-stimulated activation of MagR, which would subsequently affect neural activity and the magnetic oriented animal behaviors. Regarding to the unique magneto-sensing function of MagR, the concept for “magnetogenetics” is proposed by Dr. Zhang’s group in combination of the genetic targeting to MagR/MAR with relevant remote magnetic stimulation. In this mini-review, we give a brief introduction into the discovery of MagR/IscA and its homologues together with their high evolutionary conservation, as well as current proceedings of researches on its physiological functions. Furthermore, we proposed an intracellular biomagnetic signaling-responsive mechanism insofar as to provide an explicit explanation of how MagR/IscA1 exerts it intrinsic function in magnetogenetics.]]> 2016/12/22 0:00:00 WANG Hong-Xia, XIANG Yuan-Cai and ZHANG Yi-Guo 801true 2+ is a universal intracellular messenger playing important roles in nearly all biological processes. Recent studies of structural biology have resolved near-atom-resolution structure of many Ca²⁺ permeable ion channels in their different open/close states. These advances have revealed the molecular mechanisms for the channel construction, operation, function and regulation, and provide a fundamental basis for understanding the process of Ca²⁺ signaling and related diseases.]]> 2016/12/22 0:00:00 FAN Xue-Xin, YANG Lei, XIANG Bin and WANG Shi-Qiang 800true 2016/12/22 0:00:00 LI Sha and MA Li-Jie 799true via activating the expression of genes associated with the synthesis and uptake of cholesterol, fatty acids and triglycerides (TG). Recently, it has been shown that SREBPs have a close relationship with inflammation. SREBPs can promote the occurrence and development of inflammation. On the other hand, the inflammation can affect the expression of SREBPs, and thereby lead to dyslipidemia. Further research on the relationship between SREBPs and inflammation may provide novel direction for the prevention and treatment of diseases induced by inflammation and dyslipidemia.]]> 2016/12/22 0:00:00 PAN Yan-Jun, WANG Yan, XU Jian-Qiang, WU Jian-Feng, YU Si-Yang, ZENG Gao-Feng and ZHAO Guo-Jun 798true 2016/12/22 0:00:00 ZHOU Hua-Min, SUN Xu-Li and CHEN Jian-Ming 797true 2016/12/22 0:00:00 CHEN Hui-Ji, LIU Xin-Guang and CHEN Wei-Chun 796true in vivo are subject to be removed from blood because of homeostasis mechanisms of the body. Without homeostasis mechanisms, urine can accommodate more changes and therefore is an excellent source of biomarkers. Especially in the early stage of disease occurrence, the new biomarkers are more likely to be found in the urine. In biomarker studies, the effects of the therapeutic drugs must be taken into account. Various confounding factors can be effectively circumvented interference on urinary biomarker studies based on urine biomarker roadmap research. A novel membrane storage technique enables large-scale urine sample collection and storage economically and efficiently. Biomarkers discovery of kidney diseases are introduced and discussed also here. It can be expected that urine biomarker studies will greatly promote the development of medical technology such as human disease diagnosis, prevention, treatment or prognosis.]]> 2016/11/21 0:00:00 JING Jian and GAO You-He 795true Shigella, an enteric pathogen, causes widespread bacillary dysentery around the world. Over the past few years, the emergence of resistance to multiple antimicrobials and new serotypes has brought new challenges to the surveillance and prevention of Shigella. The rapid development of genomics contributes to a better understanding of origins, mechanisms of variation and spreading principles, and has great scientific significance to control the spread of bacillary dysentery. From the perspective of genetic source, this essay focuses on the evolutionary relationship between Shigella and E. coli, as well as the possible molecular mechanisms. For the purpose of providing reference for researching and prevention of Shigella, the article also outlines the advances on genome evolution of S. flexneri, S. sonnei and S. dysentery type 1 with a detailed description of their features on temporal and spatial distribution and of the function of variation in resistance genes during evolution.]]> 2016/11/21 0:00:00 YANG Lang, QIU Shao-Fu, LI Peng and SONG Hong-Bin 794true 2016/11/21 0:00:00 ZHU Xiao, DENG Xiao-Jun, TU Yi-Xuan, LIU Yi-Jian, ZHANG Hong-Wen and YIN Kai 793true 2016/11/22 0:00:00 BAI Jing-Kun, SHENG Cheng-Le, ZHANG Yu and WANG Jing-Xin 792true 2016/11/22 0:00:00 HU Rui and ZHU Shu-Dong 791true 2016/11/22 0:00:00 ZHOU Yue, ZHOU Ling-Na, TENG Li-Sha, WANG Jian-Feng, YUAN Meng-Ping, TANG Xiao-Wen, ZHENG Bin-Jiao and XUE Ling 790true i.e., connectivity map method, gene regulatory network method and multi-omics data integration methods were focused. The latest usage of these methods in drug discovery, especially in cancer drug development was reviewed. This review would serve as a guide for transcriptome-based drug discovery.]]> 2016/10/21 0:00:00 LIU Yang, BAI Hui, TAO Huan, HE Song, HUANG Xin, BO Xiao-Chen and WANG Sheng-Qi 789true in vivo, thus limiting its clinical applications. Recently, single domain antigen-binding fragments known as “nanobodies” or as VHH were cloned from the naturally occurring heavy-chain-only antibodies in Camelid. The beneficial features such as small size, high solubility and stability, robust specificity, and good expression in microorganisms enable the nanobody technology to be used in a broad range of applications in fundamental research, biotechnology, disease diagnosis and therapy. In this review, we outline the current status of nanobody research including 1) the similarities and differences of nanobodies compared with conventional antibody fragments, 2) the framework of VHH production from camel immunization, VHH repertoire construction, VHH biopanning, and purification of recombinant VHH, and 3) the competitive advantages of nanobody-based delivery systems in molecular imaging and tumor-targeted cancer treatment over the conventional antibody usage.]]> 2016/10/21 0:00:00 ZHOU Tao-Ran, ZHAN Shou-Bin, ZHAI Fei, WANG Yang and YI Jun 788true 2016/10/21 0:00:00 TIAN Zhi-Qi, HU Ya-Chong, LONG Jian-Gang, LIU Jian-Kang and DIAO Jia-Jie 787true 2016/10/21 0:00:00 WANG Chen, XUAN Jin-Song and FENG Yin-Gang 786true 2016/10/21 0:00:00 LIU Chang-Mei, LI Xiang and GUAN Feng 785true via electron transport chain, then Cu[Ⅱ] is reduced to Cu[Ⅰ] which bind and activate oxygen, finally LPMOs break down the glycosidic bond of polysaccharides via oxidative cleavage, generating oxidized and non-oxidized products. Recent studies demonstrate that LPMOs can significantly enhance the efficiency of lignocellulolytic enzymes in degrading crystaline cellulose. Further investigation of LPMOs can expand the understanding of their efficient degradation mechanism and provide theoretical guidance for recomposing high-efficiency degradation enzymes to lower the cost in industrial application. This review addresses the recent research progress of LPMOs and analyzes perspective of potential research fields and practical applications.]]> 2016/10/21 0:00:00 LI Xin, ZHANG Li-Li, TIAN Li, ZHANG Huai-Qiang, CHEN Guan-Jun and WANG Lu-Shan 784true + T/NK lymphoproliferative diseases (EBV⁺ T/NK-cell LPD) and characterized by recurrent or chronic symptoms of infectious mononucleosis and clonal expansion of EBV⁺ T/NK cells and with high morbidity and mortality in clinic. It remains unclear what is the cause of CAEBV due to its complexity among different cases. Clinically, it is of importance to give accurate classification of EBV⁺ T/NK-cell LPD for appropriate therapeutic strategy, however, the standards for classification are still unsettled and the treatments are less than satisfactory. To explore some clues for further study, the current understanding of the pathogenesis of CAEBV will be summarized from several aspects such as the clonal expansion of EBV infected cells, EBV related virological factors, defects in host immune system in this review.]]> 2016/10/21 0:00:00 WU Xiao-Rong, WANG Jian-Lin and DUAN Zi-Yuan 783true Htt gene which encoding huntingtin (Htt). Expanded Htt proteins form aggregates accumulated in cells and result in progressive neuronal degeneration and dysfunction. There are many hypothesis on the pathogenesis of HD, such as oxidative stress and mitochondrial dysfunction. Report on Nature in 2017 highlights that DNA repair as a shared mechanism in neurodegenerative disorders. More and more evidences indicate that DNA repair mechanisms have been implicated in Huntington’s Disease, mutant Htt triggers different types of DNA lesions and excessive activation of DNA damage response. HD is associated with cellular radiosensitivity and double strand break repair defect, and mutant Htt impact the normal function of ATM(ataxia tetangtectasia mutated) in DNA repair. Moreover, DNA repair proteins also impact the onset age of HD. Targeting ATM can ameliorates mutant Huntingtin toxicity in cells and animal models of HD. ATM has a important role in regulating celluar homeostasis and mitochondria signaling, so the mechanism of targeting ATM is more and more clear. This review introduces recent advances in HD and DNA damage response, opens a new direction for study of pathogenic mechanism and development of therapies.]]> 2017/9/21 0:00:00 ZHU Shu and TANG Tie-Shan 782true 2017/9/21 0:00:00 LIN Ling and WU Xing-Zhong 781true 2017/9/21 0:00:00 LI Yu-Zhen 780true 2017/9/21 0:00:00 HUANG Ying-Cong, MA Feng-Sen, ZHAN Hao-Hui and ZHANG Jie 779true de novo-translation and over-translation. Non-translation means the RNAs can’t be translated to proteins as many non-coding RNAs do. Part-translation describes a phenomenon that the RNA can’t translate into a peptide chain using all the information as a template, but only a part of it. Whereas the de novo-translation refers to the classical translation process. Over-translation means the RNA can encode a protein using more than their own genetic information, which only occurs in circular RNAs. The diversity of RNA’s fate extends largely our understanding of translation above the classical central dogma. Further understanding of the fate of RNA post transcription will put forward more challenging demand on the research for the functions of RNA, and meanwhile, will also present the potential solutions for comprehensive understanding of the functions of RNA.]]> 2017/7/17 0:00:00 HAO Ya-Jing, LUO Jian-Jun, ZHANG Bao and CHEN Run-Sheng 778true 2017/7/17 0:00:00 XIA Li and ZHOU Yu-Feng 777true 2017/7/17 0:00:00 ZHU Lin-Wen, XIE Yi and GUO Jun-Ming 776true 2017/7/17 0:00:00 SHEN Pan, YANG Dong and HE Fu-Chu 775true etc. With the advances in brain science and computer sciences, future clinical researches will employ neuromodulation methods interfaced on the virtual reality technology integrated multiple sensory emotional information to treat the emotional dysfunction in methamphetamine addiction.]]> 2017/6/20 0:00:00 WANG Chun-Guang, YUAN Ming, LUO Gui-Ling, LI Yong-Hui and SUI Nan 774true 2017/6/20 0:00:00 TU Chao-Feng, YUAN Shi-Min, MENG Lan-Lan, LUO Ai-Xiang and TAN Yue-Qiu 773true mt) is associated with the pathological process of aging, cancer and neurodegenerative diseases. To maintain mitochondrial protein homeostasis, cell will inspire UPR^mt program by activating the transcription of mitochondrial chaperones and proteases encoded by nuclear DNA. Exploring the mechanisms of UPRmt is essential for understanding the pathological process of aging and mitochondria-related diseases. In this review, we focus on various inducers of UPR^mt, the different mechanisms of UPR^mt, the regulatory factors, and relationship with aging, immunity and other diseases in C. elegans and mammalian cells to provide new theoretical basis and therapeutic target for these diseases.]]> 2017/6/20 0:00:00 FAN Yu-Mei, HAO Qiang, LIU Si-Ying, CHANG Yan-Zhong, DUAN Xiang-Lin and TAN Ke 772true 2017/5/22 0:00:00 YANG Jia-Jun, LIU Xia-Wei, SHU Jian, ZHANG Kun and LI Zheng 771true 2017/5/22 0:00:00 FANG Shuai and ZHAO Bo 770true 2017/5/22 0:00:00 LI Zhan-Xing and ZHU Li-Qi 769true 2017/5/22 0:00:00 ZHANG Pan, YAN Wei-Jie and ZHAO Yu-Ming 768true via exosomes, microvesicles and other transporters may play an important role in the formation of circulating miRNAs. Cell-free miRNAs, especially circulating miRNAs, not only act as endogenous signaling molecules to influence behaviors of tumor cells and their microenvironment, but also regulate invasion and metastases of breast cancer cells by communication with other signaling pathways to regulate tumor angiogenesis and epithelial-to-mesenchymal phenotypic transition of cancer cells. This article reviews the molecular mechanism of active excretion of circulating miRNAs and the clinical potential of breast cancer-related circulating miRNAs as liquid biopsy biomarkers in diagnosis, prognosis and response evaluation of breast cancer.]]> 2017/4/24 0:00:00 WAN Xiao-Qing, WANG Xue-Jian, WANG Yi-Fei, JANG Yu, LU Zhong, SHI Li-Hong, DING Yi and WANG Li-Hua 767true etc. Here, we gave a brief introduction about CAP, its generation and composition, the interaction with liquid and tissues, and some of the major applications in biomedical field, such as sterilization, blood coagulation, wound healing, skin disease and dental treatment. In addition, we focused on the application of CAP in cancer treatment. CAP can effectively induce tumor cell death, inhibit cell proliferation and migration, induce differentiation of tumor cells and suppress the potential of stem cells, and can increase the sensitivity to chemotherapy. These beneficial effects shows a promising prospects for CAP application in tumor therapy.]]> 2017/4/24 0:00:00 XU De-Hui, CUI Qing-Jie, XU Yu-Jing, LIU Ding-Xin and KONG Gang-Yu 766true 2017/4/24 0:00:00 KUANG Yan-Bei, LI Ping and LI Qiang 765true 2017/4/24 0:00:00 ZHANG Qing, XU Yi, CAO Kun, MU Xiu-Ni, ZHANG Xiao-Feng and LV Jun-Jiang 764true DLK1-DIO3 genomic region, located on human chromosome 14 (14q32), contains one of the largest microRNA clusters with 54 miRNAs in the genome. Many of these miRNAs are differentially expressed by modulating important signaling pathways in several pathologic processes and various cancers. A better understanding of the pathophysiologic importance of the DLK1-DIO3 domain-containing microRNA cluster may contribute to innovative therapeutic strategies in a range of diseases. Here we present an in-depth review of the role the microRNAs of DLK1-DIO3 region may play in controlling tissue homeostasis and in the pathogenesis of mostly cancer. The potential clinical implications of these miRNAs are also discussed.]]> 2017/4/24 0:00:00 WANG Guan-Nan, LI Dong-Jie, CHEN Wei-Na, ZHANG Cui, YANG Wen-Zhi and LI Shi-Jie 763true 2017/3/22 0:00:00 FU Bo and LIU Di 762true e.g., keys and cell phones), but also when shopping, working or dating. Given that special memory plays fundamental and important roles in daily life, it is vital to characterize how the brain represents the environment. Using fMRI and electrophysiological techniques to date, many studies have investigated spatial memory processing and neural mechanisms of hippocampus formation and neocortex. In this review, we focus on the key questions about how the brain constructs the cognitive map and which neural circuits are involved for this processing. Future studies to explore neural basis of human spatial memory will need to be highly interdisciplinary and integrative, and may contribute to the diagnosis and intervention of cognitive disorders.]]> 2017/3/22 0:00:00 WANG Lin and WANG Liang 761true Salmonella, and discuss the role of ACBD3 in pathogen replication.]]> 2017/3/22 0:00:00 HUANG Jia-Zhao, LI Ye and ZHANG Lei-Liang 760true 2017/3/22 0:00:00 ZHANG Xin-Kang, LIU Xing-Ping, ZENG Ling, YE Zong-Huang, HU Bi-Ru and WU Wen-Jian 759true 2017/3/22 0:00:00 WANG Zhi-Cai, CUI Da-Yong and HU Yu-Xin 758true 2017/2/22 0:00:00 SONG Hai-Fei, LIN Bo-Wen, GONG Cheng-Chen and CUI Ying-Yu 757true 2017/2/22 0:00:00 ZHANG Bao-Hong, XIE Fei, REN Hai-Jun and LIU Bo 756true 2017/2/22 0:00:00 WANG De-Juan, ZHOU Yang, CAO Tian-Tian and LI An-An 755true 2017/2/22 0:00:00 LIU Lu and ZHANG Zhi-Chao 754true 2017/2/22 0:00:00 OU Han-Xiao, GUO Bing-Bing, TIAN Qi-Xian, JIANG Xiang, TANG Chao-Ke and MO Zhong-Cheng 753true 2017/2/22 0:00:00 XIAO Bin, YANG Zheng-Meng, XIAO Ming, CHEN Hao and MA Qiang 752true 2017/1/17 0:00:00 YANG Jian and CAI Hao-Yang 751true SDHA, SDHB, SDHC, and SDHD, respectively. The SDH mutations play a crucial oncogenic role in paraganglioma (PGL, types 1-5), pheochromocytoma (PHEO), renal cell carcinoma (RCC), gastrointestinal stromal tumors (GIST), rare hypophyseal adenomas, and Leigh syndromes. Mutated SDH has been proved to be an important biomarker for diagnosis and a therapeutic target in these cancers. This review summarized and updated a variety of SDH mutations in the neoplasms and discussed the oncogenic role of SDH mutants in proliferation, apoptosis, invasion, migration, tumorgenesis and senescence.]]> 2017/1/17 0:00:00 CAO Zhi-Fa, CHEN Wei-Cai, YANG Pei-Pei, ZHOU Hai-Meng and OU Wen-Bin 750true Nature in 2015 by two research groups. This review introduces recent advances in endophilin A2 and highlights the functions and mechanisms of endophilin A2 in clathrin-independent endocytosis.]]> 2017/1/17 0:00:00 YU Chun-Hong and YI Zong-Chun 749true 2017/1/17 0:00:00 ZHOU Jin-Yu, LI Qian-Qian, HUANG Chun-Cui, WU Hong-Mei and LI Yan 748true 2017/1/17 0:00:00 ZHOU Zi-Han, PENG Shao-Liang, BO Xiao-Chen and LI Fei 747true 2017/12/19 0:00:00 ZHOU Ming and SUN Zhen-Xiao 746true e.g., adapted central cueing paradigm), neuroimaging techniques (e.g., ERP, fMRI, MEG) as well as neuropsychological methods (e.g., brain-damaged patients). Some studies have demonstrated that social cues (e.g., eye gaze, head orientation and biological motion walking direction) can trigger reflexive attentional orienting effect, which is unique and qualitatively distinct from the attentional effect induced by nonsocial cues (e.g., arrow) in terms of both behavioral responses and neural activities. However, other studies have found that social and nonsocial attention share common neural substrates, and there is still controversy concerning the specificity of social attention. Combined with previous evidence, the major distinction between social and nonsocial attention is plausible that social attention might be mediated by an innate and genetically determined module, while nonsocial attention may occur as a result of long-term experience (overlearning). Future research, exploring the genetic origins of social and nonsocial attention, may help to provide evidence for the existence of “social attention detector” and highlight the role of social attention in the early diagnosis and clinical intervention of autism.]]> 2017/11/20 0:00:00 JI Hao-Yue, WANG Li and JIANG Yi 745true Klf7-null mice died within the first 3 days of life due to abomoality in nervous system. Genetics and epigenetics studies showed that KLF7 is associated with obesity, type 2 diabetes, cardiovascular disease, leukemia, diffuse gastric cancer, rectal adenocarcinoma, face development disordered, oxidative phosphorylation deficient, and type 1 autoimmune pancreatitis. Functional analysis revealed KLF7 is a key regulator of neurogenesis and neuron development, and inhibit preadipocyte differentiation and promote proliferation. In addition, KLF7 mediates muscle stem cell quiescence and suppresses hematopoietic stem and progenitor cell function. However, among the SP/KLF family members, the roles of KLF7 in these biological processes are only beginning to be understood, and most of the mechanisms remain unclear. This review summarizes the latest research progress of KLF7 in the structure and fuctions, and highlights its importance in tissue development, cell proliferation and differentiation, and disease generation.]]> 2017/11/20 0:00:00 SUN Ying-Ning, WANG Wei-Yu, ZHANG Zhi-Wei, SHAO Shu-Li, LI Bo and WANG Ning 744true 2017/11/20 0:00:00 HE Yi, WEI Fang, ZHANG Shan-Shan, GONG Zhao-Jian, GUO Can, LI Xia-Yu, LI Xiao-Ling, ZHOU Ming, XIONG Wei, LI Gui-Yuan, ZENG Zhao-Yang and SHI Lei 743true etc.), and is associated with the abilities of proliferation, invasion, metastasis in tumor. Clinical studies have shown that MCM proteins are indicators of tumor proliferation and poor prognosis, and are also identified as potential targets for new treatments of cancers. With the discovery of the crystal structure of the MCM protein complex, the underlying mechanism of MCMs, especially those in the tumors, will be further elucidated. It will also help to develop novel small specific molecule inhibitors for targeting MCMs.]]> 2018/6/13 0:00:00 WANG Dong-Xing, ZHOU Jun-Nian, YUE Wen and PEI Xue-Tao 742true 2018/6/21 0:00:00 GUO Quan-Juan, HAN Qiu-Ju and ZHANG Jian 741true 2018/6/21 0:00:00 ZENG Wen-Long, WANG Meng-Xuan, LIANG Xiao-Long and DAI Zhi-Fei 740true 2018/6/21 0:00:00 LIN Gui-Jiao, WAN A-Jun, LI Hui-Li, TU Run-Qiu, XIE Xin-Jue, XIE Yi-Xuan and YUE Wei-Dong 739true 2018/7/17 0:00:00 LIU Yan-Li, JIN Xiao-Fang, MA Lin-Long, CAO Dan, GONG Zi-Ming, JIAO Chun-Hai and WEI Chao-Ling 738true etc., have some physiological and behavioral responses to the GMF, that is, resulting of changes in growth, development and reproduction or providing information to guide their migration or diffusion of some migratory animals by using the GMF playing a role as a 'map' or a 'compass'. To date, there are three generally recognized magnetic-response mechanisms (or hypotheses) of organisms, i.e., the magnetic-response mechanism based on iron minerals and depended light and radical pairs’ hypothesis. Moreover, the magnetic-response mechanism based upon the bio-compass of magnetic proteins (including CRY and MagR) reported by our Chinese scientists has aroused widespread concern, while it hasn’t been verified through experiments in vivo. At present, the change in GMF intensity is becoming more and more serious under the background of global change, while it is just beginning to study the magnetic response of organisms worldwidly (especially in China), the relevant research should be carried out in depth in order to providing scientific evidences based on bio-magnetic responses for the dealing with the changes in GMF.]]> 2018/5/17 0:00:00 HE Jing-Lan, WAN Gui-Jun, ZHANG Ming, PAN Wei-Dong and CHEN Fa-Jun 737true 2018/7/16 0:00:00 SU Guan-Yue, YU Hong-Chi, HUANG Wen-Wen, WANG Ren-Yi, HU Yi-Qing, SHEN Yang, WANG Yun-Bing and LIU Xiao-Heng 736true 2018/4/8 0:00:00 WANG Yi-Le and ZOU Lai-Quan 735true via industrial direct synthesis. Here we summarized the structure, gene editing characteristics, application progress, current limitations and future prospects of Cpf1 system.]]> 2018/6/19 0:00:00 ZHOU Chen-Chen, LIU Xie-Xie, XIE Hai-Hua and GU Feng 734true 2018/4/27 0:00:00 TIAN Hao, ZHAO Peng-Fei, ZHENG Ming-Bin, MA Ai-Qing, LUO Zhen-Yu, CHEN Shi-Chun, LU Cheng-Yu and CAI Lin-Tao 733true 2018/6/19 0:00:00 ZHAO Qian-Fu, CHEN Shi-Jun, XIAO Bing-Xiu and GUO Jun-Ming 732true 2018/4/10 0:00:00 YAO Yu-Fei, CUI Bo-Miao, XIAO Li-Ying and LI Yan 731true 2018/4/20 0:00:00 GE Yan-Shan and ZHOU Yan-Hong 730true 2018/4/8 0:00:00 GAO Jia-Hui, MO Zhong-Cheng and TANG Chao-Ke 729true 2018/6/20 0:00:00 WANG Yuan-Yuan, BAO Xiao-Ming, LING Yun-Xiang, WANG Qin-Wen and XU Shu-Jun 728true 2018/5/17 0:00:00 CHENG Xiang-Rong, WEI Yan-Jun, HUANG Xing-Wei, WANG Nan, JIANG Qi, LIU Hui and LEI Lei 727true 2018/5/17 0:00:00 YUAN Fu-Wen and TONG Tan-Jun 726true via oxidative phosphorylation, but also closely associated with some important biological processes, including cell metabolism, stress signaling induction, calcium homeostasis, production of reactive oxygen species (ROS) and apoptosis．Mitochondrial dysfunction will lead to tumor development, growth, invasion and metastasis．Mitochondrial quality control system has become a key mechanism that maintains the normal function of the mitochondria, which is mainly composed of organellar and molecular control．Organellar quality control was coordinately modulated by mitochondrial fusion/fission, mitophagy and mitochondrial biogenesis．Meanwhile, molecular quality control was regulated by mitochondrial molecular chaperones and mitochondrial unfolded protein response to achieve mitochondrial protein homeostasis．In normal circumstances, mitochondrial quality control system limits the accumulation of dysfunctional mitochondria and maintains mitochondrial quantity, morphology and protein function in stable state, which was called mitochondrial homeostasis．If the mitochondrial homeostasis is impaired, increased number of injured mitochondria in cells will lead to the disturbance of intracellular homeostasis and induce malignant transformation of normal cells．]]> 2018/5/17 0:00:00 LIU Yao, HE Xing-Bo, ZHENG Hong-Yi and HUANG Cai-Bin 725true Saccharomyces cerevisiae, budding yeast, in many respects is an ideal organism for eukaryotic CDK regulation research. In budding yeast three Cdk1 inhibitors are known: Far1, Sic1 and recently identified Cip1. Apart from inhibiting Cdk1 activity during cell cycle progression, CKIs also play crucial roles to maintain genomic stability in response to environmental stresses. This paper reviewed the researches on Cdk1 inhibitors, especially their functions on cell cycle progression and stress responses, to provide a model basis for cell cycle and cancer fundamental research.]]> 2018/5/17 0:00:00 LIU Xue-Qin, REN Ping, ZHANG Ze and ZENG Fan-Li 724true 2018/5/17 0:00:00 XU Xiao-Jun, ZHU Xin-Yu, ZHANG Rui, XUE Yan-Hong, LI Zhen-Zhen, SONG E-Li and HOU Jun-Jie 723true 2018/3/23 0:00:00 BAO Jia-Li and FU Qi-Feng 722true in vitro on account of the open system and independence of cell lives. CFPS puts forward new ideas for synthesis and assemblage of MPs. It will be a major breakthrough for the study of structures and functions of MPs when the self-assembly and dimer formation can be accomplished in vitro. Here, we summarize latest progress in using CFPS to express ORs and other MPs.]]> 2018/4/19 0:00:00 LI Jian-Yong, MAN Ya-Hui, CHEN Qian, PEI Di and WU Wen-Jian 721true 2018/4/18 0:00:00 CHEN Wei-Ying, LI Sheng-Guang and ZHANG Tao 720true 2018/4/19 0:00:00 CUI Qian, ZHAO Ke and FU Xiao-Lan 719true 2018/4/18 0:00:00 YANG Xue-Ning, YANG Jia-Jia, WAN Bai-Kun and MING Dong 718true 2018/3/21 0:00:00 LUO Bing-Sheng and LIU Jing-Hua 717true 2018/3/21 0:00:00 YANG Shi-Feng, SUN Chao, WANG Yu-Pei, CHEN Yu-Hong, ZHANG Qian-Jing and ZHANG Hong 716true 2018/3/21 0:00:00 DONG Shuang-Shuang, WANG Xiang-Yu, MING Jing-Feng, SUN Zhen-Jie, LI Xiu-Ming, WANG Na, ZHANG Yong-Jin and CAI Zeng-Lin 715true 2018/3/21 0:00:00 XU Ben-Jin, SONG Guang-Tao and QIN Yan 714true 2018/3/21 0:00:00 ZHENG Wei-Qi, LIU Ye and FU Xiao-Lan 713true 2+ on CM formation; (3) the proposed optical and antioxidant properties of CM; (4) the potential applications as a diagnostic biomarker for various human diseases, use of CM-derived lipids as gene delivery vehicles, use of CM as structural antioxidant, and CM-based photonic crystals as versatile light-modulators.]]> 2018/1/16 0:00:00 LV Wen-Hua, LIU Fei-Fei and DENG Yu-Ru 712true 2018/1/16 0:00:00 ZHOU Wen-Bo, KONG Chen-Fei, QIN Gao-Wei, WANG Yuan-Yuan, LIU Xin and WANG Xiao-Feng 711true 2018/1/16 0:00:00 XU Hong-Kai, YAN Ke-Qiang, HE Yan-Bin, WEN Bo, YANG Huan-Ming and LIU Si-Qi 710true 2+ activated potassium channels are regulated by both intracellular Ca²⁺ and membrane potential. BK channel couples membrane voltage with the intracellular signal system, that plays important roles for cellular functions. BK channel is widely and densely expressed in various tissues of many species. Recent studies have demonstrated that BK channel was expressed in cardiomyocytes and involved in the regulation of cardiac systolic and diastolic. In this work, we present some progress in the study of coupling between BK channel and L-type Ca²⁺ channel gating and the function of cardiomyocyte BK channels as well as the response to substrate stiffness. These reports will help to understand the pathophysiology of mechano-sensitive ion channel-associated heart diseases.]]> 2018/1/16 0:00:00 WU Rong, WEN Yu-Qiao, YU Yang, LIU Si-Si, sokabe m and ZHAO Hu-Cheng 709true 2018/8/27 0:00:00 FENG Zhou-Yan, GUO Zhe-Shan and WANG Zhao-Xiang 708true 2018/8/27 0:00:00 YUE Hong-Wei and HU Hong-Yu 707true 2018/9/10 0:00:00 ZHAO Xin-Yuan, QIN Wei-Jie and QIAN Xiao-Hong 706true 2018/9/14 0:00:00 GOU Xiao-Meng, SUN Hong-Liang, ZHANG Zhong-Guo, XUE Xin-Yu, HAO Jing-Zhi and ZHANG Hong-Sheng 705true 2018/6/21 0:00:00 LI Zi-Han, XIONG Ting, XIONG Xiao-Li, LU Zi-Xian, ZHOU Zhi-Gang and TU Jian 704true 2018/7/18 0:00:00 LOU Jing, CUI Ya-Juan, LIU Jian-Kang and ZHAO Lin 703true 2018/12/21 0:00:00 SHI Wen-Hao, TONG Meng-Sha, LI Kai, WANG Yu-Shen and DING Chen 702true 2018/6/22 0:00:00 ZHANG Xiang-Lin, FANG Huan and WANG Xiao-Wo 701true e.g., Young’s modulus, adhesion, and deformation) of biological samples, emerges as a new method for investigating the correlations between structure, mechanics and functions of biological systems. The biomedical applications of multiparametric imaging AFM have yielded considerable novel insights into cellular/molecular activities and the underlying mechanisms guiding pathological processes. In this paper, based on our own research in single-cell detection using AFM, the principle of multiparametric imaging AFM is presented and the progress in utilizing multiparametric imaging AFM to probe cellular and molecular mechanics is summarized. The challenges and future directions are also discussed.]]> 2018/6/21 0:00:00 LI Mi, XI Ning, WANG Yue-Chao and LIU Lian-Qing 700true 2018/11/19 0:00:00 ZENG Zhao-Lin, CHEN Jiao-Jiao and WANG Zuo 699true via ceRNA function. It provides valuable insights into the molecular mechanism of NSCLC and novel targets for precision medicine of NSCLC. This review is based on our previous discovery of lung cancer-related ceRNAs and focuses on the role of lncRNA by acting as highly/lowly expressed and therapeutic ceRNAs in NSCLC.]]> 2018/11/19 0:00:00 PAN Jin-Chang, MENG Xiao-Dan and GONG Zhao-Hui 698true 2018/9/14 0:00:00 FU Bo, MA Hong and LIU Di 697true 2018/11/19 0:00:00 LEI Wei, MIAO Shu-Mei, QIN Nian-Ci, DING Nan, HAN Xing-Long and ZHAO Zhen-Ao 696true 2018/4/18 0:00:00 ZHAO Rong-Rong, HAN Qiu-Jv and ZHANG Jian 695true in vivo applicability of CRISPR-Cas9 are under way. In this review, we outline the principles of CRISPR-Cas9, the latest research advances in the treatment of infectious diseases, the challenges and possible solutions to the technology, and look further into its future direction.]]> 2018/10/22 0:00:00 LI Gen, LIU Jun-Hua, HE Li-Jie and YIN Xiu-Shan 694true 2018/10/22 0:00:00 ZHANG Wen-Ting and YAO Yu-Feng 693true 2018/10/22 0:00:00 ZHANG Meng, SHEN Fang, DUAN Ying, MENG Yi-Ming and SUI Nan 692true 2019/12/19 15:16:47 LI Zhen and ZHAO Bo 691true 2019/12/19 15:44:25 XU Yong,ZHANG Ya-Ting,LI Jie,HONG Chuan,ZHANG Xin-Wei,GAO Guo-Fen and CHANG Yan-Zhong 690true 2019/12/19 15:54:35 TANG Qin,ZHANG Bo,FENG Ting-Ting,LIU Jing-Xuan,HAN Wen-Hao,LI Sheng-Guang and ZHANG Tao 689true 2019/12/19 16:56:34 SUN Ye-Ting,CHEN Tao-Lin,HE Du,DONG Zai-Quan,CHENG Bo-Chao,WANG Song,TANG Wan-Jie,KUANG Wei-Hong and GONG Qi-Yong 688true 2019/11/4 17:02:09 LI Tian-Rui,ZHAO Rui-Bo,ZHANG Quan and KONG Xiang-Dong 687true in vitro reverse transcription to template-switch, and greatly improved the sensitivity. At the same time, cell isolation is promoted from 96/384 well plates, droplets to nano-pores, which greatly reduced the experimental cost while increasing the throughput. The single-cell RNA-seq, with its advantages in cell heterogeneity and cell classification, has promoted the construction of cell atlas from developmental biology to normal tissue and pathological cell biology. This paper reviews the recent progress of single-cell RNA-seq and its application in human cell atlas.]]> 2019/11/5 10:17:41 NI Jian,HU Miao-Miao,WEI Ying,CHEN Rui and GUO Yan 686true in vivo or in vitro and many sites that can be modified. The special architecture make it an ideal nanoscale model in scientific fields such as biochemistry. With the modification of the protein capsid and the transformation of the core cavity, researchers have developed a series of vaccines, multifunctional diagnostic agents and versatile nanocage systems. Recent studies of MPV VLP modification have focused on the interface modification between subunits to facilitate the assemble process, and the interior or exterior modification to develop diverse applications. This paper reviews the structural characteristics of MPV VLP, and briefly introduces the expression systems and assembly mechanism. The modification of MPV VLP was summarized, with emphasis on chemical modification and modification using genetic engineering. In addition, the applications of MPV VLP in the fields of vaccine development, delivery of drug and other molecules were described with examples. Then the prospect of research on MPV VLP was discussed, focusing on the large-scale production and in-depth analysis of assembly mechanism, beneficial from the use of advanced science and technology.]]> 2019/11/5 0:00:00 LI Guo-An and ZHANG Lin 685true etc. in living organisms, which are essential for the normal life activities of organisms. De novo synthesis and design techniques have high degree of freedom and simple precursors in the synthesis and structural design of biomacromolecules, enabling new design and efficient synthesis of biomacromolecules for specific research purposes. Recently, de novo synthesis and design techniques have begun to receive attention in the fields of artificial gene combination, novel protein drug design, glycoconjugate synthesis, etc. Based on the de novo synthesis and design of biomacromolecules, the newly designed DNA or novel gene expression products, as well as glycosylation or glycoconjugates with recognition functions, can be targeted prepared. Simultaneously, the techniques will greatly advance biologically active substances such as cytokine mimics, gene therapy delivery vehicles, providing a new solution for the construction of artificial biological systems and the treatment of rare diseases. This paper reviews the de novo synthesis and design of DNA, protein and polysaccharides, expounds the related methods and applications, and finally summarizes the relationship between three kinds of substances.]]> 2019/11/5 10:52:34 XU Xin-Dong,QI Peng-Xiang,LAN Wei-Bing,CHEN Yu-Ying and CHEN Shan 684true 2019/11/5 10:56:51 PENG Qiu,LIU Liang-Zhuan and GAN Run-Liang 683true 2019/11/5 11:17:54 SHAN You-Tian,GU Ze-Wei,KONG Zhen,ZHOU Ye,LI Bing,YAN Ming-Fang,WANG Ying-Ying,CHEN Yi-Ran and JING Hong-Juan 682true 2019/9/25 0:00:00 DU Yang-Chun,TANG Jing-Lan,WANG You-Jun and ZHANG Xiao-Yan 681true 2019/9/25 0:00:00 SHEN Wen-Shu,HAN Qiu-Ju and ZHANG Jian 680true 2019/9/25 0:00:00 LIU Ji-Hao,TANG Shu-Zhi,HU Li-Hong,HUANG Ming-Dong and CHEN Zhuo 679true 2019/9/25 0:00:00 XU Meng-Bo,CUI Ming-Yang,LIU Li and LI Mei-Xia 678true 2019/7/1 10:56:54 ZHAO Xiao-Ran,WANG Xiao-Liang,WANG Ying,YANG Qin-Zheng and TANG Xin-Jing 677true 2019/7/1 10:45:54 YAN Zhi-Peng,ZENG Ni,WU Di and NI Guo-Xin 676true 2019/7/1 10:47:00 ZHOU Fang,YAN Zhi-Ping,MA Lun-Jie and LIU Xiao-Heng 675true 2019/7/1 10:48:24 SUN Xun-Wei,SUN Ying and FU Qiu-Fang 674true 2019/5/22 0:00:00 YIN Chun-Lai,ZHAO Xue-Mei,HOU Zhao-Hua,ZHANG Jian and HAN Qiu-Ju 673true 2019/5/22 0:00:00 WANG Guang-Zhi,LI Yu-Yu and XIE Lu 672true 2019/5/22 9:33:34 WANG Zhen,GAO Pei-Pei,PENG Yun-Hua,LIU Jian-Kang and LONG Jian-Gang 671true 2019/5/22 0:00:00 HU Qian-Yu,HU Ling-Jie,JIE Jun-Jin,SHEN Si-Hong and CHEN Xiao-Wei 670true 2019/5/22 0:00:00 CHEN Xi,XIAO Jian,LI Yuan-Yuan,CHEN Qiong and HU Cheng-Ping 669true 2019/4/19 10:43:17 MEI En-Dian,MA Jia-Bing,GAO Jia-Dong,LIU Yi-Xuan,QIAN Cheng,LIU Li and WEI Xu-Bin 668true 2019/4/19 10:48:00 XU Xiao-Li,WU Ling-Juan and YAN Ren-Xiang 667true 2019/4/19 10:55:15 TANG Qian-Qian,ZHANG Yi-Fan,HE Yuan,PENG Ming-Li,ZHAI Gao-Hong and FAN Hai-Ming 666true 2019/4/19 11:00:04 XU Huang-Tao,REN Wei and PAN Yong-Xin 665true 2019/4/19 11:15:27 CHEN Yu,WAN Qun,JIN Lu-Qi,YAN Chun-Lan and DING Shi-Ping 664true 2019/4/19 11:20:02 XU Xiao-Hui and HU Ping 663true etc.) and their regulatory mechanisms. We also summarized the major research methods and strategies for taking advantage of miRNAs to improve crop traits and discussed the future prospects and problems for the application of miRNAs in crop traits improvement.]]> 2019/3/25 14:24:08 JIANG Zeng-Ming,HE Juan,MO Bei-Xin,LIU Lin and XU Xiao-Feng 662true 2019/3/25 14:28:48 WANG Pan,XU Gao-Sheng,MA Wei,YE Dong-Mei,LI Yu-Xuan,LUO Wei-Ru,XIAO Yi-Yang and ZHANG Zhi-Wei 661true 2019/3/25 0:00:00 JIANG Xiao-Li,WANG Yan-Yun,WANG Ying-Ze,YU Jing and LIU Xiao-Li 660true 2019/3/25 14:37:07 LING Hao,LIU Wei-Wu,HOU Xiu-Wei,CHEN Xiao-Hui,XIAO Yu,YAN Hui and SONG Chun-Li 659true 2019/3/25 14:44:34 LI Shi-Wei,QUAN Ting-Wei,ZHOU Hang,LI An-An,FU Ling,GONG Hui,LUO Qing-Ming and ZENG Shao-Qun 658true 2019/3/25 14:47:14 XIA Wen-Ran,CHEN Si and WANG Liang 657true 2019/3/25 14:52:50 WANG Zheng-Chun,PAN Zhi-Chao,SHEN Hao-Wei and ZHOU Dong-Sheng 656true 2019/2/21 9:51:03 ZHANG Chen,DU Hao-Qi and LI Zheng 655true 2018/12/28 18:13:04 LI Shen,NIU Bo and WANG Jian-Hua 654true 2018/11/6 16:48:57 JIA Yi,DAI Jie,ZHANG Liang-Liang and XIA Huan 653true 2019/2/19 16:45:55 ZOU Yan,LIU Li-Min,QIN Feng-Xian and WANG Gui-Sheng 652true 2019/2/19 16:52:19 JI Hui-Hui,ZHAO Yong-Jie,ZHENG Zhong-Hua and DUAN Shi-Wei 651true 2019/2/19 17:04:00 YIN Shu-Fei,CHEN Xiang-Zhan,LIU Qi-Zhen,DING Zhou-Zhou,LI Tian,YANG Wei-Ping and ZHU Xin-Yi 650true 2018/12/27 10:18:31 XIANG Hong-Ying,WANG Ju-Fang,YANG Yu-Feng and LV Yan-Cheng 649true 2019/2/20 10:49:33 ZHOU Xie-Xuan,REN Rui,GAO Wan-Ling,HUANG Yun-You,ZENG Wen-Feng,KONG De-Fei,HAO Tian-Shu,ZHANG Zhi-Fei and ZHAN Jian-Feng 648true in vitro, however, the enzymes can catalyze the formation of the glycosidic linkages by transglycosylation reaction. This synthesis activity is important for the large acquisition of sialosides, which would be helpful to promote the basic research on their functions as well as their applications in food and pharmaceutical industries. This paper reviews the structure and catalytic mechanism of sialidases, physiological function, transglycosylation and their application in oligosaccharide synthesis.]]> 2019/2/20 11:15:37 GUO Long-Cheng,MA Zhong-Xuan,LU Li-Li and XIAO Min 647true via different molecular mechanism.This article reviews the biological function of PNN and its relationship with tumorigenesis.]]> 2019/1/18 0:00:00 LIU Wei-Hong,LIN Chen,YU Xiao and WANG Ping 646true 2018/11/29 0:00:00 WEN Yu-Qiao,LI Chen,SONG Guan-Bing and ZHAO Hu-Cheng 645true 2-NPs), zinc oxide nanoparticles (ZnO-NPs), gold nanoparticles (Au-NPs), silica nanoparticles (SiO₂-NPs), fullerene, single/multi-walled carbon nanotubes (SWCNTs/MWCNTs) and grapheme/grapheme oxide (GO), and analysis the difference. The nanomaterials can cause ER stress, and in turn induce apoptosis, inflammation and autophagy. They can also activate the release of Ca²⁺ from the ER Ca²⁺ stores through IP₃ pathway and further trigger calcium-regulated apoptotic cell death. Nanomaterials tend to accumulate in ER causing damage of ER and inducing ER autophagy.]]> 2019/1/18 0:00:00 WNAG Juan,XU Wen-Juan,WANG Xin-Wen,WANG Jing-Jing,WANG Mei-Mei and XU An 644true 2019/1/18 0:00:00 SU Jiu-Chang,NIE Yang,LI Long-Na and SHEN Wen-Biao 643true Mycobacteria tuberculosis (MTB) is the pathogen responsible for tuberculosis. It can exist in the infected-macrophages for a long time and trigger the disease when the appropriate conditions arise. The primary way to kill intracellular bacteria is via the oxygen-independent route. In this route, macrophages mainly rid themselves of parasites by autophagy where autophagosomes and lysosomes are fused into autophagolysosomes. However, MTB can resist to autophagy and avoid being killed by the immune system of host cells in several ways, thereby co-existing with the host. MicroRNAs (miRNA) are endogenous non-coding single-chain RNA molecules that can silence related genes expression in a post-transcriptional manner. They are crucial molecules for mediating inflammatory reactions between MTB and inflammatory cells. Recent studies found that MTB can induce the expression of certain specific miRNAs in macrophages and target genes related to autophagy and therefore inhibit triggering and progression of autophagy. This mechanism confers resistance to autophagy. The present review summarizes the role of miRNA in the resistance to autophagy by MTB.]]> 2019/1/18 0:00:00 ZHANG Yi-Yuan,YI Zheng-Jun and FU Yu-Rong 642true 2018/11/21 15:26:39 ZHANG Ying-Zhe,CHEN Tao-Lin and GONG Qi-Yong 641true 2019/1/18 0:00:00 REN Wei-Cong,MA Jiang and ZHANG Zhi-Jie 640true 2020/4/23 0:00:00 HUANG Guo-Min,WANG Yu-Pei,SUN Chao,ZHANG Xue-Tian and ZHANG Hong 639true in vivo can delay the occurrence of multiple age-related diseases, which directly proves that senescent cells are one of the important causes of age-related diseases, providing a new target for the treatment of age-related diseases. Cellular senescence is generally considered due to the activation of cell cycle inhibition pathway induced by accumulation of damages, and the cells permanently exit the proliferation cycle. Senescent cells undergo changes in cell morphology, transcriptional profiles, protein homeostasis, epigenome and metabolism. Moreover, senescent cells resist apoptosis and therefore accumulate in multiple organs and tissues in the body. Senescent cells secrete a number of inflammatory factors, leading to a local non-infectious inflammatory tissue microenvironment, which will cause organ function deterioration and a variety of age-related diseases. Therefore, several research groups have screened the library of small molecular compounds and found that certain compounds can selectively eliminate senescent cells by targeting pathways underpinning senescent cells" resistance to apoptosis. These small molecular compounds are called " senolytics ", denoting compounds for killing senescent cells. Senolytics have been shown to alleviate multiple age-related diseases and prolong the lifespan in animal models. Therefore, targeted killing of senescent cells has an important clinical application prospect for the treatment of a variety of age-related diseases so as to improve the healthy lifespan. In addition, strategies such as stem cell transplantation, gene editing and heterochronic parabiosis are also of great significance and inspiration in the development of anti-aging research. By summarizing the recent important progress in the field of senescent cell clearance and a variety of anti-aging strategies, this paper briefly reviews the history of cellular senescence research, discusses the relationship between cellular senescence and age-related diseases, emphasizing on the potential therapeutic applications by targeting senescent cells and the limitations, as well as the further research directions in this field.]]> 2020/4/23 0:00:00 CHEN Xiang-Ning,LIU Yang and JI Jun-Feng 638true 2020/4/23 0:00:00 CHEN Fu-Ming,LI Na,XING Jie-Hua,ZHENG Ming-Bin,ZHONG Ying,LUO Ying-Mei,MA Ai-Qing,CUI Liao and CAI Lin-Tao 637true 2020/4/23 14:17:43 HE Dong,HU Jia,CHEN Juan and WEI Xing 636true 2020/4/23 0:00:00 YUAN Jing,ZENG Da,JIANG Xiao-Yan,ZHOU Yan-Hong and XIAO Song-Shu 635true 2020/4/17 13:20:17 LUI Ming-Hong,JIANG Biao-Bin,BAO Zhao-Shi and WANG Jiguang 634true 2020/4/17 0:00:00 TAN Dong-Mei,TAN Yi and DUAN En-Kui 633true 2020/4/17 0:00:00 ZHANG Hua-Wei,YU Li-Jia,ZHANG Chun-Min,ZHANG Yan-Song and SHI Xiao-Dong 632true 2020/4/17 0:00:00 CAO Lei,GUO Li-Juan,GUO Xiao-Jin,GONG Yan and LI Fei 631true 2020/3/4 10:15:40 LIU Wang,CHEN Qiao and LI Yong-Hui 630true 2020/3/4 10:22:40 HUANG Yan-Xia,ZHOU Fei-Fan,ZHOU Ting,XU Hao,LIN Dan-Ying and QU Jun-Le 629true in vitro BBB model can greatly accelerate the development of central nervous system drugs. The models that have been studied can be divided into three categories: single culture, co-culture, and triple culture. These models range from simple to complex, and more similar to blood-brain barrier in vivo. This article reviews the current blood-brain barrier model, and we expect it can provide new ideas for the design of in vitro BBB models in the future.]]> 2020/3/4 10:26:31 LIN Lan and SUN De-Qun 628true 2020/3/4 10:34:26 LUO Cun-Jin,YOU Ting-Ting,LIU Tong,HE Ying,WANG Kuan-Quan and ZHANG Heng-Gui 627true 2020/10/27 0:00:00 LIU Zhi-Tao,WANG Qin-Wen,LI Guang-Yu,XU Shu-Jun and LI Li-Ping 626true 2020/12/21 0:00:00 huang xuanhe,sun ning,zhong dongxiao,chen cuicui,li ying,huang yongliang and lu yujing 625true 2020/12/21 0:00:00 YANG Xiao-Yan,ZHU Ke-Xin,GUO Zhong,DENG Yi-Dan,LI Sha and LE Yao-Jin 624true 2020/10/26 0:00:00 shi shennan,Qin xia,Wang hongyang and Cai zhenyu 623true 2020/10/26 0:00:00 Xinghong Yao,Yan Qiu,Ye Zeng and Liang Li 622true 2020/10/26 0:00:00 YANG Fang,JIA Man,DAI Rong-Yang and XIANG Yuan-Cai 621true 2020/10/26 0:00:00 LIANG Cheng-Hui,CHEN Dan,LIAO Xin-Yuan,JIANG Long-Guang,YUAN Cai and HUANG Ming-Dong 620true 2020/10/26 0:00:00 Zhang Hao Wen,Cao Hao,Wang Yu Lu and Xin Feng Jiao 619true Sporosarcina pasteurii which has the function of inducing calcium carbonate mineralization is discussed, together with the structure and function of its mineralizingcore enzyme urease.The microbial mineralization mechanism of Sporosarcina pasteurii and its related molecular mechanismsis summarized systematically. The current research status and typical application cases of mineralization applications of Sporosarcina pasteurii are introduced briefly in many fields around the world. The application prospects of corresponding microbial mineralization technology in specific environments and their deficiencies in future applications are discussed.The related analyses and discussions are of great significance for further facilitating the application of microbial mineralization technology.]]> 2020/9/22 0:00:00 PEI Di,LIU Zhi-Ming,HU Bi-Ru and WU Wen-Jian 618true 2020/9/22 0:00:00 GUO Yong,YAN Wei,HUANG Yang-Rui and QU Jun-Le 617true 2020/9/22 0:00:00 CHEN Yu-Xin,Lü Xue-Jing and HU Li 616true 2020/9/22 0:00:00 TONG Jin-Rong,ZHANG Zhao-Huan,HUANG Zhen-Hua,ZHANG Xu,SHI Jun,LIU Hai-Quan,PAN Ying-Jie and ZHAO Yong 615true 2020/9/22 0:00:00 BAI Yang,YANG Jia-Jia and ZHENG Chen-Guang 614true 2020/9/18 0:00:00 ZHOU Yi-Ni,XU Qing,SU Dan,SU Tuo,WANG Wei and YU Jing 613true 2020/9/18 0:00:00 Yang Cheng,Xia Lin,He Tong,Gou yang,Tang Yongjie,Peng Xiangui,Zhang Xi and Zhang Yunfang 612true 2020/9/18 0:00:00 TANG Lei,lipingcui,lirunfang,zhangjihong,songbin,duanwenfang,ZHANG Ji-Hong and yangfan 611true 2020/9/18 0:00:00 MU Huai-Yu,GUO Xiao-Chen,CHEN Xin-Nong,ZHU Ya-Ping and ZHANG Jun-Ping 610true 2020/9/18 10:00:20 JIANG He-Jia,WU Teng,YANG Si-Yu and ZHANG Xiao-Qin 609true 2020/4/3 0:00:00 ZHANG Xiao-Yuan,ZHANG Yan-Yan,ZHANG Xiao-Gang,LIU Xia,CHEN Mian,LIU Fei,ZHANG Dai-Zhou and LING Pei-Xue 608true etc. In this review, we overviewed the background and development history of CRISPR / Cas systems, discussed recently-investigated delivery methods including various nanocarriers, summarize the preclinical and clinical advances of CRISPR/Cas-based therapeutics, and introduced other application areas besides gene editing. Finally, we made an outlook on the challenges we need pay attention to, and the future application prospects of CRISPR/Cas technologies.]]> 2020/8/11 0:00:00 ZHAO Zi-Xuan,LI Chun-Hui,ZHOU Li-Li,ZHAO De-Yao,WENG Yu-Hua,XIA Xin-Hua and HUANG Yuan-Yu 607true in vitro, indicating that this process in cells needs the help of assembly factors. RNA polymerase assembly is a complex biological process. In recent years, the identification and functional analysis of assembly factors have made RNA polymerase assembly a hot spot. The assembly factors found in Saccharomyces cerevisiae are Rba50, Bud27 and GPN protein family. Among them, GPN protein family is an important GTPase family, which exists in archaea, yeast and higher eukaryotes, and is highly conserved. Recent studies have found that Rba50 homologous proteins (IYO and RPAP1) in plants and animals are related to cell differentiation and tissue development. Mutations in assembly factors such as GPNs are closely related to cell development and cancer development. This article reviews the latest progress of RNA polymerase assembly in eukaryotes, with a view to provide a basis for the final elucidation of RNA polymerase assembly mechanism and its association with disease occurrence.]]> 2020/8/11 0:00:00 LIU Xue-Qin,MA Lu-Jie,ZENG Pei,XIE De-Bao,XIAO Sheng-Lin and ZENG Fan-Li 606true 2020/8/11 0:00:00 LING Yun-Xiang,BAO Xiao-Ming,BAO Rong-Rong,WANG Jia and XU Shu-Jun 605true 2020/8/11 0:00:00 LU Ping-Ping and WANG Liang 604true via biological metabolic process, which allowing the targets were labeled with complementary probes through bioorthogonal reaction for molecular labeling and drug delivery in living systems. Combined the advantages of metabolic engineering and bioorthogonal chemistry, this labeling strategy has great application potential and research value in labeling, trace imaging and diagnosis in the fields of biomedical engineering. Herein we introduced the theory and research progress of bioorthogonal chemistry and metabolic engineering in biomedical fields, and also specially analyzed the application of bioorthogonal chemistry in molecular imaging and drug delivery.]]> 2020/7/17 0:00:00 HAN Yu-Tong,PAN Hong,LUO Ying-Mei,MA Ai-Qing,XING Jie-Hua,CHEN Ze,ZHENG Ming-Bin,LI Bao-Hong and CAI Lin-Tao 603true 2020/7/17 0:00:00 YANG Yi-Feng,SUN Xin-Ying,SHEN Xin-Tong,YE Ge-Xin,LOU Cheng-Tao,LI Nan,GONG Zhao-Hui and MENG Xiao-Dan 602true cis-elements of pre-mRNA and a number of protein factors. Mammalian 3" end processing machinery consists of cleavage and polyadenylation factors, cleavage and stimulating factors, cleavage factor Ⅰ and cleavage factor Ⅱ. Other protein factors include poly(A) polymerase, poly(A) binding protein, symplekin and so on. Mammalian genes usually contain multiple polyadenylation sites, and alternative polyadenylation can not only produce mRNA variants with different length of 3"UTR, but also change the CDS region of genes. As a key mechanism for the regulation of gene expression in eukaryotes, alternative polyadenylation plays an important role in cell growth, proliferation and differentiation. This paper reviews the formation of the 3" end of mammalian pre-mRNA, the composition and function of the 3" end processing machinery, the mechanism of alternative polyadenylation in various human diseases, and hope to bring some new insights to readers.]]> 2020/7/17 0:00:00 XU Ben-Jin and LIU Ling 601true 2020/7/17 0:00:00 ZHU Feng,ZHENG Gao-Li and TIAN Xue-Jun 600true 2020/7/17 0:00:00 XING De-Chun,WANG Xia,SUN Suo-Zhu,DONG Lian-Hua and YANG Jing-Ya 599true 2020/7/17 0:00:00 DU Yi-Nan,ZHANG Jin-Ming,DIAO Zhi-Jun,MA Ning,YAN Chuan-Ting and LIU Zhi-Qiang 598true 2020/6/10 0:00:00 CHEN Qian,TANG Zhi and LAI Chen-Cen 597true de novo approach. MOF-enzyme complex is more resistant to hush circumstances or protein inactivating agents than naked enzyme. Moreover, the metal-organic framework itself can be designed to be highly efficient nano-drug by using pharmaceutically active organic molecules or metal ions as ligands or metal ions. General surface modification methods were also reviewed due to their important roles for improving the solubility and stability of MOF-based DDS. In this review, recent numerous researches on the cancer therapy of MOF-based DDS have been summarized. According to the type of treatment methods, the applications of MOF-based DDS in chemotherapy, photodynamic therapy, biomacromolecules-MOF based therapy, and other combined therapies (such as radiotherapy, and immunotherapy) for cancer were introduced, respectively. Finally, we summarized the advantages and challenges of MOFs in cancer therapy, and prospected the opportunities and development of this research field.]]> 2020/6/10 0:00:00 YANG Chan,KE Guo-Liang,HUAN Shuang-Yan and ZHANG Xiao-Bing 596true 2+]_i increase (OSCA)/Transmembrane protein 63 (TMEM63) family proteins are multi-pass membrane proteins. They are broadly presented in eukaryotic cells. Previous study showed that OSCA1.1 from Arabidopsis mediated the hyperosmolality induced calcium increase in plants. Additional studies showed OSCA1.1 and its homologues were mechanosensitive ion channels. High resolution cryo-EM structures revealed that OSCA proteins were symmetric dimers and each subunit harbored an ion permeation pathway. The review will focus on recent progress on the studies of the function, structure and structural-functional relationship of OSCA channels.]]> 2020/6/10 0:00:00 WU Jing-Xiang and CHEN Lei 595true via special protein secretion systems, such as typeⅢ and typeⅣ secretion systems, into the host cells to modulate host signaling pathways. Many effectors harbor unique enzymatic activities to modify ubiquitin or the ubiquitin-conjugating enzyme Ubc13, or have E3 ubiquitin ligase or deubiquitinase activities. This review summarizes the progresses and the newest discoveries on mechanisms of host ubiquitination modulation by bacterial effector proteins.]]> 2020/6/10 0:00:00 TAN Jia-Xing,LUO Shu-Hui,ZHOU Yan and ZHU Yong-Qun 594true 2020/5/13 0:00:00 YU Xiao-Ling,JIANG Wen-Qian,ZHENG Ling,SHI Yang,YE Han-Hui and LIN Jun 593true 2020/5/13 0:00:00 CHEN Ke,ZHAO Yi-Lei,LIU Ting,CUI Yan,GUO Da-Qing,Wang Ling,LIU Tie-Jun and YAO De-Zhong 592true 2020/5/13 0:00:00 YANG Jia-Jia,JU Rong-Fang,WANG Fa-Qi and MING Dong 591true 2020/5/12 0:00:00 SUN Ya-Lun,WANG Qing-Qin,MENG Wei,YAO Li-Hua,GONG Yan-Chun and WANG Song-Hua 590true in vitro and in vivo) and inhibitors but also summarized the structural characteristics of FAP detection substrates and the potential structure-activity relationship of inhibitors. This review will provide an overview of reference values and important reference value for the development of FAP-specific detection methods and potent inhibitors.]]> 2020/5/13 0:00:00 SUN Zhao-Hui,ZOU Li-Wei and YANG Ling 589true i.e., the information input technology. For example, a potential brain stimulation device with multiple regulatory effects and multiple control methods like physical and biochemical technologies may be widely used to treat brain diseases, such as depression and epilepsy, as well as for short-term enhancement of brain power. This work may shed some light on the current research field of brain-computer interface.]]> 2021/1/29 0:00:00 GE Song,XU Jing-Jing,LAI Shun-Nan,YANG Na-Na,LIN Yan-Ni and XU Sheng-Yong 588true 2021/3/18 0:00:00 HUANG Chu-Han,ZHANG Ze-Yu,SHI Yi-Fan,HUA Qian and WEI Peng 587true 2021/3/18 0:00:00 YIN Tie-Ying,LI Yan-Hong,HUANG Yu-Hua and WANG Gui-Xue 586true 2021/3/18 0:00:00 KONG Tian-Xiang,ZHAO Yi-Xin,DU Jing and LI Ying-Jie 585true 2021/3/18 15:35:30 LI Yan,XUE Hao,CHEN Si-Si,FU Ye-Qin and LI Ming-Cai 584true 2021/3/4 0:00:00 WANG Jiu-Ju,SUN Li,SHU Hua,LIU Lu and WANG Yu-Feng 583true e.g., tools or symbols) and those with social significance (e.g., faces). Using a modified social attention task, researchers have found that eye gaze cues can influence sensory perceptual processing, the liking ratings, memory performance and other high-level cognitive processing of gazed-at objects. Furthermore, such modulation of gaze cues on object processing can be mediated by the attributes and amount of the faces as well as the pattern of gaze shifts. More importantly, this modulation effect can occur in the absence of visual awareness and is highly specific to eye gaze but not non-social cues (e.g., arrow). Research probing the underlying mechanisms implied that high-level social cognitive abilities (i.e., theory of mind, perspective taking) might play a key role in the observed modulation effect. Yet to date, the exact mechanisms mediating this modulation effect remain an important question for further investigations. Future efforts concerning the mechanisms underlying the influences of gaze cues on object processing will help to extend our understandings of social functioning and the interaction between human and environment, and have implications for both theory construction and practical application.]]> 2020/12/22 0:00:00 YU Yi-Wen,JI Hao-Yue,WANG Li and JIANG Yi 582true 2021/3/4 0:00:00 DONG Qigeqi,QIAO Jia-Xin,SUN Hong-Wei,FAN Li-Fei and Morigen 581true 2021/3/4 0:00:00 ZHANG Xin-Yuan,LI De-Zhu,LIN Yao,WU Cheng-Fang and ZHANG Jun-Fang 580true 2021/1/19 0:00:00 Li Lingjie,Cui Wei,Xu Shujun and Wang Qinwen 579true 2021/1/19 0:00:00 CHEN Yun-Liang,LI Guo-Quan,YANG Yun-Peng,JIA Wei-Dong,SHI Ai-ping and ZHANG Qi 578true 2021/1/19 0:00:00 FENG Ju-Ling,WANG Zhen-Zhen,ZHAO lei and CHEN Nai-Hong. 577true 2021/1/19 0:00:00 YuHaiqing,XuMinpeng,WanBaikun and MingDong 576true in vitro, and suppression of tumor growth in vivo, validating cell membrane gp96 as a therapeutic target. At present, the selective small-molecule inhibitors (NECA and PU-WS13), a gp96-specific monoclonal antibody (W9mAb), and an inhibitory gp96-targeted polypeptide (p37) are under development and their potential applications in the tumor targeting therapy are highlighted in this review.]]> 2021/9/23 0:00:00 QIAN Li-Yuan,LI Chang-Fei,LUO Yun-Jing and MENG Song-Dong 575true 2 is an important enzyme with many family members. As a special member of the phospholipase A₂ superfamily, secretory phospholipase PLA2G5 is expressed in both immune and non-immune cells. Studies have shown that PLA2G5 is tissue and cell specific, and its biological functions are even related to species and environment. Many researchers have studied PLA2G5 in humans as well as in transgenic and knockout mice, and have gained a deeper understanding of its biological and pathophysiological effects. The PLA2G5 gene is located on mouse chromosome 4 and human chromosome 1. It encodes a protein with a molecular mass of 14 ku, highly conserved Ca²⁺ binding loop and enzyme binding site, and contains only 6 disulfide bonds without specific sulfur bonds of group Ⅰand Ⅱ sPLA₂, N-terminal propetide, insertion and C-terminal extension. PLA2G5 has a variety of biological functions. It can not only bind to heparan sulfate proteoglycans through a cluster of negatively charged residues, but also bind to membrane phosphatidylcholine with high affinity, release arachidonic acid, initiate eicosanoid cascade reaction, and then conduct signal transduction. Meanwhile, it can help against pathogens, present antigens, serve as Th2/M2 to regulate the innate immune response, and play an anti-inflammatory or pro-inflammatory role in different immune diseases. In addition, PLA2G5 can effectively hydrolyze phospholipids in lipoproteins, which helps to control the quality of lipids and participate in lipid metabolism. PLA2G5 induces airway inflammatory diseases such as asthma and acute respiratory distress syndrome. It is closely related to cardiac homeostasis and can reduce the risk of aortic dissection, but it can also aggravate atherosclerosis and has dual effects on low density lipoprotein and perivascular fibrosis. It is a potential biomarker for detecting the progression of knee osteoarthritis and can trigger inflammatory response in rheumatoid arthritis. It can improve metabolic syndrome, fight against adipose tissue inflammation, insulin resistance, hyperlipidemia and obesity. It has antibacterial activity against Gram-positive bacteria, and Pla2g5^-/- mice are more sensitive to Candida albicans and Escherichia coli infection. Besides, mutations in PLA2G5 gene site 45 produce extra cysteine, causing conformational changes that lead to the development of benign familial retina macular disease. Mutation or overexpression of PLA2G5 can also affect the occurrence and development of human malignant tumors. Studies have shown that overexpression of PLA2G5 is a marker of poor prognosis for gliomas. A tumor mutation load model based on PLA2G5 gene can accurately predict the recurrence risk of ovarian cancer. Furthermore, several synthetic inhibitors, including silicon-directed recognition inhibitors of indole-amide-biphenyl derivatives, phospholipid analogs, and potential natural inhibitors such as olanolic acid syrenic oregano, have certain inhibitory effects on PLA2G5. These results provide theoretical bases for novel therapeutic approaches targeting PLA2G5.]]> 2021/9/23 0:00:00 CI Yu-Ying,ZHANG Wei-Dong,LIN Yong,SU Jing and ZHANG Yang 574true 2021/9/23 0:00:00 LI Tai-Ran and CHEN Gui-Ying 573true 2021/9/23 0:00:00 PENG Jin,YANG Ya-Jun and WANG Xiao-Hui 572true 2021/9/23 0:00:00 LI Hui-Dong,CHU Zhi-Yong,QIAN Xiao-Ming and LONG Cheng 571true 2021/9/23 0:00:00 FANG Yan,LIU Zheng,GAO Ying,XING De-Chun,DONG Lian-Hua and YANG Jing-Ya 570true 2021/8/24 0:00:00 WANG Xue-Ling,WANG Yi-Meng,YANG Jia-Jia and ZHENG Chen-Guang 569true 2021/8/24 0:00:00 WANG Miao,HONG Jia-Chi,ZHOU Fei-Fan and LI Peng-Cheng 568true in vitro. Regarding metabolism, nuclear magnetic resonance (NMR) spectroscopy is the most common analytical method for the study of small metabolic molecules in blood. Matching between the available NMR data and reference databases can be applied to assess significant changes in metabolites and to evaluate blood sample quality. In addition, both metabolites and proteins can be quantified through mass spectrometry (MS). Typically, they are first enriched through affinity interactions (e.g., chromatography, immunoaffinity, and magnetic approaches) and then quantified through MS. This review summarizes the metabolites, proteins, and peptides identified by MS as biomarkers for blood quality control. However, their accuracy and effectiveness have not been widely recognized. Because various techniques have been used and a series of markers have been identified, the stability and accuracy of these molecules still need to be verified for quality control. Moreover, due to the high cost of MS, these techniques are not widely used in laboratories. Therefore, in the future, new quality control parameters should be identified for blood sample assessment.]]> 2021/8/24 14:13:06 SUN Qing,LIANG Kai and LI Yan 567true de novo protein synthesis and synaptic plasticity alterations. The studies discussed here strongly indicate that various epigenetic modifications, including DNA methylation, histone modification and RNA modification, play an integral role in learning and memory, and has garnered the attention of researchers in the past decade. In this Review, we examine the involvement of different epigenetic regulators involved in memory and learning functions and provide a theoretical basis for future research.]]> 2021/7/28 0:00:00 CHANG Yuan,ZHANG Jin-Ming,ZHANG Jun-Min,GU Qiao-Fen,ZHU Wen-Peng and HAN Jing 566true 2021/7/28 10:21:19 YANG Jia-Jia,WANG Su-Tong and MING Dong 565true 2021/7/28 0:00:00 ZHENG Wei-Qi,ZHANG Yi-Chen,MA Jia-Xin,ZHAO Han,REN Zi-Yuan and ZHANG Yu 564true via binding to the LPA receptors, a series of G protein coupled receptors on cellular membrane. Autotaxin (ATX) is a secretory glycoprotein with lysophosphatidase D (lysoPLD) activity to generate LPA from lysophosphatidylcholine (LPC), which is the main source of circulating LPA. Recently, increasing evidences have revealed that ATX is highly expressed in mature adipocytes and that the ATX-LPA axis plays a role in obesity and obesity-related disorder of glucose and lipid metabolism. The ATX-LPA axis has been regarded as the novel therapeutic target for obesity-related diseases. In the present paper, we will review the research progresses of ATX-LPA axis in obesity and obesity-related diseases, such as insulin resistance and nonalcoholic fatty liver disease.]]> 2021/7/28 0:00:00 YIN Nan and ZHANG Jun-Jie 563true 2021/7/28 0:00:00 TONG Na and KUANG Shen-Bing 562true 2021/7/28 0:00:00 LI Jia,WANG You-Jun and ZHANG Xiao-Yan 561true 2021/7/28 0:00:00 ZHU Jun-Chang,ZHANG Yu-Xuan,GE Bin-Jie,Hu Pan-Jie,TANG Jia-Lü,CAI Wen-Pin and JI Jing-Zhang 560true 2021/6/24 0:00:00 JIANG Nan-Nan,LIU Jian-Xin and SHI Heng-Bo 559true 2021/6/24 0:00:00 YU Xin-Ran,LI Ying-Jie,CHEN Guan-Jun and WANG Lu-Shan 558true E. coli, T cell receptor-antigen recognition, microfilament depolymerization and Notch signaling pathway activation. This review summarized the progresses and new findings of catch bond research in cell adhesion, T cell activation, actin interaction. For cell adhesion of prokaryotes and eukaryote, catch bonds exist in a wide range of related proteins, including FimH, selectin, integrin. For T cell activation, recent research revealed that the catch bond in TCR-pMHC interaction is closely related to cancer cell development processes and this finding provides a new direction in improving T cell receptor-gene engineered T cells (TCR-T) immunotherapy. For actin interaction, the actin catch bond has been proven involving in RhoA-formin switch force-induced actin cytoskeleton alignment process. To further illustrate the prospect of catch bonds in medical research, we also discussed the potential of catch bonds in the development of anti-bacterial or anti-adhesion drugs and improvement for the TCR-T immunotherapy.]]> 2021/6/24 0:00:00 CAO Xu and CHANG Sheng-Yuan 557true in vivo for remote therapy are proposed.]]> 2021/6/24 0:00:00 LIU Ying-Xun,LI Lin-Yuan,HE Yu-Meng and REN Wei 556true 2021/6/24 0:00:00 LIU Xiao-Dong and WANG Xiao-Hui 555true 2021/5/31 0:00:00 SHEN Zi-Yue,ZHANG Shi-Yao,ZHANG Wen-Xiang,LIU Chang and CHEN Si-Yu 554true in vitro,and analyzes works concerning data size, logic density, and DNA synthesis. We also describe in vivo molecular memory systems, including the adoption of CRISPR to design the DNA storage system. Finally, we discuss various influencing factors and challenges of data storage systems based on DNA.]]> 2021/4/12 0:00:00 TENG Yue,YANG Shan,LI Jin-Yu,CUI Yu-Jun,LIU Rui-Cun and WANG Sheng-Qi 553true 2021/5/31 0:00:00 HU Liang,CHENG Jie,WANG Yi-Hua,Lü Meng-Wei and SONG Jian-Bo 552true 2021/5/31 0:00:00 WANG Ya-Nan and ZHAO Bo 551true 2021/5/31 0:00:00 MA Qing and Morigen 550true 2021/5/31 0:00:00 LIU Ying,LIU Chao,LIN Qing-Hua,ZHANG Jian-Jun,DU Wen-Jie,LIANG Jing and SUI Nan 549true 6-methyladenosine (m⁶A) modification of mRNA in aggressive breast cancer is investigated widely. In this review, we retrieve and analyze the most recent studies on m⁶A modification, and summarize the expression and the function of m⁶A regulatory proteins, including the writers, erasers and readers, in the tumorigenesis and progression of breast cancer, and point out the defects in the recent field of m⁶A-related researches, so as to provide scientific basis for diagnosis, therapies and prognosis in breast cancer.]]> 2021/5/31 0:00:00 FANG Run-Ping,XU Fei-Fei,ZHAO Lu-Ping,YU Lu,CAI Xiao-Li,YANG Zhe,ZHANG Wei-Ying,YE Li-Hong and SHI Hui 548true Ψm) and mitochondrial glycolipid metabolism, etc. Our research found that the antigens containing aluminum adjuvants can be rapidly phagocytized by macrophages and then an effective immune response can be induced. It is easy to find that the material basis of “fast phagocytosis and fast activation” should require more energy supporting. For this reason, we speculate that the biological behavior of mitochondria will be more active, and may cause “huge damage” to M? after the immune response is achieved. This review will give an overview of this phenomenon and elicit the thinking that needs to be solved in the next step.]]> 2021/5/31 14:11:46 HUANG Li-Ting,LIANG Gui-Zhao and Lü Feng-Lin 547true in vivo have focused on developing vectors. Non-viral nano-carriers developed by nanotechnology can efficiently deliver the CRISPR/Cas9 system into the body, providing a new way for the clinical application of CRISPR/Cas9 technology. In this review, we discuss the principle of CRISPR/Cas9, the current delivery forms of CRISPR/Cas9 and commonly used nano-delivery vectors. We highlight several nano-carriers including inorganic nanoparticles, polymer-based nanoparticles, lipid-based nanoparticles and others. We also summarize the characteristics, editing efficiency, applications and new studies of different nano-carriers. The applications and progresses of CRISPR/Cas9 in treating different tumors are also discussed.]]> 2021/5/31 0:00:00 QIAO Huan-Huan,ZHANG Qing-Hao and MING Dong 546true in vitro models and unsuitable animal models, which leads to 70%~80% mortality rate. Microfluidics enabled bone-on-a-chip could facilitate the resemblance of the biochemical and biophysical microenvironment of native bone tissues, which could readily be incorporated with the occurrence of breast cancer so as to recapture the bone metastasis in a single chip. The microscale chip design could be scaled up with high throughput/content settings so as to uncover the molecular mechanisms existing in bone metastasis of breast cancer and screen effective drugs for it more efficiently. In this review, we first introduce the current mechanistic understanding on bone metastasis of breast cancer and existing drugs for this disease. We then summarized the microfluidic models used for recapturing bone metastasis phenomena. We also presented high throughput designs aiming for more efficient drug discovery and development. Lastly, we discuss the advantages and challenges existing in combining high throughput setting and microfluidic models aiming for effective drug screening targeting bone metastasis of breast cancer. Together, we hope to provide a clue on how effective treatments could be discovered in the future so as to decrease the high mortality rate of bone metastasis of breast cancer.]]> 2021/5/12 0:00:00 YU Tong-Yao,YUAN Xi-Chen,WANG Dong-En,XU Hui-Yun,YANG Peng-Fei,SHANG Peng and REN Li 545true 2021/5/12 0:00:00 XIAO Shi-Di,MA Zi-Dong and MA Bin-Guang 544true 2021/5/12 0:00:00 WANG Qing-Qin,LIU Meng-Jiao,NIU Ya-Li,LI Dong-Feng,WANG Song-Hua and MENG Wei 543true 2021/5/12 0:00:00 CHEN Ke,YANG Zhao-Xi,LIAO Bai-Tao,HOU Bo-Jun,YANG Yin,LIU Tie-Jun,XIA Yang and YAO De-Zhong 542true i. e., the structural and functional properties of the corticolimbic circuitry) that could predict the transition from acute to chronic pain. For example, the functional connectivity between the medial prefrontal cortex and nucleus accumbens/hippocampus, as well as the functional connectivity between the dorsal medial prefrontal cortex and amygdala/nucleus accumbens could predict the development of chronic pain 1 year later. Besides, based on the existing theoretical model of chronic pain, we emphasized the critical role of the reinforcement learning of negative emotions as well as the dysfunctions of reward and stress systemin pain chronification. Finally, we pointed out the limitations of previous studies in this field and suggested future research directions for a better understanding of the neural mechanisms of chronic pain and pain chronification.]]> 2021/5/12 0:00:00 WANG Fei-Xue,BI Yan-Zhi and HU Li 541true 2021/5/12 0:00:00 CUI Zhong-Dan,WU Jing,TANG Jia,CHEN Qi-Cai and FU Zi-Ying 540true 2021/5/12 0:00:00 ZHUANG Hui,LIN Zi-Han,LIN Ting,CAO Xin-Yi and JIN Xiao-Feng 539true 2021/5/12 0:00:00 YI Guo-Sheng,HUANG Xue-Lin,WANG Jiang and WEI Xi-Le 538true 2021/4/26 0:00:00 LI Ping-Cui,YANG Fan,OU Xia,ZHANG Ji-Hong and WEI Da-Qiao 537true 2021/4/26 0:00:00 Huang Yang Rui,Guo Yong,Yang Zhi Gang,Yan Wei and Qu Jun Le 536true 2021/4/26 0:00:00 WANG Zhao-Xiang,FENG Zhou-Yan,YANG Gang-Sheng and ZHENG Lü-Piao 535true in vitro cardiac tissue model has received more and more attention. In this review, the origin and development of in vitro cardiac model construction are overviewed. The cell sources of cardiomyocyte and the relative techniques and methods for model construction are comprehensively reviewed. Combining with the construction technologies such as bio-printing and microfluidics,the importance and research progress of vascularized cardiac tissue model are highlighted. Finally, the future perspectives and challenges of this field are discussed in order to provide new ideas for the research and application of in vitro cardiac tissue model in drug evaluation.]]> 2021/4/26 0:00:00 MIAO Xiao-Min,WANG Ya-Qi,CHEN Jia-Ying,LAN Xing-Zi,ZENG Xiao-Han,TANG Ya-Dong and ZHANG Kun 534true etc. Under the action of hyperphosphatemia, hyperglycemia, vitamin D₃, inflammation and other factors, vascular smooth muscle cells are transformed into osteoblast-like cells to participate in vascular calcification, which induce cardiovascular and cerebrovascular adverse events. Non-coding RNA is a general term for a variety of RNA types that transcribed from the human genome but lacking the ability to encode proteins. Non-coding RNA participates in the body's physiological and pathological processes by regulating various cell activities. Studies have shown that non-coding RNA can affect the occurrence and development of vascular calcification by regulating the osteoblast-like phenotype transformation of vascular smooth muscle cells. This article reviews the regulatory role of non-coding RNA in osteoblast-like phenotypic transformation of vascular smooth muscle and vascular calcification from the aspects of microRNA, long non-coding RNA and circular RNA, which is helpful to further understand the molecular mechanism of vascular calcification and find new targets for the prevention and treatment of vascular calcification.]]> 2021/4/26 0:00:00 LIU Ke-Ke,ZENG Gao-Feng,JIANG Ting,WANG Yan and ZHAO Guo-Jun 533true 2021/4/26 0:00:00 ZHANG Shu,ZHAO Yue,CHEN Guan-Jun,YU Jun-Hong,WU Xiu-Yun and WANG Lu-Shan 532true 2021/4/26 0:00:00 CHEN Dao-Bo,WANG Jiao-Yu,XIAO Chen-Wen,WANG Yan-Li and SUN Guo-Chang 531true in-vitro cell-free expression method for protein synthesis. High-throughput protein expression and in-vitro reconstitution of membrane proteins can be realized in CFPS-containing artificial cells. This review describes various CFPS systems including E. coli extracts, rabbit reticulocytes extracts, wheat germ extracts, and yeast extracts, and summarizes the progress of cell free protein synthesis inside artificial cells. The challenges and the future directions of this field are also proposed at the end of this paper.]]> 2021/3/25 0:00:00 ZHAO Jing-Jing,WANG Xue-Jing,MU Wei and HAN Xiao-Jun 530true 2021/4/8 0:00:00 TANG Meng-Tian,ZHOU Ju-Mei,LIAO Qian-Jin,ZHOU Yu-Juan,XIONG Wei,Li Gui-Yuan,TANG Yan-Yan and NIE Shao-Lin 529true 2021/4/8 0:00:00 ZHANG Hui-Fang,ZENG Zhi-Jun and ZHOU Yan-Hong 528true 2021/4/8 0:00:00 YAN Chuan-Ting,DU Yi-Nan,HAN Jing,REN Wei and LIU Zhi-Qiang 527true 2+-selective and highly sensitive to heat, and TRPV5, TRPV6 subgroup which is highly Ca²⁺-selective and not heat-sensitive. Mounting evidences suggest that TRPV channels are responsible for membrane potential regulation and intracellular Ca²⁺ signaling, and thus regulate a large number of cellular functions, such as temperature sensation and vasodilation. Dysfunction in channel expression and/or activity has been linked to human disease like cancer and cardiovascular disease. Post-translational modifications (PTMs) involving a functional group being added to a protein, a chemical change in amino acids, and a structural change in the protein have been implicated in regulating activity, localization and interaction with other cellular molecules, thereby increasing the functional diversity of the proteome. Many studies show that TRPV subfamily channels can also undergo post-translational modifications and PTMs have an important impact on channel function. The aim of this review is to address the major advances regarding the various post-translational modifications such as phosphorylation, glycosylation, ubiquitination, SUMOylation, and covalent modification that have been reported to regulate the functions of TRPV channels. Furthermore, we also discussed the possible functions of TRPV channels before and after PTMs in physiological or pathological activities, for a better understanding of the relationship between PTM and physiological or pathological activities.]]> 2021/4/8 0:00:00 YANG Bing-Jie,TIAN Quan,WEI Xin,ZHANG Hao and YAO Jing 526true 2021/4/8 0:00:00 YANG Rui-Xia,XIE Wei-Quan,WANG Wen-Jing,YU Shui-Ling,ZHOU Zhi-Gang and TU Jian 525true 3) and hydrogen peroxide (H₂O₂). LAAOs with high substrate specificity can recognize the preferred amino acid specially. Therefore, LAAOs with high substrate specificity are promising in the application of chiral amine compounds resolution, alpha keto acid biosynthesis, and especially, in the detection of certain amino acids in clinical and food samples. Therefore, specific LAAOs has attracted wide attention in recent years. In this review, we will focus on the recent progress in LAAOs researches. We will emphasize the substrate specificity, structure-function relationship, and family evolution of these enzymes. We will also discuss the applications of these enzymes in biocatalysis and amino acid detection. This review will provide guidance for molecular mechanism research and industrial applications of LAAOs.]]> 2021/4/2 0:00:00 LU Ze-Lin,YUE Hao,ZHANG Yi-Fan,YU Shan-Shan,YANG Guang-Yu and MA Fu-Qiang 524true 2021/12/23 13:40:46 ZONG Huan-Huan,HOU Kai-Long,GUO Xin,LUO Ying and JIA Shu-Ting 523true etc.) regulating the regenerative involution in the mammary gland of dairy livestock. This review tries to uncover the internal mechanism of mammary gland remodeling and provides scientific basis to regulate it.]]> 2021/12/23 13:40:51 WU Chao-Qun,LIU Jian-Xin and SHI Heng-Bo 522true 2021/12/23 13:40:52 WU Min,GUO Jun,PAN Yue,LI Jia-Wei,LIAN Jia-Qi,WANG Zi-Xin,WANG Chao-Qun and ZHANG Feng 521true 2021/12/23 13:40:53 ZHANG Huai-Yan,LIU Rong,LI Bing,LIU Ding-Xin and XU De-Hui 520true 2021/12/23 13:40:54 GE Zhe and DING Shu-Zhe 519true 2021/11/23 15:25:20 ZHANG Xiao-Fang,LI Si-Qi,ZHANG Qiang,ZHANG Jing and LU Xiao-Dan 518true 2021/11/23 0:00:00 WANG Fei-Er,YANG Yi-Xuan and Morigen 517true 2021/11/23 0:00:00 SUN Yan-Li,Aleksey Yakovlev,LIU Si-Si,ZHAO Hu-Cheng and FENG Xi-Qiao 516true 2021/11/23 0:00:00 YE Xiao-Kang,BAI Zi-Ran,JIN Min-Li,YIN Chun-Lai and LI Xia 515true 2021/11/23 0:00:00 MENG De-Hao,ZHANG Yan-Fen,SUN Yu-Miao,GAO Xu and MA Ning 514true 2021/11/23 0:00:00 ZHANG Jiao,HE Qin,WU Ze-Kai,YU Bin,QU Jun-Le and LIN Dan-Ying 513true etc., the remaining part of the visual pathway is still functional, so the electrode array or photoelectric array can be implanted into the retinal area, and plays a role in retina to generate electric signals to stimulate the optic nerve, which transmits electrical signals with visual information to the brain. For visually impaired patients whose visual cortex is functional normally, the electrode array can also be applied to the brain's visual cortex to input electrical signals with visual information directly. In addition, external devices using artificial intelligence to convert vision into voice commands, tactile array coding, etc., can help blind patients obtain environmental information. The implantable visual aid systems mainly face the risk of biological rejection and infection, and their resolution of vision restoration is limited by the electrode size. More complete visual aid electronic devices and systems that can be worn or implanted need to be developed to benefit a large number of patients with visual dysfunction. As a result, here new ideas for implanting devices and extracorporeal aid system are proposed to provide some valuable references for this field.]]> 2021/11/23 0:00:00 LIN Yan-Ni,GE Song,YANG Na-Na,XU Jing-Jing,HAN Hong-Bin and XU Sheng-Yong 512true 2021/11/26 0:00:00 WANG Jia-Jian,OU Xia,GENG Xue-Ye and ZHANG Ji-Hong 511true 2021/11/26 0:00:00 MAO Jia-Rong,QIAN Ying,SHI Guo-Ping,WANG Jing-Jing and CHEN Yu-Gen 510true 2021/11/26 0:00:00 ZHENG Xiang,YE Sheng,ZHAO Wei and CHEN Yuan 509true 2021/11/26 0:00:00 YANG Hong-Guang,TONG Chun-Mei and DENG Hui-Min 508true 2021/11/26 0:00:00 TANG Xiang-Rong,WANG Xiao-Gang,CHEN Tao-Lin,ZHANG Miao-Chen,ZHENG Zhong,LUO Yue-Jia and GONG Qi-Yong 507true 2021/11/26 0:00:00 MA Li-Wei,WU Guo-Rong and WEI Lu-Qing 506true i.e., cancer), improving the disease detection, prevention and treatment, and providing the targets for drug design. Traditional gene-mapping approaches, such as linkage analysis and genome-wide association studies (GWAS), often predict hundreds of candidate genes. But it is costly, time-consuming and laborious to further validate these candidate genes with biological experiments. However, the number of candidate pathogenic genes can be effectively reduced by computational and prioritization methods. Considering the excellent performance of random walk with restart (RWR) in predicting the risk pathogenic genes, in this work, we comprehensively discuss the recent progresses of predicting the risk pathogenic genes with RWR from databases related with genes and diseases, the metrics of measuring the similarity between genes/diseases, the strategies of choosing the seed genes of specific disease, and the different genes/diseases network structures. We also point out the computational problems and challenges faced in the process of pathogenic genes prediction.]]> 2021/11/26 0:00:00 LIU Li-Li and ZHANG Shao-Wu 505true 2022/9/21 0:00:00 XU Rui,WANG Ke,LI Yun-Zhi and ZHANG Xiu-Hong 504true 2022/9/21 0:00:00 CHEN Yan-Wen,YUAN Shu-Ying,LIU Rui-Jie,ZHANG Shao-Xing,ZOU Lin,LU Xin-Rong,KONG Wei-Li,CHEN Li and SUN Gui-Qin 503true 2022/9/21 13:38:15 QI Hong,LI Zhi-Chao and SHI Zhi-Qiang 502true 2022/9/21 0:00:00 ZHENG Li-Yu,YAO Ren-Qi and YAO Yong-Ming 501true 3+), which makes it prone to settling and being “removed”. Marine microorganisms are presented with unique challenges to obtain essential iron ions required to survive and thrive in the ocean. To obtain enough iron source for life metabolism, microorganisms have evolved many ways to meet the demand for iron intake, among which siderophores is the most representative one. Siderophores are low molecular mass iron-binding ligands produced by marine bacteria. Microbial siderophores are multidentate Fe³⁺ chelators used by microbes during siderophore-mediated assimilation. They possess high affinity and selectivity for Fe³⁺. Among them, marine siderophore-mediated microbial iron uptake allows marine microbes to proliferate and survive in the iron-deficient marine environments. Being an important metabolic cofactor, siderophores also strongly influences the circulation of other elements. In order to better understand the role of siderophores in marine microbial ecology and deepen our understanding of marine iron cycle dynamics, this paper summarizes the types of siderophores such as hydroxamates, catecholates and carboxylates, two main siderophores synthesis pathways of microorganism and the mechanism of regulating siderophores synthesis, describes the transmembrane transport process of siderophores and several functional protein elements, the functions of siderophores such as anti-oxidative stress, regulation of pathogen virulence, formation of multifunctional iron and sulfur polymers, and anti-pathogens and so on. Although siderophores have been studied and discussed, further research can be carried out in the following aspects, such as the interaction mechanism between siderophores and marine microorganisms, the application of synthetic biology, and the coupling ability of siderophores behavior with other elements.]]> 2022/9/21 0:00:00 ZHANG Xiao-Yu,ZHU Jian-Ming,CAI Zhong-Hua and ZHOU Jin 500true 2022/9/21 0:00:00 LIU Yi-Shu,LIU Xi,ZHANG Zi-Jian,FU Xiao-Lan and LIU Ye 499true 2022/9/21 0:00:00 GAO Mei-Hong and SHANG Xue-Qun 498true 13 cps. At such a high flux, the radiation damage of protein and other biological macromolecule solution samples is very serious in experimental measurement. If there is no effective radiation protection measures, protein solution samples will be damaged by irradiation within the millisecond irradiation time, resulting in the inability to obtain effective experimental data. Radiation damage severely restricts the application of SAXS in protein solution samples. Therefore, it is of great guiding significance for the scattering experiments of protein and other biomolecular solutions to understand the generation mechanism, influencing factors and judgment criteria of radiation damage of protein solution samples, and to effectively reduce the degree of radiation damage or delay the generation time of radiation damage. On the basis of a brief introduction to the basic concepts of irradiation damage mechanism, influencing factors, and irradiation dose of biomolecular solution samples, this paper summarizes the criteria and protective measures of radiation damage in synchrotron radiation SAXS experiments. In addition, this paper also compares the advantages and disadvantages of various protective measures, discusses the available acquisition time of SAXS-beamline scattering data on the high energy photon source (HEPS) under construction, and points out that the protective agents of irradiation damage are a valuable research direction.]]> 2022/9/21 0:00:00 XING Xue-Qing,LIU Chao,MO Guang,SHI Ying and WU Zhong-Hua 497true 2022/9/21 0:00:00 WANG Xiao-Li,PANG Yi-Quan,HOU Li-Wei,HE Xin-Yu,GE Chuang,MU Xiao-Jing and XU Yi 496true etc.) are currently in preclinical studies, clinical trials or have been approved in clinic, showing good safety and clinical efficacy. It is generally believed that oncolytic viruses target and kill tumor cells by selectively replicating themselves in tumor cells, and finally lysing and killing tumor cells. At the same time, they can stimulate the immune responses of the body, thus enhancing the antitumor immunity, the tumor cells can be targeted and killed with no obvious side effects. The combination of oncolytic virus and immune checkpoint by gene recombination and the breakthrough of tumor immunotherapy have made the application of oncolytic virus more extensive, however, there are still some bottleneck problems such as virus targeting, security and administration route. This review provides a comprehensive and detailed overview of the development of oncolytic viruses. We list some viruses have been used as candidates for lysis of cancer cells and the clinical trials in the field of oncolytic virotherapy. And we discuss about the immunological mechanism of oncolytic virus targeting to kill tumors, and the challenges and prospects in the future.]]> 2022/8/19 0:00:00 YANG Hao,ZHANG Shao-Geng and YANG Peng-Hui 495true 2022/8/19 0:00:00 WANG Yuan,MA Feng-Sen,WANG Yan-Ni,XIU Xue-Liang,LIU Yong,SONG Wei-Min and HU Xia-Xia 494true etc. The MARK4 gene encodes two alternatively spliced isoforms, L and S that differ in their C-terminal region. These isoforms are differentially regulated in human tissues including central nervous system. The isoform MARK4S is highly expressed in the normal brain and is presumably involved in neuronal differentiation and the isoform MARK4L is upregulated in hepatocarcinoma cells and gliomas. MARK4 exhibits are multi domain structure comprised of an N-terminal header, a catalytic kinase domain, a linker, UBA domain, spacer, and a kinase-associated domain at the C-terminal end. Over-expression of MARK4 is associated with the onset of neurodegenerative diseases such as Alzheimer’s disease, metabolism disorders and cancer. Therefore, MARK4 is being considered as a most suitable drug target for cancer, Alzheimer’s disease and other neurodegenerative diseases and its structural features are employed in the development of new therapeutic molecules. In this paper, the structure and biological functions of MARK4 and the related diseases mediated by MARK4 were reviewed, and the research progress of MARK4 inhibitors was summarized.]]> 2022/8/19 0:00:00 ZHOU Jian,YE He-Yang,YIN Xiu-Shan and LI Jian 493true 2022/8/19 0:00:00 GOU Yuan-Yuan,ZHANG Wei,LI Bao-Yu,SHEN Ya-Xuan,CUI Dan-Ni and SHI Jia-Qi 492true TREX1, RNASEH2A, RNASEH2B, RNASEH2C, and SAMHD1, RNA-related genes ADAR1 and IFIH1, and two recently identified genes, LSM11 and RNU7-1 whose correct activity is required for histone expression. Aberrant DNA metabolism or damaged histone expression activates IFN signaling through the cGAS-STING axis, while RNA errors sensitize the MDA5-MAVS axis. Thus, despite these 9 mutations all leading to the aberrant activation of IFN signaling, they can rely on different mechanisms, implicating that even having the same symptoms clinically the optimized treatment can be different. We thus argue the importance and necessity of diagnosing at the genetic level to the treatment of complicated symptoms and hope this review benefits the understanding of the pathogenesis of autoimmune diseases.]]> 2022/8/19 0:00:00 LI Wei,YANG Han and MU Xin 491true 2022/8/19 0:00:00 ZHENG Xiao-Ci,WU Die and XU Xin 490true 2022/8/19 0:00:00 XU Lan and REN Li-Cheng 489true 2022/8/19 0:00:00 YANG Jing,GAO Lan-Yu,YANG Yi-Lin,YANG Mao-Yuan and REN Yong-Gang 488true + channel activation and Na⁺ channel inactivation caused by kilohertz signals. Finally, we raise several key issues on KHFAC stimulation of peripheral nerves that need to be addressed in the future. We highly suggest further determination of the effective stimulus parameters, nerve responses, and underlying mechanisms involved in different species for successful translation of KHFAC block, especially in human beings.]]> 2022/8/19 0:00:00 YI Guo-Sheng,ZHAO Qiang,BAI Rui-Feng,WEI Xi-Le and WANG Jiang 487true 2022/8/19 0:00:00 LIU Li-Mei,CHEN Xiao-Jin,SUN Shi-Wei,WANG Yu,WANG Hui,MEI Shu-Li and WANG Yao-Jun 486true 2022/7/20 0:00:00 ZHAO Sha,YAN Zi-Juan,ZHANG Shu,YU Jun-Hong,WU Xiu-Yun and WANG Lu-Shan 485true via their reaction products (H₂O₂ or hydroquinone), or facilitating glycoside hydrolase to degrade lignocellulose. According to the structure and sequence similarity, the enzymes from AA3 family were further subdivided into 4 subfamilies, mainly including cellobiose dehydrogenase, aryl-alcohol oxidase and glucose oxidoreductase, alcohol oxidase, pyranose oxidoreductase. On account of the high expression level, efficient catalysis, diversity of biotransformation, and fast electron transport kinetics, AA3 enzymes have become an interesting target for electrochemical biosensors. In order to improve the performance parameters of biosensors, a tremendous development has been obtained in the field ranging from the production of new AA3 enzymes with tailor-designed properties, such as the improved specific activity, low O₂ sensitivity and enhanced redox mediator interaction, to their efficient immobilization in a variety of nanomatrices. Thus in this paper, we provide an overview of the phylogenetic, molecular, and catalytic properties of CAZy-AA3 family enzymes, and the latest research progress of AA3 enzymes used in electrochemical biosensors was also summarised. In the development trend of the future study, it calls for the combination of protein engineering skills with expertise on redox mediator/polymer synthesis and electrochemistry to facilitate the application of AA3 enzymes in biosensor.]]> 2022/7/20 0:00:00 ZHANG Zhen-Yu,GONG Wei-Li,MA Yao-Hong,ZHU Si-Rong,WANG Bing-Lian,HAN Qing-Ye and CHEN Yan-Ru 484true 2022/7/20 0:00:00 WANG Zhi-Hui and ZHANG Jian 483true 2022/7/20 10:49:48 BAI Zi-Ran,LIN Qian,YU Yu-Di,YE Xiao-Kang,YANG Chen,LI Xia and WANG Guan 482true + inactivation and K⁺ activation. In most neurons, the action potentials are initiated in the axon initial segment, and the threshold variability at this site is the crucial factor that determines how neurons transfer spatiotemporal information. However, the action potentials in electrophysiological experiments are recorded in the cell body or proximal dendrite. The threshold variability at these sites is higher than that in the axon initial segment, which mainly arises from the backpropagation of axonal action potentials. Based on somatic recordings, it is shown that the spike threshold dynamics determines the transformation principle of spatiotemporal information in the neurons, which enhances the temporal coding, feature selectivity, gain modulation, and coincidence detection. In this paper, we first introduce the conception of spike threshold and its calculation methods. Then, we present an exhaustive review on the main findings of the spike threshold variability and its origins in recent years, and mainly discuss the significance of spike threshold variability for neuronal coding. Finally, we raise several key issues on the spike threshold that need to be addressed in the future.]]> 2022/7/20 0:00:00 YI Guo-Sheng,ZHAO Qiang,WEI Xi-Le and WANG Jiang 481true 1 cm in rats and >3 cm in humans). In addition to autologous transplantation, stem cell transplantation will promote peripheral nerve regeneration, improve myelin sheath formation and nerve survival. Neurotrophic factors include nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) can promote neuronal differentiation, axon growth and synaptic connection. New biomaterials including chitosan scaffold (CS), silk fibroin (SF), 3-hydroxyoctanoic acid co-3-hydroxydecanoic acid/polycaprolactone (P(3HO-3HD)/PCL75/25) or acellular cauda equina allograft (ACEA) can support and guide the growth of axon. Combined with 3D printing technology, personalized neural conduits can be designed and manufactured. Electroacupuncture stimulation of Huan-jump point (GB 30) and Zusanli point (ST 36) can prevent apoptosis of neurons and promote the growth of axon. The combination of several materials and formation of tissue engineered nerve graft (TENG), will have better effects on repairing of nerve injury. Thus, the role and mechanisms of these methods in the repair of peripheral nerve injury were reviewed, and their clinical application was prospected.]]> 2022/7/20 0:00:00 XIAO Yu,WENG Qiu-Yan,SHAO Lei,XUE Yang,WU Can,GUO Lei,NIU Yan-Fang,Bao Xiao-Ming and XU Shu-Jun 480true 2022/7/20 0:00:00 SUN Zong-Peng 479true 2+ homeostasis, changes in microtubule polymerization rate, stress response, and changes in the expression of the circadian clock gene cry can partially explain the above phenomena. In view of the existing problems such as inconsistent parameters and unclear mechanism in biological magnetic induction research, combined with the advantages of zebrafish, the authors propose the potential direction of zebrafish in magnetic biology research in the future: to establish magnetic fields and biological parameters controllable magnetic biology research model based on zebrafish; non-invasive in vivo tracking of related life activities, visualized study of magnetic biological phenomena; research on the relationship between magnetic fields and biological rhythms based on Cry protein.]]> 2022/7/20 0:00:00 TANG Long-Sheng,TIAN Xiao-Fei and REN Da-Long 478true 2022/7/20 0:00:00 YIN Lin,SHEN Jun-Cheng and YANG Li-Qun 477true 2022/7/20 0:00:00 TANG Qian,REN Wen-Sheng,CAO Hong-Yu,WANG Li-Hao and ZHENG Xue-Fang 476true etc.) and communication methods used by both prokaryotic and eukaryotic microorganisms, and discussed the impact of these communication languages ??on the interaction in intraspecies (same microorganisms), interspecies (different microorganisms), and interkingdom communication (microorganisms and hosts). This review is aiming to interpret this interesting cross discipline deeply, to understand the form, mechanism and purpose of microbial communication language better, and to obtain a new approach for the interpretation of microbial behavior and the analysis of ecological events based on chemical ecology.]]> 2022/6/21 0:00:00 CHENG Ke-Ke,ZENG Yan-Hua,CAI Zhong-Hua,HE Yong-Hong and ZHOU Jin 475true 2022/6/21 0:00:00 MA Jin-Zhe,HAN Yang-Yang,YAO Yi-Ting,FU Zi-Ying,CHEN Qi-Cai and TANG Jia 474true i.e., task dynamics, target valence) and individual factors (i.e., anxiety, fearfulness, autistic quotient, and social cognitive disorders). This modulation effect emerges from infancy and matures with age. It occurred rapidly and is associated with the two different attentional components (i.e., the early orienting and the later disengagement). Both the separate and integral neural processing of facial expressions and gaze directions, involving the brain regions of the amygdala and the posterior superior temporal sulcus, were implicated in this modulation. Apart from facial expressions, other types of social information contained in faces (e.g., trustworthiness, familiarity, facial dominance, social status, and groups) could also modulate the gaze-triggered orienting, which potentially engages the frontal eye field and the frontoparietal attention network. A systematic review of the behavioral evidence of the modulation and its neural mechanisms has significant theoretical and clinical implications. On the one hand, it will deepen our understandings of the relationship between face processing and gaze-triggered orienting. On the other hand, it may also contribute to the diagnosis and intervention of social cognitive disorders.]]> 2022/6/21 0:00:00 YUAN Tian,JI Hao-Yue,YU Yi-Wen,WANG Li and JIANG Yi 473true 2022/6/21 0:00:00 HE Xiao-Ting,DONG Jie-Xian,SHEN Xing,WANG Hong,SHEN Yu-Dong and XU Zhen-Lin 472true etc. are important factors for the successful delivery of siRNA drugs. At present, the design of siRNA drug nanocarriers mainly includes 4 strategies: loading siRNA drugs on the surface of nanocarriers, co-assembly of siRNA drugs and nanocarriers, nanocarriers encapsulating siRNA drugs, and siRNA self-assembly. At this stage, the use of nanocarriers to achieve siRNA drug delivery has made great progress. With the in-depth research and application development, the precise controlled preparation, precise targeted delivery and multifunctionalization of siRNA drug nanocarriers have achieved good results. However, there are still some problems that need to be overcome by researchers. For example, when siRNA drugs are used in the clinic, there are still problems such as inaccurate structure design of targeted drugs, serious off-target effects, difficulty in achieving endosome escape, and difficulties in large-scale preparation of nanocarriers. Because of this, only 3 siRNA drugs have been approved for marketing, namely Onpattro (Patisiran), Givlaari (Givosiran) and Oxlumo (Lumasiran) developed by Alnylam Pharmaceuticals. How to prepare siRNA drugs on a large scale is a major problem facing the clinical application of siRNA drugs, and it will become a research hotspot. At the same time, with the development of computer technology, combined with artificial intelligence, machine learning and other technologies, drug design with the aid of big data analysis is becoming a new research and development trend. Intelligent design and precise regulation of siRNA nanomedicine, and the design of multifunctional siRNA nanomedicine that integrates targeting, tracing, and co-delivery with other drugs to achieve synergy is also one of the future development directions of siRNA nanomedicine.]]> 2022/6/21 0:00:00 ZHANG Qiong-Dan,CHEN Zhao-Xia,LI Fu-Yao and ZHANG Yu 471true 2022/6/21 0:00:00 ZHOU Ling-Li and YE Mao 470true VHL gene inactivation, which leads to the accumulation of HIF-2α and ultimately promotes the initiation and progression of RCC. So, HIF-2α can act as a new therapeutic target in RCC. Although HIF-2α is generally regarded as “undruggable”, the allosteric inhibitors PT2385/PT2977 have been successfully developed, which perform pharmacological effects by specifically antagonizing the formation of HIF-2α/HIF-1β heterodimers. Based on the structure of HIF-2α/HIF-1β heterodimers, an extensive screening of small-molecule libraries was performed and 130 potential HIF-2α inhibitors were generated. After further considering the potency, selectivity and oral viability, PT2385 and PT2977 were chosen, in which PT2385 for in vitro studies and PT2977 for clinical development. PT2977 can selectively inhibit the expression of HIF-2α targeted genes in cultured RCC cells, but do not affect HIF-1α targeted genes. Preclinical and clinical trials have demonstrated that HIF-2α inhibitors are effective in blocking cancer cell growth, proliferation, and tumor regression in RCC. These data also indicated that these inhibitors are more effective and better tolerated and have few side effects than standard drugs in treating RCC. Prolonged HIF-2α inhibitors treatment can also produce drug resistance, which can be partly attributed to key amino acid mutations in binding domain of HIF-2α to inhibitors. These advances mean that HIF-2α allosteric inhibitors are expected to play an important role in the clinical treatment of RCC.]]> 2022/6/21 0:00:00 GUO Zhen-Qing,LI Hong-Qiang,SUI Ai-Xia and GUO Xiao-Qiang 469true 2022/6/21 0:00:00 WANG Miao,WANG Xin-Yu,LI Hong-Ming and ZHANG Hong-Sheng 468true ) channel to close, causing endothelial cell membranes to depolarize; the binding of some receptors and ligands and the opening and closing of ion channels require the participation of VGCC, such as the opening and closing of potassium ion channels with bradykinin as activator and cation channels with histamine as activator. Hence,in view of the important functions of VGCC in regulating the excitability, secretion and migration of endothelial cells, in-depth and extensive research on VGCC is of great significance for revealing and treating endothelial functional diseases such as essential hypertension and atherosclerosis.]]> 2022/6/21 10:55:45 LI Shuang-Jun,PAN Jun and CUI Yu-Hong 467true etc, and then polarize to the M2 phenotype under the action of PGE2, WISP, IL-10, GM-CSF, MIC-1, and other chemokines and cytokines, shaping immunosuppressive and tumor-promoting TME. Therefore, the interaction between TAMs and CSCs plays an important role in promoting tumor growth, metastasis, and chemoresistance. This paper reviews the research progress on the interaction between CSCs and TAMs in TME and the potential target in the interaction of CSCs and TAMs for novel cancer therapy. These emerging insights provide a roadmap for the development of novel anti-cancer therapeutic strategies that disrupt this dynamic circuit in specific tumor types.]]> 2022/6/21 0:00:00 SHI Yu-Lu,YANG Sheng-Fu,TANG Lei and ZHANG Ji-Hong 466true 2022/4/22 0:00:00 TIAN Zhi,ZHANG Yuan and LI Zheng-Gong 465true 2022/4/22 0:00:00 ZHANG Nai-Xin,XU Cheng-Zhi,WU Yun-Pu,QIAO Chuan-Ling and CHEN Hua-Lan 464true in vivo and in vitro experimental researches. Low-frequency (<300 kPa) ultrasound causes severe bleeding due to the generation of standing waves and large cavitation bubbles that induce high stress on the vessel wall. High frequencies (>3 MHz) lead to the attenuation of acoustic pressure, reducing the therapeutic efficacy. In general, the frequency of 0.8-2 MHz is used for clinical treatment while guaranteeing therapeutic efficacy and safety. In order to avoid side effects such as tissue damage and temperature rise at high intensity, low-intensity (0.7-1.25 W/cm²) ultrasound was employed in clinical trials. Ultrasound pulse parameters and exposure time should be determined in relation to the lesion, ultrasound intensity and frequency. In ultrasound therapy, the administration of drugs (rtPA, atorvastatin, tongxinluo, streptokinase, urokinase) and microbubbles (MBs) encapsulated by a lipid shell, such as ultrasound contrast agent (UCA), provides an opportunity to further enhance the therapeutic effects. Their concentration and dosage used in treatment varied depending on the treatment object, and they should be reasonably selected considering adverse effects including hemorrhage. The debris removed from plaques should be small enough (<10 μm) not to cause blockage of the capillaries. Otherwise, a suction technology that can collect the debris in the vessel must be incorporated with this ultrasound technology. In addition, it is necessary to combine a monitoring system that can evaluate and monitor the degree of tissue damage in real time during treatment. Magnetic resonance imaging (MRI) and computed tomography (CT) can be combined to detect the sign of bleeding, while a thermocouple, ultrasound imaging, infrared thermal imaging and MRI can be used to predict the thermal damage by measuring tissue temperature invasively or non-invasively.]]> 2022/4/22 0:00:00 RI Jong-Hyok,XU Li-Sheng,XU Jia-Lin,GUO Li-Ting,CUI Hui-Ying and YAO Yu-Dong 463true 2022/4/22 0:00:00 MA Yi-Bo,MA Dong-Nan and GUO Jun-Ming 462true 2022/4/22 0:00:00 WANG Li,XIE Yu-Long and ZHOU Feng 461true 2022/4/22 0:00:00 CHEN Zhen-Lin,CAO Yong and HE Si-Min 460true Fam132b with the coding sequence of 10 kb. ERFE protein is a glycol protein which belongs to the C1q/TNF-related protein family, and there are 340 and 354 amino acids in mouse and human, respectively. It has been reported that Fam132b mRNA was detected in colon, skeletal muscle, brain, heart and other tissues, while it was rich in bone marrow after phlebotomy. It has been shown that ERFE plays important roles in glucose and fat metabolism, erythropoiesis and iron metabolism through hepcidin and transferrin receptors. Moreover, recent advances in relationships between ERFE dysregulation and diseases including β-thalassemia and chronic kidney disease, as well as the detection of ERFE in clinic and fundamental researches, give a further understanding the role of EPO/ERFE/hepcidin-FPN1 in regulating iron metabolism to provide a potential therapeutic target for treating diseases with iron metabolism disorders.]]> 2022/4/22 0:00:00 GUAN Peng,WAN Shuang-Shuang,GUO Yue-Tong,YANG Wen-Jing,GUO Jia-Shuai,GAO Guo-Fen,CHANG Yan-Zhong and YU Peng 459true 2022/4/22 0:00:00 Lü Mei,XU Ze-Jun,SUN Ren-Ren,MO Zhong-Cheng and XIE Yuan-Jie 458true 2022/3/21 0:00:00 SHI Wen,HU Fang-Fang,YIN Tie-Ying and WANG Ya-Zhou 457true 2022/3/21 0:00:00 HUI Zi-Ye,YU Han-Jie,SHU Jian,REN Xia-Meng and CHEN Wen-Tian 456true 2022/3/21 14:53:04 WU Jian-Le,LU Xiao-Lu,BIAN Shui-Gen,ZHU Jin-Mei,ZHANG Jin,JIANG Feng and LI Jian 455true in situ hybridization, high-throughput sequencing, in situ sequencing, and live cell barcodes, respectively. Each of them has its advantages and disadvantages so that should be applied in different situations, and it is foreseeable that these spatial transcriptome technologies will continue to be improved, including preventing RNA degradation, improving detection throughput and efficiency, reducing costs, and obtaining complete spatial single-cell transcriptomes. At the same time, based on the acquisition of cell spatial information, future spatial transcriptome technologies will be combined with the dimension of time, further improve the level of transcriptome research from the perspective of spatiotemporal transcriptome, and continuously deepen the understanding of the true characteristics of tissue cells, so as to advance the understanding of developmental processes, cancer and other malignant diseases and the development of new treatments.]]> 2022/3/21 0:00:00 WEI Ying,ZHANG Xiao-Dan,HU Miao-Miao,WU Zhong-Qin,CHENG Ming and GUO Yan 454true etc, are attracting more and more attention for being used as hemostatic materials due to their excellent biocompatibility, biodegradability and procoagulant activity. This review discusses several types of hemostatic materials and the corresponding hemostatic mechanisms. Our focus is tailored towards the basic structure, hemostatic mechanism, commercial products and the latest scientific research progress of the above-mentioned bio-derived hemostatic materials. Finally, the tendencies of their development are prospected.]]> 2022/3/21 0:00:00 YU Le-Jun and LIU Chen-Guang 453true Pseudomonas biofilm matrix, which can enhance the tolerance of bacteria for environment, antimicrobials and host defense. Pseudomonas mainly produce three key extracellular polysaccharides implicated in biofilm formation: alginate, Psl and Pel, and their synthesis and transport depend on the corresponding alginate, Psl and Pel biosynthetic systems. Therefore, this review comprehensively summarizes the progress on structural biology of Pseudomonas biofilm formation-related three exopolysaccharide biosynthetic systems, and describes the known structures and functions of proteins in these three systems. On this basis, new insights are put forward for future research directions, which can lay a solid theoretical foundation for formation mechanism and control strategies of Pseudomonas biofilm.]]> 2022/2/21 0:00:00 LIU Jia-Wen,WU Qian,ZHANG Zhao-Huan,TONG Jin-Rong,HUANG Zhen-Hua,LIU Jing,PAN Ying-Jie and ZHAO Yong 452true 2022/2/21 0:00:00 ZHANG Meng,LI Yue,ZHANG Lei,ZHOU Ming-Xue,LI Si-Nai and LIU Wei-Hong 451true 2022/2/21 0:00:00 ZHANG Qiang,XU Can and TANG Chao-Ke 450true 2022/2/21 0:00:00 ZHANG Xiao-Zhe,XIANG Nan and NI Zhong-Hua 449true in vivo such as neural development, angiogenesis, organ development, cell proliferation, tumor and inflammatory response. However, the physiological processes of Slit-Robo are highly diverse, and how these differences are regulated remains unknown. We thus expect more basic and translational research.]]> 2022/2/21 0:00:00 WANG Shu,GAN Wei-Dong,JIN Jin-Xiang,SHI Qing-Qing and SUI Cheng-Zhi 448true via Keap1-Cul3-Rbx1 complex. Additionally, Keap1 has also been widely studied as a tumor suppressor protein, and mutation or abnormally deletion of Keap1 alleles contributes to different kinds of diseases. The study of Keap1 has mainly concentrated on the Keap1-Nrf2 axis, but rarely extends to downstream substrates. Given that the great importance of Keap1 in cells, this review summarizes the current research status of Keap1, including ubiquitin-proteasome system, Keap1’s structure and function, the mutation of Keap1, the substrates of Keap1, and Keap1-related diseases. It may provide a new thought for targeted therapy of Keap1-associated diseases through discussing the challenges of Keap1-related fields in clinic.]]> 2022/2/21 0:00:00 NI Xiao-Qi,CHEN Xi-Wei and JIN Xiao-Feng 447true Flaviviridae including hepatitis C virus and Coronaviridae including SARS-CoV-2 are pathogens causing a variety of human infectious diseases. Understanding the interaction between virus and host is of great significance for screening therapeutic cellular targets and developing exosome-based vaccines. Accumulating studies have shown that exosomal protein and RNA play inhibitory roles for viruses. Moreover, Flaviviridae and Coronaviridae could hijack exosome-mediated cellular communication to harm the hosts and promote virus spread. In current review, we summarized the recent progress on the interaction between Flaviviridae/Coronaviridae and exosome, shedding the mechanistic insights into Flaviviridae/Coronaviridae induced exosome.]]> 2022/2/21 0:00:00 REN Yong-Wen,LI Peng and ZHANG Lei-Liang 446true 2022/2/21 0:00:00 GUO Yue,HAN Lu-Wen,QI Zhi-Hao,DU Xin-Qi,GUAN Song-Lei and JIA Yu 445true e.g., force and heat), which possess a broad range of applications in cancer therapy. To realize the precise delivery in vivo, magnetic nanomaterials induced magnetic actuation under static magnetic field has been the focus of biomedicine research. For instance, magnetic drug delivery systems such as nano-trajectory, nano-drugs have shown promise in efficient intratumoral accumulation of drugs. Inspired by a natural physiologic phenomenon in the tumor microenvironment and multiple physicochemical effects by external stimulation, a variety of endogenous-responsive and magnetic field-stimulated drug delivery systems were constructed. Magnetic nanomaterials loaded with drugs can actively penetrate into tumors under low-frequency alternating magnetic fields, resulting in their uniform distribution through the entire tumor tissue. Under a medium-frequency alternating magnetic field, magnetic nanomaterials produce heat and reactive oxygen species, which can facilitate the active drug release on-demand for cancer treatment. All those effects depend on size, composition, morphology, surface functionalization of magnetic nanomaterials. Owing to their easy surface functionalization, it presents an exciting opportunity in the modularized design and operation of an all-in-one system (imaging, targeted drug delivery, magnetothermal effect, nano-enzyme catalysis, etc.), which can achieve image-guided precise cancer theranostics. In this review, we focused on how to improve the magnetic nano-targeted drug delivery efficiency for tumor treatment, including the potential applications of magnetic targeted drug therapy, passive targeted magnetic hyperthermia and active targeted magnetic hyperthermia in enhancing the efficacy of cancer therapy. We highlighted the mechanisms underlying magnetically-actuated delivery and controlled release of drug. We also considered perspectives and challenges in tumor targeted therapy based on magnetic nanomaterials. Although the biomedical research based on magnetic nanomaterials has made great progress, most of the research is still in the stage of animal testing, and there is a long way to go to realize its clinical application in diagnosis and treatment. There is a series of challenges need to be overcome. (1) Designing safer and more efficient magnetic nanomaterials is needed. For example, improving magnetic properties of magnetic nanomaterials to achieve efficient magnetic targeted drug delivery; optimizing magnetic nanomaterials to avoid its penetration into the normal tissue. (2) Clarifying the regulation mechanism of magnetic nanomaterial-mediated effects on cell fate and disease treatment. (3) Understanding the interaction between magnetic field and living body, such as the effect of magnetic field on living body metabolism and clearance. (4) Developing safe and controllable magnetic field-generating equipment, control system and analysis software, etc. With the in-depth understanding of the biological effects of magnetic nanomaterials, a new discipline “magnetobiology” will be established soon.]]> 2022/12/20 0:00:00 TANG Qian-Qian,WU Rong-Qian,FAN Hai-Ming,LIU Xiao-Li and Lü Yi 444true in vitro self-assembly strategy (e.g., top-down, anti-solvent precipitation, template-assisted precipitation) and in vivo self-assembly strategy. Especially, nanodrugs prepared by in vivo self-assembly method can be targeted and self-assembled at the target location, reducing adverse reactions and achieving higher efficacy. Besides, the application of carrier-free nanodrugs in biomedical fields including anticancer, antibacterial, anti-inflammatory as well as antioxidant are comprehensively reviewed. Finally, the future challenges and development trends of carrier-free nanodrugs are also prospected, which may provide a theoretical basis for the rational design of more effective self-assembly vector free nano drugs and the feasibility of clinical application.]]> 2022/12/20 0:00:00 CHEN Ting-Ting,CHENG Hao-Yan,LI Zhen,JIN Bao-Sheng,CHEN Wei-Rui,HUANG Rui,WANG Wen-Xia and ZHENG Jun-Xia 443true via greater permeability and retention (EPR) and increased active targeting by modification of antibodies, peptides, aptamers, or small molecules to identify particular organ or cell receptors can give further advanced benefits. The design, assembly, and surface modification of nano-drug delivery devices confer different therapeutic effects in malignancies. Organic such as micelles, nanogels and dendrimers and inorganic such as carbon nanotubes, gold nanoparticles, magnetic nanoparticles, mesoporous dioxide silicon nanoparticles, and quantum dots nanocarriers are the most common forms of nanocarriers. Traditional prostate cancer therapies include drawbacks such as adverse effects, minimal effectiveness, and inadequate absorption. Chemotherapy can result in the development of drug resistance in prostate cancer, hence the development of new, effective, customized therapies is essential. Because of their intrinsic nanoscale features, nano-drug delivery systems, such as nano-delivery systems paired with chemotherapy, radiation, photodynamic treatment, and hyperthermia, can increase the therapeutic benefits of conventional therapeutic agents. Such therapies have the potential to significantly increase the survival rate of prostate cancer patients. This article discusses sophisticated nano-drug delivery technologies for PCa treatment, as well as its future potential.]]> 2022/12/20 0:00:00 LIU Xue-Yi,HAO Yi,SONG Hui-Jia,CHONG Tie and GAO Rui-Xia 442true 2022/12/20 0:00:00 LIU Jing,ZHANG Zhao-Huan,WU Qian,TAO Qian,HUANG Zhen-Hua,PAN Ying-Jie and ZHAO Yong 441true 2022/12/20 0:00:00 LI Bo-Nan,NING Gang,SUN Tian-Song,WU Hui,HE Qing-Hu,TANG Qian-Li and ZHOU Xing 440true 2022/12/20 0:00:00 XIE Zhe,LI Yi-Fan,WANG Xiao-Xiang,PAN Xiang,ZHANG Yi-Lian,CAO Qian,TIAN Hao-Yu and YIN Gui-Cao 439true 2022/12/20 0:00:00 WANG Zhong-Qun,ZHANG Li-Li,ZHAO Yun-Yun,LI Li-Hua and YUAN Wei 438true m/z range, and the spectra analysis is complex. The isolation window sequential fragmentation method reduces the number of precursor ions in tandem mass spectra and the size of the isolation window through a variety of acquisition strategies, effectively reducing the complexity of spectra interpretation. With the development of mass spectrometry instruments, the size of isolation window of the tandem mass spectra acquired by DIA may be close to the size of DDA, enabling the integration of DIA and DDA processes. The 4D-DIA method obtains the corresponding relationship between precursor and fragment ions through additional data dimensions, which improve the selectivity of precursor and greatly reduce the complexity of spectral analysis. The 4D-DIA method is also an important advance for future DIA data collection. According to the characteristics of DIA data, relevant data analysis methods were designed, which mainly included spectral library search method, protein database direct search method, pseudo-MS/MS spectra identification method and de novo sequencing method, as showed in the figure above. The spectral library search method uses the spectral library information for data extraction, which has high peptide identification sensitivity, but have certain requirements on the quality and number of spectral libraries; the protein database direct search method does not require preprocessing of tandem mass spectra and construction of spectral libraries, and directly matches the theoretical tandem mass spectrum of peptide with experimental tandem mass spectrum, but the time complexity is high; pseudo-MS/MS spectra identification method uses the spectra splitting algorithm to split the tandem mass spectrum to obtain multiple pseudo-MS/MS spectra containing single peptide fragment ions, then combined with traditional DDA software to search pseudo-MS/MS spectra; de novo sequencing method directly models the pseudo-MS/MS spectrum through deep learning to predict peptides, has the advantage of identifying sequences of new species, but it is difficult to guarantee the number and reliability of the identification results. The reliability evaluation of the peptide-spectrum matches mainly includes re-ranking by machine learning and false discovery rate estimation of the reported results. Although the DIA method has achieved rapid development in recent years, and has better performance than DDA in terms of depth coverage, there are still shortcomings and improvement in 3 aspects: in-depth analysis, accurate identification and accurate quantification. With the optimization of mass spectrometry acquisition and the development of data analysis, DIA acquisition technology can provide further support for high throughput, full-coverage analysis of proteomics, especially in large cohort data analysis, after further solving the above-mentioned shortcomings. All of them can obtain complete protein maps and explain their underlying life laws, promoting the development of the field of proteomics. In this paper, the DIA data collection method, data analysis method, software and identification result reliability assessment method are sorted and reviewed, and the future development direction is prospected.]]> 2022/12/20 0:00:00 HOU Xin-Hang,ZHOU Pi-Yu,GONG Peng-Yun,FU Jia-Le,LIU Chao and WANG Hai-Peng 437true 2022/10/21 0:00:00 ZHOU Xin-Yu,WEN Ya-Tong,QIAO Si-Yue and LI Yong-Hui 436true etc. for oncolytic therapy, and have been used in clinical and achieved good therapeutic effect. With the continuous development of oncolytic viruses, there are currently 4 oncolytic viruses approved for marketing: Rigvir?, Oncorine?, Imlygic? and Delytact?. Currently many viruses used in tumor treatment. Since the influenza virus were first discovered in the 1900s as a “beneficial” virus to alleviate leukemia, there have been studies that prove that influenza viruses have the ability to kill tumor cells. Researchers have made many attempts in the process of fighting influenza. The process of developing inactivated vaccines, live attenuated vaccines, and subunit recombinant influenza vaccines accumulated valuable experience for further building oncolytic viruses. Influenza viruses were one of the first viruses to be used in tumor treatment. With the development of molecular biology, it is now possible to artificially intervene in many of the traits of viruses. The mechanism of oncolytic influenza virus become more and more in-depth, and the current mode of action of oncolytic influenza virus can be summarized as the following 3 points: (1) the virus directly lyses tumor cells; (2) viruses activate immunity to kill tumor cells; (3) viruses expressing exogenous genes as vectors improves both of these abilities. In this review, the modified influenza virus has stronger selectivity for pancreatic enzymes secreted by tumor cells with interferon-deficient RAS mutations to improve tumor targeting. The single-chain antibody encoding CTLA-4 or HER-2 enhances the anticancer specificity of influenza virus and acts as the carrier of foreign genes IL-2, IL-15, GM-CSF and anti-PD-1 to activate immunity are reviewed.]]> 2022/10/21 0:00:00 LIANG Liang,TANG Lei,SHI Hua-Ran,FANG Zhong-Yue,Ou Xia,YANG Fan,ZHANG Ji-Hong and YANG Jing-Hui 435true 2022/10/21 0:00:00 YU Yu-Yang,HOU Kai-Long,TONG Jin-Kai,ZHANG Yan-Duo and JIA Shu-Ting 434true 2022/10/21 0:00:00 LIU Ying,XIONG Zhong-Hua,XIA Bin-Yuan and CHEN Shan 433true 2022/10/21 0:00:00 JIA Xiao-Li,HU Nan,WANG You-Wei and LI Xiao-Hong 432true in vitro transcription (IVT) mRNA, with promising potential for the treatment of malignant tumors. The outbreak of the COVID-19 pandemic in the early 21st century has greatly promoted the application of mRNA technologies in SARS-CoV-2 vaccines. Meanwhile, the research and development of the mRNA cancer vaccine has become a priority. A number of key technologies, including mRNA production strategies, delivery systems, anti-tumor immune strategies, etc., have made dramatic improvements and modifications. These technologies accelerated the research progress and clinical applications of mRNA therapy, thereby greatly overcoming the bottleneck problem, such as the instability, inefficient deliveries, and weak immunogenicity of the mRNA vaccines in the past. This review provides a detailed overview of the production, delivery systems, immunological mechanisms, and anti-tumor immune response strategies for mRNA cancer vaccines. We list some mRNA cancer vaccines that have been used as candidates for cancer treatment and the clinical trials in the field of tumor immunotherapy. In addition, we discuss about the immunological mechanism of the mRNA vaccines to destroy tumors, as well as the challenges and prospects for the future.]]> 2022/10/21 0:00:00 DENG Zhuo-Ya,TIAN Yu-Ying and YANG Peng-Hui 431true in vitro environments. It can also be used in the fields of skin wound regeneration, skin tumor, immune and metabolic diseases, treatment of inflammatory diseases and drug screening. Meanwhile, skin organoids can not only make up for the deficiencies of existing in vitro skin models in terms of structure and function, but also enable high-throughput screening of drugs or raw materials, reducing the time and economic costs in the later stages of drug screening. However, due to the limitations of current technology, the types and functions of organoids cannot be fully realized to realistically simulate the physiological conditions in the body such as lipid metabolism and blood circulation. Moreover, issues such as consistency and standardization of mass-produced organoids need to be addressed, such as source cells, structure and function, which require the establishment of appropriate standards based on practical applications. Based on this, this paper details the cell sources involved in skin organoids construction and their applications in recent years and several skin appendages like organs that have been constructed and provides an outlook on the future development and optimization of skin organoids.]]> 2022/10/21 0:00:00 WANG Min,ZHANG Lin-Feng,XU He-Ran,ZHANG Xiao-Na,HUA Jing-Lin,ZHANG Tian-Tian,ZHAO Feng-Nian and ZHU Zi-Ying 430true etc. The vast majority of type I toxin proteins target the cell membrane. One known mechanism of action is the formation of pores in the cell membrane, resulting in a decrease in membrane potential or destruction of the cell membrane, thereby inhibits the ATP synthesis or leads to the bacterial death; another possible mechanism of action is that the toxin proteins act on the cell membrane, changing the shape of the cell and causing it to enter a dormant state. The complexity of the type I toxin protein-membrane mechanism and the diversity of its biological functions are much more complex beyond our expectations. Therefore, it is important to analyze the assembly mechanism of type I toxin protein in different membranes and their structural characteristics, which is also the key to revealing its structure-function relationship. This article summarizes the reported structural characteristics and biological functions of the type I TA system, explores the formation of different structures in the cell membrane that affect its function combined with the prediction of its transmembrane domains, and analyzes the key factors affecting its mechanism of action. It brings opportunities for the treatment of drug-resistant bacteria, and also brings ideas for the research of new antibacterial drugs.]]> 2022/10/21 0:00:00 YU Ru,ZHAO Li-Ling,LI E-E,CHEN Ming-Cui,ZHAO Li,GUO Chen-Gang,YU Jia-Feng and CAO Zan-Xia 429true e.g. positive autoregulation motif, mutual inhibition motif) is bi-stability (or multi-stability). Based on our numeric simulation, the network motifs with feedback loops have different steady-state response characteristics although they all bi-stability (or multi-stability), which result in the different biological functions they can describe. Many studies also indicated that stochastic noise from internal or external could affect the number of stable-steady states and hysteresis of the network motifs with bi-stability (or multi-stability). Furthermore, the bi-stable network motifs have been used to model many biological processes, such as cell cycle and embryonic development, to reveal their mechanism. The network motifs are too simple to model complex biological processes, which generally involved in interactions between lots of biomolecules. Potential function, as a powerful tool in the field of dynamical system, is widely used to uncover the state transition properties of high-dimensional biomolecular networks. Many methods have been proposed to reconstruct the potential function of equilibrium systems and non-equilibrium systems based on network dynamics. Using these methods, a vast number of studies revealed the state transition mechanism of various biological processes, such as cell differentiation, cancer initiation, etc. The state of biomolecular network generally migrates from one stable steady state to another abruptly and drastically under the effect of resilience. However, detecting tipping points of state transitions in system level is impossible based on network dynamic, due to the complexity and nonlinearity of biomolecular networks. To fill this gap, many indicators have been proposed to predict the upcoming tipping points from biological data under network perspective, such as dynamic network biomarker (DNB). And these indicators were also used to detect the critical transitions in the development of various diseases (e.g., diabetes, influenza, cancer). So far, the study of biomolecular network resilience has been helped us to understand the mechanism of state transitions in many biological processes. However, there are still some important issues that have not been resolved. (1) Studying the resilience of large-scale biomolecular networks which consist of thousands of biomolecules; (2) reconstructing potential function of large-scale biomolecular networks based on biological data; (3) control biomolecular network resilience.]]> 2022/10/21 0:00:00 LI Yan and ZHANG Shao-Wu 428true 2023/8/14 11:13:35 CHEN Si,LIN Yu-Kun,SONG Chun-Yan,ZHI Shuai,LI Yi and YANG Dan-Ting 427true in vitro have been demonstrated. Therefore, the basic work flow, detection principle and characteristics of non-nucleic acid molecular diagnosis based on CRISPR/Cas molecular diagnosis sensor system are reviewed in this paper. It is expected to provide a basis for the application of CRISPR/Cas-based molecular diagnostic system in in vitro diagnosis.]]> 2023/8/14 11:13:50 LI Zhuo,ZHOU Jian,WANG Xin and XU Pu 426true e.g. Verubecestat, Semagacestat) or immunotherapies (e.g. AN1792, Crenezumab) in clinical trials have failed. There are many problems in the process of clinical trials. Firstly, AD animal models are diversified, but their applicability and practicability are still controversial. Secondly, the lack of convenient and effective biomarkers in the clinical diagnosis of AD that leads to unsatisfactory selection of the subjects. Thirdly, the investigational drugs have potential safety risks in patients and the treatment period is short. Therefore, the failure of clinical trials targeting Aβ suggests that the experimental design needs to be more rigorous and the role of Aβ in the disease needs to be reexamined. In addition, other factors including Tau hyperphosphorylation, neuroinflammation, oxidative stress together with Aβ participate in the progression of AD, meaning the amyloid cascade hypothesis may be no longer sufficient to comprehensively summarize the symptoms and pathogenesis of AD, hence the combination of multiple factors influence the pathogenesis of AD should be pay more attention. This article reviews the formulation and development of amyloid cascade hypothesis, the role of Aβ in AD progression and the therapeutic effect of the treatment targeting Aβ. We are hoping to provide a comprehensive overview of Aβ for understanding the pathological mechanism of AD, which may be useful in diagnosing and treating AD.]]> 2023/8/14 11:13:52 XIAO Biao,CHU Chao-Yang,SHAN Jiang-Hui,WANG Qing-Juan,SHEN Wei,XIE Kai and LI Li-Ping 425true 2023/8/14 11:14:03 LI Xi,WANG Miao and ZHOU Fei-Fan 424true Mycobacterium tuberculosis (Mtb), which can enter the body and invade body organs via respiratory infection, and is a major threat to global public health. Early-time diagnosis and effective treatment are indispensable for TB control. However, limited by poor specificity, low sensitivity, long culture cycle and high requirements for laboratory equipment, current clinical TB diagnostics usually result in low diagnostic efficiency, misdiagnosis and missed diagnosis. On the other hand, poor therapeutic effect of clinical TB treatments is induced by the appearance of Mtb drug resistance (induced by irregular drug supply, poor patient treatment compliance, and improper medication regimens) and low-efficiency anti-TB drug bioavailability (caused by physiological barriers including host cell shielding, granuloma block and biofilm construction). Drug resistance, poor therapeutic effect and poor patient compliance characterize traditional TB treatment strategies, which accelerate the global spread of TB. Hence, rapid, accurate TB point-of-care (POC) diagnosis, and safe, efficient TB treatment methods are urgently needed to control the global TB pandemic. In this review, we summaries that compared with the current diagnostic technologies, nano-diagnostic technologies show great advantages in high sensitivity, specificity and rapid detection, which can superiorly meet with diagnostic needs such as clinical treatment or home monitoring. We also highlight that nanoparticle systems can significantly enhance the bioavailability and targeting of anti-TB drugs. The nanoparticles can help reduce drug administration frequency and toxic side effects, overcoming the limitations of conventional TB therapies. Nanotechnology-based TB diagnosis and anti-TB treatments are still limited by large-scale production, biocompatibility, cost-effectiveness, reproducibility, etc., making it difficult for comprehensive clinical use shortly. Finally, we outline the potential future directions to achieve breakthrough developments. Multidisciplinary interdisciplinary convergence and intensified combination of nanotechnology, medicine, and engineering is the key solution for future TB care development.]]> 2023/8/14 11:14:03 DAI Gui-Qin,HE Zhuo-Jun,LIU De-Liang,ZHAO Peng-Fei,LIAO Ming-Feng,SONG Li-Jun,YANG Qian-Ting,ZHAO Wen-Chang and Zheng Ming-Bin 423true S. aureus, which can cause diseases such as inflammation and food poisoning. SEs possess superantigen activity and can form ternary complexes with the variable region of T-cell receptor (TCR) and MHC class II molecule, i.e., TCR-SEs-MHC class II molecule, which could directly stimulate up to 30% of T lymphocytes to produce a large numbers of cytokines such as tumor necrosis factor-α (TNF-α), interleukin 2 (IL-2), IL-6, and interferon γ (IFN-γ), resulting in toxic shock syndrome (TSS). Among the common SEs, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) are the most studied due to higher toxicity and frequency in reported incidents. Specially, about 70% of S. aureus food poisoning are caused by SEA, while, SEB was listed as an offensive biological warfare agent in 1960s. At present, there are few comprehensive review paper on treatment strategies for SEs poisoning. Hence, the review firstly introduces the classification, structure, and toxic effects of SEs, and then the ternary complexes of TCR-SEs-MHC class II molecular interaction sites are analyzed focusing on SEA and SEB. Furthermore, we summarize the recent advance in the filed of active and passive immunotherapy for SEs poisoning around SEA and SEB. We highlight the state of art and new developments on active immunotherapy mainly includes attenuated vaccine, subunit vaccine and other vaccines and passive immunotherapy that is mainly based on monoclonal antibody and genetic engineering antibody. Finally, we discuss and prospect the current limitations and future development of immunotherapy for SEs including synthetic peptide vaccine, single cell technology and nanobody isolation.]]> 2023/8/14 11:14:07 LI Qing,DOU Lei-Na,WEN Kai,YU Xue-Zhi,YU Wen-Bo,SHEN Jian-Zhong and WANG Zhan-Hui 422true 2023/8/14 11:14:09 DUAN Yu,YAO Ren-Qi,DAI Xin-Gui and YAO Yong-Ming 421true 2023/8/14 11:14:11 YUN Zhi-Qiang,YAO Ting-Ting,LI Tao and YI Xue-Jie 420true via local or vascular injections. The exogenous mitochondria may fuse with endogenous mitochondria or replace damaged mitochondria DNA after entering the cell by actin internalization. Tissue dissociation and differential filtration is an innovation from McCully’s team, it can separate 2×10¹⁰ high-purity functional mitochondria from 0.18 g fresh tissue in less than 30 min. Up to date, the treatment outcomes of MT on heart, brain, kidney, lung and liver acute I/RI have already been more explored. However, there are still many challenges in the clinical application of MT. First of all, there is no standardized transplantation procedure to confirm details, such as dose, mode and time. Secondly, the exact mechanism on MT’s positive action is unclear. Last but not least, further studies on the safety of MT are still needed. This article reviews the role of MT in I/RI treatment and related mechanisms over the past 10 years.]]> 2023/8/14 11:14:13 ZHU Lin,NIU Qi-Fang,RUAN Han-Jin,MAO Ming-Hui and HAN Zheng-Xue 419true etc. Through stable isotope analysis of multiple elements (C, N, O, H, S) in various body tissues (such as hair, nails, teeth and bones), the birthplace, living areas and eating habits of individuals can be inferred, which could provide important clues for the confirmation of individual identity. The principle of stable isotope technology is briefly introduced, the types of elements used for individual provenance and the information characteristics contained in stable isotopes in different human tissues are systematically expounded, the current research and application is summarized, the existing problems are analyzed and the future development of stable isotope technology in individual provenance is prospected in this paper.]]> 2023/8/14 11:14:15 QIN Hao,YU Zi-Yang,HUANG Yang,HU Can,Zhu Xiao-Han,Xie Wei-Ya,Guo Hong-Ling,Wang Ping,LI Ya-Jun,Zheng Ji-Li,ZHU Jun and MEI Hong-Cheng 418true +T cells to become cytotoxic T cell lymphocytes (CTLs). As a result, CTLs kill primary tumors as well as non-irradiated tumor metastases. However, the mechanism of the AE induced by RT is extremely complicated, and there are fewer studies on the roles of macrophages, p53, and exosomes in radiation-induced AE. In addition, compared with conventional RT, carbon ions beam has the advantages of high linear energy transfer (LET), high relative biological effectiveness (RBE), low oxygen enhancement ratio (OER), complex DNA damage, and the potential to activate stronger immunogenicity of tumor cells. Moreover, the mechanism of the AE induced by carbon ions radiotherapy (CIRT) is unclear. This article summarizes the complex molecular mechanisms of AE induced by conventional RT and CIRT, and elucidates the difference between the two radiation types. We found CIRT may lead to increased DAMPs released from irradiated tumor cells, and enhance the inhibition of tumor cell metastasis compared with conventional RT. We therefore propose that CIRT can induce a stronger AE than conventional RT. This article provides a theoretical basis for finding more effective radiotherapeutic approaches in the future.]]> 2023/8/14 11:14:17 GAO Yu-Ting,LI Yuan and JIN Xiao-Dong 417true i.e., the neural representations of prediction when the stimulus was omission, and prediction-related neural oscillation patterns. Furthermore, this review presented major neurophysiological evidence and neural structures that support the hierarchical structure. Finally, the development of the predictive coding related research is prospected from the aspects of deepening theoretical research, helping disease diagnosis and treatment, and inspiring the brain-computer interface technology. It is believed that a deeper comprehension of the computational model and neural representations of prediction coding in visual and auditory neural activity would offer up new perspectives on how perceptual neural activity in the brain functions.]]> 2023/7/19 12:03:06 MENG Jia-Yuan,YAO Wang,MENG Qiang-Fan,LI Xiao-Yu,WANG Hao,XU Min-Peng and MING Dong 416true etc. Both “appearance” and “disappearance” are changes in topological features. The presence of topological perception and subcortical pathways may be the neural basis for early warning. In primates, the peripheral area of retina is distributed mainly with rod cells, the visual information processing in this area is mainly processed by subcortical visual pathway, this type of retinal structure appeared in more than one hundred million years ago. The area close to the center of the retina is the fovea, the visual information processing in this area is mainly processed by visual cortex, cone cell density increased greatly, the visual spatial resolution becomes very high. This structure emerged only 50 million years ago, so our eyes span at least 50 million years from the peripheral region to the central region. It is a Mosaic of an older structure and a younger one, and their coexistence gives us perfect vision. When we consider the significance of the existence of subcortical visual pathway, we should also consider the function of cortical pathways.]]> 2023/7/19 12:03:09 YU Zhao-Qian,ZHAO Xu-Dong,YANG Li-Chuan,MENG Qian-Li and QI Ren-Li 415true etc. However, its internal mechanism is not fully known. Several studies suggested that lipid metabolism in liver, adipose tissue, intestinal tract, and skeletal muscle may contribute to the difference between DIO and DR. Additionally, the changes of gastrointestinal hormone secretion and intestinal inflammation would cause these two phenotypes. Moreover, there was a significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice, which may play an important role in the development of the obese phenotype. The gut-brain axis made the contributions to the control of food intake and obesity. And the hypothalamic-pituitary-thyroid (HPT) axis function and deiodinases activity might be involved in different propensities to obesity. Difference of NPY/AGRP, POMC/CART and their receptor gene expressions in hypothalamic arcuate nucleus was also the basis of the difference between the two phenotypes. But all these changes of physiology are strongly related to genetic mutations and genotype.]]> 2023/7/19 12:03:10 QIN Lian,LI Liang-Ming,LIU Shu-Jing,WANG Xin-Zhuang,ZHU Guang-Ming,YANG Jia-Pei and YANG Gui-Rong 414true via targeting mRNA or protein. While lncRNA and circRNA play diverse roles in the regulation of mitochondrial structure and function by ncRNA-miRNA-mRNA triple networks, which provide us more perspective to understand the explicit role of ncRNA in mitochondria and heart pathophysiology. However, only a little ncRNA encoded by mitochondrial genome have been confirmed in the process of heart failure. Besides, it is still unclear that how does the ncRNA encoded by nuclear genome transport to mitochondria and vice versa. Moreover, recent studies discovered many other mitochondria encoded ncRNA, such as piRNA and small ncRNA shorter than 200 nucleotides derived from tRNA, rRNA or lncRNA, play important roles in many diseases. It has a broad prospect in investigating the various roles of mitochondria encoded ncRNA. Therefore, this work aims to provide some new ideas and targets for the clinical research and therapy for heart failure via reviewing the newly recent researches about the regulation mechanism of new ncRNAs on mitochondria function in the process of heart failure.]]> 2023/7/19 12:03:12 WANG Shuo and ZHAO Yun-Gang 413true 2023/7/19 12:03:13 YANG Yan,GAN Ni-Cui,PENG Ning-Xin,ZHANG Lan-Xuan,ZHANG Ji-Hong and LI Jin-Yuan 412true 2023/7/19 12:03:14 SHANG Jing,HU Xin,ZHAO Rui-Nan,QI Qi,GONG Xue,XUAN Yang,QUAN Chun-Shan and ZHANG Yan-Mei 411true 2023/7/19 12:03:16 ZENG Bin,LIANG YU-Jie,DENG Zhi-Qin,SU Ai-Yuan and DUAN Li 410true LD₅₀), it can treat a variety of medical diseases, including heroin and cocaine withdrawal symptoms, spinal cord injury, traumatic brain injury, tumor, neuropathic pain, and visceral pain. Cancer pain is generally treated with opioids, but it has certain dependence and addiction. After decades of unremitting exploration, researchers have made gratifying progress in the application of TTX in the field of biomedicine, especially in the treatment of cancer-related pain. Here we first review voltage-gated sodium channels (VGSCs), which are transmembrane proteins composed of a large α subunit and one or more β subunits. VGSCs play an important role in pain and are typically classified as TTX-sensitive or TTX-resistant channels. Furthermore, we focus on roles of three VGSC subtypes Nav1.7, Nav1.8 and Nav1.9, and present the current status of research progress in the field of cancer-related pain. We also discuss the binding sites, tolerability, delivery and supply of TTX. Finally, we summarize the most relevant recent advances in the clinical development, efficacy and safety of TTX as a drug for relieving cancer pain, showing the promise of TTX in cancer pain relief. On this basis, the limitations of existing research are pointed out, and the research directions of TTX in relieving cancer pain and the development of targeted analgesic drugs in the future are prospected.]]> 2023/7/19 12:03:17 ZHANG Meng-Qian,CHU Zhi-Yong,QIAN Xiao-Ming,WANG Zi-Han,LIU De-Xiang and LONG Cheng 409true 2023/7/19 12:03:18 YANG Yang,ZHANG Yi-Yin,Lü Hong-Yan,CAO Shi-Cheng,YAO Ting-Ting and YI Xue-Jie 408true 2023/7/19 12:03:20 WU Ya-Han,WU Jing-Jing and WU Fan-Hong 407true 2023/7/19 12:03:22 ZHANG Cai-Da,QI Yong-Hao,MI Ya-Xuan,ZHANG Yun-Zhi,QIN Hao-Jie,LIU Dong,LI Xiao-Bing and REN Li-Mei 406true 2023/7/19 12:03:23 YUAN Lin,LU Dong-Xiao and LI Jin-Hua 405true 2023/7/19 12:03:25 WANG Meng,LI Xiao-Qin and GAO Bin 404true 2023/6/20 16:48:57 XING Chen,MA Jing-Chao,YUN Han-Qi,LIU Qing-Jing,CHANG Xiao-Yue,WANG Yan-Qing and ZHOU Wen 403true 2023/6/20 16:49:05 ZHENG Si-Rui,LIAO Jian-Hong,CHEN Ze,PAN Hong,HUANG Zun-Nan,ZHENG Ming-Bin and CAI Lin-Tao 402true via enhanced permeability and retention effect (EPR) and are internalized into tumor cells by endocytosis or pinocytosis. Subsequently, liposomes are intracellularly cleaved to release drugs, thereby killing tumor cells. Liposomes that rely on the EPR effect are called passive targeting liposomes, which lack the ability to specifically recognize target tissues. However, active targeting liposomes can achieve targeting delivery via the specific binding between the targeting modifiers on the surface of liposomes and receptors on the surface of tumor cells. These receptors such as peptides, carbohydrates, ligands, antibodies and nucleic acid aptamers on the surface of tumor cells overexpress due to rapid growth of tumor cells and needs of nutrients and related growth factors. Thus, liposomes can be reasonably designed according to these specific receptors. Recent years, some studies have reported biomimetic liposomes by coating the cell membrane on the surface of liposomes, however, the research on biomimetic liposomes is still in its infancy, and there are still many problems to be solved. Additionally, since the length is limited, biomimetic liposomes are not reviewed in this paper. Taken together, liposomes as potential drug carriers, not only protect drugs, but also reduce side effects, importantly, they can precisely target tumor tissues through introducing targeting modifiers. In this work, we review the improvement of targeting function of liposome by five targeting modifiers including peptides, carbohydrates, ligands, antibodies and nucleic acid aptamers, and summarize the existing advantages and challenges of various targeted modifications. Finally, this review is expected to provide scientific reference for the LPs drug delivery system study and theoretical basis for the drug development.]]> 2023/6/20 16:49:12 DU Sang,CUI Shao-Hui,CHEN Xing-Yan and ZHANG Shu-Biao 401true 2023/6/20 16:49:15 ZHAO Qiao-Ya,CHANG Heng-Rui and CHANG Yan-Zhong 400true 2023/6/20 16:49:18 ZOU Jian-Wen,JIN Bao-Ling,CHEN Qi-Cai and FU Zi-Ying 399true 2023/6/20 16:49:20 TAN Hao-Lan,HE Hong,GONG Li,GE Chuang and XU Yi 398true 2023/6/20 16:49:26 HE Yong-Fei,PANG Yi-Quan,GE Chuang and XU Yi 397true etc.) to achieve varied stimulation effects. NIBS can alter cortical excitability and modulate neuroplasticity in the targeted region or other brain regions connected to the targeted region. When NIBS is applied to memory related brain areas, it may disrupt or alter memory-related neural circuit activity thereby changing memory related emotion or behavioral performance. In this review, we summarize recent studies using NIBS (transcranial magnetic stimulation, TMS, and transcranial direct current stimulation, tDCS, mainly) interventions for trauma- or substance-use-related memory during memory reconsolidation, along with theoretical basis from brain imaging or preclinical evidence from rodent studies. There are two basic ideas for NIBS interventions in maladaptive memories, to enhance activity in extinction-related neural circuit by TMS or tDCS, or to suppress activity in brain areas related to maladaptive emotional or motivational processing during memory reconsolidation. Both ideas got supporting results from research in the laboratory, while there has been no convincing evidence from clinical application yet. This review summarizes research evidence about the application of NIBS in fear and addiction memory intervention and hopes to contribute to breed insights for the development of NIBS treatment for memory-related psychiatric disorders targeting reconsolidation process.]]> 2023/6/20 16:49:29 ZENG Yuan,LI Yong-Hui,SHEN Xun-Bing and DONG Xin-Wen 396true e.g., microglia and astrocytes), and activating or inhibiting downstream intracellular signaling pathways, including p38MAPK, AMPK, ERK, JAK2/STAT3, PI3K/AKT, and SIRT1/PGC-1α, etc., and subsequently regulate cognitive function. Importantly, APN and LEP may also act as key mediators in the improvement of diabetic cognitive dysfunction by physical exercise. This study aimed to open up ideas for further enriching the theoretical system of “fat-brain” crosstalk, and developing and refining the diagnosis and treatment strategies of diabetic cognitive dysfunction through analyzing the relationship between APN or LEP and diabetic cognitive dysfunction, sorting out the underlying biological mechanism of APN and LEP regulating cognitive function, and exploring the possible mechanism of exercise-mediated APN and LEP in improving diabetic cognitive dysfunction.]]> 2023/6/20 16:49:30 ZONG Bo-Yi,LI Lin,LI Shi-Chang and SUN Peng 395true in vivo, and which molecular mechanisms are responsible for responding to mechanical signals. The research in this field will provide important reference for understanding the neurological diseases and nerve regeneration.]]> 2023/6/20 16:49:40 SUN Yan-Li,ZHAO Hu-Cheng and FENG Xi-Qiao 394true 2023/6/20 16:49:41 LI Jing-Wei,YANG Hao-Yu,HU Li and Lü Xue-Jing 393true + and heat gating. Studies have shown that there are common processes of the three gating mechanisms, but no way to affect a single gating mechanism. From the angles of physiological function, gating mechanism and drug discovery, this paper reviews the distribution and expression, functions and features as well as structural characteristics of TRPV1 channel. This paper focuses on three gating mechanisms and the progress of TRPV1 modulators in drug discovery. TRPV1 modulators are a exceptional analgesia drug, and have been studied in cardiovascular diseases, itch, cough, psychiatric disorders and diabetes. With the emerging of artificial intelligence (AI)-assisted drug design and the continuous exploration of gating mechanism, we should have confidence in the future of TRPV1 modulators.]]> 2023/3/22 0:00:00 WEI Xin-Miao,YANG Qi-Fan,TIAN Jia-Hao,YANG Hang,PAN Li and DING Jun-Jie 392true 43℃) and H⁺ (pH<6.0). TRPV1 is highly permeable to Ca²⁺. Previous studies found that TRPV1 mainly distributes in nervous system and mediates pruritus and pain response. Recent studies have shown that TRPV1 also widely distributes in non-nervous cells such as mast cells, bladder epithelial cells, monocytes, skin keratinized epithelial cells, islet cells and so on. TRPV1 has a wide range of functions and can mediate beneficial or harmful biological effects on the body. In the nervous system, TRPV1 related signal pathway mainly mediates itching and pain response. Relevant studies in pancreatic cells have shown that the upregulation of TRPV1 can alleviate the process of diabetes, but studies in pulmonary epithelial cells, pulmonary vascular endothelial cells, bronchial smooth muscle cells, etc. have shown that the upregulation of TRPV1 can accelerate the development of respiratory diseases. In addition, TRPV1 has dual effects of promotion or inhibition on the disease progression in cardiovascular system, digestive system and skin system. In cancer research, it was also found that the upregulation of TRPV1 played an important antineoplastic effect, which could inhibit the proliferation, invasion and migration of tumor cells in human tongue squamous cell carcinoma, prostate cancer, breast cancer and so on, arrest the cell cycle and induce cell apoptosis. At present, many studies have been carried out on the mechanism of TRPV1, among which the mechanism of TRPV1 mediating itching and pain is relatively in depth. TRPV1 has become a promising therapeutic target due to its extensive functions. New drugs targeted to TRPV1 have been developed to ameliorate diabetes, cardiovascular diseases, and some kinds of cancers. This paper introduces the latest progress in the distribution, structural characteristics and functions of TRPV1, and focuses on the research progress of pruritus and pain related signaling pathways mediated by TRPV1. We also introduced the Chinese herbal medicine with TRPV1 as the target, looking forward to providing theoretical guidance for taking TRPV1 as a potential therapeutic target by combination of traditional Chinese medicine and modern medicine.]]> 2023/3/22 0:00:00 LIU Xia-Yang,LI Zhuang,ZHOU Xin-Yue and GUO Xiao-Hong 391true via reverse cholesterol transport (RCT), which is thought to be the basis of HDL’s anti-atherogenic properties. The inverse association between high-density lipoprotein-cholesterol (HDL-C) level and the risk of clinical events resulting from atherosclerosis is widely accepted. Therefore, targeting HDL therapeutically presents an attractive strategy for treating atherosclerotic cardiovascular disease. However, multiple epidemiological evidences have demonstrated that raising HDL-C does not certainly confer a clinical benefit. The cholesterol content of HDL may provide limited information on their antiatherogenic properties and the composition and particles’ structure provide more information on their functionality. HDL particles are, however, highly heterogeneous in structure and intravascular metabolism. Many critical proteins and enzymes have been discovered to regulate the levels, composition and structure of HDL. This paper mainly reviews the effects of various molecules on HDL metabolism and remodeling processes, as well as the research progress of related drugs targeting the above processes. Based on the relationship between HDL and RCT, we reviewed four aspects of AS therapeutic strategies for HDL modulation: (1) promoting cholesterol efflux from peripheral cells; (2) enhancing HDL esterification; (3) influencing HDL remodeling; (4) affecting hepatic uptake and intestinal excretion of HDL, which may provide a theoretical reference for a more comprehensive evaluation of the anti-atherogenic effects of HDL.]]> 2023/3/22 0:00:00 ZHANG Ya-Ling,ZHENG Gui-Qiong,LUO Shi-Yu,GAO Yi and SUN Shao-Wei 390true 2023/3/22 0:00:00 TIAN Xiao-Mao,XIANG Bin,LIU Feng and WEI Guang-Hui 389true etc. WM plays a key role in many complex cognitive processes, thus to understand how it may be affected by low-dose ketamine is informative and important for its clinic use. Here we review the studies showing that acute or chronic use of low-dose ketamine will impair working memory in a sophisticated way. The possible mechanisms underlying such impairments include breaking the excitation/inhibition (E/I) balance in the PFC, changing the short-term and long-term synaptic plasticity, activating the DA pathway, etc. We also pointed out that to fully reveal the effects of low-dose ketamine on WM and related neural mechanism, future multi-facet studies combining behavioral tests, electrophysiology, neuroimaging, histology, etc, and with more comparable dosage and time of medication would be needed. We hope that this review will be instrumental for facilitating appropriate use of low-dose ketamine in clinical settings.]]> 2023/3/22 0:00:00 ZHAO Zhi-Ping, NIE Chuang, JIANG Cheng-Teng, LUO Wei-Wei, GU Jian-Wen, YU Shan 388true 1-32, BNP_1-30, BNP_3-32 and pro-B-type natriuretic peptide (proBNP). Accurate detection of BNPs will help us understand the deeper pathophysiological mechanisms of heart failure, and make precise clinical decision on the diagnosis and treatment.]]> 2023/3/22 0:00:00 YU Yi-Pin,TAN Duo-Ting,YANG Liu,ZHONG Li-Qin,SHENG Dan,HUANG Ru-Jia,HU Zhi-Xi and LIANG Hao 387true 2023/3/22 0:00:00 LI Qiong,WANG Fu-Yan,ZHANG Xiao-Qin,YU Zhi-Peng,TANG Zi-Hang and SHEN Hao-Wei 386true in situ hybridization (ExFISH) and Click-ExM can achieve super-resolution imaging in nonprotein biomolecules, such as RNA, lipids, and polysaccharides. Expansion pathology (ExPath) can be used for clinicopathologic specimens imaging. The combination of ExM and light-sheet microscope can improve the image resolution to super-resolution level in the deep imaging depth. The application of ExM in super-resolution microscopy can further increase the resolution of images to 10-30 nm. In this paper, we reviewed the basic principles of ExM and its derivative technology, the research progress of combining ExM with different imaging technologies, the application progress of ExM in observing different types of biological samples, and the prospective of spreading ExM technology in the future.]]> 2023/3/22 0:00:00 YANG Zhen-Yu,GUAN Miao and SUN Zheng-Long 385true in vitro living cells and in vivo living cells have become very important. However, the structure of many organelles in living cells are at the nanoscale. Traditional optical imaging techniques cannot observe nanoscale biological structures due to the limitation of the optical diffraction limit. Therefore, optical super-resolution imaging technology is an effective tool to study the structure and function of subcellular organelles. Among all optical super-resolution microscopy techniques, stimulated emission depletion (STED) super-resolution imaging technology has the capabilities of real-time, three-dimensional super-resolution and tomographic imaging. Therefore, the STED is very suitable for nanoscale live cell and vivo imaging studies. Moreover, STED super-resolution imaging technology has been widely used for super-resolution dynamic observation of living cells and even living mouse cells after decades of development. This paper summarized the research progress of STED super-resolution imaging in the fields of in vitro living cells and in vivo mouse neurons in recent years, and introduces the development status of fluorescent dyes and fluorescent proteins for STED super-resolution imaging of in vitro and in vivo living cells. In vivo cells super-resolution imaging is very meaningful for understanding the nature of cells, but it has been more than 20 years since the STED super-resolution imaging technology was proposed to the present, and there are still very few literatures on in vivo cells super-resolution imaging. The main problem is that very few probes are available for in vivo cells super-resolution imaging. At the same time, the depth of in vivo cells super-resolution imaging is also very limited, mainly due to the lack of fluorescent probes in the infrared band. Finally, the future application prospects of in vivo cells super-resolution imaging are prospected.]]> 2023/3/22 0:00:00 ZHOU Han-Qiu,ZHU Yin-Ru,HAN Hong-Yi,WANG Lu-Wei,YANG Zhi-Gang,YAN Wei and QU Jun-Le 384true 3H₆O₃), also known as 2-hydroxypropionic acid, propanoic acid, is a type of hydroxy acid. It is an essential metabolite of human and microbial cells. In diagnosis and medical management, determination of lactate level in serum is greatly required, and it is also important to measure lactate in fermentative foods to access their quality. Therefore, how to detect lactic acid in different samples with high throughput has become the focus of different researches. The traditional lactic acid detection methods are complicated, time-consuming and laborious, or requires expensive detection equipments. However, the electrochemical enzymatic L-lactate biosensors combining the robustness of electrochemical techniques with the specificity of biological recognition processes showed great advantages over the conventional analytical techniques in size, cost, sensitivity, selectivity, response speed and sample pre-treatment, which show a broad application prospects. There are two main types of lactate biosensors based on L-lactate oxidase (L-LOD) and L-lactate dehydrogenase (L-LDH). Designing a successful enzyme-based L-lactate biosensor requires assembling the enzyme onto a solid carrier and selecting an appropriate transduction strategy between the enzyme and the electrode. Due to the restriction of enzyme molecular structures, reaction mechanism and electrode materials, the traditional lactate biosensors have some limitations in sensitivity, selectivity and stability. Therefore, an increased research was performed to improve the performance of lactate sensors according to the characteristic of the enzymes and the electron transfer type. In this paper, we provide an overview of the structural characteristics, origin and catalytic mechanism of L-LOD and L-LDH, and discuss three strategies, including electrode material modification, enzyme immobilization and enzyme engineering modification, to improve the performance of enzyme electrode based lactate biosensors. In addition, the lactate biosensors were compared and analyzed on the basis of different carriers including membrane, transparent gel matrix, hydrogel carrier, nano-particles, etc. Finally, we comprehensively described the merits and demerits of current commercial lactate sensors and preconceive how emerging new technologies may benefit to future lactate biosensor design.]]> 2023/3/22 0:00:00 CHEN Yan-Ru,GONG Wei-Li,MA Yao-Hong,WANG Bing-Lian,ZHANG Zhen-Yu,MENG Qing-Jun,YANG Yan,YANG Jun-Hui,LIU Qing-Ai and ZHENG Lan 383true 2023/3/22 0:00:00 LAI Xin-Yi,WANG Jing-Nan,HU Xiao,LIN Wan-Zhen,XU Hui-Feng and YU Li-Shuang 382true 2) nanomaterials have been widely used in biosensors due to their unique properties such as large specific surface area, adjustable band gap and high electron mobility. This paper introduces electrochemical, field effect transistor (FET), surface-enhanced Raman scattering (SERS), colorimetric method and dual-mode biosensor based on MoS₂ nanomaterials. Among them, MoS₂ electrochemical biosensor uses the redox reaction between target and biological probe to analyze the concentration of target. It has the advantages of high sensitivity, fast response speed and simple operation, but its experimental cost is high, so low-cost experimental methods need to be developed in the future. When MoS₂ acts on FET, it is used as the channel material to contact the analyte, and the gate applies bias voltage to realize the current change. It is small in size and high in sensitivity, but there are few reports on the detection of biomolecules in actual human samples. Therefore, it is necessary to focus on solving the problem of compatibility between sensor and biological solution in the future. MoS₂ nanocomposite SERS biosensor can be combined with chemical enhancement and electromagnetic enhancement to achieve singlemolecule detection. Its sample consumption is small and no special treatment is required, but the large-scale optical analysis system of its detection process is complex and expensive. Therefore, the simplification of optical analysis equipment and detection system is a problem to be further studied. MoS₂ nanocomposite colorimetric biosensor utilizes its peroxidase activity to catalyze the color change of the chromogenic substrate. It has the advantages of easy operation and low cost, but its sensitivity is not high and the reaction time is long. Therefore, in the future, it is necessary to find high-performance MoS₂ nanomaterials to achieve fast and highly sensitive detection. MoS₂ nanocomposite dual-mode biosensor is based on one material to form two detection signals, combining two analytical methods for substance detection, with strong specificity and high accuracy. At present, how to extract a variety of information and apply it to dual-mode detection is still the focus of research, and the integration of detection instruments in dual-mode sensing will also be the trend of future development. Based on the analysis and conclusion of this paper, which provides ideas for the further application and future research directions of MoS₂ biosensors in the field of biological detection.]]> 2023/2/22 0:00:00 FANG Wen-Hui,ZHANG Yu,ZHAI Ying-Jiao,LI Jin-Hua and XU Ming-Ze 381true 2023/2/22 0:00:00 LIANG Yu,CHEN Tian-Qi,LI Kai,FAN Li and LI Liang 380true 2023/2/22 0:00:00 CHEN Tian-Qi,LIANG Yu,FAN Li,LI Kai and LI Liang 379true 2023/2/22 0:00:00 FANG Zhong-Yue,LIANG Liang,Lü Wei-Min,ZHANG Lan-Qing,YANG Fan,ZHANG Ji-Hong and OU Xia 378true Saccharomyces cerevisiae (S. cerevisiae) is a classic model organism for eukaryotic genome synthesis and transfer in the context of synthetic biology. However, the molecular mechanism underlying the yeast cell fusion remains to be fully understood, thereby limiting its synthetic biology application. In S. cerevisiae, mating initiates when cells respond to pheromones that trigger MAPK (mitogen-activated protein kinase) cascade, following with polarization, cell wall remodeling, membrane fusion, and karyogamy. This review discusses the current state of knowledge and progress regarding cell fusion in S. cerevisiae as well as the proteins involved in these events. Especially, the study of the possible “fusase” Prm1 provides a direction for promoting the manipulation of cell fusion. We further propose a hypothesis about the intracellular transport and maturation process of Prm1, which reasonably explains the regulation mechanism of site-directed aggregation of Prm1 at the plasma membrane. Notably, this review stresses the synthetic biology applications of yeast mating signaling pathway in biological components, biological devices and systems, and multicellular interactions. Such elements, including pheromone-responsive promoters, G protein-coupled receptors, scaffold proteins, transcription factors, bistable switches, tuners and chassis cells. Together they contribute to the applications of biosensors and metabolic engineering. Strategies such as rationally engineering of modular circuits and optimizing the reproductive pathway will promote the maneuverability of cell fusion. Moreover, many innovative synthetic biology tools, such as microfluidics, omics research, genome editing, and machine learning, allow researchers to examine the complex physiological activities and improve fusion efficiency. Our study lays foundation for the study of cell-fate decision system and the application of yeast cell fusion in the large genome transfer.]]> 2023/2/22 0:00:00 ZHANG Yi-Qing,WANG Yu-Jiao,WANG Chen-Yu,LIU Ying,ZHONG Sen-Lin,WU Hui-Lan and LIU Guan-Nan 377true 2023/2/22 0:00:00 SHI Xiao-Dong,ZHAO Han and LIU Dong-Shan 376true via its specific receptor serum stimulation-2 (ST2), thereby regulating the host immune response and playing key roles in the pathogenesis of occurrence and progression of various diseases. The immune regulation of DC by IL-33 mainly involves signal pathways, such as NF-κB, p38 MAPK, and STAT1/3, in turn mediating the maturation, differentiation, and inflammatory response of DC. In addition, DC is an important source of the secretion of IL-33, which enhances the immune reaction and Th2 response through a positive feedback amplification loop. IL-33 activated DCs can promote tumor immunity and resist pathogen invasion, and also participate in the development of autoimmune and inflammatory diseases. This paper reviews the potential role and underlying mechanism of IL-33 in regulating DC immune response in order to provide a foundation for further research into its immune function and modulatory pathway in diseases.]]> 2023/2/22 0:00:00 HE Peng-Yi,ZHENG Li-Yu,ZHU Xiao-Mei and YAO Yong-Ming 375true Arabidopsis and rice, the studies on maize miRNAs are still relatively limited. The understanding of functions and regulatory mechanisms of miRNAs in maize is essential for engineering important agronomic traits genetically through molecular breeding. In this article, we review the discovery and identification of maize miRNAs, most of which are tissue-specific and spatiotemporally expressed. Up to now, a total of 325 mature miRNAs from 174 precursors were identified in maize genome, belonging to 29 miRNA families. We also systematically summarize the functions of key components in maize miRNA biogenesis pathways, including DCL, AGO and HEN1. Mutations in these miRNA processing proteins result in pleiotropic developmental phenotypes, suggesting the important regulatory roles for miRNAs in maize development. MiRNAs whose functions have been characterized in maize growth and development are discussed, including those involved in root formation, leaf morphogenesis, grain maturation and reproductive development. Furthermore, function of miRNAs in responses to abiotic stresses, such as salt stress, drought stress, temperature stress and nutrition stress are elaborated, with the highlight on miR169-NF-YA, miR399-PHO2, and miR528-LAC3 regulatory modules. We also discuss the current existed issues and future perspectives in maize miRNA study. Despite the identification of a large number of maize miRNAs, research on the functions and regulatory mechanisms of miRNAs in maize is still very limited, and it is still required to generate essential genetic materials and take advantage of multiple experimental strategies to perform in-depth and systematic studies on miRNA and their target genes. It is believed that miRNAs are valuable gene resources and a better understanding of miRNA-mediated regulatory network would be beneficial for engineering maize varieties with improved agronomic traits.]]> 2023/2/22 0:00:00 PAN Jin-Kang,LI Jing and LIU Lin 374true via bioactive molecules, such as microRNA (miRNA), proteins or lipids. It has been reported that EXs is a tool for the communication of miRNA and target cells due to its highly stability, lowly toxicity and immunogenicity and specifically targets. Current studies have found that EXs derived from different cells play different roles in diabetes complications. EXs miRNA can mediate renal tubular cell oxidative stress, pyroptosis and differentiation, and inhibit podocyte migration and apoptosis in diabetic kidney disease; EXs miRNA in diabetic retinopathy can inhibit endothelial cell growth, metastasis and angiogenesis, and inhibit retinal vascular inflammation and apoptosis; EXs miRNAs can regulate dorsal root ganglion neuron growth and inhibit neurovascular inflammation in diabetic peripheral neuropathy; EXs miRNAs in diabetic cardiomyopathy can regulate cardiomyocyte apoptosis and angiogenesis, inhibit myocardial inflammation and fibrosis. In addition, the change of EXs miRNA level can reflect the development of diabetes complications. Therefore, EXs miRNAs are expected to become new biomarkers and therapeutic targets for the prevention and treatment of diabetic complications in the future. However, the role of EXs miRNA on the diagnosis of diabetes complications is still unclear, and the mechanism of EXs miRNA on the improvement of diabetes complications are needs to be explored. It was reported that exercise benefits for the prevention and treatment of diabetes complications. Although acute or long-term exercise can regulate the expression of EXs miRNA, the regulation of EXs miRNA expression via acute or long-term interval and resistance exercise are few studies. Moreover, exercise plays a beneficial role in the pathological regulation of diabetes complications via the regulation of EXs miRNA or exerkines by improving endothelial cell function and insulin sensitivity, maintaining fat metabolism balance and inhibiting apoptosis, and promoting “cross talk” between tissues and organs. In the future, the specific mechanism of exercise-mediated EXs miRNA to improve diabetic complications still needs to be further explored.]]> 2023/2/22 0:00:00 TANG Shao-Kai,GENG Yuan-Wen,LIN Qin-Qin,LI Ruo-Ming and WANG Bai-Hui 373true 2023/2/22 0:00:00 YANG Yang,MA Tie,CAO Shi-Cheng,YAO Ting-Ting,LIU Xiao-Long and YI Xue-Jie 372true 2023/2/22 0:00:00 SHAN Bao-Lian,ZHANG Li-Xin,Xu Fang-Zhou,XU Min-Peng,YU Hai-Qing,WEI Si-Wen and MING Dong 371true 　　杨福愉先生原籍浙江宁波镇海，1927年10月30日出生于上海市，1946年毕业于上海南洋模范中学，1950年毕业于浙江大学化学系，1960年在前苏联莫斯科大学生物系获哲学副博士学位，回国后一直在中国科学院生物物理研究所工作，历任生物物理研究所副研究员、研究员，1991年当选为中国科学院学部委员(院士)；曾任生物物理研究所副所长、学术委员会主任、生物大分子国家重点实验室主任等职，是中国生物膜领域的主要奠基人之一。
　　杨福愉先生1950年毕业于浙江大学后，进入中国科学院（上海）实验生物学研究所，在贝时璋先生等老一辈科学家的言行垂范下获得科学启蒙；1956~1960年留苏期间，获得了系统的科研训练；回国后在生物物理研究所带领线粒体结构与功能研究小组，研究电离辐射对线粒体氧化磷 酸化功能的影响，从此确立了为之奋斗一生的“生物膜结构与功能”这一重要研究方向。
　　杨福愉先生长期围绕膜脂-膜蛋白相互作用及其调控机理开展系统、深入的原创性研究。提出镁离子通过改变膜脂流动性影响ATP酶的结构与活性模型，为膜脂物理状态影响膜蛋白的结构与功能提供清晰的实例；在此基础上开展跨膜钙离子浓度梯度调节膜蛋白的构象与活性的研究，揭示膜脂物理状态调控钙ATP酶及G蛋白偶联跨膜信号转导通路的新机制；发现胰凝乳蛋白酶不只是消化酶，还介导溶酶体-线粒体细胞凋亡新途径。同时，杨福愉先生非常重视基础理论研究与实际应用的结合。曾在核爆炸现场承担放射生物学科研任务，总结出的慢性放射病早期诊断生化指标为核安全打下基础；用“匀浆互补法”预测农作物杂交优势，为促进农业增产提供科学依据；开展克山病病因的研究，提出“克山病是一种心肌线粒体病”的观点等。在研究中，杨福愉先生善于以多学科交叉融合的研究方法从不同层次开展研究，研究成果彰显开拓性、富于原创性。杨福愉先生在国内外学术期刊发表科研论文200余篇，出版《生物膜》等专著2部，在国际上产生深远影响，获得广泛承认，先后获得国家自然科学奖、中国科学院自然科学奖、何梁何利奖等重要奖项。
　　杨福愉先生重视学术团体、学术会议、学术期刊在科学研究中的重要作用，曾任中国生物物理学会理事、中国生物化学与分子生物学学会副理事长、北京市生物化学与分子生物学学会理事长、《生物物理学报》主编等职，积极推动1981年首届全国膜生物学讨论会举办，并担任首届会议大会主席。
　　杨福愉先生重视青年人才培养。作为2013年中国生物物理学会贝时璋杰出贡献奖得主，杨福愉先生于2018年向贝时璋奖捐款30万元，用于表彰后续贝时璋青年奖获奖者，表达了老一辈科学家对生物物理学领域青年科技工作者的殷切期望。
　　先贤虽去，风范永存。杨福愉先生的家国情怀与学术精神将永远指引我们奋斗！
　　杨福愉先生千古！
（感谢黄有国研究员为此文撰写提供历史线索和整理、凝练素材。）]]> 2023/1/16 14:59:47 WEI Tao-Tao 370true Schizosaccharomyces pombe, Mus musculus, Homo sapiens, Drosophila melanogaster and Arabidopsis thaliana. Although it is conserved in lower fungi, basidiomycetes and Schizosaccharomyces, ERI-1 is lost in filamentous ascomycetes and most budding yeasts. As an important regulator of RNAi, ERI-1 was first identified in a screen for mutants with enhanced sensitivity to dsRNA in Caenorhabditis elegans. It negatively regulates RNAi through degrading siRNA and miRNA. However, the C. elegans ERI-1 can completely bind to the core endogenous RNAi component DCR-1 to inhibit exogenous RNAi and promote specific endogenous siRNA production. The Schizosaccharomyces pombe ERI-1 degrades heterochromatin siRNA and influences the formation of heterochromatin. In addition, ERI-1 plays conservative roles in the 3" terminal modification of 5.8S rRNA. Moreover, the mammalian ERI-1 binds to the ACCCA sequence and excises two unpaired nucleotides, thus participating in the processing and degradation of histone mRNA at the end of S phase. The influenza A virus interacts with ERI-1 to promote viral transcription and proliferation, suggesting that ERI-1 has the potential to be a target of anti-virus drugs. This review summarizes the recent advances of ERI-1 functions in multiple RNA processing pathways, and further discusses the evolutionary loss and medical potentials of ERI-1. Suggestions about future research topics are also provided.]]> 2023/1/16 14:59:48 ZHANG Yi-Ran,LIU Hui-Quan,TANG Zhe and JIN Qiao-Jun 369true 2023/1/16 15:00:26 HOU Jing-Yu,LI Zhen-Wei,HU Yuan,LIU Xiao-Wen and SHOU Kang-Quan 368true 2023/1/16 15:00:28 LI Chun-Chan,YANG Jia-Jia,LIU Jin-Zhen,ZHENG Chen-Guang,TIAN Yu-Tao,HE Feng and MING Dong 367true 2023/1/16 15:00:28 ZHANG Chen,HE Feng,ZHANG Hao,WANG Xue,SONG Xi-Zi,XU Min-Peng and MING Dong 366true 2 reductase /CO dehydrogenase” hybrid system as examples. Besides, we briefly describe the working process and two different electron transfer pathways of the hybrid system, the direct pathway of “sacrificial agent-semiconductor-enzyme” and indirect pathway of “sacrificial agent-semiconductor-intermedia-enzyme” Finally, we summarize some limitations in the past research, such as the toxicity of semiconductor materials and the low electronic utilization efficiency, we propose new prospects and research directions in bionic organelle and optimization of the reaction chain.]]> 2023/1/16 15:00:30 Li Guan-Lin,Li Mei-Yu,Li Xue-Chen and Cui Dai-Zong 365true FBN gene, the knockout of Olfr734 receptor cannot fully explain the effect of ASP gene on reproduction. In addition, whether the effect of ASP on testosterone is only centrally and not peripherally, further studies are needed to confirm. Revealing the effect of ASP gene on reproductive function will help to explain the molecular mechanism of adipokines involved in regulating male reproductive function. Exercise is an effective means to improve metabolic syndrome and enhance reproductive function. Exercise can regulate the level of adipokines. At present, there are few studies on exercise and ASP, and there is controversy. Only by increasing the experimental research on the effect of exercise on ASP can better explain the exact effect of exercise on ASP; exercise can also reverse the reproductive effect caused by metabolic imbalance. Functional decline, the relationship between exercise and ASP and reproduction in metabolic syndrome can be explored in the future.]]> 2023/1/16 15:00:39 Lü Hong-Yan,YANG Yang,CHANG Bo and YI Xue-Jie 364true e.g., IL-27 promotes Th1 cell differentiation in CD4+ T cells and can inhibit differentiation in a highly polarized state of Th1 cells. In CD8+ T cells, IL-27 promotes their proliferative activation and thus plays a role in the immune response and the efficacy of subunit vaccination. In B cells, due to different activation patterns and differentiation stages, IL-27 also has a dual role. It enhances the phosphorylation levels of STAT1 and STAT3 in naive B cells and promotes B cell proliferation; but in memory B cells, its effect is weakened and cannot promote B cell proliferation. In osteoblasts (OB) and osteoclasts (OC), IL-27 promotes OB differentiation mainly through Smad2/3 and STAT1, and inhibits OB differentiation through M-CSF/sRANKL in bone marrow-derived macrophage-like cells OC generation, thereby participating in the regulation of bone growth and remodeling. In addition, the latest research has confirmed that IL-27 can directly target adipocytes, promote adipocyte (AD) thermogenesis, and improve insulin sensitivity through the p38MAPK-PGC-1α signaling pathway, which also suggests that IL-27 plays an important role in metabolic great potential in disease. This article reviews the structure and biological function of IL-27, aiming to provide a reference for the research and application of IL-27.]]> 2023/1/16 15:00:40 LI Meng-Huan,YANG Yang,MA Qian-He,YI Xue-Jie and CHANG Bo 363true via the three core elements: NSF (N-ethyl-maleimide sensitive factor ATPase), SNAP (soluble NSF attachment protein), and SNAREs (soluble NSF attachment protein receptors). SNAP is an adaptor attaching NSF to SNAREs, which are the proteins directly mediate the membrane fusion. After membrane-membrane fusion, SNAREs must be reactivated by NSF for the next round of fusion. It is vital that NSF is the sole ATPase to regenerate active SNAREs. SNF inactivation represses the reactivation of SNAREs and thereby disrupting the fusion between autophagosomes and lysosomes after ischemic stroke. Subsequently, the autophagic/lysosomal dysfunction in neurons is created to aggravate the neurological injury. Additionally, the insufficiency of the tethering proteins and inefficiency of the GTPases are also the pathologies to interrupt the fusion between autophagosomes and lysosomes. Accordingly, the impaired autophagic flux in neurons may be restored by facilitating fusion of autophagosomes with lysosomes, via pharmacological intervene, gene modulation, microenvironment amelioration, or mTOR signaling regulation. Finally, based on the mechanism of autolysosome formation, more therapeutic clues may be sought to alleviate neurological injury after ischemic stroke.]]> 2023/1/16 15:00:46 QIU Miao-Miao,HE Hong-Yun and DENG Yi-Hao 362true e.g., passive viewing vs. strategical processing), consolidation (e.g., sleep vs. no sleep), and retrieval (e.g., recognition vs. cued-recall) phases may differently affect the selectivity of emotion-induced memory enhancement. Hitherto, the cognitive and neural mechanisms underlying the emotional memory trade-offs and broadening effects remain unclear. There is a debate on whether the memory trade-offs effect is an automatic process independent of attention narrowing and post-stimulus elaboration. Besides, a few studies reveal that a core neural network involving the amygdala, hippocampus, fusiform, temporal pole, and inferior frontal gyrus is associated with the trade-offs effect, with the activation of some other brain regions dependent on valence and arousal levels of the stimuli. Further research needs to compare the mechanisms of the emotion-induced memory broadening with those of the trade-offs at both behavioral and neural levels, particularly taking a closer look at the automaticity of and the forms of memory representations involved in these effects. In addition, extending these effects from spatial to other (e.g., temporal) dimensions may help elucidate how emotional signals selectively enhance the memory of complex scenes from different perspectives.]]> 2023/1/16 15:00:48 FAN Chen-Xuan,CHEN Yu-Jie,WANG Ying and JIANG Yi 361true 2023/1/16 15:00:49 ZHANG Chao,WU Jian-Feng and WANG Li-Han 360true FDR) is inaccurate and (2) validation of single identification cannot be supported. Thus, the identification results that passed the TDA-based FDR control need to be further validated and other validation methods which are used after TDA-FDR filtration (referred to as Beyond-TDA methods) have been developed to enhance peptide validation. This paper reviews TDA and its extensions as well as Beyond-TDA methods and discusses the advantages and disadvantages of each method. In the first part of this paper, we introduce the goal of proteomics, the process of mass spectrometry acquisition and analysis, the validation problem, and the early statistical methods to evaluate the identification credibility. Then, in the second part of this paper, we describe in detail the ordinary TDA-FDR method, including the assumption that random matches are equally likely to appear in target and decoy databases, the construction methods to generate the decoy database, and the computational formula of TDA-FDR. We also introduce the extensions of TDA-FDR on ordinary subclasses of peptides, variant peptides, modified peptides, proteogenomics peptides, cross-linking peptides, and glycopeptides. However, TDA cannot model the homologous incorrect peptides, thus TDA-FDR underestimates the actual false rate. So, after TDA-FDR filtration, it is necessary to use more strict validation methods, i.e., Beyond-TDA methods, which are reviewed in detail in the third part of this paper, to control validation credibility. In this part, four kinds of methods are introduced, including validation methods based on search space (trap database validation and open search validation), spectra similarity (synthetic peptide validation and theoretical spectra prediction), chemical information (retention time prediction and stable isotopic labeling validation) and machine learning technology (Percolator, pValid, and DeepRescore). Lastly, we summarize the content of this paper and discuss the future improvement directions of validation methods.]]> 2023/1/16 15:04:18 ZHOU Wen-Jing,ZENG Wen-Feng,CHI Hao and HE Si-Min 359true 2023/12/22 11:25:00 CHEN Hao,LI Qiang and ZHANG Jian 358true 2023/12/22 11:25:02 JI Wen-Bo,LI Yun-Jian,CAI He-Ping,CHEN Guan-Ru,TIAN Jie-Yong,HU Lei,DAI Hai-Ming and LIU Hai-Peng 357true 2023/12/22 11:25:04 TANG Yu,ZHOU Zi-Juan,ZHOU Kuai-Le,LIU Lei,ZHOU Ce-Fan and TANG Jing-Feng 356true 2023/12/22 11:25:08 LIN Peng,CHEN Qian,QIAN Jing and WANG Yan 355true 2023/12/22 11:25:12 CHEN Yan-Hua,MO Zhong-Cheng,LIU Yan-Li,QIU Yuan and LIU Long-Fei 354true 2+, Mg²⁺, Zn²⁺, Na⁺, K⁺, and other trace metals. As an α-kinase, TRPM7 can autophosphorylate its serine and threonine residues, or phosphorylate endogenously targeted substrates such as myosin II. Through the joint action of the two domains, TRPM7 participates in various physiological processes such as Mg²⁺ homeostasis regulation, cell proliferation, differentiation, adhesion and migration, and ultimately affects cell differentiation and embryonic development. Dysfunction of TRPM7 has been associated with multiple neurodegenerative diseases, tissue fibrosis, ischemic injury as well as the occurrence and development of tumors. Genetic or pharmacological deficit of the TRPM7 relieves ischemic neuronal injury and inhibits the proliferation and migration of tumors, while up-regulating or restoring TRPM7 decreases blood pressure, maintains normal embryonic development and may be an effective strategy to treat the neurodegenerative disorders. However, whether TRPM7 is a promising target for the development of clinical drugs remains elusive. Nowadays, several small molecules display activation or inhibitory activities on the TRPM7 channel, and have been successfully used to uncover new cellular roles of TRPM7 in physiological and pathological conditions. Nonetheless, selective and potent TRPM7 modulators are limited. This review summarizes the research progress on the physiological and pathological functions of TRPM7 and its small-molecule modulators, which may provide new therapeutic strategies for TRPM7-related diseases and new directions for the development of novel TRPM7 regulators.]]> 2023/12/22 11:25:14 WANG Yun-Qi,GUAN Zi-Yue,GAO Zhao-Bing and ZHENG Yue-Ming 353true 2023/12/22 11:25:16 MA Xin-Yue,HUANG Chun-Cui,ZHAO Yao and LI Yan 352true 2023/12/22 11:25:17 LI Jian-Ping,HE Li-Dong,HU Yi-Li,WEN Jian-Ming,MA Ji-Jie and WAN Nen 351true 2023/12/22 11:25:28 ZHU Qian-Yun,ZHANG Zhi-Guo,LIANG Zhen,ZHANG Li,LI Lin-Ling,ZHANG Shao-Rong and HUANG Gan 350true 2023/12/22 11:25:34 ZHANG Yang-Kai,HU Mi,LIN Hui-Ling,TANG Wan-Ying,OUYANG Yu-Xin,HE Ping-Ping and OUYANG Xin-Ping 349true 2023/12/22 11:25:36 ZHENG Qian-Wen,YANG Yan-Ling and WANG Ya-Yun 348true e.g., facial expressions, emotional language, and videos). Neuroscience research showed that BTX-A injection could attenuate amygdala activity, and could affect the neurocognitive function of reward system and other cerebral cortex as well. These findings can be interpreted by facial feedback hypothesis and social feedback hypothesis from the individual and social perspectives respectively. For subjects who received the injection, BTX-A reduces feedback from facial muscles thus impairing emotional experience and processing. According to this hypothesis, proprioceptive signals from facial muscles are conducted to the mesencephalic trigeminal nucleus and locus coeruleus, the latter of which sends direct projections to the thalamus, basal ganglia, and cerebral cortex related to motor, cognition, and emotion. In interpersonal communication, the observer’s emotional experience becomes similar to the subject who has received BTX-A injection through facial mimicry, and the subject’s emotional experience is also affected by the observer in turn. The mirror neuron system plays an important role in the process. Based on the existing researches, this review proposed an integrated model to explain the cognitive and neural mechanisms of how BTX-A injection affects emotional processing, which deepens the neural basis of facial feedback and social feedback for expression recognition and emotion processing. The model illustrates the roles of facial feedback and social feedback respectively as “signal resource” and “amplifier” of emotional processing caused by BTX-A injection, and the relationship between them. Specifically, the changes in muscles induced by facial mimicry causing emotional synchronization in social feedback process is in line with facial feedback process. The interaction of the two emotional processes could also cause multiple overlapping effects, which exist in both individual emotional processes and interpersonal interactions. Future studies should expand the aspects and levels of emotional processing, such as focusing on subliminal emotion processing and emotion regulation; further explore the mechanisms of how BTX-A injection affects emotional processing using neuroimaging technologies; improve the research paradigms to study the causal relationship between facial feedback and emotional processing; explore the mechanisms and application of BTX-A in the treatment of mental illness like depression; compare the effects of BTX-A injection and other invasive facial procedures on emotional processing. Further research will not only improve the understanding of cognitive and neural mechanisms underlying emotion but also have potential implications in mental health and medical cosmetology.]]> 2023/12/22 11:25:39 MIAO Xiao-Fan,BI Yi-Fan and LIU Ye 347true 6A modification is one of the most prevalent RNA modifications in nature with important functions in RNA stability, pre-mRNA splicing, translational regulations and likely others. m⁶A modifications in eukaryotes are believed to be mainly carried out by two related methyltransferases, METTL3 and METTL16 based on mammalian nomenclature. METTL16, similar to METTL3, has a large variety of RNA substrates, including pre-mRNA, rRNA, snRNA and lncRNA. Therefore, a unifying molecular function seems farfetched for the METTL16-installed m⁶A modification. In addition, METTL16 carries out important function in translational regulation independent of its methyltransferase activity, adding another layer of functional complexity to this highly conserved enzyme. In this review, we summarize the domain architecture of METTL16 and homologous proteins, indicating the conserved functional domains as well as the mammalian specific VCR domain suggestive of additional function of the higher enzymes. We summarize the confirmed METTL16-methylated RNA substrates as the pre-mRNA for SAM synthetase (MAT) in men and worms, and the U6 small nuclear RNA (snRNA) in yeast, plants, worms and men. Although the role of m⁶A modification in regulating SAM levels by alternative splicing might represent a case of convergent evolution, this proposition lacks support from plant studies of METTL16. The lack of m⁶A modification on U6 snRNA, an essential component of the spliceosome, has been identified in genome-wide studies as the cause for the splicing defects of specific introns in yeast and plants. How much of this function of U6 modification is conserved remains unclear. Mammalian METTL16 has been shown to carry out methylation-independent function by interacting with the machinery for protein synthesis. In addition, METTL16 was originally identified as the interacting protein of the triple-helix forming MALAT1, a long non-coding RNA highly expressed in certain tumors. However, whether MALAT1 is a methylation substrate of METTL16 and what underlies the biological significance of the METTL16-MALAT1 interaction remain under characterized. While knock-out mutants of METTL3 proteins suffer mild organismal consequences, those of METTL16 cause much more severe physiological abnormalities. How the conserved METTL16 enzymes fulfill an array of diverse and essential functions promises to be one of the fascinating directions in RNA biology.]]> 2023/11/22 14:15:43 GONG Juan,HUANG Wu-Qiang and RONG Yi-Kang 346true 2023/11/22 14:15:47 KONG Ling-Kai and WU Jun-Hua 345true 2023/11/22 14:15:49 LI Cai-Wen,CHEN Qin,XUAN Yu-Ming and FU Xiao-Lan 344true 2023/11/22 14:16:24 SHI Yong-Hui and WANG Dong-Mei 343true e.g. anorexia nervosa) or excessive energy deposits (e.g. obesity, diabetes) mainly caused by imbalance between energy intake and energy consumption. And, in severe cases, metabolic disorders impair growth and reproductive function. The central nervous system, especially the hypothalamus, is vital for regulating energy metabolism and balance. Hypothalamus Kisspeptin (encoded by the Kiss1 gene) have well-established roles in regulating reproductive axis and function. Recent evidence suggests that Kisspeptin signaling is critical for metabolism and energy balance. AVPV/PeN Kiss1 neurons send inhibitory GABAergic projections to the PVH and dorsomedial hypothalamic nucleus (DMH) as described. While, Arc Kiss1 neurons can release excitatory transmitter glutamate to PVH and DMH. And, Arc Kisspeptin directly excites POMC/CART neurons through mGluRs group I. In addition, Arc Kiss1 neurons inhibit Arc NPY/AgRP neurons through mGluRs group II/III or release inhibitory transmitters to Arc NPY/AgRP neurons by an indirect way. Besides, energy imbalance can stimulate the release of leptin and adiponectin from adipose tissue, insulin from pancreas and ghrelin from gastrointestinal tract. These peripheral metabolic factors can directly or indirectly stimulate Kiss1 neurons in hypothalamus. This review focuses on the metabolism function of Kisspeptin neurons in the energy input and energy expenditure, which provides important implications of Kisspeptin-based therapies for metabolic-related diseases.]]> 2023/11/22 14:16:26 SUN Ling-Yu,YAN Yi and CHEN Jing 342true 2023/11/22 14:16:28 ZHANG Qi,ZHAO Xiao-Xuan and LI Xin-Wang 341true 2023/11/22 14:16:35 YIN Shi-Yun and CHEN Guo-Bao 340true 2023/11/22 14:17:43 YANG Jia-Pei,YANG Gui-Rong,QIN Lian,WANG Xin-Zhuang,ZHU Guang-Ming,LI Liang-Ming and YANG Wen-Qi 339true via β-elimination of glycosidic bonds. They produce various oligosaccharides with unsaturated uronic acid at the non-reducing end, or 4,5-unsaturated uronic acid monomers mannuronate (ΔManUA) and guluronate (ΔGulUA). Fucoidans usually consist of a backbone of α-1,3-L-fucopyranose residues or alternating α-1,3-linked and α-1,4-linked L-fucopyranosyls, and side branches containing glucose, galactose, rhamnose, xylose, mannose or glucuronic acid. The fucopyranose residues may be substituted with sulfate. The highly modified structure of fucoidans can significantly affect the cleavage of glycosidic linkages. Therefore, hydrolases that act on a branched chain and sulfatases are required for the primary degradation. Subsequently, L-fucoses are produced by a series of sulfatases and fucosidases belonging to GH29, GH95, GH107, GH141, GH151, or GH168 families. Laminarin, the storage polysaccharide in algae, is composed of a linear backbone of 20-30 residues of β-1,3-linked-D-glucopyranose and a branched chain of β-1,6-linked-D-glucopyranose. The glycosidic bond in its backbone can be broken by endo-β-1,3-laminarinases (EC 3.2.1.6 and EC 3.2.1.39) and exo-β-1,3-glucanases (EC 3.2.1.58). The β-1,6-glucanase (EC 3.2.1.75) releases glucose by breaking the glycosidic bond in the branched chain of laminarin. Algae-derived polysaccharides and their oligosaccharides have shown health beneficial effects, such as immunomodulatory, antitumor, anti-inflammatory, and other activities, which possess great potential as alternative, renewable resources in cosmetics and functional foods. In this review, we mainly focus on the efficient degradation of brown algae, and summarize the mechanisms adopted by these enzymes for catalysis and conformation changes of substrate specific recognition. Furthermore, it will provide insights for the precise customization of oligosaccharides and the construction of industrial biorefinery platform, thereby promoting the efficient conversion of brown algae.]]> 2023/11/22 14:17:50 LI Xue,WU Xiu-Yun,LI Ying-Jie and WANG Lu-Shan 338true 2023/11/22 14:28:30 QIU Jia-Rong,ZHU Meng-Lei,ZHANG Liang-Qing,ZENG Xian-Hai,JIN Yu-Feng and DENG Jia-Hui 337true 2023/11/22 14:28:38 SHI Qing-Xia,YIN Ting,ZHENG Ming-Bin and CAI Lin-Tao 336true 2023/11/22 14:28:46 JING Wei and MA Fu-Qiang 335true 2023/11/22 14:28:53 YU Zhu-Ying,JI Fan,GUO Jing-Yu,LU Tong-Yi,XIA Zhao-Sha,ZHANG Ning-Bo,SUN Yao-Jie and WANG Yu 334true in-situ monitoring of bacterial QS signal molecules and QS process by the way of combining the photoelectric sensors and microfluidic control.]]> 2023/11/22 14:28:57 LIU Zhi-Xu,TAN Hao-Lan,HE Hong,XU Yi,GE Chuang and ZHANG Yang 333true 2024/9/19 20:40:49 ZHU Yun-Chi and LU Zu-Hong 332true Science in 2018 mapped the complete atlas of organ and tissue development from fertilization and captured dynamic gene expression profiles in zebrafish and frogs through single-cell transcriptomics. Unfortunately, relying solely on single-cell omics analysis falls short in effectively and comprehensively deciphering the intricate cellular network information. Single-cell multi-omics empower researchers to systematically decode cell heterogeneity and developmental trajectories at the individual cell level by combining transcriptomics, epigenomics, proteomics, and metabolomics analyses. These emerging technologies play a significant role in life sciences, enabling the elucidation of critical early primate embryonic development events from a multi-dimensional perspective, including zygotic genome activation (ZGA), X-chromosome dosage compensation, origins of primordial germ cells (PGCs), mechanisms of cell fate determination, and pivotal events in gastrulation and early organogenesis.This article chronicles the advancement of pivotal technologies, from single-cell histology to multi-omics, beginning with the single-cell transcriptome and culminating in a comprehensive analysis according to the central dogma of molecular biology. It highlights the transition from a singular to a holistic perspective in cellular analysis and reviews the application of multi-omics techniques in unveiling early primate embryonic development. Finally, it delves into the application of multi-omics technologies in enhancing our understanding of early primate embryonic development and explores future possibilities, directions, and challenges in this rapidly evolving field. In doing so, it emphasizes the critical role of interdisciplinary approaches, combining insights from genetics, molecular biology, and bioinformatics to foster innovations in reproductive medicine and developmental biology. The integration of such technologies offers the promise of breakthroughs in understanding complex biological processes, potentially leading to novel therapeutic strategies and advancements in reproductive health and medicine.]]> 2024/9/19 20:40:51 PAN Zhi-Hui,GUO Rong-Rong,ZHANG You-Yue and TAN Tao 331true 2024/9/19 20:40:53 WU Xi-Qian,ZHANG Xi-Lei,JIANG Yi and WANG Liang 330true 2024/9/19 20:40:54 ZHAO Hu-Cheng,SUN Yan-Li,QIAN Shu-Le and FENG Xi-Qiao 329true 2024/9/19 20:40:55 JIN Jia-Bei,GE Yi-Dong and JIN Xiao-Feng 328true 2024/9/19 20:40:57 TANG Yi,WANG Guo-Tai,JIANG Yu-Han and CAO Zhong-Qiang 327true in vivo, making it the preferred delivery tool for gene therapy of monogenic genetic diseases. Alipogene triprivec, also known as Glybera, was approved by the European Medicines Agency in 2012. It is the first gene therapy drug that uses recombinant AAV1 vector to directly deliver a highly active LPL protein S447X mutant to muscle cells for the treatment of patients with hereditary LPL deficiency. To enhance the targeted transduction efficiency of AAV carriers, recombinant AAV8.TBG.hLDLR utilizes the tissue tropsim of AAV8 to liver, meanwhile utilizes a liver specific thyroxine binding globulin promoter to control gene transcription, thereby achieving liver cell specific high expression of human low-density lipoprotein receptors (LDLR). In patients with familial hypercholesterolemia, AAV8.TBG.hLDLR treatment effectively lower the level of plasma LDL for a long time, thus preventing the occurrence of atherosclerosis.Proprotein convert subunit kexin 9 (PCSK9) is secreted by liver cells. PCSK9 binds and transports LDLR to lysosomes for degradation, preventing the circulation and regeneration of LDLR, leading to accelerated degradation of LDLR and finally resulting in the accumulation of low-density lipoprotein cholesterol in plasma.Using AAV to deliver Cas9 of Staphylococcus aureus and gRNA targeting the Pcsk9 gene can knock out Pcsk9 in mouse liver, leading to a long-term significant decrease in plasma cholesterol levels in mice. Hepatocyte specific angiopoietin related protein 3 (Angptl3) is an endogenous inhibitor of LPL. Using the AAV9 mediated AncBE4max system and the dCas9 mediated single base gene editing system to introduce early termination codons, the knockout of Angptal3 in liver cells was achieved with an average knockout efficiency of 63.3%. After 2-4 weeks of administration in mice, the Angptl3 protein was completely undetectable in the peripheral blood, and serum triglycerides and total cholesterol decreased by 58% and 61%, respectively. Ring finger containing protein 130 (RNF130) is an E3 ubiquitin ligase. Research has shown that overexpression of RNF130 using AAV2/8 leads to ubiquitination degradation and redistribution of LDLR on the cell membrane, significantly reducing LDLR expression on liver cells and increasing plasma LDLC levels, while knocking out Rnf130 gene using the AAV-CRISPR system results in the opposite effect. This AAV mediated RNF130 function study proves that RNF130 is a posttranslational regulatory protein of LDLR and plays an important role in the regulation of serum LDLC. As mentioned above, recently, various lipid-lowering gene therapy drugs carried by different serotypes of adeno-associated virus have been applied in clinic or are undergoing clinical trials, and adeno-associated virus has emerging to be an important tool for lipid metabolism research.This article reviews the new progress of adeno-associated virus vectors in lipid metabolism study and lipid-lowering gene therapy.]]> 2024/9/19 20:40:59 YAN Zi-Yang,WANG Qian-Ru,HUANG Xiao-Fei and CAO Chun-Yu 326true 2024/9/19 20:41:01 OUYANG Fei-Fan,RASHEED Madiha,LI Bo and DENG Yu-Lin 325true KRAS, CDKN2A, TP53, and SMAD4. Most pancreatic cancer patients are affected by environmental risk factors such as age, sex and diet. Malignant pancreatic cancer is associated with non-invasive, preneoplastic lesions that are thoughted to be precursors, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN) and mucinous cystadenoma (MCN). In recent years, people have gradually improved the therapy and diagnosis of pancreatic cancer, and the contribution of imaging technology, which enhancing the usage of minimally invasive pancreatectomy that typically includes pancreaticoduodenectomy and distal pancreatectomy. However, combined administration of the chemotherapeutic gemcitabine and erlotinib is still considered a potential first-line treatment for advanced pancreatic cancer, but the development of chemoresistance often leads to poor therapeutic outcomes. Based on the current research progress for pancreatic cancer, its treatment currently remains one of the most important challenges in the medical field. Although some new treatment options have been provided, there were minor clinical success achieved and therefore new safe and effective therapies of pancreatic cancer are still an urgent need for patients. Among these new therapies for pancreatic cancer, short peptide-based treatment protocols have attracted great attention. Peptide is a compound formed by linking α-amino acids together in peptide chains. It is also an intermediate product of proteolysis. The short peptide-based therapy has many advantages such as precise targeting, easy preparation and low toxicity. Short peptides usually act as tumor suppressors by targeting and recognizing tumor-specific expressed proteins. Currently, there is an increased interest in peptides in pharmaceutical and development research, and approximate 140 peptide therapeutics are currently being evaluated in clinical trials. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity and simplicity of modification. Peptides have high bioactivity and excellent biodegradability. Clinically, short peptides are increasingly used as combination drugs with chemotherapy for tumor treatment. Peptides can induce cancer cell death by numerous mechanisms and peptides have emerged as a promising drug for the treatment of pancreatic cancer. Here we mainly review the roles of peptides on Wnt/β-catenin, NF-κB, autophagy, and the use of peptides as tracer in pancreatic cancer. We also analyzed the benefits and disadvantages existing in the development process of short peptides, which provide the feasibility of targeted short peptides to become new therapeutic approaches for cancer therapy.]]> 2024/6/26 13:27:37 LIU Yuan,DONG Xue-Ying,ZHOU Ce-Fan and TANG Jing-Feng 324true etc. Although transfected with a variety of cells, it is mainly enriched in immune cells and liver cells because immune cells express toll-like receptors and liver cells express low-density lipoprotein receptors. mRNA vaccines and drugs are mainly divided into non-replicating mRNA (nrmRNA), self-amplifying RNA (saRNA), trans-amplifying RNA (taRNA) and circular RNA (circRNA).This article reviews how these 4 types of vaccines and drugs work, and compares their advantages and disadvantages. Due to its inherent immunogenicity, instability, and low delivery efficiency in vivo, mRNA vaccines and drugs have been unable to enter the clinic. This article describes in detail how to reformation and modify the 5"cap, 5"UTR, 3"UTR, ORF, 3"Poly(A) and some nucleotides of mRNA to eliminate its immunogenicity and instability. Due to the low efficiency of the delivery carrier, the researchers optimized it. This article briefly introduces the application of non-viral vectors and their targeting, specifically involving the mechanism of action of various types of delivery vectors and their advantages and disadvantages, and summarizes some of the current targeting vectors. Targeted carriers can improve the delivery efficiency of mRNA to specific tissues and prevent side effects of systemic exposure, such as liver injury. The specific methods of using mRNA vaccines and drugs to treat cancer are as follows: mRNA can be used to encode and transcribe tumor-associated antigens, tumor-specific antigens (TSAs), therapeutic antibodies, cytokines, tumor suppressors, oncolytic viruses, CRISPR-Cas9, CARs and TCRs, so as to play an anti-tumor role. In this paper, the specific mechanism of the above methods and the current research and development of corresponding mRNA vaccines and drugs are briefly reviewed. The successful development of the COVID-19 mRNA vaccine has brought mRNA technology to the attention of the world and brought new and effective means for the prevention and treatment of cancer. mRNA vaccines and drugs have the advantages of short development cycle, dual immune mechanism, safety, high efficiency and large-scale production. At the same time, there are also many areas that need further improvement, such as the development of ideal target TSAs, the in-depth development of saRNA, taRNA and circRNA, the development of targeted nano-delivery for different tissues and organs, the expansion of mRNA administration routes, and the development of mRNA that can be stably stored at room temperature or even high temperature. These problems need to be further studied and solved. In addition to cancer therapy, mRNA vaccines and drugs can also be used in the treatment of infectious diseases, genetic diseases, regenerative medicine and anti-aging. mRNA vaccines and drugs are a very promising platform, and we believe that they will benefit cancer patients in the near future.]]> 2024/9/19 20:41:05 WEI Zhi-Meng,DANG Sheng,LI Guang-Chen,GAO Lan-Zhu and ZHAI Jing-Bo 323true Bmal1 and Clock can significantly reduce cardiac fatty acid and glucose utilization rates, increase myocardial lipotoxicity, weaken the circadian rhythm of myocardial triglyceride metabolism, and lead to abnormalities in the circadian clocks of other peripheral organs. Exercise, as a zeitgeber, can independently regulate the cardiac circadian clock apart from the central circadian clock. Additionally, exercise, as an important means to improve cardiovascular function, may regulate cardiac metabolic activity and the transcription of clock genes by activating the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic-adrenal-medullary axis (SAM) and regulating energy metabolism, thereby maintaining the stability of the cardiac circadian clock and promoting heart health. Future research on the molecular mechanisms of exercise regulation of the cardiac circadian clock will help clarify the role and impact of clock genes in cardiac metabolism and physiological activities, providing new preventive and treatment strategies for shift workers, night owls, and patients with cardiovascular diseases. Therefore, future research should focus on (1) the mechanisms by which exercise regulates cardiac metabolic activity and the circadian clock, (2) the effects and mechanisms of exercise on the disruption of cardiac circadian clock induced by light-dark cycle disturbances, and (3) the effects of exercise on the metabolic activity and circadian rhythms of other peripheral organs regulated by the cardiac circadian clock.]]> 2024/9/19 20:41:28 KONG Xiang-Hao,WANG Man-Da and YU Liang 322true + is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.]]> 2024/9/19 20:42:19 TIAN Jian-Lu,WANG Hong-Juan,CHEN Huan,HOU Hong-Wei and HU Qing-Yuan 321true 2024/9/19 20:42:21 YI Na,ZHAO Guang-Bin,KANG Ke-Lai,YAO Yi-Ren,GUO Ke-Li,ZHAO Jie,ZHANG Chi,MIAO Lei,WANG Le and JI An-Quan 320true 30 Hz) waves. θ waves mainly correspond to the temporal organization of memory items; γ waves are related to information maintenance; α waves indicate inhibition of irrelevant information. These neural oscillations can be regulated by external rhythmic stimulation, gradually synchronizing to the rhythm and phase of external stimulation. This phenomenon is called neural entrainment. Non-invasive brain stimulation (NIBS) can regulate working memory related neural oscillations through entrainment, and has the potential to become a method to enhance working memory performance. Another possible intervention approach to improve working memory is to enhance the excitability of key brain regions involved in working memory through NIBS. In this review, we reviewed more than 50 studies applying NIBS for working memory in healthy adults, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and other NIBS techniques. In terms of research paradigm, working memory NIBS studies with healthy adults usually adopt classic working memory behavioral paradigms, e.g., n-back tasks with numbers or space positions, Sternberg tasks, relatively few stimulating sessions, mainly focus on the simultaneous or short-term effects on behavioral performance. For stimulation sites, the prefrontal cortex (especially dorsolateral prefrontal cortex (DLPFC) is the most commonly choice for it’s a vital role in functions such as information maintenance and cognitive resource allocation. The parietal lobe (especially the intraparietal sulcus (IPS) also plays an important role in information maintenance and manipulation, and is the second common stimulation site after DLPFC. Studies targeting the temporal lobe, occipital lobe, and motor cortex are relatively limited. For stimulation methods, TMS studies mainly use repetitive TMS (rTMS) and θ burst stimulation (TBS) with stimulating frequency in θ or γ band, one-sided or bilateral prefrontal cortex as the stimulation site. The specific intervention effects may also depend on the phase of the neural oscillation that TMS targets. For tDCS studies, anodal stimulation of DLPFC or parietal lobe is widely utilized. The heterogeneous intervention effects such as relatively weak enhancement or impairment of working memory performance after intervention, may result from varied stimulation protocol or participants’ factors (e.g., small sample size, inconsistent baseline levels). For tACS studies, the most widely used stimulation frequencies are θ and γ bands, usually with in-phase manner, fixed or individualized frequencies. Enhancement of working memory performance has been reported for both settings, and the effects are also affected by stimulation parameters, task difficulty and baseline levels of participants. Transcranial random noise stimulation (tRNS), temporal interference stimulation (TIS), transcranial ultrasound stimulation (TUS) are emerging NIBS techniques, of which TIS and TUS can stimulate deep brain regions. Current studies modulating working memory based on these cutting-edge techniques are limited, but they have potential in mechanism exploration and clinical applications in working memory research.]]> 2024/8/15 12:31:21 LI Li-Li,LI Yong-Hui,SHEN Xun-Bing and DONG Xin-Wen 319true via depressing Kelch like ECH associated protein 1(Keap1)/nuclear factor erythroid-2-related factor (Nrf2)/antioxidant response element (ARE) antioxidant pathway and activating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Overtraining induces mitochondrial quality control disorder and mitochondrial dysfunction, and thus triggers health impairment through inhibiting mitochondrial biogenesis and fusion, stimulating mitochondrial fission, and over-activating autophagy/mitophagy. Overtraining can also produce muscle, skeletal and joint trauma, then circulating monocytes are abundantly activated by injury-related cytokines, and in turn generate large quantities of proinflammatory IL-1β, IL-6, TNF-α, causing systemic inflammation and inflammatory health injury. Overtraining induces excessive pathological endoplasmic reticulum stress (ERS) and severe health damage via PERK-eIF2α, IRE1α-XBP1 and ATF6 pathways which activated by proinflammatory signals. Overtraining also induces excessive apoptosis and harmful health consequences via Bax/Bcl2-Caspase 3-mediated mitoptosis which activated by oxidative stress and inflammation or even CHOP and Caspase 12-dependent ERS apoptosis. Nonetheless, it should be importantly emphasized that oxidative stress and inflammation are the central and pre-emptive mechanisms of overtraining and its health damage. Although the efficient strategies for preventing and controlling overtraining are scientifically and reasonably arranging and planning training intensity, training volume, and recovery period, as well as accurately assessing and monitoring physical function status in the early stage, yet various anti-inflammatory, anti-oxidant, anti-apoptotic, or anti-aging drugs such as curcumin, astaxanthin, oligomeric proanthocyanidins, silibinin, hibiscus sabdariffa, dasatinib, quercetin, hydroxytyrosol, complex probiotics, astragalus polysaccharides, semaglutide and fasudil also have an irreplaceable positive effect on preventing overtraining and its relevant health damage via depressing oxidative stress, mitochondrial quality control disorder, proinflammatory signals, endoplasmic reticulum stress, apoptosis and so on. We hope that this review can help us further grasp the features, mechanisms and regularity of overtraining, and provide an important reference for athletes and sports fan to conduct scientific training, improve training effectiveness, extend exercise lifespan, and promote physical and mental health.]]> 2024/8/15 12:31:23 QIAN Shuai-Wei,KOU Xian-Juan and LI Chun-Yan 318true 2024/8/15 12:31:24 LI Shuang,CHEN Zhi,HUANG Yun-Xia,ZHAO Guo-Jun and JIANG Ting 317true 2024/8/15 12:34:49 CHEN Dong-Xue,LI Yun-Long,WEI Da-Qiao and HUANG Fen 316true 2024/8/15 12:34:51 HE Shu-Xin,YU Chang-Shun,JIA Xiao-Dong,CHEN Jian-Chun and YAN Ke-Qiang 315true 2024/8/15 12:34:52 WANG Yin-Feng,CHEN Wen-Li and LUO Fu-Cheng 314true 2024/8/15 12:34:55 MENG Zi-Ye,JIANG Miao,GAO Min,ZHAO Zi-Gang,XU Xiu and ZHAO Zhen-Ao 313true 2024/8/15 12:34:57 CAO Xin,ZHANG Jin-Ping,TU Li-Ying and ZOU Yun-Lian 312true 2024/6/21 15:50:31 ZHANG Shuai and LIU Sen 311true etc. Existing works have revealed and verified that disruption of neuronal microenvironment homeostasis caused by loss of ionic homeostasis (e.g., excessive accumulation of intracellular Na⁺ and Cl^- as well as extracellular K⁺), imbalance of excitatory and inhibitory neurotransmitters (e.g., excessively high concentration of Glu and low concentration of GABA in the extracellular space or synaptic clefts), depletion of energy metabolism substances (e.g., insufficient supply of O₂ and ATP or excessive energy consumption due to abnormal neuronal discharges), cytotoxic swelling, etc., which can induce the generation and development of seizures. In combination with related works on the neuronal microenvironment dynamics modeling methods, we finally discuss and summarize the future research directions. It is expected to give a comprehensive perspective on the development trends and research progress in this field, and provide the favorable theoretical foundations for further research on the dynamic nature of epileptic discharge patterns and the neural mechanisms of epilepsy.]]> 2024/8/15 12:35:00 LI Duo,LI Si-Hui,LI Qiang and ZHANG Rui 310true de novo lipogenesis (DNL), fatty acid oxidation (FAO) and very low density lipoprotein-mediated lipid export. With diverse health-promoting effects, exercise is a cheap and effective intervention for the prevention and treatment of NAFLD. Amelioration of impaired lipid metabolism acts as an important mechanism by which exercise protects against NAFLD. However, how exercise ameliorates lipid metabolic dysregulation is still unclear. Skeletal muscle is not only a vital organ of motion, but also has an endocrine function, it secretes numerous myokines which mediates exercise-induced benefits on our body. Irisin is a small peptide derived from proteolytic cleavage of fibronectin type III domain containing protein 5 (FNDC5). As a myokine, its production is regulated by exercise and it play an important role in exercise-induced protection against obesity-related chronic diseases, such as NAFLD. A growing body of research has demonstrated that Irisin ameliorates lipid metabolic dysregulation in NAFLD. Irisin mediated inhibition of hepatic DNL and FAO has been reported. However, the effect of Irisin on fatty acid uptake and lipid export is still unknown. In the present review, we summarized the researches focusing on how exercise regulated irisin production and the effect of Irisin on lipid metabolism on NAFLD. To clarify the above problems will help us to better understand the role of irisin on exercise-mediated protection against NAFLD.]]> 2024/8/15 12:35:01 HUANG Kai-Ling,YANG Xin-Cheng,LI Liang-Ming and YANG Wen-Qi 309true 2024/8/15 12:35:03 WANG Si-Qi,YAN Xiang-Yun,LI Yan-Qiu,LUO Fang-Li,YAO Jun-Peng,MA Pei-Tao,HOU Yu-Jun,QIN Hai-Yan,SHI Yun-Zhou and LI Ying 308true etc. Therefore, targeting the dysregulated components of the Hippo pathway may be an effective strategy for treating various diseases. Increasing evidence indicates that the Hippo pathway is excessively activated in the development of neurodegenerative diseases, manifested by increased expression of MST1 and downregulation of YAP. Stabilizing the Hippo pathway levels has shown improvements in AD and PD. However, most studies on the Hippo pathway in AD and PD focus on changes in the expression levels of Hippo pathway components, and research in other neurodegenerative diseases is still lacking. Therefore, further investigation is needed to fully understand the mechanistic role of the Hippo pathway in neurodegenerative diseases. Meanwhile, miRNA, similarly dysregulated in neurodegenerative diseases and serving as biomarkers, is a primary target for miRNA therapy in neurodegenerative diseases, including AD and PD. Activating or inhibiting dysregulated miRNAs is the main strategy of miRNA therapy during the neurodegenerative disease development. Evidence suggests that the interaction between the Hippo pathway and miRNA can result in widespread biological effects and crosstalk in the occurrence of different types of diseases. However, studies on the interplay between the Hippo pathway and miRNA in neurodegenerative diseases are relatively scarce. In this paper, we predicted the miRNAs related to Hippo pathway through bioinformatics database, and further screened the miRNAs with crosstalk relationship with Hippo signaling pathway through experiments in combination with PubMed. Then, the mechanism of action of Hippo signaling pathway related miRNAs in AD and PD is further elucidated. It is reported that the Hippo pathway and its related miRNA may exert neuroprotective effects by reducing oxidative stress, improving neuroinflammation, stabilizing autophagy levels, maintaining neuronal mitochondrial function, and ameliorating blood-brain barrier dysfunction, thereby delaying the progression of AD and PD. However, research on miRNA directly regulating the Hippo pathway to improve AD and PD is limited, and observations of the Hippo pathway and its related miRNA in other neurodegenerative diseases are scarce. However, considering the regulatory relationship between the Hippo pathway and miRNA in multiple diseases and their respective roles in key mechanisms of neurodegenerative diseases, such as oxidative stress and neuroinflammation, the crosstalk between miRNA and the Hippo pathway holds a crucial regulatory role in the development of neurodegenerative diseases. Thus, the interaction pathways of the Hippo pathway and its related miRNA may be a pivotal avenue for exploring effective therapeutic strategies for neurodegenerative diseases in the future.]]> 2024/7/19 14:47:10 LIU Xing-Ran,ZHANG Meng and KOU Xian-Juan 307true Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibit GSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.]]> 2024/7/19 14:47:17 CHU Chao-Yang,XIAO Biao,SHAN Jiang-Hui,CHEN Shi-Yu,ZHANG Chu-Xia,ZHOU Yu-Yu,FANG Tian-Yuan,LIN Zhi-Cheng,XIE Kai,XU Shu-Jun and LI Li-Ping 306true 2 (derived from plant sources) and vitamin D₃ (synthesized naturally in human skin upon exposure to sunlight). Vitamin D’s primary function is to facilitate the absorption of calcium and phosphorus, which are crucial for maintaining healthy bones. Beyond its role in bone health, vitamin D significantly influences the immune system, muscle function, cardiovascular health, and the regulation of brain functions. A deficiency in vitamin D can lead to various chronic diseases such as rickets, osteoporosis, decreased immunity, increased risk of mental disorders, and cancers. The synthesis of vitamin D in the human body, both peripherally and centrally, relies on sunlight exposure, dietary sources, and various supplements. As a neuroactive steroid, vitamin D impacts both the physiological and pathological processes of the nervous system and plays a key role in brain health. It profoundly affects the brain by regulating neurotransmitter synthesis and maintaining intracellular calcium balance. As an essential chemical molecule, vitamin D participates in complex signal transduction pathways, impacting neurotransmitter functions and synaptic plasticity. Vitamin D’s role in regulating dopamine (DA)—a neurotransmitter critical for motivation, reward perception, and other higher cognitive functions—is particularly noteworthy. Recent studies have revealed that vitamin D not only promotes the synthesis of DA but also plays a role in regulating DA levels within the brain. It exerts neuroprotective effects on DA neurons through anti-inflammatory, antioxidant actions, and neurotrophic support, thereby creating an optimal environment for DA neurons, influencing neuronal structure, and affecting the movement of calcium ions within nerve cells, positively impacting the overall health and functionality of the DA system. Furthermore, vitamin D can regulate the synthesis and release of DA, thus affecting the signal transmission of various DA neural projection pathways in the brain. This function is vital for understanding the complex interactions between neural mechanisms and their effects on key behaviors and cognitive functions. This review aims to delve deeply into the synthesis, metabolism, and pathways of vitamin D’s action, especially its regulatory mechanisms on DA neurons. Through this exploration, this article seeks to provide a solid theoretical foundation and research framework for a deeper understanding of vitamin D’s role in motivation and reward behaviors. This understanding is crucial for appreciating the broader significance of vitamin D in the fields of neuroscience and neurology. In summary, research and discoveries regarding vitamin D’s impact on the nervous system highlight its importance in neural health and function. These insights not only enhance our understanding of the complex workings of the nervous system but also open new avenues for the prevention and treatment of neurological diseases. The exploration of vitamin D’s multifaceted roles offers promising prospects for developing new therapeutic strategies, underscoring the compound’s potential in addressing a range of neural dysfunctions and diseases. As research continues to evolve, the profound implications of vitamin D in the field of neurology and beyond become increasingly apparent, marking it as a key target for ongoing and future scientific inquiry.]]> 2024/7/19 14:47:28 WANG Hua-Lin,ZHAO Xu-Dong,LIU Ran,LI Ke and HOU Li-Juan 305true 2024/7/19 14:47:35 ZHANG Jin-Ping,WANG Yue-Qing,WANG Mo,WANG Xin-Yue,MOU Xiao-Qin,ZHENG Xi,CHENG Chuang,HE Jing,ZOU Li-Li and LIU Xiao-Wen 304true etc., and shows influence in patients’ response to treatment. Therefore, apoE has become a potential biomarker and treatment target for cancer. Further research of apoE will help us build deep and systematic understanding of etiology of cancer to promote the prevention and to develop new therapeutic strategies for cancer. In this review, we introduced the properties of apoE from the views of biophysics, biochemistry, molecular biology, evolution and epidemiology, in which we demonstrated the similarities and differences among the structures of 3 subtypes of apoE; we also recapitulated the role of apoE in the genesis and development of cancers in main types of malignancies including gastric cancer, colorectal cancer, hepatobiliary cancer, melanoma, pancreatic cancer, etc.; we summarized the relationship between apoE and the hallmarks of cancer, highlighting the position of apoE in immune system and its critical role for understanding the different nature of immunological background of cancers originated from different organs, and discussed its potential value for application as tumor biomarkers and therapeutic targets by demonstrating the structures of its subtypes. We further discussed the possibility of transferring the drug designing strategy of “structure corrector” from neurology to oncology.]]> 2024/7/19 14:47:37 GAO Bo-Wen,WANG Li and XU Yang 303true 2024/7/19 14:47:38 FENG Shu-Wei,ZHANG Min-Xin,WU Xiao-Qiu,LIN Heng-Yi and BING Tao 302true etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.]]> 2024/7/19 14:47:39 LI Zhen-Wei,HOU Jing-Yu,LIN Yu-Ze,ZHANG Zhi-Qi,LIU Shang-Yi,LIU Xiao-Wen and SHOU Kang-Quan 301true in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.]]> 2024/7/19 14:47:41 DAI Xin-Yu,LI Bin,JIN Dan,YI Xue-Jie,HUANG Rui-Qi and GAO Hai-Ning 300true 2024/7/19 14:47:47 HE Zhuo-Jun,CHEN Yu-Ying,ZHOU Yang,DAI Gui-Qin,LIU De-Liang,LIU Meng-De,GAO Jian-Hui,CHEN Ze,DENG Jia-Yu,LIANG Guang-Yan,WEI Li,ZHAO Peng-Fei,LU Hong-Zhou and ZHENG Ming-Bin 299true etc. By changing the design of microfluidic structures, integrating detection methods and modifying specific antibodies, ICP chips have shown great potential in the fields of rapid enrichment and pre-processing of targets, separation of targets and highly sensitive detection. Finally, it is pointed out that ICP chips are facing challenges in improving enrichment efficiency and selectivity, and solving the problems of fluid control, mixing and transport to match the biological properties of target assay, and that microfluidic ICP chips have been continuously promoting the development of ICP chips through the improvement of materials, chip design and integration of multifunctional units, opening up new possibilities in the field of biochemical analysis methods and applications. It can be seen that microfluidic ICP chips have the advantages of low sample flow rate, good separation and enrichment, high detection efficiency, and easy integration and miniaturization, which have shown good research significance and practical prospects in the field of biochemical detection.]]> 2024/7/19 14:47:50 HE Zhi-Heng,WANG Xiao-Li,GE Chuang and XU Yi 298true etc. of the fixed target method are briefly introduced in the article. With the advancement and development of technologies such as free electron lasers and detectors, various sampling methods for serial crystallography are constantly being innovated and optimized. By selecting appropriate sample delivery methods, it will be possible to improve experimental efficiency, reduce sample consumption, and open up new possibilities for researchers in the field of structural biology of biomacromolecules.]]> 2024/7/19 14:47:52 LI Ling-Hao,LI Bing and WENG Tsu-Chien 297true 2024/7/19 14:47:55 ZONG Shao-Jie,DONG Fang,CHENG Yong-Xin,YU Da-Hua,YUAN Kai,WANG Juan,MA Yu-Xin and ZHANG Fei 296true in situ hybridization (smFISH) is a method for imaging single mRNA molecule in fixed cell or tissue using oligonucleotide probes coupled with fluorophores. It can realize real-time study of interested transcripts by RNA localization and quantification. smFISH is widely suitable for many types of biological samples such as cell and tissue sections. It was invented in 1982 which opened up the application of visualizing single molecules. However, due to its shortcomings such as poor binding specificity, Raj et al. optimized this technique in 2008, using 48 independent probes that were separately coupled with fluorophores to locate transcripts. In contrast, methods using multiple labeled probes can distinguish false positive or false negative results due to a single probe misbinding or unbinding event. However, with the continuous application of the technique, it was found that the scheme still has many technical defects, such as low probe specificity, weak fluorescence intensity, low hybridization efficiency, and high background fluorescence. Since then, a series of derivative technologies have been developed. For example, HCR-FISH is a multi-fluorescence in situ hybridization method based on orthogonal amplification and hybridization chain reaction, which significantly improves the problem of weak signal. SeqFISH amplifies the signal and reduces nonspecific binding by continuously hybridizing the mRNA in the cell, imaging it, and stripping the probe in order to barcode RNA. MERFISH utilizes combination labeling, continuous imaging and other technologies to increase detection throughput, and uses binary barcodes to offset single-molecule labeling and detection errors, with more advanced built-in error correction functions to effectively improve the accuracy of results. ClampFISH uses biological orthogonal click chemistry to effectively lock the probe around the target and prevent the probe from disengaging in amplification microscopy. RNAscope amplifies its own signal while simultaneously suppressing the background by using novel probe design strategy and hybridization-based signal amplification system. Split-FISH uses splitting probes for signal enhancement to accurately detect single RNA molecule in complex tissue environments. AmpFISH achieves imaging of short RNA molecules by preparing long single-strand DNA concatemers through controlled rolling circle amplification. CircFISH uses two unique sets of probes (PC probes and PL probes) to distinguish between linear and circular RNAs. π-FISH rainbow enables simultaneous detection of DNA, RNA, and proteins at the single-molecule level with π-FISH target probes. HT-smFISH is more suitable for large or high throughput form of systematic experiments. With the development of technology, the subsequent data analysis process is particularly important. Different analysis software, such as dotdotdot and FISH-quant v2, also improve the process of smFISH. The excellent ability of smFISH to visualize single molecule of RNA makes that it is widely used in basic biological disciplines such as tumor biology, developmental biology, neurobiology, botany, virology. In this paper, we reviewed the basic principle of smFISH technology, its development process and improvement, limitations of smFISH technology and how to avoid them, its derivative technologies include HCR-FISH, SeqFISH, MERFISH, ClampFISH, RNAscope, Split-FISH, AmpFISH, CircFISH, π-FISH rainbow and HT-smFISH. The application progress of smFISH in different biological disciplines, such as developmental biology, tumor biology, neurobiology. Finally, the development prospect of smFISH technology is prospected.]]> 2024/7/30 17:10:30 RUI Han,SUN Zheng-Long and GUAN Miao 295true etc. In summary, this review aims to introduce the dynamic modification of protein SUMOylation on various immune cells and the application of various inhibitors, thereby exploring its role in the TME. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs. In conclusion, the TME is a complex and dynamic environment that plays a crucial role in the development and progression of tumors. Understanding the intricate interactions within the TME and the role of PTMs, particularly SUMOylation, could provide valuable insights into the mechanisms of tumor development and potentially lead to the development of novel therapeutic strategies. The study of SUMOylation and its effects on various immune cells in the TME is an exciting and promising area of research that could significantly advance our understanding of tumor biology and potentially lead to the development of more effective treatments for cancer. This is a challenging but hopeful field, and we look forward to future research that can bring more breakthroughs.]]> 2024/7/30 17:10:31 ZHAO Pan-Pan,YU Jun-Xu,CHE Ya-Ning,LIANG Hui-Yi and HUANG Chao 294true 2024/7/30 17:10:32 CAO Can,TAO Yong-Guang and SHI Ying 293true 2024/7/30 17:10:32 JIANG Xi-Zhong,QIAO Shi-Yu,JIANG Tong,YAN Ying,XU Ying and WU Tong 292true 2024/7/30 17:10:33 HONG Tian,ZHANG Qin-Fen and FAN Jiao-Jiao 291true KIAA0319 gene is a DD-associated gene, potentially affecting reading ability by influencing brain development. This review provides an overview of the impact of KIAA0319 gene on brain development in fish, non-primate mammals, primate mammals, and humans. In studies involving fish, the kiaa0319 gene was found to be expressed in the brain, eyes and ears of zebrafish. In mammalian studies, abnormal Kiaa0319 gene expression affected neuronal migration direction and final position, as well as dendritic morphology during embryonic development in rats, leading to abnormal white and gray matter development. Knocking down the Kiaa0319 gene impaired the primary auditory cortex in rats, resulting in phoneme processing impairment similar to DD. In mice, Kiaa0319 overexpression affected the neuronal migration process, causing delayed radial migration of neurons to the cortical plate. Knockout of the Kiaa0319 gene led to abnormal development of the gray matter in mice, resulting in reduced volume of the medial geniculate nucleus and then impacting auditory processing. In primate studies, research on marmosets found that KIAA0319 gene is expressed in the visual, auditory, and motor pathways, while studies on chimpanzees revealed that KIAA0319 gene abnormalities primarily affected the gray matter volume and microstructure of the posterior superior temporal gyrus, morphology of the superior temporal sulcus and gray matter volume of the inferior frontal gyrus. The impact of KIAA0319 gene on human brain development is mainly concentrated in the left temporal lobe, where abnormal KIAA0319 gene expression caused reduced gray matter in the left inferior temporal gyrus, middle temporal gyrus and fusiform gyrus, as well as reduced white matter volume in the left temporoparietal cortex. Abnormalities in KIAA0319 gene also led to decreased hemispheric asymmetry in the superior temporal sulcus. The above-mentioned brain regions are crucial for language and reading processing. It is analyzed that the abnormalities in the DD-associated KIAA0319 gene affect neuronal migration and morphology during brain development, resulting in abnormal development of subcortical structures (such as the medial geniculate nucleus and lateral geniculate nucleus) and cortical structures (including the left temporal cortex, temporoparietal cortex and fusiform gyrus) which are involved in human visual and auditory processing as well as language processing. Impairment of the medial geniculate nucleus affects the information transmission to the auditory cortex, leading to impaired phoneme processing. Abnormalities in the magnocellular layers within the lateral geniculate nucleus hinder the normal transmission of visual information to the visual cortex, affecting the dorsal visual pathway. The left temporal lobe is closely related to language and reading, and abnormalities in its gray matter and connections with other brain areas can affect the language and word processing. In summary, abnormalities in the KIAA0319 gene can partly explain current research findings on the cognitive and neural mechanisms of DD, providing a genetic basis for theoretical models related to DD (such as general sensorimotor theory and the magnocellular theory). However, the mechanism of developmental dyslexia is complex, and there are mutual influences between different DD-associated genes and between genes and the environment, which require further exploration.]]> 2024/7/30 17:10:33 CHEN Jie,YU Xiao-Yun,YANG Yi-Ming and BAI Jian-E 290true via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.]]> 2024/7/30 17:10:34 XUE Yan,LI De-Zhu,XIE Hui-Ying,JIANG Chuan-Miao and ZHANG Jun-Fang 289true 2024/7/30 17:10:35 DAI Yu-Xi,HE Yu-Xiu and CHEN Wei 288true in vivo has been limited and enthusiasm for developing it to treat obesity-related complications has been dampened. However, FGF1 was found to induce cell proliferation primarily through FGFR3 and FGFR4, but its metabolic activity was mainly mediated by FGFR1. That is, FGF1 activity that promotes mitosis and anti-obesity-related complications appears to be separable. Currently, many engineered FGF1 variants have been developed, such as FGF1^ΔHBS, MT-FGF1^ΔHBS, FGF1^?NT, ?nFGF1, FGF1^R50E. Although the effect of FGF1 or its analogues on obesity-related complications has been demonstrated in many rodent studies, there are no relevant clinical results. This may be due to the unknown safety and therapeutic efficacy of FGF1 in large animals and humans, as well as concerns about tumorigenesis that hinder its development into a lifelong therapeutic agent. This review summarizes recent advances in the development of FGF1-based biologic drugs for the treatment of obesity-related complications, highlights major challenges in clinical implementation, and discusses possible strategies to overcome these obstacles.]]> 2024/7/30 17:10:35 JI Wei-Xiu,LI Meng and ZHAO Yun-Gang 287true Rev-erbα, also known as nuclear receptor subfamily 1 group D member 1 (Nr1d1), is a crucial regulatory factor in organisms. It exhibits circadian rhythmic expression in metabolically active tissues such as skeletal muscles, heart, liver, and adipose tissue, responding to various environmental stimuli. Rev-erbα plays a significant role in regulating circadian rhythms, metabolic homeostasis, and other physiological processes, earning its designation as an “integrator” of the circadian system and metabolism. Rev-erbα establishes complex connections with other clock genes through the transcriptional-translational feedback loop (TTFL), which is important for the rhythmic output of biological clock system and for the relative stability of phases and cycles. Mitochondrial biogenesis is a physiological process initiated by cells to maintain energy homeostasis by using existing mitochondria as a template for self-growth and division. As the “energy factory” of organism, disruptions in mitochondrial biogenesis are closely associated with the development of various diseases. Studies have shown that not only the factors involved in mitochondrial biogenesis have circadian oscillations, but also the morphology, dynamics and energy metabolism of mitochondria themselves have cyclic fluctuations throughout the day, suggesting that mitochondrial biogenesis is regulated by the biological clock system, in which the clock gene Rev-erbα plays a key role, it drives mitochondrial biogenesis and synergistically regulates autophagy to normalize a number of physiological processes in the body. Rev-erbα is sensitive to both internal and external environmental changes, and disruptions in circadian rhythms, metabolic diseases, and aging are significant inducers of changes in Rev-erbα expression, and its concomitant inflammation and oxidative stress may be an intrinsic mechanism for inhibiting mitochondrial biogenesis. Therefore, the enhancement of mitochondrial biogenesis by regulating the Rev-erbα activity status may be an important way to improve the pathology and promote the health of organism. Exercise, as a commonly accepted non-pharmacological tool, plays an important role in enhancing mitochondrial biogenesis and promoting health. It has been found that there is a close relationship between exercise and Rev-erbα. On the one hand, exercise stimulation directly affects the expression of Rev-erbα, especially high-intensity and long-term regular exercise; on the other hand, Rev-erbα achieves indirect regulation of exercise capacity by mediating processes such as skeletal muscle mitochondrial biogenesis and autophagy, muscle mass maintenance, energy metabolism and skeletal muscle regeneration. Based on the above findings, it is hypothesized that Rev-erbα may serve as a key bridge between exercise and mitochondrial biogenesis. Exercise enhances the transcriptional response of Rev-erbα in the nucleus, upregulates the expression of Rev-erbα protein in cytoplasm, activates the AMP-activated proteinkinase (AMPK)/ silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, regulates Ca²⁺ flux and downstream signaling molecules; meanwhile, exercise can upregulate antioxidant gene expression and alleviate oxidative stress through Rev-erbα, which ultimately enhances the function of mitochondria, and promotes mitochondrial biogenesis. In conclusion, the clock gene Rev-erbα emerges as a crucial target for exercise-induced enhancement of mitochondrial biogenesis. In this paper, the biological characteristics of Rev-erbα, the role of Rev-erbα in regulating mitochondrial biogenesis and the factors that may influence it, the interaction between exercise and Rev-erbα, and the potential mechanism of exercise-induced mitochondrial biogenesis via Rev-erbα are sorted out and discussed, which can provide theoretical references to the mechanism of exercise-promoted mitochondrial biogenesis.]]> 2024/7/30 17:10:37 YANG Ting-Ting,CHENG Feng-Jia,GAO Yang and YU Liang 286true ATG8 gene in yeast, many homologous genes have been identified in plant. The LIR/ AIM-docking site (LDS) of ATG8 protein contains W and L pockets and is responsible for binding to AIM. The ATG8 protein binds to UIM-containing proteins via UIM-docking site (UDS) instead of LDS. UDS is in the opposite position to LDS, so the ATG8 can bind both AIM and UIM proteins. Secondly, the structure and function of ATG8-binding proteins, especially the selective autophagy receptors, were systematically described. The protein NBR1 and Joka2, as proteaphagy receptors, guide ubiquitination protein aggregates to autophagosome for degradation by binding to AIM and ATG8 in Arabidopsis and tobacco, respectively. AtNBR1 also promotes plant immunity by binding the capsid protein of cauliflower mosaic virus and silencing suppressor HCpro of turnip mosaic virus, mediating pathogen autophagy. AtNBR1 still degrades chloroplast by microautophagy under photoinjure or chlorophagy during ibiotic stress. And the protein ORM mediates the degradation of plant immune receptor flagellin sensing 2 (FLS2) through AIM binding to ATG8. Interestingly, ATI1 and ATI2 participate in both chlorophagy and ERphagy. Otherwise, ER membrane protein AtSec62, soluble protein AtC53, and ubiquitin-fold modifier1-specific ligase 1 (UFL1) can be directly bound to ATG8 as ER autophagy receptors. As pexophagy receptor, AtPEX6 and AtPEX10 bind to ATG8 via AIM and participate in pexophagy. RPN10, as a 26S proteasome subunit, whose C-terminal UIM1 and UIM2 bind ubiquitin and ATG8, respectively, mediates the selective autophagy degradation of 26S proteasome inactivation when fully ubiquitinated. Plant-specific mitochondrial localization proteins FCS-like zinc finger (FLZ) and friendly (FMT) may also be mitophagy receptors. CLC2 binds to ATG8 via the AIM-LDS docking site and is recruited to autophagy degradation on the Golgi membrane. The tryptophan-rich sensory protein (TSPO) in Arabidopsis was involved in clearing free heme, porphyrin and plasma membrane intrinsic protein 2;7 (PIP2;7) through the combination of AIM and ATG8. The conformation of GSNOR1 changes during anoxia, exposing the interaction between AIM and ATG8, leading to selective degradation of GSNOR1. At last, the ATG8 binding proteins involved in autophagosome closure, transport and synthetic synthesis was summarized. For example, plant-specific FYVE domain protein required for endosomal sorting 1 (FREE1) is involved in the closure of autophagosomes during nutrient deficiency. Therefore, according to the recent research advances, the structure and function of plant ATG8-binding proteins were systematically summarized in this paper, in order to provide new ideas for the study of plant selective autophagy and autophagy.]]> 2024/7/30 17:10:37 ZHANG Feng-Juan,JING Hong-Juan,ZHOU Guang-Zhou,QIN Shuai-Jia and HAN Chu-Yan 285true + T cells were transformed into CD4⁺ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.]]> 2024/7/30 17:10:38 MA Guo-Rong,YANG Yong-Ze,MENG Xin,GAO Yu-Ting,LI Shu-Zhi,GUO Hong-Zhang and JIN Xiao-Dong 284true DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.]]> 2024/7/30 17:10:39 CHEN Dan-Dan,QIN Ke-Ning,Lü Chun-Li,ZENG Jian-Ye and WANG Xiao-Min 283true Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection and glycan editing. Biochemically, ENGase can specifically hydrolyze β-1,4 glycosidic bond between the two N-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.]]> 2024/5/21 19:59:51 LU Xin-Rong,TONG Yong-Liang,KONG Wei-Li,ZOU Lin,SHEN Dan-Feng,Lü Shao-Xian,LIU Rui-Jie,ZHANG Shao-Xing,ZHANG Yu-Xin,HOU Lin-Lin,SUN Gui-Qin and CHEN Li 282true in vitro. Additionally, studying such models offers a unique perspective for the prevention and treatment of neurodegenerative diseases. In this review, we summarize relevant research on functional network construction based on recording the electrical signals of neuronal networks cultivated on MEA. We focus on two aspects: 2D neuronal networks and 3D brain organoid development, as well as the effects of open-loop and closed-loop electrical stimulation on neuronal network plasticity. Lastly, we provide an outlook on the future applications of studying neuronal network plasticity using in vitro cultured networks.]]> 2024/5/21 19:59:55 SHAO Qi,MENG Wei-Wei,LI Xiao-Hong and SHAO Wen-Wei 281true 2024/5/21 20:00:04 ZHANG Ya-Ning and ZHANG Yi-Fei 280true 2024/5/21 20:00:06 ZHANG Yu-Xin,LIU Rui-Jie,ZHANG Shao-Xing,YUAN Shu-Ying,CHEN Yan-Wen,YE Yi-Lin,LIN Qian-Ge,LU Xin-Rong,TONG Yong-Liang,CHEN Li and SUN Gui-Qin 279true 2024/5/21 20:00:07 LEI Qian,DENG Yi-Hao and HE Hong-Yun 278true CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinic acid to regulate cysteine accumulation in vivo. Elevated levels of cysteine have been shown to be cytotoxic and neurotoxic, and this is the first important step in the breakdown of cysteine metabolism in mammalian tissues. The human CDO1 gene is located on chromosome 5q23.2. Studies have shown that deletion or epigenetic silencing of this chromosomal region contributes to tumorigenesis. It is highly expressed in the liver and placenta, and weakly in the heart, brain and pancreas. CDO1 is a tumor suppressor gene (TSG) with a wide range of functions, which can be involved in various biological processes such as tumor cell proliferation, differentiation, apoptosis and iron death, thus affecting the tumor development. CDO1 is epigenetically regulated in human cancers, compared to normal tissues. The CDO1’s mRNA or protein expression levels were significantly down-regulated in tumor tissues, whereas promoter DNA methylation of the CDO1 gene usually accumulates with the progression of human cancers. Aberrant hypermethylation on the CDO1 promoter is a common event in tumor cells, which leads to transcriptional inactivation and silencing of the CDO1 gene. High frequency of methylation of CDO1 gene promoter methylation region in a variety of tumors including breast, oesophageal, lung, bladder, gastric and colorectal cancers. CDO1 gene promoter methylation levels reflect cancer progression and malignant tumorigenesis, which is a common molecular indicator explaining poor prognosis in human cancers. Treatment with 5-aza-2′-deoxycytidine (a drug that promotes demethylation) reactivated the CDO1 expression in most cancer cell lines, indicating that the transcriptional expression of CDO1 is closely correlated with its promoter methylation level, CDO1 gene promoter methylation and tumor progression have also received increasing attention from researchers. It was found that CDO1 gene promoter hypermethylation can be used as an early tumor marker for clinical aid diagnosis and helps to differentiate cancerous from benign diseases. It was also found that CDO1 promoter DNA methylation showed reliable tumor monitoring potential in human body fluids, and furthermore, the degree of CDO1 promoter methylation was strongly correlated with resistance to chemotherapy with tumor drugs, which would be helpful in evaluating the efficacy of chemotherapeutic drugs. Thus, CDO1, a common promoter methylation gene in human cancers, is closely associated with the development of a wide range of tumors and is one of the most promising candidate genes for assessing tumor-specific epigenetic changes. This article reviews the biological functions of CDO1 and its promoter DNA methylation in tumors, focusing on the mechanism of CDO1 DNA promoter methylation in tumors, with a view to providing theoretical guidance for the clinical diagnosis and treatment of tumors with CDO1 as a potential therapeutic target.]]> 2024/5/21 20:00:09 ZHOU Yu,YU Hong-Bo,CAO Yuan and WANG Jun-Jie 277true 2024/5/21 20:00:12 LI Xiang and LI Ye 276true 2024/5/21 20:00:21 WU Sheng-Quan,YANG Meng and LIU Xin-Guang 275true 2024/5/21 20:00:24 ZHAO Ge,LUO Yuan,LI Ya-Ping,YAN Yan-Qing and LIU Shu-Jing 274true 2+ imbalance, mPTP opening, mitochondrial swelling, and release of pro-apoptotic proteins all lead to mitochondrial dysfunction and myocardial function impairment. Exercise is an effective intervention to prevent myocardial ischemia-reperfusion injury, and its protective effect is closely related to the intensity of exercise, the length of exercise time, the type of exercise and the internal exercise ability. The mitochondrial mechanism of exercise protection against myocardial ischemia-reperfusion injury is determined by many factors. During reperfusion, the heart after trained is better able to maintain energy homeostasis, maintain ΔΨ_m and limit mPTP activation, maintain ATP synthesis. Activation of the sarcoK_ATP and/or mitoK_ATP channels by exercise induces cellular and/or myocardial hyperpolarization, protecting the mitochondria and myocardium during MI/R. Exercise-trained hearts can regulate calcium homeostasis during MI/R and limit mitochondrial Ca²⁺ overload. Exercise training can improve the activity of mitochondrial antioxidant enzymes to clear ROS and regulate mitochondrial Ca²⁺ concentration during MI/R. Exercise can increase the bioavailability of NO near mitochondria and indirectly achieve exercise-induced myocardial protection through protein S-nitrosylation and the eNOS-NO pathway is related to mitochondrial biogenesis after exercise training. Exercise training can also affect mitochondrial dynamics during MI/R by preventing mitochondrial division and promoting mitochondrial fusion. Exercise training can promote autophagy of damaged mitochondria and reduces apoptosis through mitochondria too, thus helping to maintain the function of mitochondrial bank. Besides these, exercise training leads to the production of motor factors (mainly from the muscles, but also from the brain, red blood cells, and other tissues) that contribute to remote regulation of the heart. This paper reviews the mitochondrial mechanism of MI/R, the protective effect of exercise on MI/R and the role of mitochondria in it, in order to provide more theoretical basis and new therapeutic targets for the diagnosis and treatment of heart disease, and provide new targets for drug research and development. In future clinical treatment, it is expected that sports pills targeted mitochondria can treat MI/R injury for bedridden people who cannot exercise or people who do not want to exercise through new technological means such as nanoparticle packaging.]]> 2024/5/21 20:00:26 JI Wei-Xiu,GENG Yi,WANG Shuo and ZHAO Yun-Gang 273true 2024/5/21 20:00:31 JIN Dan,DAI Xin-Yu,LIU Miao,YI Xue-Jie and GAO Hai-Ning 272true 2024/5/21 20:00:45 QIU Yi,MA Wei-Wei,ZHANG Hui-Juan and TU Yi-Heng 271true –1. In terms of AEI methods, researchers improved the detection sensitivity, spatial resolution, signal to noise ratio and other performance indicators by improving AEI methods and optimizing AEI systems. In terms of ABI, it can utilize the acoustoelectric coupling mechanism to endow the target area with spatial features of ultrasound, and achieve noninvasive high resolution EEG detection. We review the important research achievements and significance layer by layer from the perspectives of feasibility verification, method system optimization, and clinical application exploration in acoustoelectric imaging. In terms of ACI, it can be used to quantitatively evaluate the spatial distribution and dynamic changes of cardiac current field, providing a new idea for real-time monitoring of cardiac electrophysiological state before and after surgery. We summarize and review the important research achievements and significance of ACI at each stage: in phantom, in vitro and in vivo. Finally, we discuss the future research direction by focusing on the challenges faced by key technical links such as focused ultrasound targeting, ultrasonic spatial coding and decoding, acoustoelectric sensing detection, and imaging system integration, in order to provide basis and inspiration for AEI technology system and clinical transformation.]]> 2024/5/21 20:00:59 ZHOU Yi-Jie,SONG Yi-Bo,SONG Xi-Zi,HE Feng and MING Dong 270true etc. As a good simplicity and low-cost analytical testing tools, they show good prospects in the field of rapid testing. Therefore, the rapid and sensitive detection of foodborne pathogens can be realized by combining the efficient recognition ability of CRISPR/Cas system and the simplicity of paper-based analytical devices. In this paper, we briefly introduce an overview of the CRISPR/Cas system for nucleic acid detection, and this section focuses on an overview of the features and principles of the class 2 system, including types II, V and VI, which uses a single effector. The application of CRISPR/Cas system based test paper analysis, lateral flow assay and microfluidic paper-based chips for the detection of foodborne pathogens are highlighted in the paper, and finally the advantages, current challenges and future prospects of CRISPR/Cas system in combination with paper-based analytical devices to establish detection methods are discussed.]]> 2024/5/21 20:01:05 LI Peng-Ru,SHEN Xing,MENG Jing-Nan,LUO Lin,WANG Juan and XU Zhen-Lin 269true Mesp2, leading to the formation of repetitive structures in somites. Advancements in live reporter and 2D culture systems have revealed that coupling delays in cell communication can maintain the synchronous segmentation clock between adjacent cells. Studies have shown that these coupling delays are controlled by Lfng gene, it can adjust coupling delays to fit in-phase oscillations by increasing the time required for intercellular DLL1-Notch signaling. To sum up, the dual homeostasis of opposing signaling gradients determines the segment boundaries, the distance traveled by a molecular oscillator in one oscillation cycle determines the somite size, and the delayed coupling in intercellular signaling regulates the synchronization of clock oscillations. These three factors interact with each other to form a segmentation clock network coordinating somitogenesis. Recent studies have revealed that the intercellular coupling delay mechanism is a major factor influencing the maintenance of oscillation synchronization. Intercellular coupling delay errors, such as increased or decreased delay time, can desynchronizing intercellular oscillations and resulting in somite fusion. However, the mechanisms governing how intercellular communication becomes involved in oscillation synchronization remains unclear. Congenital scoliosis (CS) is a result of anomalous development of the vertebrate which associate with somitogenesis malformation. We observed that deficiency or overdose of vitamin A intake in gestation may lead to CS. While the deep mechanism of how RA signaling regulates oscillation synchronization still need to be detected. With the rapid development of 3D culture systems, researchers have successfully recapitulated the formation of somite-like structures with antero-posterior identity and indicated that the rate of metabolism is directly proportional to that of development. In summary, deconstructing the segmentation clock in vitro facilitates the dissection of regulation networks of the segmentation clock and offers an excellent proxy for studying the metabolic regulation of somitogenesis speed across species and the mechanisms underlying the formation of bilateral symmetry. It also creates a platform for exploring dysregulation mechanisms involved in the development of pathological somite defects.]]> 2024/4/19 9:40:43 SUN Qing,WANG Yu,Jian CUO-A,HAO Yan and LI Yan 268true 2024/4/19 9:40:58 ZHAO Xiang-Dong,WANG Le,MA Lu-Jie,XIE De-Bao,GAO Meng-Di,MENG Ya-Nan and ZENG Fan-Li 267true in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.]]> 2024/4/19 9:41:02 WU Xin,YU Han-Jie,BAO Xiao-Juan,WANG Yu-Zi and LI Zheng 266true 2024/4/19 9:41:05 CHEN Yu-Hua,ZHENG Biao,CHENG Di,HE Yu-Lin and MO Zhong-Cheng 265true et al. reported Cas12a (Cpf1) as a member of the Class II type V CRISPR/Cas12a system, which possesses endonuclease activity. This finding holds great promise for its application in the field of biotechnology. In 2018, Doudna’s team first applied the CRISPR/Cas12a system for detecting HPV nucleic acid. The system comprises the following essential components in vitro detection: Cas12a, the crRNA sequence complementary to the target DNA, the PAM sequence, and the ssDNA reporter. Cas12a possesses a typical RuvC domain, displaying a canonical bilobed architecture that consists of a recognition (REC) lobe and a nuclease (NUC) lobe. The REC lobe contains the REC1 and REC2 domains, and the NUC lobe includes RuvC, PAM-interacting (PI), Wedge (WED), and bridge helix (BH) domains. The mature crRNA for Cas12a has a length of 42-44 nt, consists of repeat sequence (19/ 20 nt) and spacer sequence (23-25 nt). The crRNA spacer sequence has been found to require a length of 18 nt to achieve complete cleavage activity in vitro. Additionally, mutation in the bases of crRNA can indeed affect the activity of Cas12a. The PAM sequence plays a critical role in the recognition and degradation of DNA by the CRISPR/Cas system, enabling the system to distinguish between self and non-self genomic materials. Cas12a can effectively target the spacer sequence downstream of a T-rich PAM sequence at the 5" end. LbCas12a and AsCas12a both recognize the PAM sequences of 5"-TTTN-3", while FnCas12a recognizes the PAM sequences of 5"-TTN-3". All of these PAM sequences are located upstream on the non-template strand (NTS) at the 5" end. Cas12a (Cpf1), guided by the crRNA, binds to the target DNA by recognizing the PAM sequence. It exhibits the ability to induce arbitrary cleavage of ssDNA within the system while cleaving the target ssDNA or dsDNA. According to this feature, an array of nucleic acid detection methods has been developed for tumor detection and infection diagnostics, such as the DETECTR (RPA-CRISPR/Cas12a method) and HOLMES (PCR-CRISPR/Cas12a method) in 2018. Then, in 2019, Cas12aVDet (one-step detection method), where Cas12a protein was immobilized on the upper wall of the reaction tube. This not only prevented contamination from opening the tube but also reduced the detection reaction time. In 2021, the dWS-CRISPR (digital warm-start CRISPR) was developed as a one-pot detection method. It serves as an accurate approach for quantitatively detecting SARS-CoV-2 in clinical specimens. With the innovation of scientific technology, the high-sensitivity signal transduction technology has also been integrated with the CRISPR/Cas12a system, enabling direct detection of nucleic acids, and eliminating the need for nucleic acid amplification steps. Here, we elaborated the detection principles of CRISPR/Cas12a in in vitro detection. We discussed the different stages leading to the catalytic pathway of target DNA, and the practical applications of Cas12a in nucleic acid detection. These findings revealed a target interference mechanism that originates from the binding of Cas12a-guided RNA complex to complementary DNA sequences within PAM-dependent (dsDNA) regions. The crRNA-DNA binding activates Cas12a, enabling site-specific dsDNA cleavage and non-specific ssDNA trans-cleavage. The release of Cas12a ssDNase activity provides a novel approach to enhance the sensitivity and specificity of molecular diagnostic applications. Before these CRISPR/Cas12a-based nucleic acid detection methods can be introduced into clinical use, substantial work is still required to ensure the accuracy of diagnosis. Nevertheless, we believe that these innovative detection tools based on CRISPR/Cas will revolutionize future diagnostic technologies, particularly offering significant assistance in pathogen infection diagnosis for developing countries with relatively poor healthcare conditions and high prevalence of infectious diseases.]]> 2024/4/19 9:41:10 DANG Sheng,ZHANG Shuai and ZHAI Jing-Bo 264true etc., but their specificity, sensitivity and accuracy for the detection of chimeric RNA are poorly understood. With the development of sequencing technology, second-generation sequencing technology has shown strong data processing capabilities and can detect chimeric RNA through high-throughput sequence analysis. Currently, detection methods making use of high-throughput sequencing datasets includes FusionCatcher, SOAPfuse, EricScript, etc. For validation of the detected chimeric RNA, the commonly used methods include PCR, RPA, agarose gel electrophoresis, sanger sequencing, etc. The development of newly introduced techniques has led to the discovery of different novel chimeric RNA, the third and fourth generation sequencing has also been developed and nearly mature, and the sequencing technology taking PacBio as an example has also brought a new dawn to the discovery of chimeric RNA, but each of them has its advantages and disadvantages, mainly focusing on its cost, false positive rate, detection time, etc. This paper basically describes various different techniques that can be utilized for the detection and validation of chimeric RNA.]]> 2024/4/19 9:41:18 WANG Guang-Fu,DING Yong-Wei,TANG Yue and QIN Fu-Jun 263true 2024/4/19 9:41:19 ZUO Si-Cheng,WANG Dan,MO Yong-Zhen,LIU Yu-Hang,CAI Jiao-Di,GUO Can,XIONG Fang and CHEN Guo-Qun 262true de novo synthesis pathway. With the discoveries of enzymes involved in salvage pathway of sugar nucleotide synthesis and the development of one-pot multienzyme (OPME) method, the synthesis of sugar nucleotides was greatly simplified. Cell factory method employs the microbial living cells as a “processing plant” by engineering their metabolic pathways through genetic engineering technology. The cell factory method has high yield, and has been applied for efficient synthesis of several sugar nucleotides. Moreover, the strategy of gram-scale synthesis of multiple rare sugar nucleotides by cascade reactions from common sugar nucleotides using sugar nucleotides synthases cloned from different sources was illustrated. In recent years, the synthesis cost of sugar nucleotides has been further reduced through various ways, such as regeneration of nucleotides, regeneration of organic cofactors, and application of immobilized enzyme technology. Furthermore, through the continuous improvement of sugar nucleotide purification process, the use of high concentration of multi-enzyme cascade and rapid non-chromatographic purification process, the synthesis of multiple sugar nucleotides and their derivatives from monosaccharides was achieved, which gradually broke the limitations of the existing strategy. With the efficient synthesis of sugar nucleotides, their applications in various fields have been increasingly explored, including the synthesis of glycans and glycoconjugates, biochemical characterization of glycosyltransferases and bioorthogonal labeling strategies, which are of great significance to the research of biochemistry, glycobiology and the development of related pharmaceutical products.]]> 2024/4/19 9:41:23 HAO Meng,LIAN Jia-Qi,ZHANG Cui-Lu and GUAN Wan-Yi 261true etc. may become damaged, which adversely affects the repair function of normal cells around the wound, resulting in the formation of chronic wounds. The effectiveness of wound dressings as a treatment is well known. They can offer temporary skin damage protection, prevent or control wound infection, create an environment that is conducive to mending skin damage, and speed wound healing. Traditional dressings like gauze, cotton balls, and bandages, however, have the drawbacks of having no antimicrobial properties, having weak adhesive properties, having poor mechanical properties, being susceptible to inflammation, obstructing angiogenesis, needing frequent replacement, and being unable to create an environment that is conducive to wound healing. As an innovative bandage, self-assembled hydrogel has great water absorption, high water retention, superior biocompatibility, biodegradability and three-dimensional (3D) structure. With properties including hemostasis, antibacterial, anti-inflammatory, and antioxidant, the synthesized raw material itself and the loaded active compounds have a wide range of potential applications in the treatment of skin injuries and wound healing. This research begins by examining and discussing the mechanism of cross-linking in self-assembled hydrogels. The cross-linking modes include non-covalent consisting of physical interaction forces such as electrostatic interactions, π-stacking, van der Waals forces, hydrophobic interactions, and metal-ligand bonds, covalent cross-linking formed by dynamic covalent bonding such as disulfide bonding and Schiff bases. And hybrid cross-linking with mixed physical forces and dynamic covalent bonding. The next part describes the special structure and excellent functions of self-assembled hydrogels, which include an extracellular matrix-like structure, the removal of exogenous microorganisms, and the mitigation of inflammation and oxidative stress. It goes on to explain the benefits of using self-assembled hydrogels as dressings for skin injuries. These dressings are capable of controlling cell proliferation, loading active ingredients, achieving hemostasis and coagulation, hastening wound healing, and controlling the regeneration of the injured area. The development of self-assembly hydrogels as dressings is summarized in the last section. The transition from purely non-covalent or covalent cross-linking to hybrid cross-linking with multiple networks, from one-strategy action to multi-strategy synergy in exerting antimicrobial, anti-inflammatory, and antioxidant effects and from single-function to multi-functioning in a single product. Additionally, it is predicted that future developments in self-assembled hydrogels will focus on creating biomimetic gels with multi-strategy associations linkage from naturally self-assembling biomolecules peptides, lipids, proteins and polysaccharides; improving the properties and cross-linking of raw materials to enhance the storage capabilities of hydrogels and cross-linking techniques, realizing the recycling of hydrogels; conducting additional research and exploration into the cross-linking process of hydrogels; and realizing the gel’s controllable rate of degradation. Furthermore, combining 3D printing and 3D microscopic imaging technology to design and build one-to-one specialized gel dressings; using computer simulation and virtual reality to eliminate the time factor, resulting in self-assembled hydrogels that perfectly fit the ideal dressing.]]> 2024/4/19 9:41:24 LI Chao,GUO Yu-Feng and DANG Xu-Hong 260true 2024/4/19 9:41:27 XUE Yu,LIU Hai-Wei and LI Yang 259true e.g., face, biological motion) and their emotional characteristics affect pupil size. In essence, pupil size is believed to reflect an individual’s perception of social stimuli. It goes beyond simple physical properties and encompasses the processing of complex social information, including social contexts and interactions. The modulation of pupil size in response to social stimuli is believed to be driven by two key mechanisms: emotional arousal and social attention. When individuals encounter emotionally charged social cues, their pupils tend to dilate, indicating heightened emotional engagement. Similarly, the dilation of pupils when individuals focus on specific social cues suggests an increased allocation of cognitive resources to process relevant social information. Furthermore, the connection between pupil size and social information processing has provided intriguing findings in individuals with autism spectrum disorder (ASD). Known for their significant social deficits, individuals with ASD exhibited abnormal pupillary responses when presented with social stimuli. These findings raise the possibility of utilizing pupillary responses as a potential index for identifying individuals with ASD at a relatively younger age. Moreover, the incorporation of pupillary response measurements in the diagnosis holds great promise in transcending the limitations of the minimum diagnostic age. This can have important implications both in terms of theoretical understanding and practical applications related to the diagnosis and intervention of ASD.]]> 2024/4/19 9:41:42 GE Yi-ping,LI Shuo,WANG Li and JIANG Yi 258true etc. One way that environmental factors can affect gene expression is through epigenetic mechanisms. Epigenetics is a branch of genetics that studies the heritable changes in gene expression that are not caused by changes in DNA sequence. Epigenetic mechanisms include histone modifications, DNA methylation, and non-coding RNA regulation. These mechanisms can modulate the chromatin structure and accessibility, thereby affecting the transcriptional activity of genes. Chromatin is a complex of DNA and proteins that forms the chromosomes in the nucleus of the cell. The chromatin structure can be altered by adding or removing chemical groups to histones (proteins that wrap around DNA) or DNA itself. These chemical groups can either activate or repress gene expression by changing the affinity of transcription factors (proteins that bind to DNA and initiate transcription) or other regulatory molecules. Non-coding RNAs are RNA molecules that do not code for proteins but can regulate gene expression by interacting with DNA, RNA, or proteins. Epigenetic mechanisms provide a link between environmental stimuli and gene expression, and play an important role in various physiological and pathological processes, including drug addiction. Recent studies have shown that epigenetic mechanisms are involved in the regulation of neurotransmitter systems and neural plasticity in response to METH exposure. Neural plasticity is the ability of neurons to change their structure and function in response to experience or injury. Neural plasticity is essential for learning, memory, adaptation, and recovery. The expression of some genes related to METH addiction is altered by epigenetic modifications, such as histone acetylation, methylation, ubiquitination, and non-coding RNA regulation. These epigenetic changes may affect the synaptic function and morphology, neuronal connectivity, and circuitry formation in the brain regions implicated in METH addiction. Moreover, some epigenetic modifications may persist for a long time after METH withdrawal, suggesting that they may contribute to the development and maintenance of METH addiction. In this article, we review the current literature on the epigenetic mechanisms of METH addiction. We will first introduce METH and its pharmacological effects, and then discuss the epigenetic regulation of neurotransmitter systems and neural plasticity by METH. We will focus on the changes of histone, DNA, and RNA during METH addiction, and the possible causes and consequences of their relationship with METH addiction. We will also provide some perspectives on the potential applications of epigenetic interventions for METH addiction treatment.]]> 2024/4/19 9:41:45 LIU Ming-Xin,SI Zi-Zhen and LIU Yu 257true Nts) project to the tuberal nucleus (TU) via GABA signaling to suppress hedonic feeding.]]> 2024/4/19 9:41:46 MU Lian-Wei,WANG Ya-Rong,YAN Meng-Si and SHU Lin-Jie 256true 2024/4/19 9:41:48 ZHAO Jin-Jing,ZHOU Yang-Fan,ZHANG Bing-Ao,YI Ming,JIANG Hong and XU Sheng-Yong 255true BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.]]> 2024/3/20 17:39:06 WANG Yao,CHEN Guo-Jiang,FENG Jian-Nan,SHI Yan-Chun,WANG Jing and ZHENG Yuan-Qiang 254true e.g. PINK1, autophagy/beclin-1 regulator 1 (AMBRA1), acylglycerol kinase (AGK)) to enhance/reduce PINK1-Parkin-dependent mitophagy.]]> 2024/3/20 17:39:16 ZHANG Duo,XIA Zhi and SHANG Hua-Yu 253true Escherichia coli (E. coli), transcription tends to be coupled with translation, which is usually manifested in the mutual regulation of transcription and translation such as transcription polarity, transcription attenuation and synchronization of transcription and translation rates. Indirect coupling and physical coupling are two different models of the coupling. Indirect coupling maintained by the alarmone (p)ppGpp may require the assistance of DksA and TufA proteins. Physical coupling could be divided into those mediated by NusG or RfaH factors and those induced via “collision” under non-factor condition. Changes in transcription or translation in response to pressure will lead to mutual transitions among several coupling modes. Coupling is necessary for normal gene expression, and its release will contribute to adverse events such as transcription termination, R-loop formation, conflict between replication and transcription and mRNA cleavage. The related technologies of structural biology have clearly demonstrated the structural details and characteristics of partial coupled expressomes. These technologies, combined with methods like multiomics analysis, will provide deeper insights into the coupling. Significantly, the study of the coupling may bring new ideas for development of the targeted antibiotics.]]> 2024/3/20 17:39:17 SHEN Chong-Jie and Morigen 252true 2024/3/20 17:39:18 XING Ji-Xiang,LI Han-Shuang,LI Hai-Cheng and ZUO Yong-Chun 251true 2024/3/20 17:39:22 JIN Jun-Jie,LI Jing,HU Guang-Xuan,WU Ruo-Meng and YI Xue-Jie 250true 2024/3/20 17:39:28 FENG An-Ni,SUN Ren-Ren,XIAO Yu-Bo,ZENG Zhao-Ming,MO Zhong-Cheng and XIE Yuan-Jie 249true 2024/3/20 17:39:30 WANG Tian-Mu,REN Wu-Jing and TIAN Zhen-Jun 248true 3O₄ nanoparticles with peroxidase-like activity in 2007, a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays, inflammation control, antioxidant damage and tumor therapy, playing a key role in disease diagnosis and treatment. We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity. A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn²⁺, which induces the production of reative oxygen species (ROS) in tumor cells by breaking down H₂O₂ in physiological media through Fenton-like action, thereby inhibiting tumor cell growth. To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy, the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H₂O₂. In pathological states, where excess superoxide radicals are produced in the body, superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels, thereby protecting normal cells and slowing down the degradation of cellular function. Based on this principle, an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis. Starvation therapy, in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen, attenuates glycolysis and the production of intermediate metabolites such as nucleotides, lipids and amino acids, was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth. Furthermore, by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site, a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate. All these effects depend on the size, morphology, composition, surface modification and environmental media of the nanozyme, which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme. Although some progress has been made in the research of nanozymes in disease treatment and diagnosis, there are still some problems, for example, the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo, and the toxic effects of some heavy metal nanozymes material itself. Therefore, the construction of nanozyme systems with multiple functions, good biocompatibility and high targeting efficiency, and their large-scale application in diagnosis and treatment is still an urgent problem to be solved. (1) To improve the selectivity and specificity of nanozymes. By using antibody coupling, the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells. It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues, thereby improving targeting during tumor therapy. Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme. (2) To explore more practical and safer nanozymes and their catalytic mechanisms: biocompatible, clinically proven material molecules can be used for the synthesis of nanoparticles. (3) To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring. Thus, it can go out of the laboratory and face the market to serve human health in more fields, which is one of the future trends of nanozyme development.]]> 2024/3/20 17:39:33 LIU Hang,LI Yi-Xuan,QIN Zi-Tong,ZHAO Jia-Wen,ZHOU Yue-Jie and LIU Xiao-Fei 247true 2024/3/20 17:39:34 WU Wen-Ya and WANG Liang 246true 2024/3/20 17:39:35 XU Ling,WEI Cui-Na,LU Xian-Fu and LI Yi-Ming 245true 2024/3/20 17:39:36 SUN Jin-Yuan,YANG Yi,LUO Wen-Hao,ZHANG Hong and LUO Yang 244true 2024/2/22 16:33:02 YANG Hao-Ying,LIU Run-Han,FANG Meng-Ke,LIU Yang and ZHENG Meng 243true ATRX, IDH1, p53, etc. The lack of ALT glioma cell lines and preclinical ALT glioma models has limited the mechanistic studies of ALT glioma. Therefore, this review listed ALT glioma cell lines that derived from primary culture or gene editing in the last decade, as well as the xenografted animal models established by ALT glioma cell lines, and discussed the role and significance these cell and animal models play in preclinical studies.]]> 2024/2/22 16:33:04 TONG Jin-Kai,YAN Si-Xiang,ZHANG Yan-Duo,HOU Kai-Long,ZHANG Ke,ZHANG Hao-Nan,CHANG Shun and JIA Shu-Ting 242true 2024/2/22 16:33:05 LUO Xia and JIN Xiao-Feng 241true e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.]]> 2024/2/22 16:33:07 WAN Xing-Yu,GUO Huan-Ping,HUANG Rui-Hao,WANG Xiao-Qi,ZENG Ling-Yu,WU Tao,XIA Lin and ZHANG Xi 240true 2024/2/22 16:33:10 WANG Yun-Feng,ZHUANG Wan-Ru,MA Xian-Bin,NIE Wei-Dong and XIE Hai-Yan 239true _n+1X_nT_x (n=1-4), where M represents transition metal elements (such as Ti, Nb, Ta, etc.), X represents carbon and/or nitrogen, and T_x represents surface terminations (such as —OH, —F, =O, etc.). In recent years, MXenes have been widely applied in the biological field due to their high biocompatibility, abundant surface groups, good conductivity and photothermal properties. Due to the strong absorption of laser in the near infrared region, strong X-ray attenuation ability and surface easily modified by various molecules or nanoparticles, MXenes have been used as photothermal agents and contrast agents in the tumor therapy and tumor diagnosis. This paper reviews the application of MXenes and MXenes-based composites in tumor therapy and active targeting tumor therapy. According to the modal of action on tumor cells, it was divided into monotherapy, bimodal therapy and trimodal therapy. Among them, the monotherapy mainly used the photothermal properties of MXenes for photothermal therapy, studies have found that MXenes QDs can be used for chemodynamic therapy. In addition, sonodynamic therapy can also be achieved by loading the sonosensitizers on the surface of MXenes. Bimodal therapy and trimodal therapy are mainly used to load anticancer drugs, photosensitizers, metal particles and other substances on the surface of MXenes to achieve combination therapy. In contrast to the limited treatment efficacy and possible side effects arising from monotherapy, the development of bimodal therapy and trimodal therapy may harbor the collective merits of respective individual treatments and give rise to much higher anticancer efficacy at lower dosage of therapeutic agents administered, thus avoiding high-dose-induced side effects. The combined use of multiple treatments displayed superior advantages over monotherapy in producing an improved therapy outcome. According to the modal of entry into tumor cells, it was divided into passive targeting and active targeting. Active targeting therapy was mainly divided into homologous targeting therapy and targeting agents targeting therapy. The strategy of homologous targeting therapy was to coat MXenes with tumor cell membrane and increased the uptake of MXenes by tumor cells. Targeting agents targeting therapy used targeting agents to specifically bind to the receptors on the surface of tumor cells, subsequently, the precise uptake of MXenes by tumor cells was achieved. Finally, the current challenges and future development trends of MXenes in preparation technology and tumor therapy are discussed.]]> 2024/2/22 16:33:13 LIU Mei-Qing,ZHAO Lu,BAI Yun-Feng and FENG Feng 238true 2024/2/22 0:00:00 ZHANG Jie-Jie,NIU Chun-Yan,DONG Lian-Hua,YANG Yi,LI Hui-Jie and YANG Jing-Ya 237true 2024/2/22 16:33:17 HUANG Hui-Wei,LI Li-Hua,LUO Lin,SHEN Yu-Dong,LEI Hong-Tao and XU Zhen-Lin 236true e.g., sleep deprivation), this loss is compensated by extending or strengthening subsequent sleep. These phenomena are known as sleep homeostasis. The dysregulation of sleep homeostasis accompanies brain-related diseases such as schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. More importantly, it can significantly undermine the basis of traditional sleep hygiene practices for these diseases. Therefore, clarifying the mechanisms of sleep homeostasis is important for therapy, but it remains an unsolved mystery. In addition to pharmacological treatment, non-invasive brain stimulation has become one of the most promising tools for clinical treatment in recent years due to its low cost, portability and low incidence of side effects. In order to promote relevant technologies, this review will focus on the electrophysiological mechanisms of sleep homeostasis. We first discuss the electrophysiological marker of sleep homeostasis, slow-wave activity, then move to the neuronal firing rates, finally discuss more aspects of sleep homeostasis, including differences in brain area, sleep stages, learning and individual differences.]]> 2024/2/22 16:33:18 XIAO Xue,CHEN Dong,LIU Jia-Li and WANG Liang 235true etc. Cells can achieve intercellular signal communication by secreting and receiving exosomes. Through interaction of ligand molecules on the exosome membrane with receptors on the surface of other cytoplasmic membranes, exosomes can activate cell signal transduction or fuse with the cell membrane to release its contents into the cytoplasm to exert regulatory functions. In the central nervous system, exosomes secreted by neurons and various glial cells can mediate wired synaptic signal transmission, but mainly play a role similar to neuromodulator by way of volume transmission. In this paper, the biogenesis of exosomes and important functional components are described in detail, and the characteristics of neural exosomes in the biogenesis, content sorting and controlled release are compared with those of synaptic vesicles. We further review the research progress on the physiological functions of neural exosomes on the central nervous system and their roles in the occurrence and development of neurodegenerative diseases and major depressive disorder. We also prospect the application of exosomes in the early diagnosis and targeted therapy of nervous system diseases.]]> 2024/2/22 16:33:19 WANG Zi-Yuan,BAI Yu-Xuan,CAO Gang and DAI Jin-Xia 234true 2024/2/22 16:33:26 QIANG Long-Zheng,MAO Hai-Guang,WANG Meng-Ting,QI Li-Li and WANG Jin-Bo 233true V7 family and large-conductance Ca²⁺- and voltage-activated K⁺ (BK_Ca) channels are expressed in many tissues, therefore, their physiological importance is evident from the various disorders linked to dysfunctional K_V7 channels and BK_Ca channels. Thus, it is extremely important to learn how potassium channels are regulated by PUFAs. The aim of this review is to provide an overview of the effects of PUFAs on K_V7 channels and BK_Ca channels functions, as well as the mechanisms underlying these effects. In summarizing reported effects of PUFAs on K_V7 and BK_Ca channels mediated currents, we generally conclude that PUFAs increase the current amplitude, meanwhile, differential molecular and biophysical mechanisms are associated with the current increase. In K_V7 channels the currents increasement are associated with a shift in the voltage dependence of channel opening and increased maximum conductance in K_V7 channels, while in BK_Ca channels, they are associated with destabilization the pore domain closed conformation. Furthermore, PUFA effects are influenced by auxiliary subunits of K_V7 and BK_Ca channels, associate with channels in certain tissues. although findings are conflicting. A better understanding of how PUFAs regulate K_V7 and BK_Ca channels may offer insight into their physiological regulation and may lead to new therapeutic strategies and approaches.]]> 2024/1/19 11:49:58 SUN Yu-Jiao,CHANG Chao,WU Zhen-Hua,ZHANG Yi-Fei and TIAN Yu-Tao 232true 3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn²⁺SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn²⁺SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn²⁺SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn²⁺ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O₂^? to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O₂^? into the inner sphere, and avoid O₂^?/Mn²⁺ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH^-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.]]> 2024/1/19 11:50:23 ZHANG Xu,ZHANG Lei,XU Peng-Lin,LI Tian-Ran,CHAO Rui-Qing and HAN Zheng-Hao 231true in vitro anti-tumor efficacy. Moreover, some of these compounds have entered clinical trials. This review summarized the direct and indirect strategies for the treatment of cancers targeting mutant p53, with a primary focus on the mechanisms of action of small molecule compounds that reactivate mutant p53 protein or degrade mutant p53 protein. The aim is to provide assistance for the development of innovative drugs targeting mutant p53 protein in the future.]]> 2024/1/19 11:50:24 WANG Ruo-Ya,ZHANG Yuan,ZHANG Ji-Hong and YU Fei 230true 2+-dependent channel properties, and plays a crucial role in maintaining normal Ca²⁺ signaling in systemic physiology, particularly in ADPKD chronic kidney disease. Structurally, PC2 protein consists of six transmembrane structural domains (S1-S6), a polycystin-specific “tetragonal opening for polycystins” (TOP) domain located between the S1 and S2 transmembrane structures, and cytoplasmic N- and C-termini. Although the cytoplasmic N-terminus and C-terminus of PC2 may not be significant in the gating of PC2 channels, there is still much protein structural information that needs to be thoroughly investigated, including the regulation of channel function and the assembly of homotetrameric ion channels. This is further supported by the presence of human disease-associated mutation sites on the PC2 structure. Moreover, PC2 synthesized in the endoplasmic reticulum is enriched in specific subcellular localization via membrane transport and can assemble itself into homotetrameric ion channels, as well as form heterotrimeric receptor-ion channel complexes with other proteins. These complexes are involved in a wide range of physiological functions, including the regulation of mechanosensation, cell polarity, cell proliferation, and apoptosis. In particular, PC2 assembles with chaperone proteins to form polycystic protein complexes that affect Ca²⁺ transport in cell membranes, cilia, endoplasmic reticulum, and mitochondria, and are involved in activating cell fate-related signaling pathways, particularly cell differentiation, proliferation, survival, and apoptosis, and more recently, autophagy. This leads to a shift of cystic cells from a normal uptake, quiescent state to a pathologically secreted, proliferative state. In conclusion, the complex structural and functional roles of PC2 highlight its critical importance in the pathogenesis of ADPKD, making it a promising target for therapeutic intervention.]]> 2024/1/19 11:50:27 WANG Kai,HUANG Yuan,ZHOU Ce-Fan,TANG Jing-Feng and CHEN Xing-Zhen 229true via the hydrophobic acid pathway. In addition, since sulforaphane is easy to be absorbed and metabolized, wrapping sulforaphane with nanomaterials can improve its bioavailability and stability, prolong its action time in human body, and better utilize its therapeutic effect. In terms of mechanism of action, sulforaphane can activate Nrf2 and HSF1 signaling pathways, induce the expression of phase II detoxification enzymes HO-1, NADPH, GST and HSP, thus regulating the concentration of oxidative stress ROS in vivo; inhibit NF-κB signaling pathway, thus suppressing the expression of inflammatory factors TNF-α, IL-1 and IL-6; regulate epigenetic modifications, thus inhibiting HDAC and DNMT, and increasing the concentration of histone H3 and H4. By regulating the expression levels of the above factors, sulforaphane can affect the occurrence and development of cancer, neurodegenerative diseases and other diseases. In recent years, several phase I/II clinical trials have shown that sulforaphane has good drug-generating properties. For example, researchers have found that patients with skin cancer have not shown any health problems and their corresponding functional problems have improved greatly after long-term use of sulforaphane. This suggests that in the future sulforaphane has a very high medicinal potential for the treatment of cancer and neurodegenerative diseases. In this paper, we review the pharmacokinetics, target of action and safety of sulforaphane and its research progress in tumor and neurodegenerative diseases to provide a reference for the future application of sulforaphane in the treatment of tumor and neurodegenerative diseases.]]> 2024/1/19 11:50:30 WU Jian-Le,LIU Xi-Jian,LIU Ru-Hua,JIANG Feng and MIAO Dan 228true 2024/1/19 11:50:32 QU Jun,YAN Shuang,LEI Long-Tian-Yang,OUYANG Fei-Jun,ZHANG Hai-Tao and QIN Xu-Ping 227true 2024/1/19 11:50:35 WEI Gan-Jiang,WANG Ling,ZHU Jing-Nan,WANG Xiao,ZANG Yu-Ran,ZHENG Chen-Guang,YANG Jia-Jia and MING Dong 226true 2024/1/19 11:50:36 SUN Ying,SUN Xun-Wei,WANG Yi-Fan and FU Qiu-Fang 225true i.e., spatiotemporal-based grouping, object-based grouping, and feature-based grouping, according to different grouping cues (spatiotemporal continuity, global perception and organization of objects, and surface featural similarity). Grouping based on multiple cues will produce greater effects compared with one cue, this is the additive effect. The study of additivity is important for understanding the cognitive mechanisms of different grouping effects, the attentional mechanisms, and resource allocation in individual dynamic visual tracking. This study summarized previous behavioral and neuroimaging research and systematically explored the non-additivity based on different surface features and the additivity based on surface features and specific spatiotemporal features. Exploring the mechanism of additivity effects provides us with new insight into understanding grouping effects. For future studies, researchers need to thoroughly investigate the neural mechanisms of different kinds of groupings. This can not only provide explanations for the additivity of groupings but also provide substantial evidence for the classification of groupings.]]> 2024/1/19 11:50:37 WANG Chun-Di,LI Shu-Ting and DENG Hu 224true 2024/1/19 11:50:39 HONG Tian,LI Jing-Wen,LI Ren-Ai,CHEN Er-Ning,ZHAO Lu-Lu and DU Mei-Hong 223true etc. HITS-CLIP combines high-throughput sequencing with UV cross-linking immunoprecipitation. The 254 nm UV cross-linking and RNAase digestion steps allow the technology to capture transient intracellular RBP-RNA interactions. However, there are limitations in the efficiency of UV cross-linking, with low resolution and high intrinsic background noise. For PAR-CLIP, photoactivatable ribonucleoside was incorporated into RNA molecules, and RBP cross-linked with RNA by 365 nm UV light to improve cross-linking efficiency and resolution. Cross-linking mediated single-base mutations provide more accurate binding site information and reduce interference from background sequences. Long-term alternative nucleotide incorporation, on the other hand, can be cytotoxic and may skew experimental results. iCLIP can identify RBP-RNA cross-linking sites at the single nucleotide level through cDNA circularization and subsequent re-linearization steps, but it has more experimental procedures, and partial cDNAs lost in the circularization step are inevitable. eCLIP discards the radioisotope labeling procedure and reduces RNA loss by ligating adaptors in two separate steps, greatly improving the library-building efficiency, and reducing bias associated with PCR amplification; however, the efficiency of immunoprecipitation cannot be visually assessed at the early stage of the experiment. The irCLIP technique replaces radioisotopes with infrared dyes and greatly reduces the initial number of cells required for the experiment; however, an infrared imaging scanner is essential for the irCLIP application. To address more particular scientific issues, derivative CLIP-related techniques such as PAPERCLIP, cTag-PAPERCLIP, hiCLIP, and tiCLIP have also been developed in recent years. In practice, the aforementioned CLIP approaches have their advantages and disadvantages. When deciding on a technical strategy, we should take into account our experimental objectives and conditions, such as whether we need to precisely define the RNA site for binding to RBP; whether we have the necessary experimental conditions for working with radioisotopes or performing infrared imaging; the amount of initial sample size, and so on. In addition, the CLIP technique has a relatively large number of procedures and can be divided into several successive experimental modules. We can try to combine modules from different mainstream CLIP technologies to meet our experimental requirements, which also gives us more opportunities to improve and refine them and to build more targeted derivative CLIP technologies according to our research objectives.]]> 2024/1/19 11:50:42 DU Ya-Qiong,WANG Wan-Yao,GAO Fan,XU Yang and SHI Wen-Tao 222true 2024/1/19 11:50:46 SHEN Kai,GAO Fei,HUANG Xu-Qiang,LU Xiao-Peng,ZHOU Hui-Min,LI Wei-Rong and TIE Di 221true in vitro and in vivo in recent years, and provides a forward-looking perspective on future development directions.]]> 2024/6/4 15:08:53 XU Lin,HU Bo,ZHENG Lu-Lu,JIANG Shao-Ping,RUAN Shao-Bo and HUANG Yuan-Yu 220true 2024/6/26 13:33:56 LI Jia-Qi,SHI Rui-Xing,XU Jia-Yao,ZHENG Lu,WANG Ni-Ni,LI Ga-Long,FAN Hai-Ming and HE Yuan 219true 2024/6/21 12:24:30 HUANG Ning-Ning,QI Li-Li,WANG Jin-Bo,WANG Meng-Ting and WU Yu-Qin 218true 2024/7/3 14:21:29 WU Yi-Ying,ZHANG Wei and KONG De-Zhi 217true In vitro cellular models are crucial for elucidating the underlying mechanisms of neuroinflammation. Investigating neuroinflammatory signaling pathways is essential for understanding the intricate network of molecules and cells involved. Key signaling pathways such as NF-κB, MAPK, PI3K/AKT, Nrf2/HO-1, and NLRP3 play critical roles in regulating neuroinflammation. During inflammation, activation of glial cells involves multiple signaling pathways simultaneously, primarily orchestrated by two key factors: MAPK and NF-κB. These pathways guide the inflammatory cascade, leading to the release of numerous inflammatory factors and reactive oxygen species (ROS). These inflammatory factors and ROS have dual effects. Firstly, they can directly harm neighboring neurons, promoting the accumulation of abnormal proteins and triggering neuronal apoptosis. Secondly, inflammatory factor receptors on cell membranes can initiate positive feedback loops that exacerbate the inflammatory response. Neuroinflammation encompasses various cell types within the central nervous system, forming a complex and interconnected malignant cycle. This ultimately culminates in irreversible brain damage. Moreover, innovative therapeutic approaches targeting specific signaling pathways and molecular targets show promise in treating diseases related to neuroinflammation.Various cellular models are commonly employed to investigate neuroinflammation, each focusing on different aspects: pathogen-related models involve substances like lipopolysaccharide(LPS), amyloid β-protein(Aβ), CpG-DNA, and viruses; cytokine models utilize interferon-γ(IFN-γ); metabolic stress models include oxygen-glucose deprivation(OGD), 1-methyl-4-phenylpyridinium (MPP⁺), rotenone, and oxyhemoglobin; environmental toxin models encompass substances such as bisphenol A (BPA), particulate matter (PM2.5), various metals, and nanoparticles; additive substance models involve alcohol, morphine, and methamphetamine (METH). Each model offers distinct advantages and drawbacks for studying neuroinflammation. In conclusion, research on these cellular models and their associated signaling pathways provides crucial insights into the mechanisms underlying neuroinflammation-related diseases. These insights are essential for developing effective therapeutic strategies and advancing clinical practice to address the complexities of neuroinflammatory diseases.]]> 2024/7/3 14:27:06 DING Ye,SUN Bin-Lian and LI Wei-Ling 216true 2024/6/7 18:54:02 SUN Zhong-Guang,LI Ting-Ting,ZHANG Ming-Chen,ZHANG Hui,CHEN Ming-Hua and FENG Li-Xu 215true C/EBPβ, C/EBPδ, and PPARγ. KLF15 KO mice show reduced lipogenesis and increased lipolysis, highlighting its importance in fat storage and energy balance. In brown adipose tissue (BAT), KLF15 regulates genes involved in lipid uptake and thermogenesis, such as CD36, Slc25a20, and Cpt1a. KLF15 KO mice fail to maintain body temperature during fasting-induced cold exposure, demonstrating the critical role of KLF15 in BAT metabolism and energy balance. Specifically, KLF15 forms positive feedback loops with adipogenic transcription factors such as glucocorticoid receptor (GR), PPARγ, and C/EBP, promoting adipocyte differentiation and maturation. In BAT, KLF15 is crucial not only for regulating lipid uptake but also for promoting non-shivering thermogenesis by regulating thermogenic genes, thereby helping to maintain body temperature in cold environments. In protein metabolism, KLF15 regulates key enzymes involved in branched chain amino acid (BCAA) metabolism, such as BCAT2 and ALT, which are essential for gluconeogenesis and maintaining blood glucose levels. KLF15 KO mice show reduced expression of these enzymes, leading to impaired amino acid catabolism. KLF15 regulates muscle protein synthesis and degradation through the mTOR pathway and E3 ubiquitin ligases (e.g., Atrogin-1 and MuRF1), indicating its significance in muscle protein metabolism and stress response, especially in glucocorticoid-induced muscle atrophy. Studies have shown that KLF15 expression in muscle tissue is regulated by GR. Glucocorticoids regulate KLF15 expression through GR, which in turn affects the mTOR signaling pathway, inhibiting protein synthesis and promoting protein degradation. This mechanism is particularly significant in glucocorticoid-induced muscle atrophy. KLF15 also responds significantly to exercise, particularly acute endurance exercise and long-term aerobic training. Acute endurance exercise increases KLF15 expression in muscle and adipose tissue, enhancing lipid synthesis and protein catabolism. In contrast, chronic exercise reduces KLF15 expression, improving insulin sensitivity and mitigating diabetes-induced myopathy. However, further research is needed to explore the effects of different forms of exercise on KLF15 and its specific roles in various tissues. In conclusion, KLF15 plays a crucial role in maintaining overall metabolic balance. It regulates glucose, lipid, amino acid, and protein metabolism, responding to nutritional status and exercise to maintain energy homeostasis. The role of KLF15 in glucose metabolism involves regulating gluconeogenesis and glucose uptake, in lipid metabolism through regulating fat synthesis and breakdown, and in protein metabolism through influencing branched-chain amino acid metabolism and muscle protein synthesis and degradation. Future research should continue to delve into the specific mechanisms of KLF15 in different metabolic pathways, especially its regulatory roles under various exercise forms and nutritional states, to provide new perspectives and theoretical foundations for treating metabolic diseases.]]> 2024/9/10 14:31:21 YI Xue-Jie,LI Meng-Huan,YANG Yang,WAN Gen-Meng,DUAN Zi-Qiang and CHANG Bo 214true in vivo, and ultimately generates the active metabolite, benzopyrene dihydroxy epoxide (B[α]PDE) to exert a strong carcinogenic effect. In this paper, we provide an overview of the mechanisms involved in the malignant transformation of bronchial epithelial cells induced by B[α]PDE in terms of DNA base mutations, DNA repair function, related signaling pathways and epigenetic variations. B[α]PDE covalently binds to DNA bases to form B[α]PDE-DNA adducts, which cause DNA base mutations, inducing malignant transformation of bronchial epithelial cells and ultimate tumor formation. Interestingly, it was found that B[α]PDE-DNA adducts showed a high GC-dependent distribution and the single-nucleotide resolution profile of DNA damage profile was highly similar to that of mutations previously identified in the lung cancer genomes of smokers. B[α]PDE can also regulate the expression or silencing of proto-oncogenes and oncogenes by activating the classical AhR signaling pathway, as well as the PI3K/AKT/mTOR and NF-κB signaling pathways, inducing epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, and interfering with cellular metabolism and the cell cycle, thereby inducing the development of lung cancer. The genes mutated in B[α]PDE-induced malignant transformation of bronchial epithelial cells include the proto-oncogenes RAS, KIF11, and PPP1R13L as well as the oncogenes PHLPP2 and p53. B[α]PDE exposure leads to single nucleotide polymorphisms in the 3"-UTR of DNA repair enzyme gene, which inhibits the transcription of genes encoding proteins related to DNA damage repair, and subsequently affects the cell cycle, proliferation, and apoptosis of tumor cells. B[α]PDE exposure can induce lung carcinogenesis and progression by inducing hypomethylation of specific gene promoter regions to activate proto-oncogenes and hypermethylation to silence oncogenes. The aberrantly expressed miRNAs or lncRNAs may regulate the expression and signaling of lung cancer-related genes, thereby affecting lung cancer-related biological functions, including cell proliferation, apoptosis, migration and invasion. Poly(ADP-ribose) glycohydrolase (PARG) regulates DNA damage repair and maintains genomic stability, whereas silencing PARG inhibits B[α]PDE-induced deterioration of bronchial epithelial cells. B[α]PDE exposure induces metabolic reprogramming in cancer cells, which provides energy to cancer cells rapidly proliferation by increasing glucose uptake and glycolysis, and also regulates cancer cell growth and survival by affecting lipid and nucleic acid metabolism. In conclusion, in B[α]PDE-induced lung cancer, epigenetic changes such as DNA methylation, miRNAs, lncRNAs, metabolic reprogramming, and PARG work together to form a complex regulatory network that affects gene expression, cellular metabolism, and genomic stability. An in-depth study of the mechanism of B[α]PDE-induced malignant transformation of bronchial epithelial cells can provide a theoretical basis for the study of potential targets for the development of anti-tumor drugs, which will help to guide the prevention and treatment of lung cancer in polluted environments and exposure to smoky environments, and also provide theoretical support for the Healthy China measures of tobacco control and smoking ban.]]> 2024/6/25 17:03:46 YIN Zhang-Ya,LI Cong-Ya and ZHU Jun-Lan 213true 2024/7/10 15:38:53 ALan,LI Shuang-Yan,XU Gui-Zhi,WANG Long-Long and ZHENG Wei-Ran 212true 2024/5/30 15:08:02 LI Chuan-Bao,LI Chen-Hui and XUE Li 211true 2024/5/31 15:14:22 GUO Jun-Xia and LIU Sen 210true 2024/6/26 13:18:57 YANG Zi-Yan,JIANG Zhao-Hong,ZHOU Qian-Yi and CHEN Zhi-Ming 209true 2024/11/22 12:21:14 ZHANG Shi-Jia,ZHENG Juan-Xia and WANG Cheng-Wei 208true R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1^R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)-mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1^R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1^R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α-KG) and NADPH, so that the mutant IDH1^R132H catalyzes the hydrogenation of α-KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α-KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α-KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1^R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1^R132H mutant glioma.]]> 2024/5/31 13:51:41 YAN Si-Xiang,LI Yi-Fan,LI Yao,LI Yi-Xuan,LI Xiang-Xiu,TONG Jin-Kai,JIA Shu-Ting and DAN Ju-Hua 207true 2+ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.]]> 2024/11/22 12:21:19 MA Wen-Min,CHEN Xuan-Qi,MA Hong-Xia,ZHANG Wen-Hui,KONG Ling-Cong,ZHOU Yu-Jia,HU Yuan-Yuan and JIA Yu 206true 2024/6/27 18:53:57 JIN Dan,HUANG Rui-Qi,YAO Ting-Ting,YI Xue-Jie and GAO Hai-Ning 205true 2+, which enhances lipid peroxidation and reactive oxygen species (ROS) generation, ultimately leading to cell death. Studies show disrupted iron metabolism in PD patients, with elevated iron levels in dopaminergic neurons of the substantia nigra correlating with disease severity. Iron chelation therapy has shown promise in alleviating PD symptoms by reducing brain iron levels, highlighting the significance of iron metabolism in PD pathogenesis. Lipid peroxidation, a hallmark of ferroptosis, involves the oxidation of polyunsaturated fatty acids (PUFAs) in cell membranes, compromising membrane integrity and increasing permeability. Elevated lipid peroxidation in the substantia nigra contributes to neuronal damage in PD. Enzymes such as ACSL4 and LPCAT3, crucial in PUFA metabolism, play significant roles in ferroptosis. Exercise has been shown to modulate these enzymes, potentially reducing lipid peroxidation and preventing ferroptosis in PD. Glutathione (GSH) metabolism is another crucial factor in ferroptosis regulation. GSH depletion impairs ROS detoxification, exacerbating oxidative stress and lipid peroxidation. PD patients exhibit reduced GSH levels in the substantia nigra, making dopaminergic neurons more vulnerable to oxidative damage. Exercise enhances GSH synthesis and activity, mitigating oxidative stress and ferroptosis in PD. α-Synuclein aggregation, a hallmark of PD, is closely linked to iron metabolism and oxidative stress. Excessive α-synuclein binds to iron, promoting its aggregation and inducing ferroptosis. Exercise has been found to reduce α-synuclein accumulation and its pathological phosphorylation, potentially through the upregulation of neuroprotective proteins like DJ-1 and Irisin. These proteins enhance antioxidant defenses and facilitate α-synuclein degradation, providing a protective effect against PD progression. Additionally, glutamate excitotoxicity, driven by dysregulated glutamate metabolism and receptor activity, contributes to ferroptosis in PD. Exercise modulates glutamate levels and receptor expression, reducing excitotoxicity and iron-induced neuronal damage. In conclusion, emerging research suggests that exercise may inhibit ferroptosis through multiple mechanisms, including regulation of iron metabolism, enhancement of antioxidant defenses, reduction of α-synuclein aggregation, and modulation of glutamate metabolism. These findings highlight the potential of exercise as a non-pharmacological intervention in the prevention and treatment of PD. Further research is needed to elucidate precise mechanisms and optimize exercise protocols for maximum therapeutic benefit.]]> 2024/6/7 22:53:34 LU Dong-Lei,ZHANG Wen-Yu,TAN Si-Jie and YANG Feng-Ying 204true 2024/6/27 18:56:23 DING Dao-Bo,MU Wen-Jun,LI Xin,CHEN Huan,HOU Hong-Wei and HU Qing-Yuan 203true in vitro and in vivo toxicology experiments, it was found that the nanozyme demonstrates good biocompatibility and safety. It did not cause any significant changes in body weight, hematological indicators, or histopathology. These findings indicate the potential for its clinical applications. Based on current research results and discoveries, nanozymes have broad application prospects in the biomedical field. There are numerous potential research directions and application areas that are worthy of further exploration and development. Although there have been preliminary studies on the catalytic performance of nanozymes, further research is needed to thoroughly investigate their catalytic mechanisms. Further exploration of the interaction between nanozymes and substrates, reaction kinetics, and factors affecting catalytic activity will help to better understand their mechanism of action in the field of biocatalysis.]]> 2024/6/27 18:50:08 CHEN Shi-Qun,WANG Yi-Li,CHEN Zuo-Hong,WANG Hao and ZHANG Xiao-Dong 202true Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.]]> 2024/11/22 12:23:04 LI Hong-Ru,LEI Cai-Hong,LIU Shu-Wen,YANG Yuan,CHEN Hai-Xia,ZHANG Run,CUI Yin-Jie and LI Zhong-Zheng 201true 2024/11/22 12:23:06 ZHAO Chang-Hong,WANG Fei-Fei,LIAN Hong-Qiang and WANG Ye-Ying 200true etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.]]> 2024/11/22 12:23:07 WANG Cheng-Yun,LAN Xin-Yue,GU Jia-Xuan,GAO Xin-Ru,ZHU Long-Jiao,LI Jun,FANG Bing,XU Wen-Tao and TIAN Hong-Tao 199true in vivo, the main way is decorporation therapy, which mainly uses specific decorporation agents to selectively bind radionuclides to form stable non-toxic complexes, thereby preventing their deposition in the body, accelerating excretion, and reducing the total accumulation of radionuclides in human tissues. At present, internal radionuclide decorporation agents promote the release of radionuclides from the body mainly by stopping the entry of radionuclides into the body, ion exchange, chelation, and binding of exportants to carriers. But recent studies have found that lysosomal exocytosis, the natural clearing function of activated cells, also has a significant exportation effect. In this paper, we first introduced and analyzed the mechanism and research status of radionuclide decorporation agents that have been used in clinical practice, such as the blocking effect of potassium iodide, the ion exchange effect of Prussian blue, the chelation effect of DTPA, and the urine alkalinization effect of sodium bicarbonate. The second part introduces the mechanism and research status of promising radionuclide decorporation agents. Among them, 3,4,3-LI (1,2-HOPO) and 5-LIO (Me-3,2-HOPO) are the most promising ones and have been approved for phase I clinical trials. Others such as catecholamines, polyethyleneimine and fullerenes are also being studied with great potential. Polyethyleneimine, as a biological macromolecular chelator, has more chelating sites and stronger targeting effects than small molecule chelators, and has achieved a real breakthrough in decorporation. Fullerenes are known as “free radical sponges” with good free radical scavenging ability and antioxidant properties. In recent years, biomaterials have been widely used in the field of radionuclide decorporation, which has greatly improved the decorporation efficiency. Chitosan and pectin have shown great advantages in promoting radionuclide decorporation, chitosan can adsorb metal ions through electrostatic interaction and chelation, and can also react with free radicals to remove free radicals generated after radionuclides enter the body. Pectin can promote uranium efflux, but the exact mechanism remains unclear. Liposomes and nanomaterials as carriers enhance the intracellular drug delivery, prolong the retention time of drugs in the body, reduce adverse reactions, and make the traditional efflux enhancers glow with new vitality and have good development prospects. The last part summarizes and looks forward to the future research direction of radionuclide decorporation agents. At present, the research on decorporation agents at home and abroad is mostly stuck in the stage of drug development and drug synthesis, and few have actually entered the clinical trial stage. Therefore, the optimization of existing decorporation agents and the development of new ligands are critical. The targeting, biological safety, oral availability, and treatment needs of large-scale contamination scenarios are still the focus of attention. In addition, from the point of view of the mechanism itself, it is a new idea to promote the emission of radionuclides by activating potential channels, which can be continuously explored.]]> 2024/11/22 12:23:10 KOU Bing-Yan,GUO Yu-Feng,DANG Xu-Hong and LIU Xiao-Ming 198true via ER-LD bridging structures, enabling localized lipid production and surface expansion, ultimately resulting in the formation of mature LDs. Biochemical and biophysical approaches have revealed important features of this process, underscoring the critical roles of ER membrane biophysical properties and specific phospholipids. Structural biology and proteomic studies have identified key regulators—particularly Seipin and FIT2—as central players in LD biogenesis. This review systematically summarizes recent advances in the molecular mechanisms of LD biogenesis. It delves into the processes of LD nucleation, membrane budding, and expansion in eukaryotic cells, with a special focus on how core factors such as Seipin and FIT2 dynamically regulate LD morphology. In addition, it examines the mechanisms and pathways by which class I and class II proteins are targeted to LDs, compares LD biogenesis involving different neutral lipid cores, and discusses the disease relevance of specific regulatory proteins. Finally, the review outlines critical unresolved questions in the field of LD biogenesis, offering clear directions for future research and providing a comprehensive framework for deepening our understanding of LD formation and its implications for disease intervention.]]> 2025/6/28 9:12:19 YU Yue,JI Wei-Ke and XIONG Juan 197true 2025/6/19 14:50:24 LIU Yao-Zhou,BIAN Zheng,HUANG Chun-Cui and LI Yan 196true THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4research (1) The fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.]]> 2025/7/11 16:32:37 HUANG De-Ying,LI Yan-Hong,BAI Xiu-Feng and LIU Yi 195true e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid beta protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ-oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.]]> 2025/6/23 15:13:47 CHEN Ke-Han,YANG Zheng-Jiang,GAO Zi-Xin,YAO Yuan,YAO De-Zhong,YANG Yin and CHEN Ke 194true 2025/8/1 10:06:27 ZHENG Li-Ling,LIN Yong-Luan,CHEN Mei-Ling,ZHONG Zheng-Yan and ZHONG Shuping 193true 2025/6/23 16:48:37 FANG Jia-Wen,ZHE Chao,XU Ling-Ting,LI Lin-Hai and XIAO Bin 192true 2025/6/12 18:30:47 ZHAO Mao,FENG Jin-Qiu,GAO Ze-Qi,WANG Ping and FU Jia 191true 2025/7/10 11:06:12 NING Wei-Chen,HUA Yu,YOU Hui-Ling,LI Qiu-Shi,WU Yao,LIU Yun-Long and HU Zhen-Xin 190true via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.]]> 2025/7/4 7:59:17 ZHANG Tong-Tong,ZHANG Hao-Zhuo,HE Li,LIU Jia-Wei,WU Jia-Zhen,SU Wen-Hua and DAN Ju-Hua 189true via its receptor tyrosine kinase receptor B (TrkB), while also diminishing local inflammation in peripheral tissues by influencing macrophage polarization. Exercise, as a non-pharmacological intervention, is extensively employed to enhance metabolic disorders. A crucial mechanism underlying its efficacy is the significant induction of BDNF expression in central (hypothalamus, hippocampus, prefrontal cortex, and brainstem) and peripheral (liver, adipose tissue, intestines, and skeletal muscle) tissues and organs. This induction subsequently regulates inflammatory responses, ameliorates metabolic conditions, and decelerates disease progression. Consequently, BDNF is considered a pivotal molecule in the motor-metabolic regulation axis. Despite prior suggestions that BDNF may have a role in the regulation of exercise-induced inflammation, systematic data remains inadequate. Since that time, the field continues to lack structured descriptions and conversations pertinent to it. As exercise physiology research has advanced, the academic community has increasingly recognized that exercise is a multifaceted activity regulated by various systems, with its effects contingent upon the interplay of elements such as type, intensity, and frequency of exercise. Consequently, it is imperative to transcend the prior study paradigm that concentrated solely on localized effects and singular mechanisms and transition towards a comprehensive understanding of the systemic advantages of exercise. A multitude of investigations has validated that exercise confers health advantages for individuals with metabolic disorders, encompassing youngsters, adolescents, middle-aged individuals, and older persons, and typically enhances health via BDNF secretion. However, exercise is a double-edged sword; the relationship between exercise and health is not linearly positive. Insufficient exercise is ineffective, while excessive exercise can be detrimental to health. Consequently, it is crucial to scientifically develop exercise prescriptions, define appropriate exercise loads, and optimize health benefits to regulate bodily metabolism. BDNF mitigates metaflammation via many pathways during exercise. Initially, BDNF suppresses pro-inflammatory factors and facilitates the production of anti-inflammatory factors by modulating bidirectional transmission between neural and immune cells, therefore diminishing the inflammatory response. Secondly, exercise stimulates the PI3K/Akt, AMPK, and other signaling pathways via BDNF, enhancing insulin sensitivity, reducing lipotoxicity, and fostering mitochondrial production, so further optimizing the body’s metabolic condition. Moreover, exercise-induced BDNF contributes to the attenuation of systemic inflammation by collaborating with several organs, enhancing hepatic antioxidant capacity, regulating immunological response, and optimizing “gut-brain” axis functionality. These processes underscore the efficacy of exercise as a non-pharmacological intervention for enhancing anti-inflammatory and metabolic health. Despite substantial experimental evidence demonstrating the efficacy of exercise in mitigating inflammation and enhancing BDNF levels, numerous limitations persist in the existing studies. Primarily, the majority of studies have concentrated on molecular biology and lack causal experimental evidence that explicitly confirms BDNF as a crucial mediator in the exercise regulation of metaflammation. Furthermore, the outcomes of current molecular investigations are inadequately applicable to clinical practice, and a definitive pathway of “exercise-BDNF-metaflammation” remains unestablished. Moreover, the existing research methodology, reliant on animal models or limited human subject samples, constrains the broad dissemination of the findings. Future research should progressively transition from investigating isolated and localized pathways to a comprehensive multilevel and multidimensional framework that incorporates systems biology and exercise physiology. Practically, there is an immediate necessity to undertake extensive, double-blind, randomized controlled longitudinal human studies utilizing multi-omics technologies (e.g., transcriptomics, proteomics, and metabolomics) to investigate the principal signaling pathways of BDNF-mediated metaflammation and to elucidate the causal relationships and molecular mechanisms involved. Establishing a more comprehensive scientific evidence system aims to furnish a robust theoretical framework and practical guidance for the mechanistic interpretation, clinical application, and pharmaceutical development of exercise in the prevention and treatment of metabolic diseases.]]> 2025/6/23 11:07:20 DAI Yu-Xi,WANG Wei-Huan and HE Yu-Xiu 188true via restoring the number of dopaminergic neurons in the SN and striatum, increasing striatal dopamine contents, and reducing α-synuclein (α-syn) accumulation in the SN. In addition, BDNF also alleviates motor symptoms of PD by enhancing long-term potentiation and increasing the spine density of spiny projection neurons in the striatum, while GDNF by inhibiting neuroinflammation in the SN via suppressing the activation of microglia, reducing interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expressions, reducing the phosphorylation of inhibitor of nuclear factor kappa Bα (IκBα), and increasing the anti-inflammatory factors IL-10 and transforming growth factor-β (TGF-β). Secondly, exercise, a main trigger for irisin secretion from skeletal muscle, can improve PD motor symptoms by stimulating the irisin/adenosine monophosphate-activated protein kinase (AMPK)/Sirtuin-1 (SIRT1) pathway. Specifically, irisin alleviates motor symptoms in PD through multiple mechanisms, including inhibiting excessive mitochondrial fission by reducing the expressions of dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1), alleviating the apoptosis of dopaminergic neurons by increasing B-cell lymphoma 2 (Bcl-2) expression and reducing Bcl-2-associated X protein (Bax) and caspase 3 expressions, and restoring the number of dopaminergic neurons. Thirdly, new biomarkers of PD (cathepsin B and Fetuin-A) also play roles in PD development. Cathepsin B can promote the clearance of pathogenic α-syn in PD by enhancing the function of lysosomes, including strengthening the lysosomal degradation capacity, elevating the transport rate, and increasing the activity of lysosomal glucocerebrosidase (GCase). Fetuin-A has been demonstrated to improve PD by restoring the number and the morphology of Purkinje cells, which are the only efferent neurons in the cerebellar cortex and play an important role in maintaining motor coordination. This review aims to facilitate a deep understanding of the mechanism by which exercise improves PD motor symptoms and provide a theoretical basis for promotion of exercise in PD.]]> 2025/6/19 14:48:04 PENG Jin,LIU Yu and WANG Xiao-Hui 187true in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β-protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.]]> 2025/7/11 16:22:53 XU Lu-Tao,LI Qian,HAN Shu-Lei,CHEN Huan,HOU Hong-Wei and HU Qing-Yuan 186true in vivo tracking of cellular processes has opened new avenues for early and accurate disease detection. In the realm of disease treatment, quantum dots serve as versatile nanocarriers for targeted drug delivery. Their nanoscale size and surface modifiability allow them to transport therapeutic agents to specific sites, improving drug bioavailability and reducing off-target effects. Additionally, quantum dots have shown promise as photosensitizers in photodynamic therapy (PDT). When exposed to specific wavelengths of light, quantum dots interact with oxygen molecules to generate reactive oxygen species (ROS), which can selectively destroy malignant cells, vascular lesions, and microbial infections. This targeted approach minimizes damage to healthy tissues, making PDT a promising strategy for treating complex diseases. Despite these advancements, the translation of quantum dots from research to clinical application faces significant challenges. Issues such as toxicity, stability, and scalability in industrial production remain major obstacles. The potential toxicity of quantum dots, particularly to vital organs, has raised concerns about their long-term safety. Researchers are actively exploring strategies to mitigate these risks, including surface modification, coating, and encapsulation techniques, which can enhance biocompatibility and reduce toxicity. Furthermore, improving the stability of quantum dots under physiological conditions is crucial for their effective use in biomedical applications. Advances in surface engineering and the development of novel encapsulation methods have shown promise in addressing these stability concerns. Industrial production of quantum dots also presents challenges, particularly in achieving consistent quality and scalability. Recent innovations in synthesis techniques and manufacturing processes are paving the way for large-scale production, which is essential for their widespread adoption in clinical settings. This article provides an in-depth analysis of the latest research progress in quantum dot applications, including drug delivery, bioimaging, biosensing, photodynamic therapy, and pathogen detection. It also discusses the multiple barriers hindering their clinical use and explores potential solutions to overcome these challenges. The review concludes with a forward-looking perspective on the future directions of quantum dot research, emphasizing the need for further studies on toxicity mitigation, stability enhancement, and scalable production. By addressing these critical issues, quantum dots can realize their full potential as transformative tools in disease diagnosis and treatment, ultimately improving patient outcomes and advancing biomedical science.]]> 2025/4/11 8:37:28 SHEN Ji-Sheng, QI Li-Li, WANG Jin-Bo, KE Zhi-Jian, WANG Qi-Chao 185true 2025/5/19 14:05:50 GAO Fan, YANG Ming, CHEN Zhong 184true 2025/5/11 14:09:41 Lü Meng-Lin, LIU Xing-Ran, KOU Xian-Juan 183true 2025/5/6 21:09:11 ZHAO Yi-Ge, JIANG Zhao-Hong, ZHOU Qian-Yi, CHEN Zhi-Ming 182true 2025/6/5 15:59:15 TAO Lin-Jie, XU Fan-Ding, GUO Yu, LONG Jian-Gang, LU Zhuo-Yang 181true Myc, which drives the upregulation of polyamine biosynthetic enzymes, resulting in excessive intracellular polyamine production. Additionally, M2-polarized tumor-associated macrophages (M2-TAMs) contribute to polyamine accumulation by upregulating arginase-I (Arg-I), an enzyme that catalyzes the conversion of arginine into ornithine—a key precursor in the polyamine biosynthetic pathway. These combined sources lead to sustained polyamine enrichment in the TME, contributing to immune dysfunction and supporting tumor progression. Moreover, polyamines indirectly affect T cell activity by modulating macrophage polarization and directly suppress tumor cell apoptosis, further promoting an immunosuppressive environment. This review highlights the multifaceted roles of polyamines in modulating tumor-infiltrating T cell function, with a particular focus on their influence on CD4+ T cell differentiation, CD8+ T cell cytotoxicity, and immune checkpoint molecule expression. Recent studies suggest that polyamines suppress CD4+ T cell activation and differentiation by modulating the MAPK/ERK signaling pathway. Additionally, polyamines can impair T cell receptor (TCR) signaling and promote immune evasion through the upregulation of PD-L1 expression on tumor cells. These effects collectively contribute to weakened antitumor T cell responses. Polyamine blocking therapy (PBT), which primarily targets polyamine biosynthesis and transport, has emerged as a novel adjunctive immunotherapeutic strategy in cancer treatment. By reducing polyamine levels in the TME, PBT restores T cell effector functions and alleviates immunosuppression. Notably, studies have demonstrated that combining PBT with ICIs produces synergistic antitumor effects and may overcome resistance to ICI monotherapy. Although research has revealed the inhibitory effects of polyamines on T cell immune function, the underlying regulatory mechanisms remain to be fully elucidated. Moreover, due to compensatory mechanisms employed by tumor cells to maintain polyamine homeostasis, multi-targeted approaches may be necessary to achieve safe and effective therapeutic outcomes. Future PBT strategies may benefit from the integration of multi-omics technologies and the development of nanocarrier-based drug delivery systems, which could collectively enhance their specificity, efficacy, and applicability in cancer immunotherapy. This review systematically elucidates the immunomodulatory effects of polyamines on T cell function within the TME and provides theoretical support and novel insights for the advancement of tumor immunotherapeutic strategies.]]> 2025/5/15 10:41:55 AI Yuan-Bao, HUANG Xue-Mei, LIU Sen 180true 2025/5/18 10:40:11 LI Pei-Yang, LI Feng-Qi, HOU Xiao-Jun, LI Xue-Ren, MU Xin, LIU Hui-Min, PENG Shou-Chun 179true etc.), and signaling pathways such as Wnt/β-catenin and PEAK1. eIF5A can influence tumor cell proliferation, invasion, and metastasis by regulating EMT-related signaling pathways. The known signaling pathways through which eIF5A regulates EMT include the canonical Smad signaling pathway and non-canonical pathways such as Rho/Rac1, Twist, STAT3, and MAT1. Additionally, certain miRNA family members, such as miR-30b, miR-599, and miR-203, can bind to the 3"-UTR of eIF5A2, inhibiting its expression and subsequently suppressing the EMT process in cancer cells, including gastric cancer and colorectal cancer. GC7, an inhibitor targeting the key enzyme DHPS involved in eIF5A modification, has been shown to reverse the EMT mechanism in oral squamous cell carcinoma, lung cancer, and breast cancer by regulating cytokine-mediated signaling pathways, including HIF-1α, STAT3/c-MYC, and Twist. However, to date, no inhibitors directly targeting eIF5A have been developed. In recent years, the mechanism of eIF5A activation catalyzed by DHPS and DOHH has become increasingly clear. As the only protein involved in lysine deoxyhydroxymethylation, DHPS may play a more critical role than eIF5A in the overall signal transduction process. Through in-depth analysis of the DHPS protein structure and its active site, researchers have shifted their approach to DHPS inhibitor development from substrate analog inhibitors (such as GC7, CNI-1493, DHSI-15, etc.) to allosteric inhibitors (11g, 26d, 8m, GL-1, etc.). GC7 is not suitable for clinical trials due to its lack of specificity and low bioavailability, and the therapeutic potential of novel allosteric inhibitors has yet to be clarified. Therefore, there is a significant gap in the development of covalent drugs targeting DHPS for cancer treatment in clinical settings. This paper reviews the research progress on eIF5A in regulating EMT, focusing on the molecular mechanisms by which eIF5A influences tumor cell invasion and migration. It also discusses the characteristics and current limitations of inhibitors targeting the hypusine pathway, aiming to provide insights for studying tumor metastasis mechanisms and drug discovery.]]> 2025/4/9 15:11:00 PENG Can-Ming, WANG Juan-Ping, LIU Sen 178true 2025/4/17 14:50:37 JI Wei-Xiu, Lü Jia-Lin, MA Yi-Fan, ZHAO Yun-Gang 177true 2025/6/3 10:08:30 CHENG Xin-Yue, YAO Feng-Hua, ZHANG Hui, YAO Yong-Ming 176true in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.]]> 2025/5/21 7:16:57 LI Zhen-Hua, MA Hui-Zhen, WANG Hao, LIU Chang-Long, ZHANG Xiao-Dong 175true 2025/5/24 7:16:09 YANG Xin, LI Ke, LIU Ran, ZHAO Xu-Dong, WANG Hua-Lin, MAO Lan-Qun, HOU Li-Juan 174true 2025/4/4 12:43:16 WANG Peng-Xiao,CHEN Le-Rong,WANG Zhen,LONG Jian-Gang and PENG Yun-Hua 173true Caenorhabditis elegans, serving as the primary ATP supplier for cell division and differentiation while also acting as a key regulator of zinc ion homeostasis, membrane dynamics, and apoptotic signaling. This review systematically summarizes the essential mitochondrial mechanisms at different stages of sperm development, highlighting their multifaceted contributions beyond energy metabolism. Mitochondria are crucial for maintaining the health and stability of the gonads by regulating key apoptotic execution proteins that facilitate the proper elimination of damaged or unnecessary germ cells. Additionally, mitochondria dynamically adjust their energy supply to meet the metabolic demands of different stages of germline development. During early spermatogenesis, mitochondria provide ATP to fuel mitotic and meiotic divisions, support cellular differentiation, and regulate H⁺ and Zn²⁺ exchange to maintain cytoplasmic homeostasis, thereby ensuring the proper maturation and functionality of sperm cells. As spermatogenesis progresses, mitochondria participate in processing and sorting essential sperm proteins, such as major sperm protein (MSP), and contribute to the formation of membranous organelles (MOs), which are critical for subsequent activation events. During sperm activation, mitochondria play a dual role in ensuring a successful transition from immotile spermatids to fully functional spermatozoa. First, they provide ATP to facilitate pseudopod formation, MO fusion, and ion channel regulation, all of which are essential for sperm motility and fertilization potential. Second, mitochondria regulate the quality and quantity of functional mitochondria within sperm cells through mitopherogenesis—a recently discovered process in which mitochondrial vesicles are selectively released, ensuring that only healthy mitochondria are retained. This quality-control mechanism optimizes mitochondrial function, which is crucial for sustaining sperm motility and longevity. Beyond their traditional role in energy metabolism, mitochondria may also contribute to protein synthesis during spermatogenesis and activation. Recent evidence suggests that mitochondrial ribosomes actively translate specific proteins required for sperm function, challenging the long-standing belief that spermatozoa do not engage in de novo protein synthesis after differentiation. This emerging perspective raises important questions about the role of mitochondria in regulating sperm activation at the molecular level, particularly in modulating oxidative phosphorylation (OXPHOS) protein composition to optimize ATP production. In summary, mitochondria serve as both the central energy hub and a crucial regulatory factor in sperm activation, metabolic homeostasis, and reproductive success. Their involvement extends beyond ATP generation to include apoptotic regulation, ion homeostasis, vesicle-mediated mitochondrial quality control, and potential contributions to protein synthesis. Understanding these mitochondrial functions in C. elegans not only deepens our knowledge of nematode reproductive biology, but also provides valuable insights into broader mechanisms governing mitochondrial regulation in germline cells across species. These findings open new avenues for future research into the interplay between mitochondria, energy metabolism, and sperm function, with potential implications for reproductive health and fertility studies.]]> 2025/3/7 16:40:58 CHANG Zhan-Xin,MIAO Long and WANG Peng 172true 2025/3/10 16:46:04 FENG Jia-Jia,GUO Meng,OUYANG Zheng and Lü Bin 171true via retrograde communication. When mitochondrial dysfunction or environmental stress compromises cellular demands, mitochondria issue retrograde signals to solicit nuclear support. Studies demonstrate that mitochondrial retrograde signaling pathways operate in pathological contexts such as oxidative stress, electron transport chain (ETC) impairment, apoptosis, autophagy, vascular tension, and inflammatory responses. Mitochondria-related diseases exhibit marked heterogeneity but invariably result in energy deficits, preferentially affecting high-energy-demand tissues like muscles and the nervous system. Consequently, mitochondrial dysfunction underlies myopathies, neurodegenerative disorders, metabolic diseases, and malignancies. Dysregulated retrograde signaling triggers proliferative and metabolic reprogramming, driving pathological cascades. Mitochondrial retrograde signaling critically influences tumorigenesis and progression. Tumor cells with mitochondrial dysfunction exhibit compensatory upregulation of mitochondrial biogenesis, excessive superoxide production, and ETC overload, collectively promoting metastatic tumor development. Recent studies reveal that mitochondrial retrograde signaling—mediated by altered metabolite levels or stress signals—induces epigenetic modifications and is intricately linked to tumor initiation, malignant progression, and therapeutic resistance. For instance, mitochondrial dysfunction promotes oncogenesis through mechanisms such as epigenetic dysregulation, accumulation of mitochondrial metabolic intermediates, and mitochondrial DNA (mtDNA) release, which activates the cytosolic cGAS-STING signaling pathway. In normal cells, miR-663 mediates mitochondrion-to-nucleus retrograde signaling under reactive oxygen species (ROS) regulation. Mitochondria modulate miR-663 promoter methylation, which governs the expression and supercomplex stability of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and assembly factors. However, dysfunctional mitochondria induce oxidative stress, elevate methyltransferase activity, and cause miR-663 promoter hypermethylation, suppressing miR-663 expression. Mitochondrial dysfunction also triggers retrograde signaling in primary mitochondrial diseases and contributes to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Current therapeutic strategies targeting mitochondria in neurological diseases focus on 5 main approaches: alleviating oxidative stress, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, mitochondrial protection, and insulin sensitization. In AD patients, mitochondrial morphological abnormalities and enzymatic defects, such as reduced pyruvate dehydrogenase and α-ketoglutarate dehydrogenase activity, are observed. Platelets and brains of AD patients exhibit diminished cytochrome c oxidase (COX) activity, correlating with mitochondrial dysfunction. To model AD-associated mitochondrial pathology, researchers employ cybrid technology, transferring mtDNA from AD patients into enucleated cells. These cybrids recapitulate AD-related mitochondrial phenotypes, including reduced COX activity, elevated ROS production, oxidative stress markers, disrupted calcium homeostasis, activated stress signaling pathways, diminished mitochondrial membrane potential, apoptotic pathway activation, and increased Aβ42 levels. Furthermore, studies indicate that Aβ aggregates in AD and α-synuclein aggregates in PD trigger mtDNA release from damaged microglial mitochondria, activating the cGAS-STING pathway. This induces a reactive microglial transcriptional state, exacerbating neurodegeneration and cognitive decline. Targeting the cGAS-STING pathway may yield novel therapeutics for neurodegenerative diseases like AD, though translation from bench to bedside remains challenging. Such research not only deepens our understanding of disease mechanisms but also informs future therapeutic strategies. Investigating the triggers, core molecular pathways, and regulatory networks of mitochondrial retrograde signaling advances our comprehension of intracellular communication and unveils novel pathogenic mechanisms underlying malignancies, neurodegenerative diseases, and type 2 diabetes mellitus. This review summarizes established mitochondrial-nuclear retrograde signaling axes, their roles in interorganellar crosstalk, and pathological consequences of dysregulated communication. Targeted modulation of key molecules and proteins within these signaling networks may provide innovative therapeutic avenues for these diseases.]]> 2025/3/21 16:15:27 ZHANG Wen-Long,QUAN Lei and ZHAO Yun-Gang 170true via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.]]> 2025/4/10 10:49:54 LI Jin-Ru,DUAN Yu,DAI Xin-Gui and YAO Yong-Ming 169true 2025/3/20 11:17:37 WANG Qing-Qing,LIU Ya,LIU Wei and LONG Wei 168true via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.]]> 2025/4/4 12:48:32 SHI Wan-Rui,CUI Li-Gang and LIANG Xiao-Long 167true in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.]]> 2025/4/11 10:03:06 CHEN Meng-Meng,HU Nan,BAO Shuang-Qing and LI Xiao-Hong 166true 2025/3/26 10:58:10 TANG Xiao-Xia,ZHANG Shu-Jia,ZHANG Ying and WANG Li 165true via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.]]> 2025/4/4 12:46:28 XING Wen-Xiao,LUO Fu-Cheng and Lü Tao 164true 2025/3/7 15:03:45 GUO Xing-Chen,XIE Yan,WEI Xin-Shuo,LI Wen-Fen and SUN Ying-Yu 163true 2025/4/16 16:32:44 SHEN Ruo-Bing,SHEN Wen-Wen and GAO Shu-Gui 162true 2025/4/4 12:56:17 HE Dan,LI Shi-Guo and ZHAN Ai-Bin 161true 2025/2/24 11:15:28 YANG Chao,SONG Zi-Yi,WANG Chang-Xin,KUANG Yuan-Yuan,CHENG Yi-Jing,REN Ke-Xin,LI Xue and LIN Yan 160true via the nuclear factor κB (NF-κB) pathway, thereby contributing to the pathogenesis of T2DM. Peripheral 5-hydroxytryptamine (5-HT), primarily synthesized by enterochromaffin (EC) cells in the gut, interacts with 5-hydroxytryptamine receptors (5-HTRs) in key insulin-target tissues, including the liver, adipose tissue, and skeletal muscle. This interaction influences hepatic gluconeogenesis, fat mobilization, and the browning of white adipose tissue. Elevated peripheral 5-HT levels may disrupt glucose and lipid metabolism, thereby contributing to the onset and progression of T2DM. Within mitochondria, 5-HT undergoes degradation and inactivation through the enzymatic action of monoamine oxidase A (MAO-A), leading to the generation of reactive oxygen species (ROS). Excessive ROS production and accumulation can induce oxidative stress, which may further contribute to the pathogenesis of T2DM. Platelets serve as the primary reservoir for 5-HT in the bloodstream. The activation of the TLR4 signaling pathway on the platelet surface, coupled with reduced expression of the 5-HT transporter on the cell membrane, leads to elevated serum 5-HT levels, potentially accelerating the progression of T2DM. Therefore, inhibition of TLR4 and reduction of peripheral 5-HT levels could represent promising therapeutic strategies for T2DM. This review explores the synthesis, transport, and metabolism of peripheral 5-HT, as well as its role in TLR4-mediated T2DM, with the aim of providing novel insights into the clinical diagnosis, treatment, and evaluation of T2DM.]]> 2025/3/5 11:36:35 ZHANG Yi-Ying,ZHANG Ping,YANG Bo and CHANG Xiao-Tong 159true e.g., Bcl-2 and Mcl-1) and enhances host antiviral immunity by regulating the NF-κB and interferon signaling pathways. Moreover, ATG12 deficiency can lead to mitochondrial biogenesis impairment, energy metabolism disorders, and substrate-dependent metabolic shifts, underscoring its pivotal role in cellular metabolic homeostasis. At the disease level, dysregulation of ATG12 expression is closely linked to tumorigenesis and cancer progression. By modulating the dynamic balance between autophagy and apoptosis, ATG12 influences cancer cell proliferation, metastasis, and chemoresistance. Notably, ATG12 is abnormally overexpressed in multiple cancers, including breast, liver, and gastric cancer, highlighting its potential as a therapeutic target. Furthermore, in neurodegenerative diseases such as Parkinson’s disease, ATG12 mitigates protein toxicity by enhancing mitochondrial autophagy. In cardiovascular diseases, it alleviates ischemia-reperfusion injury by regulating cardiomyocyte autophagy and apoptosis, demonstrating its broad regulatory role across various pathological conditions. Genetic studies further underscore the clinical significance of ATG12. Polymorphisms in the ATG12 gene (e.g., rs26537 and rs26538) have been significantly associated with the risk of head and neck squamous cell carcinoma, hepatocellular carcinoma, and atrophic gastritis. Notably, the risk allele of rs26537 enhances ATG12 promoter activity, leading to its overexpression and promoting tumorigenesis. These findings provide a molecular basis for individualized risk assessment and targeted interventions based on ATG12 genotype. Despite significant progress, many aspects of ATG12 biology remain unclear. The precise regulatory mechanisms of its post-translational modifications (e.g., ubiquitination and acetylation) are yet to be fully elucidated. Additionally, the molecular pathways underlying its non-canonical functions, such as metabolic regulation and immune modulation, require further investigation. Moreover, the functional heterogeneity of ATG12 in different tumor microenvironments and its role in drug resistance warrant in-depth exploration. Future research should integrate advanced technologies such as cryo-electron microscopy, single-cell sequencing, and organoid models to decipher the intricate regulatory network of ATG12. Additionally, developing small-molecule inhibitors or gene-editing tools targeting its protein interaction interfaces (e.g., the ATG12-ATG3 binding domain) may help overcome current therapeutic challenges. Through interdisciplinary collaboration and clinical translation, ATG12 holds promise as a next-generation molecular target for precision intervention in autophagy-related diseases. This review summarizes the structure and function of ATG12, its role in autophagy initiation, its physiological functions, and its involvement in disease pathogenesis. Furthermore, it discusses future research directions and potential challenges, emphasizing ATG12’s potential as a biomarker and therapeutic target in autophagy-related diseases.]]> 2025/2/17 0:00:00 LIU Wei,TIAN Rui,ZHOU Ce-Fan and TANG Jing-Feng 158true 2025/1/21 16:26:58 FENG Tian-Yang,DENG Le,XU Gou,LI Li and GUO Miao-Miao 157true 2025/1/20 11:20:27 CHEN Xin-Nong,YANG Ying-Xi,GUO Xiao-Chen,ZHANG Jun-Ping and LIU Na-Wen 156true 2025/1/8 11:39:08 ZHANG Yu and ZHANG Xiu-Feng 155true 2025/3/5 11:34:41 SONG Jia-Lu,JIN Yi-Xin,MU Xing-Yu,JIANG Yu-Huan and WANG Jing 154true Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.]]> 2025/2/28 11:03:22 ZHAO Ya-Qi,QI Li-Li,WANG Jin-Bo,HU Xu-Qi,WANG Meng-Ting,MAO Hai-Guang and SUN Qiu-Zhen 153true Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.]]> 2025/1/23 9:18:06 ZHAO Ya-Qi,ZHANG Lin-Lin,MA Xiao-Meng,JIN Zhen-Kai,LI Kun and WANG Min 152true etc., and further exerts neuroprotective effects, but tACS mainly maintains the normal function of cholinergic neurons to exert the effects. For the alleviation of cerebrovascular dysfunction, tDCS has particular advantages in optimizing the neural vascular unit and improving the blood-brain barrier. For astrocytes, tDCS attenuates inflammatory responses by inhibiting their activation. In contrast, the effect of tACS on the activation state of microglial cells is still controversial for enhancement in AD mice and inhibition in patients. For Aβ levels, the effects of tDCS in AD patients are also inconclusive, but in AD rodents, tDCS may regulate molecular pathways related to Aβ production and degradation, thereby removing Aβ. In addition, tACS reduces p-tau levels in AD patients, but tDCS shows a trend toward reduction. In short, the effect of tES on Aβ and p-tau needs further investigation. Regarding neuroplasticity, tDCS improves cortical and synaptic plasticity, but tACS improves only synaptic plasticity. However, both techniques do not affect the molecular level associated with plasticity. On the other hand, this review has summarized some interesting findings of tES in non-AD rodents that may be relevant to the pathological mechanisms of AD. For neuroprotection, tDCS can promote neurogenesis, GABAergic and glutamatergic neurotransmission, modulate neuroprotection-related signaling pathways, reduce oxidative stress, and protect hippocampal neurons. In addition, tDCS inhibits conversion of microglia to the M1 phenotype and promotes conversion to the M2 phenotype, thereby reducing neuroinflammation. Importantly, tDCS induces changes in molecular indices associated with synaptic plasticity. These findings in non-AD rodents provide a reference for understanding the potential effect and possible mechanism of tES in AD and for exploring new approaches to treat other diseases with similar pathological features. In addition, tES has shown some effects in AD rodents, such as tACS improving plasticity, that have not been studied in non-AD rodents. These effects suggest the particular complexity of the pathological mechanisms of AD, which should be considered when applying the results of tES studies in non-AD rodents to AD rodents. In conclusion, this review provides a comprehensive overview of the neuromolecular mechanisms of tES in AD research and highlights its promise as a non-invasive brain stimulation technique in the treatment of AD. Furthermore, tES will play an indispensable role in the treatment of neuropsychiatric disorders and in the study of brain function.]]> 2025/1/8 11:42:18 YUAN Yuan,CHEN Zhuang-Fei and FU Yu 151true 2025/1/21 16:40:43 ZHANG Yu-Feng,WANG Wei,LU Zi-Jun,Lü Jiao-Jiao and LIU Yu 150true in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.]]> 2025/2/19 17:29:46 KANG Zi-Yuan,YU Tong,LI Chao,ZHANG Xue-Hua,GUO Jun-Hui,LI Qi-Chang,GUO Jing-Xing and XIE Hao 149true Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus (MRSA), the bactericidal effects are primarily mediated by endogenous porphyrins (e.g., protoporphyrin III, coproporphyrin III, and uroporphyrin III), which exhibit strong absorption peaks between 400-430 nm. Upon irradiation, these porphyrins are photoexcited to generate cytotoxic reactive oxygen species (ROS), including singlet oxygen, hydroxyl radicals, and superoxide anions, which collectively induce oxidative damage to cellular components. Early studies by Endarko et al. revealed that (405±5) nm blue light at 185 J/cm2 effectively inactivated L. monocytogenes without exogenous photosensitizers, supporting the hypothesis of intrinsic photosensitizer involvement. Subsequent work by Masson-Meyers et al. demonstrated that 405 nm light at 121 J/cm2 suppressed MRSA growth by activating endogenous porphyrins, leading to ROS accumulation. Kim et al. further elucidated that ROS generated under 405 nm irradiation directly interact with unsaturated fatty acids in bacterial membranes, initiating lipid peroxidation. This process disrupts membrane fluidity, compromises structural integrity, and impairs membrane-bound proteins, ultimately causing cell death. In contrast, Gram-negative bacteria such as Salmonella, Escherichia coli, Helicobacter pylori, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibit more complex inactivation pathways. While endogenous porphyrins remain central to ROS generation, studies reveal additional photodynamic contributors, including flavins (e.g., riboflavin) and bacterial pigments. For instance, H. pylori naturally accumulates protoporphyrin and coproporphyrin mixtures, enabling efficient 405 nm light-mediated inactivation without antibiotic resistance concerns. Kim et al. demonstrated that 405 nm light at 288 J/cm2 inactivates Salmonella by inducing genomic DNA oxidation (e.g., 8-hydroxy-deoxyguanosine formation) and disrupting membrane functions, particularly efflux pumps and glucose uptake systems. Huang et al. highlighted the enhanced efficacy of pulsed 405 nm light over continuous irradiation for E. coli, attributing this to increased membrane damage and optimized ROS generation through frequency-dependent photodynamic effects. Environmental factors such as temperature, pH, and osmotic stress further modulate susceptibility, sublethal stress conditions (e.g., high salinity or acidic environments) weaken bacterial membranes, rendering cells more vulnerable to subsequent ROS-mediated damage. The 405 nm blue light inactivates drug-resistant Pseudomonas aeruginosa through endogenous porphyrins, pyocyanin, and pyoverdine, with the inactivation efficacy influenced by bacterial growth phase and culture medium composition. Intriguingly, repeated 405 nm exposure (20 cycles) failed to induce resistance in A. baumannii, with transient tolerance linked to transient overexpression of antioxidant enzymes (e.g., superoxide dismutase) or stress-response genes (e.g., oxyR). For Gram-positive bacteria, porphyrin abundance dictates sensitivity, whereas in Gram-negative species, membrane architecture and accessory pigments modulate outcomes. Critically, ROS-mediated damage is nonspecific, targeting DNA, proteins, and lipids simultaneously, thereby minimizing resistance evolution. The 405 nm blue light technology, as a non-chemical sterilization method, shows promise in medical and food industries. It enhances infection control through photodynamic therapy and disinfection, synergizing with red light for anti-inflammatory treatments (e.g., acne). In food processing, it effectively inactivates pathogens (e.g., E. coli, S. aureus) without altering food quality. Despite efficacy against multidrug-resistant A. baumannii, challenges include device standardization, limited penetration in complex materials, and optimization of photosensitizers/light parameters. Interdisciplinary research is needed to address these limitations and scale applications in healthcare, food safety, and environmental decontamination.]]> 2025/2/27 16:44:21 BI Ruo-Hong,WU Rong-Qian,Lü Yi and LIU Xiao-Fei 148true c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.]]> 2024/11/6 14:41:23 WANG Xin-Die,FENG Da-Li,CUI Xiang,ZHOU Su,ZHANG Peng-Fei,GAO Zhi-Qiang,ZOU Li-Li and WANG Jun 147true 2024/11/6 14:43:28 WANG Yong-Lang,CHEN Si-Si,LI Qi-Long,GONG Yu,DUAN Xin-Yue,DUAN Ye-Hui,GUO Qiu-Ping and LI Feng-Na 146true 2024/11/12 11:44:50 TIAN Lian-Chen,YUAN Ya-Yi and DANG Xu-Hong 145true e.g., two touch or temperature stimuli) are presented simultaneously, leading to amplified perceptual strength and quicker reaction times. Additionally, certain external factors, such as cooling, can increase sensitivity to other sensory inputs, further promoting facilitative integration. In contrast, inhibitory effects may also emerge when stimuli from different sensory modalities interact, particularly between touch and pain. Under such conditions, one sensory input (e.g., vibration or non-noxious temperature stimulation) can effectively reduce the perceived intensity of the other, often resulting in reduced pain perception. These facilitative and inhibitory interactions are critical for efficient processing in a multi-stimulus environment and play a role in modulating the experience of somatosensory inputs in both normal and clinical contexts. The neural mechanisms underlying multimodal somatosensory integration are multi-tiered, encompassing peripheral receptors, the spinal cord, and various cortical structures. Facilitative integration relies on the synchronous activation of peripheral receptors, which transmit enhanced signals to higher processing centers. At the cortical level, areas such as the primary and secondary somatosensory cortex, through multimodal neuron responses, facilitate combined representation and amplification of sensory signals. In particular, the thalamus is a significant relay station where multisensory neurons exhibit superadditive responses, contributing to facilitation by enhancing signal strength when multiple inputs are present. Inhibitory integration, on the other hand, is mediated by mechanisms within the spinal cord, such as gating processes that limit transmission of competing sensory signals, thus diminishing the perceived intensity of certain inputs. At the cortical level, lateral inhibition within the somatosensory cortex plays a key role in reducing competing signals from non-target stimuli, enabling prioritized processing of the most relevant sensory input. This layered neural architecture supports the dynamic modulation of sensory inputs, balancing facilitation and inhibition to optimize perception. Understanding the neural pathways involved in somatosensory integration has potential clinical implications for diagnosing sensory disorders and developing therapeutic strategies. Future research should focus on elucidating the specific neural circuitry and mechanisms that contribute to these complex interactions, providing insights into the broader implications of somatosensory integration on behavior and cognition. In summary, this review highlights the importance of multimodal somatosensory integration in enhancing sensory perception. It also underscores the need for further exploration into the neural underpinnings of these processes to advance our understanding of sensory integration and its applications in clinical settings.]]> 2024/11/24 21:10:02 ZHANG Yu,ZHANG Ming and KONG Ya-Zhuo 144true in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.]]> 2024/12/8 9:37:44 ZHOU Peng,WANG Xin,LUO Qian and ZHAO Chao 143true FoxA genes belong to a conserved family of transcription factors, that play a crucial role in regulating embryonic development, cellular differentiation, and disease pathogenesis. Initially identified as hepatocyte nuclear factor 3α (Hnf3α), FoxA is pivotal in activating liver-specific genes and contributing to liver morphogenesis. Studies have shown that FoxA proteins interact with specific DNA sequences and nucleosome-bound DNA, altering the local chromatin structure to regulate gene expression. The unique ability has earned them the designation of “pioneer factors”. The FoxA family comprises three members: FoxA1, FoxA2, and FoxA3. FoxA1 is predominantly expressed in endoderm-derived organs such as the lungs, liver, pancreas, and prostate, where it regulates hormone metabolism, cell cycle, and cell proliferation. FoxA2 is primarily expressed in the floor plate of the vertebrate spinal cord, where it plays a key role in establishing the dorsal-ventral patterning of the neural tube. FoxA3 is mainly expressed in the testes, where it regulates germ cell formation. FoxA genes exhibit functional diversity in embryonic development across different species, offering insights into their evolutionary roles. For instance, zebrafish embryos with mutations in the foxa2^-/- gene can survive, providing an opportunity to study embryonic development mechanisms. Currently, a growing body of research suggests that FoxA genes are involved in early embryonic development, cancer, and metabolism-related diseases. This paper summarizes the discovery, expression patterns, and biological functions of the FoxA genes while identifying key scientific questions that remain unresolved. It aims to provide readers a solid scientific basis for understanding the molecular mechanisms through which FoxA genes regulate embryonic development and contribute to cancer pathogenesis.]]> 2024/12/18 13:01:30 WANG Jing-Han and YANG Li-Xin 142true 2024/12/18 13:04:16 LI Ao-Yun,LU Zhan-Chuang,CAO Li,CHEN Si,JIANG Hui,CHEN Chang-Chun and CHEN Lei 141true e.g., combining EEG with functional near-infrared spectroscopy) and advancements in source localization algorithms can further improve the spatial precision of biomarkers. Leveraging machine learning and artificial intelligence technologies to develop intelligent diagnostic tools will accelerate the clinical adoption of EEG biomarkers in DOC diagnosis and prognosis, allowing for more precise evaluations of consciousness states and personalized treatment strategies.]]> 2024/12/31 9:31:01 WANG Zhong-Peng,LIU Jia,CHEN Long,XU Min-Peng and MING Dong 140true 2024/12/31 11:54:00 WANG Shu-Wan and WANG Zhuo 139true 2025/1/3 17:12:31 WEN Rui-Ming,HUANG Rui-Qi,CHANG Yi-Xing,XU Ke and YI Xue-Jie 138true 2O. Meanwhile, TEs also undergo nucleophilic attack by intramolecular oxygen atom, nitrogen atom, or carbon atom to achieve macrolactonization, macrolactamization, or Claisen condensation, respectively. There are two main classes of TEs involved in natural product biosynthesis. Type I TEs (TEIs) are commonly found in type I cis-AT PKS, trans-AT PKS, NRPS, and fungal PKS/NRPS, which are mainly located at the end module of synthase. In addition to TEIs, there is also a class of free type II TE (TEIIs), which catalyzes the release of incomplete or incorrectly extended intermediates during PKs and NRPs biosynthesis. Besides, a distinct class of free TE was identified in the chain release of polyether backbones, such as monensin and nanchangmycin. Since 2001, more than 20 crystal structures of TEs from diverse PKSs and NRPSs have been solved. The structural elucidation of TEs has unlocked the mystery of their structural and functional interaction, laid the foundation for the TE classification and mechanistic insight into the substrate selectivity and catalytic efficiency of TE, which further promotes the understanding of the chain release mechanism of natural products and better served the rational design of TE. Previous articles have systematically reviewed the structure, function, and regulatory mechanism of different TE families. Horsman et al. also reviewed the diversity, structure, and mechanism of TEs in PKSs and NRPSs. They put forward an insightful view that TEs might act as logic gates for substrate loading and chain releasing during the biosynthesis of natural products. It provides an important perspective for studying the evolution and functional prediction of TEs. This review summarizes the structural characteristics of various TE, focusing on the structural consistency of thioesterase to the catalytic mechanism. Additionally, this review follows the progress and limitations on the catalytic mechanism and computational simulation of type I TE, providing a detailed analysis of the chemical essence of thioesterase-catalyzed chain release reactions. This review aims to deliver revealing suggestions for the structural elucidation and mechanistic insights of TE, as well as its rational design for improved chain release of unnatural products.]]> 2024/12/21 7:51:21 ZHOU Yu-Cong,SHI Ting,LU Chen-Yang,LIU Hao and BAI Lin-Quan 137true 2024/10/18 15:56:38 JIANG Miao,JIANG Li-Na,DONG Yue-Hong,YAO Yong-Ming,ZHAO Zi-Gang and NIU Chun-Yu 136true 2024/10/5 22:20:14 CHEN Shi-Yu,LIN Zhi-Cheng,YING Jia-Qin,LI Wan-Yi,LIU Zhi-Tao,FANG Tian-Yuan,ZHOU Yu-Yu,ZHANG Chu-Xia,XIE Kai,XU Shu-Jun and LI Li-Ping 135true via its phosphatase domains, which regulate downstream signaling pathways involved in cell proliferation, differentiation, and cytoskeletal organization. The CSPGs/PTPσ axis has been identified as a major molecular pathway contributing to the inhibition of remyelination in MS. The upregulation of CSPGs and PTPσ in MS lesions has been associated with a failure of OPCs to remyelinate damaged axons effectively. Preclinical studies have shown that pharmacological inhibition or genetic ablation of PTPσ can alleviate the inhibitory effects of CSPGs on OPC migration and differentiation. For instance, systemic administration of the PTPσ inhibiting peptide intracellular sigma peptide (ISP) has been shown to enhance OPC differentiation, promote remyelination, and restore motor function in animal models of MS, highlighting the potential of targeting CSPGs/PTPσ as a therapeutic approach for MS. Furthermore, CSPGs and their receptors have been implicated in modulating other biological processes such as immune cell infiltration, synaptic plasticity, and axonal regeneration, which are relevant to the pathogenesis of MS and other neurodegenerative diseases. CSPGs are known to activate downstream signaling pathways, such as the Rho/ROCK, Akt, and ERK pathways, which regulate cytoskeletal dynamics and gene expression in OPCs, ultimately affecting their ability to mature into myelinating oligodendrocytes. Additionally, CSPGs can interact with the N-cadherin/β-catenin pathway, influencing cell adhesion and signaling in OPCs, thereby modulating myelin repair capacity. Given the multifaceted roles of CSPGs/PTPσ in CNS pathology, targeting this pathway represents a promising therapeutic strategy. This article aims to provide a comprehensive overview of the biological properties of CSPGs and PTPσ, focusing on their roles in the inhibition of myelin regeneration. Specifically, it discusses how CSPGs/PTPσ signaling modulates various aspects of OPC biology, including autophagy regulation and immune modulation. Moreover, the review explores potential therapeutic strategies aimed at disrupting CSPGs/PTPσ interactions, such as the use of small-molecule inhibitors, neutralizing antibodies, or gene therapies. In summary, a deeper understanding of CSPGs/PTPσ-mediated signaling in OPCs and other cell types within MS lesions may reveal novel therapeutic targets for promoting remyelination and functional recovery. This review provides a detailed analysis of current findings and highlights the need for further research to translate these findings into effective treatments for MS patients.]]> 2024/10/18 14:57:48 WANG Jing-Tong,LUO Fu-Cheng and CHEN Wen-Li 134true 2024/10/25 17:12:52 WU Mei-Lin, WANG Yi-Fan, DUAN Wen-Jing, DANG Wang-Jie, HAN Jing, REN Wei, DUAN Hai-Jun 133true 2024/10/18 15:26:52 HUANG Ming,CHEN Jin-Xiu,ZHANG Yu-Le,DONG Xiang,CAO Chun-Yu and WU Hong-Yan 132true Bacteroides, Bifidobacterium and Clostridium butyricum undergo significant alterations. These changes lead to a decline in the metabolites produced by the gut flora, including short chain fatty acids (SCFAs), bile, indole and indole derivatives. As a result, the homeostasis of the gut microbiota becomes disrupted, leading to an imbalance in the intestinal microbial ecosystem. The interaction between the intestinal flora and its metabolites and the intestinal immune system has been studied and a high correlation between the intestinal flora and the immune function of the intestinal mucosa has been proposed. Under normal circumstances, a healthy immune system and gut flora are mutually reinforcing and promote the health of the host. However, with age, the integrity of intestinal mucosa and the homeostasis of intestinal flora are disrupted, resulting in a decline in the immune response and regulatory capacity and an inability to respond effectively to various exogenous insults. Meanwhile, the ongoing damage to the immune system further exacerbates the imbalance in the gut flora. Changes in the gut flora of the elderly affect the diversity and levels of key immune molecules such as defensins and immunoglobulin A (IgA). Abnormal expression of immune molecules in the gut also leads to changes in the composition of the gut microbiome, affecting gut health and potentially increasing the risk of disease. The metabolites of intestinal flora interact with intestinal receptors, activate relevant signalling pathways, directly regulate immune cells and control the immune system, influence the intestinal barrier and intestinal immune functions, and exert immunoregulatory effects on the intestine. As the relationship between gut flora and immune aging becomes clearer, future research can explore strategies for targeted regulation of gut flora for anti-aging and immune enhancement. In this paper, we further explore the regulation of gut flora and gut immune function by dietary intervention and fecal microbiota transplantation (FMT) to achieve the goal of delaying immune aging. Dietary intervention promotes the growth of beneficial bacteria by adjusting the structure of the elderly’s diet and supplementing with microbial preparations, maintaining the intestinal barrier and reducing chronic inflammation. FMT involves the transplantation of faeces from healthy individuals into recipients to improve mucosal integrity and promote microbial diversity. This paper has discussed the complex mechanism between aging, gut flora and immune response, highlighted the research progress of gut flora anti-aging methods, with the aim of providing a reference for research on targeted gut flora regulation to promote gut mucosal immune function for health promotion and anti-aging.]]> 2024/10/5 22:50:20 GUO Wen-Wen,QI Li-Li,WANG Meng-Ting,KE Zhi-Jian,MAO Hai-Guang and WANG Jin-Bo 131true 2024/10/14 22:19:35 LUO Bo-Yu and TENG Yue 130true 2024/10/14 22:23:07 GUO Yan-Guang,WEI Shuang-Hong,WANG Yun-Le,CHEN Si,HOSSEIN Chamkouri,CHEN Peng,SI Jian-Min,NIU Chao-Shi and CHEN Lei 129true 2024/10/8 21:14:50 LUO Wei,GAO Wen-Yue,WANG Yu-Hang,LIU Yan-Song and AI Lei 128true 2024/10/26 15:02:50 LI Yu-Qing,JIE Hui-Cong,GUO Jiang-Zi-Hui,LIU Tiao-Tiao and ZHENG Xu-Yuan 127true etc., and the semi-analytical methods include ray-tracing method and hybrid angular spectrum method. Simulation tools based on numerical methods synthesize various forms of wave propagation in media, such as nonlinear effects, scattering and diffraction, and are widely used in academic research. The k-Wave toolbox based on the k-space pseudo-spectral method and various programs based on the time-domain finite-difference method are the most widely used simulation tools in the current tFUS accurate simulation and experimental research. Although the finite element method has the advantage of dealing with complex boundary conditions, the excessive consumption of computational resources limits its direct application in complex 3D simulations. Compared to numerical methods, semi-analytical-based simulations cannot accurately model full-wave effects, but their computational speed makes them more suitable for clinical scenarios where simulation time is critical. Ray-tracing, developed by Insightec, is currently the only phase-correction method that has been used in clinical applications. Based on geometric acoustic principles, ray tracing enables near real-time tFUS phase correction. At the same time, the hybrid angular spectroscopy method shows higher accuracy in precise targeting than the conventional ray tracing method. In addition, the hybrid application of different simulation methods significantly improves the simulation efficiency and accuracy, e.g., the boundary element method can be coupled with the finite element method to limit the computational area to the region involving only the skull, which drastically reduces the computational load. In recent years, the acoustic simulation for tFUS has continued to make progress, but there is still a huge room for improvement in terms of computational efficiency and accuracy, and the optimal use of computational resources and the combination of multiple simulation techniques may be the direction of the future development of simulation technology. In this paper, the research on simulation techniques based on numerical, semi-analytical and hybrid methods commonly used in the field of tFUS in recent years is reviewed and sorted out, and the research and application of various simulation methods are summarized and prospected.]]> 2024/10/14 22:27:01 CHEN Guo-Wei,WANG Xue,HE Feng,ZHANG Hao,XU Min-Peng and MING Dong 126true TMEM43 gene. This protein consists of 400 amino acids and has 4 transmembrane domains and 1 membrane-associated domain. TMEM43 is localized to various biological membranes within the cell, such as the cell membrane and nuclear membrane, where it forms transmembrane channels for various ions. Additionally, TMEM43 is expressed in many species, showing high genetic similarity, especially with the four transmembrane domains being highly conserved. Current studies on the TMEM43 gene are still in its early stages, mainly focusing on its association with arrhythmogenic right ventricular cardiomyopathy (ARVC) and cancer. However, recent studies suggest that pathogenic mutations in TMEM43 may cause auditory neuropathy spectrum disorder (ANSD). Patients with TMEM43 p.Ser372Ter exhibited late-onset progressive ANSD. Impact of TMEM43 pathogenic mutations on individual hearing was likely mediated through effects on gap junction (GJ) structures on glia-like supporting cells (GLS), cell membranes. The TMEM43 p.Arg372Ter pathogenic mutation primarily affected the structure and function of TMEM43 protein, leading to premature termination of protein translation and the production of a truncated protein. Abnormal TMEM43 protein significantly reduced K⁺ influx in GLS cells, disrupting the endolymphatic K⁺ circulation and cochlear microenvironment homeostasis. When K⁺ circulation was obstructed, the endocochlear potential (EP) became abnormal, impairing the physiological function of hair cells and potentially leading to hearing impairment. However, it is important to note that studies on the mechanism is limited, and more experimental evidence is needed to confirm this hypothesis. Currently, there is a significant gap in research on TMEM43 and hearing loss, with many issues remaining unresolved. While TMEM43 has been studied in relation to hearing loss in humans, zebrafish, mice, and rats, the research is still preliminary. Detailed investigations into the molecular pathogenic mechanisms, the impact of mutations on hearing damage, and related therapeutic strategies are needed. Additionally, as a newly identified hearing loss-related gene, the mutation frequency and incidence of hearing disorders associated with TMEM43 have not been effectively quantified. For example, the ClinVar database listed 829 mutation sites for the TMEM43 gene, with only three mutations related to auditory neuropathy: c.605A>T (p.Asn202Ile), c.889T>A (p.Phe297Ile), and c.1114C>T (p.Arg372Ter). Aside from the aforementioned TMEM43 c.1114C>T (p.Arg372Ter) mutation observed in patients, the other two mutations were experimentally induced and have not been found in patients. Consequently, these mutations have been classified as unknown significance. We reviewed the current understanding of TMEM43 and hearing loss, analyzed its role in ear development and sound conduction, and explored the impact of TMEM43 gene variations on hearing loss, aiming to provide new insights for future research and precision medicine related to TMEM43.]]> 2024/10/28 10:39:33 CUI Rong-Jie and LI Yun-Long 125true 2024/9/4 15:49:49 LIN Hui-Ling,OUYANG Yu-Xin,TANG Wan-Ying,HU Mi,PENG Mao,HE Ping-Ping and OUYANG Xin-Ping 124true 2024/9/5 16:40:16 DONG Zi-Xuan and MA Zhan-Ke 123true 2024/9/20 21:58:15 WU Ting-Ting,JIA Si-Qi,CAO Shu-Zhu,ZHU De-Xin,TANG Guo-Chao,SUN Zhi-Hua,DENG Xing-Mei and ZHANG Hui 122true Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.]]> 2024/8/28 23:30:38 SHAN Jiang-Hui,CHU Chao-Yang,CHEN Shi-Yu,LIN Zhi-Cheng,ZHOU Yu-Yu,FANG Tian-Yuan,ZHANG Chu-Xia,XIAO Biao,XIE Kai,WANG Qing-Juan,LIU Zhi-Tao and LI Li-Ping 121true 2024/8/31 23:32:43 ZHANG Yu-Meng,TIAN Yu-Shan,LI Jie,MU Wen-Jun,YIN Chang-Feng,CHEN Huan and HOU Hong-Wei 120true 3H₆O₃, is an intermediate product of glucose metabolism in the body and a raw material for hepatic gluconeogenesis. Under physiological resting conditions, the body mainly relies on aerobic oxidation of sugar and fat for energy supply, so the blood lactate concentration is lower. However, during exercise, the enhanced glycolysis in skeletal muscles leads to the significant release of lactate into the bloodstream, causing a marked increase in blood lactate concentration. Traditionally, lactate has been regarded as a metabolic waste product of glycolysis and a contributor to exercise-induced fatigue. Nevertheless, recent studies have revealed that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism, serving not only as an energy substance alongside glucose but also as a vital component in various biological pathways involved in cardiac energetics, muscle adaptation, brain function, growth and development, and inflammation therapy. Two primary pathways can elevate lactate levels in neurons during exercise. One is peripheral skeletal muscle-derived lactate, which can enter the bloodstream and cross the blood-brain barrier into the brain with the assistance of monocarboxylate transporters (MCTs) from the solute carrier family 16 (SLC16). The other is the central brain-derived pathway. During exercise, neuronal activity is enhanced, promoting the secretion of neuroactive substances such as glutamate, norepinephrine, and serotonin in the brain. This activates astrocytes to break down glycogen into lactate and stimulates glutamate from the presynaptic terminal into the synaptic cleft. It upregulates the glucose transport protein-1 (GLUT-1) expression, allowing astrocytes to convert glucose into lactate through glycolysis. The lactate is produced via peripheral pathways and central pathways during exercise are transported by astrocyte membrane monocarboxylate transporters MCT1 and MCT4 to the extracellular space, where neurons take it up through neuronal cell membrane MCT2. The lactate in neurons can serve as an alternative energy source of glucose for neuronal functional activities, meeting the increased energy demands of synaptic activity during exercise, and maintaining energy balance and normal physiological function in the brain. Additionally, acting as a signaling molecule lactate can enhance synaptic plasticity through the SIRT1/PGC-1α/FNDC5 and ERK1/2 signaling pathways, lactate can promote angiogenesis by upregulating VEGF-A expression through the PI3K/Akt and ERK1/2 signaling pathways, stimulate neurogenesis via the Akt/PKB signaling pathway, and reduce neuroinflammation through activation of the “lactate timer”. Overall, lactate contributes to the protection of neurons, the promotion of learning and memory, the enhancement of synaptic plasticity, and the reduction of neuroinflammation in the nervous system. While lactate may serve as a potential mediator for information exchange between the peripheral and central nervous systems during exercise, further experimental research is needed to elucidate its action mechanisms in the nervous system. In addition, future studies should utilize advanced neurophysiological and molecular biology techniques to uncover the importance of lactate in maintaining brain function and preventing neurological diseases. Accordingly, this article first reviews the historical research on lactate, then summarizes the metabolic characteristics and neuronal sources of lactate, and finally explores the role and mechanisms of exercise-induced lactate in the nervous system, aiming to provide new perspectives and targets for understanding the mechanisms underlying exercise promotion of brain health.]]> 2024/9/5 16:42:24 MA Jing,BO Shu-Min and CHENG Yang 119true 2024/9/27 14:41:10 WANG Yun-Teng,LIANG Jia-Qi,SU Wan-Tang,ZHAO Li and LI Yan 118true etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.]]> 2024/8/28 21:53:00 WANG Xing-Bao,MA Yao-Hong,XUE Yun-Long,HUANG Xiao-Zhen,SHAO Yue,YU Yi,WANG Bing-Lian,LIU Qing-Ai,ZHANG Li-He and GONG Wei-Li 117true etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.]]> 2024/9/10 12:29:44 HU Huan,ZHANG Hong,WANG Jian,WANG Li-Wen,LIU Qian,CHENG Ning-Wen,ZHANG Xin-Yue and LI Yun-Lan 116true SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.]]> 2024/9/26 10:49:04 XIA Yong-Hang,DENG Hao,HU Li-Ling,LIU Wei and TAN Xiao 115true 2024/10/2 8:06:25 LUO Rui-Xin,GUO Si-Ying,LI Xin-Yi,ZHAO Yu-He,ZHENG Chun-Hou,XU Min-Peng and MING Dong 114true 2024/10/8 21:18:25 SHANG Peng,LIU Jun-Yu,WANG Sheng-Hang,YANG Jian-Cheng,ZHANG Zhe-Yuan,LI An-Lin,ZHANG Hao and ZENG Yu-Hong 113true 2024/8/28 20:47:02 WANG Si-Wen,YIN Xiao-Xiao,GAO Lin-Lin,GUI Wen-Jun,HU Qiao-Xia,LOU Qiong and WANG Qin-Wen 112true etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.]]> 2024/8/27 13:46:30 YIN Han,LI Yu,FAN Yu-Chuan,GUO Shuai,HUANG Yuan-Yu,LI Yong and WENG Yu-Hua 111true etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.]]> 2024/8/27 13:42:53 ZHU Gui-Zhen,YE Qiao,LUO Yuan,PENG Jie,WANG Lu,YANG Zhao-Ting,DUAN Feng-Sen,GUO Bing-Qian,MEI Zhu-Song and WANG Guang-Yun 110true 2024/8/27 13:52:05 ZHANG Yu,CHI Hong-Xia,YANG Wu-Ri-Tu,ZUO Yong-Chun and XING Yong-Qiang 109true 1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.]]> 2024/8/25 19:46:15 CHEN Lin-Fang,ZHANG Jia-Fan,GUO Ye-Ning,HUANG Hui-Zhong,HU Kang-Hong and YAO Chen-Guang 108true 1-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.]]> 2024/7/25 14:58:50 GAO Bo,LAI Yi-Ning,GE Yi-Tong and CHEN Wei 107true 2024/7/24 15:36:04 LI Yu-Meng,LIU Jing-Kai,CHEN Zi-Xuan and DENG Yu-Lin 106true in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.]]> 2024/7/19 15:44:42 HOU Li-Juan,GENG Ya-Xuan,LI Ke,HUANG Zhao-Yang and MAO Lan-Qun 105true 2024/8/28 19:51:31 HU Zhi-Cai,ZHANG Zhen,WANG Jiang,LI Gui-Ping,LIU Shan and YU Hai-Tao 104true e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.]]> 2024/8/2 12:40:35 CHENG Chuang,WANG Yue-Qing,MOU Xiao-Qin,ZHENG Xi,HE Jing,WANG Jun,TAN Chao,LIU Xiao-Wen and ZOU Li-Li 103true via the thalamic mediodorsal nuclei, while endogenous pain descending inhibition triggered by conditioning stimulation can be weakened via the thalamic ventromedial nuclei. Psychological factors may contribute to the development of low back pain. The mechanisms governing the generation, maintenance, and alleviation of low back pain in weightlessness differ from those observed in normal gravitational environments. This presents a significant challenge for space medicine research. Therefore, the elucidation of the occurrence and development mechanism of low back pain in weightlessness is important for the prevention and treatment during space flight. To reduce the incidence of low back pain during long-term missions on the space station, astronauts may choose to wear specialized space clothing that can provide axial physiological loads, designed to stimulate both musculature and skeletal structures, mitigating potential increases in vertebral column length, diminished lumbar curvature, and intervertebral disc edema and/or muscular atrophy. Additionally, assuming a “fetal tuck position” described as the knees to chest position may increase lumbar IVD hydrostatic pressure, subsequently reducing disc volume, rectifying diminished lumbar curvature, and alleviating dorsal root nerve tensions. Moreover, this position may reduce type IV mechanoreceptor facilitation and nerve impulse propagation from the sinuvertebral nerves of the annulus fibrosus. Elongated posterior soft tissues (apophyseal joint capsules and ligaments) with spinal flexion may potentially stimulate type I and II mechanoreceptors. It is also recommended to exercise the paraspinal muscles to prevent and alleviate the decrease in their cross-sectional area and maintain their structure and function. Photobiomodulation has been proved to be an effective means of activating the pain descending inhibition pathway of the central nervous system. In addition, astronauts should be encouraged to participate in mission-related activities and strive to avoid psychological problems caused by the long-term confinement in a small space station. The article presents a concise review of potential causes and targeted treatment strategies for low back pain induced by space flight or simulated microgravity in recent years. Its objective is to further elucidate the mechanisms underlying the occurrence and development of low back pain in weightless environments while providing scientific evidence to inform the development of guidelines for preventing, treating, and rehabilitating low back pain during long-term space flights.]]> 2024/8/16 15:28:44 LIU Yan-Feng,LEI Jing and YOU Hao-Jun 102true 2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO₂ plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.]]> 2024/7/25 17:52:36 FU Zhuo-Zhi,WU Ya-Cen,LI Mei-Xi,YIN Ping-Ping,LIN Hai-Jun,ZHANG Fu and YANG Yu-Xiang 101true in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.]]> 2024/8/14 19:06:08 SONG Xiao-Hui,PAN Ming-Yu,XU Jian-Feng,HUANG Zheng-Yu,PAN Qing and LI Qing-Ning 100true 2025/10/29 14:57:25 FANG Tian-Yuan,ZHOU Yu-Yu,ZHANG Chu-Xia,ZHOU Chen-Xuan,CHEN Shi-Yu,LIN Zhi-Cheng,LEI Bin,CHEN Lu-Yi,YING Jia-Qin,CHEN Hui,JIANG Yi,HUANG Yu-Han,YE Zhi-Tao and LI Li-Ping 99true e.g., cell membranes, metabolites, or biomacromolecules) through methods such as biomineralization, electrostatic assembly, surface modification, and genetic engineering. This enables programmable design from the nanoscale to the macroscale, demonstrating broad application prospects and attracting extensive research interest. First, microbial-nanomaterial hybrid systems are classified based on the types of nanomaterials (organic, inorganic, organic-inorganic) and microorganisms (bacteria, fungi, viruses, algae, probiotics). Both types of systems leverage the unique catalytic selectivity of microorganisms and the diverse physicochemical properties of nanomaterials to achieve multidimensional synergy. Their synergistic mechanisms involve both the biochemical processes of microorganisms and the surface/interface reactions of nanomaterials, representing a multidisciplinary achievement spanning microbial interface engineering, biomimetic catalysis, controllable nanomaterial fabrication, and interfacial transport and reaction processes. Next, the application progress in biomedical fields (such as anti-infection, intestinal diseases, and cancer therapy) and energy conversion (e.g., light-driven hybrid systems for proton reduction to hydrogen, CO₂ reduction and conversion, and nitrogen fixation) is elaborated in detail, highlighting their significant advantages in functional integration and synergistic performance. Microorganism-nanomaterial hybrid systems combine the specific recognition and precise metabolic capabilities of microorganisms with the catalytic, drug-delivery, and optoelectronic functions of nanomaterials, enabling the construction of various multifunctional synergistic platforms for catalysis, diagnosis, and therapy. These advances have greatly promoted development in nanomedicine, energy, and environmental applications. In medical contexts, such systems utilize the natural chemotaxis of microorganisms for precise targeting, achieve controlled drug release through environmentally responsive delivery and metabolic regulation, and enhance therapeutic efficacy via combined chemical-biological treatments and immune modulation. Improved biosafety can be achieved through attenuated microbial designs and nanomaterial coatings, offering diverse strategies for the precise treatment of various diseases. In the energy sector, the excellent light-harvesting properties of semiconductor materials and the precise catalytic capabilities of biological systems have been integrated to successfully construct light-driven biocatalytic systems, significantly improving light utilization efficiency. Finally, this review discusses the key challenges facing the practical application of these systems. Nanomaterials may exert toxic effects on microorganisms, impairing their activity and raising environmental safety concerns. The potential release of engineered nanomaterials into ecosystems necessitates careful risk assessment and long-term monitoring. In real-world environments, microbial functions are easily compromised, nanostructures are prone to damage, and reactive oxygen species (ROS) tend to accumulate, resulting in insufficient system stability. Stringent culture conditions, costly raw materials, and significant batch-to-batch variability hinder large-scale production and commercialization. The synergistic mechanisms between microorganisms and nanomaterials are not yet fully understood, particularly regarding molecular-level interactions and long-term compatibility. In medical applications, off-target risks persist due to unpredictable microbial colonization and immune responses, while environmental applications lack sufficient selective recognition capabilities, indicating a need for improved targeting and specificity. Furthermore, interdisciplinary barriers between biology, materials science, and engineering complicate collaborative innovation, and the absence of well-established standards for evaluation, regulation, and scalability also constrains further development. Future efforts should focus on enhancing biocompatibility, optimizing fabrication processes, and establishing comprehensive safety and performance standards to accelerate the transition of these promising systems from laboratory research to real-world applications.]]> 2025/9/25 16:28:20 CHEN Ren-Ju, LUO Bang-Lan, QUAN Chun-Shan, LI Chun-Bin, LIN Feng, ZHANG Yan-Mei 98true e.g., pH, ionic strength, enzymatic degradation), and limited functional diversity. To address these drawbacks, extensive research has been devoted to modification strategies aimed at enhancing stability, structural integrity, and cargo protection. Polysaccharide modification enables the formation of stable core-shell structures through electrostatic interactions, hydrogen bonding, and steric hindrance. Coatings with pectin, chitosan, or alginate improve stability across a broad range of pH values and ionic strengths, enhance resistance to gastric digestion, and enable sustained release in the intestine, thereby improving bioavailability. Polyphenol modification introduces hydrogen bonding, hydrophobic interactions, and occasionally covalent cross-linking, which modify nanoparticle structure and surface properties. These composites exhibit improved hydrophilicity, colloidal stability, and resistance to oxidative or UV-induced degradation, along with intrinsic antioxidant activity. Lipid modification leverages hydrophobic interactions with oils or fatty acids to form composite nanoparticles or Pickering emulsions. This approach increases the loading capacity for hydrophobic compounds, creates a protective barrier, and enhances oral bioavailability by promoting emulsification and intestinal absorption. Additional strategies include the incorporation of auxiliary proteins (e.g., casein, whey protein) to improve stability and emulsifying capacity, as well as the use of inorganic nanomaterials (e.g., SiO₂, AuNPs) to impart mechanical reinforcement, antibacterial properties, and stimuli-responsive functions. Genetic engineering further allows molecular-level tailoring of amino acid sequences to fine-tune hydrophobicity, amphiphilicity, and self-assembly behavior. These engineered nanocarriers exhibit advanced functionalities. They enable sustained and stimuli-responsive release triggered by pH, redox potential, enzymes, temperature, or light, facilitating on-demand delivery that maximizes efficacy while minimizing off-target effects. Targeting can be achieved passively through the enhanced permeability and retention (EPR) effect, or actively via conjugation with ligands, antibodies, or peptides that recognize specific receptors. The applications of these systems are broad. In functional foods and nutraceuticals, prolamin-based carriers improve the stability, bioavailability, and controlled release of sensitive bioactive ingredients, supporting personalized nutrition. In biomedicine, they enhance oral drug delivery, enable targeted cancer therapy with reduced systemic toxicity, and serve as scaffolds for tissue engineering. In agriculture, they facilitate the controlled release of pesticides, fertilizers, and growth regulators, helping to reduce environmental contamination and promote sustainable practices; they are also being explored for smart food packaging applications. Despite significant progress, challenges remain in clinical and industrial translation. There is an urgent need for standardized characterization methods, comprehensive in vivo safety and efficacy evaluations, and scalable, regulation-compliant manufacturing processes. Future research should adopt rational design principles to develop multi-stimuli-responsive and sustainable systems. The integration of artificial intelligence and data-driven approaches may further accelerate the development of personalized theranostic platforms and co-delivery systems. Continued innovation is expected to solidify the role of prolamin-based nanocarriers in advancing global health and sustainable development.]]> 2025/10/16 16:35:31 HUANG Yun-Jie,Qi Li-Li,MEI Han-Fang,WANG Meng-Ting,YU Yong and WANG Jin-Bo 97true e.g., IL-6, TNF-α), while simultaneously activating protein degradation systems including the ubiquitin-proteasome system (UPS) and autophagy-lysosomal pathway (ALP), ultimately leading to accelerated protein breakdown and muscle atrophy. These circulating inflammatory factors can also compromise blood-brain barrier integrity, activate microglia, trigger neuroinflammation, and consequently damage synaptic structures and neuronal function, thereby accelerating cognitive decline in this comorbidity. Mitochondrial dysfunction presents as impaired oxidative phosphorylation efficiency, excessive reactive oxygen species (ROS) production, and dysregulated mitochondrial quality control. This not only results in inadequate cellular energy supply but also enables mitochondrial-derived factors (e.g., extracellular mtDNA) to activate innate immune pathways such as cGAS-STING, propagating stress signals and amplifying tissue damage in both muscle and brain. Additionally, gut microbiota dysbiosis impairs intestinal barrier function, increases lipopolysaccharide (LPS) translocation into circulation, and reduces short-chain fatty acid (SCFA) production. These changes induce systemic inflammation and metabolic disturbances that further impact muscle metabolism and promote pathological protein accumulation in the brain, thereby establishing a gut-brain-muscle axis that exacerbates the progression of this comorbidity. Exerkines represent a class of biologically active signaling molecules—including cytokines, peptides, metabolites, and exosomes—secreted by various tissues in response to exercise. These exerkines mediate systemic adaptations and protective effects through endocrine and paracrine actions on target organs. Key exerkines such as IL-6, irisin, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-21 (FGF-21), lactate, and cathepsin B (CTSB) play central roles in coordinately ameliorating the comorbidity of sarcopenia and cognitive impairment. The beneficial effects of these exerkines are mediated through multiple mechanisms including inflammation modulation, energy metabolism remodeling, neuroprotection, and enhanced neuroplasticity. As a non-pharmacological intervention, exercise effectively stimulates the production and release of exerkines, thereby targeting the comorbidity through multiple pathways. Aerobic exercise elevates lactate levels and activates the Sirt1/PGC-1α pathway, improving cerebral metabolism and cognitive function. Resistance training significantly upregulates IGF-1, irisin, and CTSB expression, enhancing muscle anabolism and hippocampal function. Other modalities like high-intensity interval training (HIIT) and traditional practices also help modulate inflammatory status and optimize the neurotrophic environment through the action of various exerkines. Different exercise types work synergistically by engaging distinct signaling pathways and exerkine combinations, collectively alleviating chronic inflammation, correcting mitochondrial dysfunction, and optimizing gut microecology to achieve concurrent musculoskeletal and cognitive protection against this comorbidity. Synthesizing current evidence, this review emphasizes the necessity of transcending a single-organ perspective by recognizing muscle and brain as an integrated functional unit, with exerkines playing a pivotal role in the muscle-brain axis. The field nevertheless faces several challenges: the secretion dynamics of exerkines during aging remain unclear, mechanisms underlying individual differences in exercise response require elucidation, and the compensatory and imbalance characteristics of exercise-induced exerkine networks across disease stages need further characterization. Future research should employ large-sample cohorts and randomized controlled trials integrated with multi-omics technologies to establish personalized exercise interventions based on exerkine profiling for managing this comorbidity. Parallel efforts should focus on developing quantifiable efficacy assessment systems to provide robust theoretical foundation and practical guidance for precise management of the comorbidity of sarcopenia and cognitive impairment and the promotion of healthy aging.]]> 2025/10/17 13:15:11 XIA Jun-Mei,DENG Qi,HAO Hong-Tao and LIANG Ji-Ling 96true 2025/10/20 11:23:43 LI Ting-Ting,LIU Yu,LI Hong,WANG Shi-Da and ZHANG Hai-Feng 95true via shared understanding and shared intentionality. Together, these processes support the construction of group-level shared cognition. Finally, this article summarized the current challenges in research on the driving mechanisms of BBC and provided an outlook for future development. First, it is necessary to theoretically establish a hierarchical model of brain-brain coupling based on a hierarchy of cognitive complexity, systematically distinguishing between the characteristics of BBC driven by low-level processes and higher-level interpersonal shared cognitive mechanisms. Second, at the methodological and technical level, future development of multimodal hyperscanning systems such as EEG-fNIRS and closed-loop hyper-transcranial alternating current stimulation could comprehensively analyze the dynamic evolution of BBC related to shared cognition in the temporal, spatial, and frequency domains. In summary, this article constructed a theoretical framework for the driving mechanisms of BBC across social contexts, hoping to provide a methodological basis for controlling the driving factors of naturalistic paradigms in social neuroscience research.]]> 2025/10/17 13:09:11 WANG Zheng-Yi,SHU Lei-Jin,YU Hai-Qing,CHEN Yuan-Fang,XU Min-Peng,JUNG Tzyy-Ping and MING Dong 94true Akkermansia abundance and the Firmicutes/Bacteroidetes (F/B) ratio, but reduced Bifidobacterium abundance, indicating a bidirectional regulatory effect on gut microbial structure. MD significantly increased the Shannon index as well as the abundance of Akkermansia, Bifidobacterium, and Bacteroidetes, while decreasing Firmicutes abundance and the F/B ratio, suggesting a balanced and sustained improvement in gut microbial composition. In contrast, IF significantly decreased the PD index while increasing Akkermansia and reducing Firmicutes, reflecting partial structural optimization but limited enhancement of phylogenetic diversity; long-term interventions were associated with a decline in Shannon diversity, indicating limited stability. Subgroup analyses revealed distinct moderator effects. Under VLCKD, improvements in microbial diversity were more pronounced among individuals with BMI≤30 kg/m² and those aged >30 years, and meta-regression confirmed that the magnitude of diversity gains increased with age. Regarding BMI, increases in Akkermansia abundance were most evident in individuals with BMI 30-35 kg/m², whereas Bifidobacterium abundance significantly decreased in the same range, suggesting a threshold-dependent microbial response to adiposity. With respect to age, both Akkermansia (increase) and Bifidobacterium (decrease) exhibited significant changes in individuals aged >40 years. In terms of intervention duration, Akkermansia increased significantly within 6 weeks, while Bifidobacterium decreased within 12 weeks. For MD, increases in Shannon diversity were consistently observed across all BMI, age, and duration subgroups; notably, Akkermansia abundance increased significantly among participants with BMI>30 kg/m², aged 30-50 years, and during interventions ≤6 months, while Bifidobacterium abundance rose markedly in participants with BMI≤30 kg/m², aged 40-50 years, and during interventions of 6-12 months. Under IF, Shannon diversity increased significantly in individuals with BMI≤30 kg/m² and aged >40 years but declined when the intervention exceeded 4 weeks, suggesting reduced long-term stability. In conclusion, VLCKD, MD, and IF all modulate gut microbiota in obesity but differ in magnitude, direction, and durability. VLCKD exerts strong yet dual effects—enhancing diversity while reducing beneficial taxa; MD shows stable, sustained modulation; whereas IF offers selective improvements but lowers phylogenetic diversity with limited persistence. Future studies should conduct large, multicenter randomized controlled trials to determine optimal intervention duration, confirm the moderating roles of age and BMI, and develop personalized microbiota-based dietary strategies for obesity management and gut health improvement.]]> 2025/10/17 13:19:47 WANG Shun,BAO Zi-Han,ZHAO Meng-Qi,LI Zi-Yang,WANG Xun-Ling and LIU Feng-Hu 93true via nucleation-dependent polymerization mechanism, in which follows sigmoidal growth kinetics with three steps: lag phase, growth phase, and plateau phase. The formation and subsequent distribution of these pathological amyloid fibrils are closely related to the onset and progression of NDs. Additionally, the aberrant aggregation of these disease-associated proteins proceeds via liquid-liquid phase separation (LLPS) and liquid-to-solid phase transition (LSPT) leading to amyloid fibril formation in the condensed phase. The phase transition from liquid-like droplets or dynamic condensates to solid-like hydrogel or amyloids is intimately linked to the pathogenesis of several NDs. In this review, we discuss two typical pathways of amyloid fibrils formation. One route involves aggregation in the bulk solution environment, proceeding via nucleation and elongation steps to form amyloid fibrils. In this scenario, protein aggregation initiates with the nucleation step to form oligomeric nuclei. Then the nuclei serve as templates for the subsequent elongation step ultimately leading to the formation of amyloid fibrils. When sufficient fibrils have formed during self-assembly, the secondary nucleation is triggered to generate new species of oligomers and fibrillar aggregates. The other route of fibril formation occurs in the condensed phase through LLPS and LSPT to form amyloid aggregates and deposits. The occurrence of a phase separation leads to the liquid-like droplets formation during the early stage of aggregation. Over time, these dynamic biomolecular condensates gradually solidify and ultimately evolve into a hydrogel state enriched by amyloid aggregates through a phase transition process. Evidence indicates that pathological phase transitions are early events in the pathogenesis of several NDs. It should be noted that these two routes are not independent or mutually exclusive. They are interconnected and function cooperatively during aberrant aggregation. The pathological progression of NDs is closely related to the dominant aggregation pathway involved in aberrant aggregation. Moreover, the molecular mechanisms underlying the formation of pathogenic amyloid deposits are intricately linked to the structural and functional characteristics of aggregates. These aggregates may not only directly participate in fibrillization, but also indirectly promote the development of NDs by affecting the normal physiological cellular functions. Therefore, in-depth research on the structural and functional properties of both intermediates and fibrils is of great significance for understanding the molecular mechanisms of protein misfolding and aberrant aggregation. Overall, this paper reviews the amyloid deposition and pathological phase transitions in NDs. By delving into the molecular mechanisms of amyloid fibrillization, the aim is to better understand the pathogenesis of NDs, and to provide valuable insights into the development of therapeutic strategies targeting amyloid aggregation and aberrant phase transition.]]> 2025/8/1 9:00:38 LIANG Yu-Han,CHENG Wan-Ru,YANG Shuo,FENG Shuang and NIU Zheng 92true KRAS, c-Myc and EGFR are abnormally activated, cancer cell will secrete various cytokines and chemokines, thereby recruiting various immunosuppressive cells to the TME and causing exhaustion of CD8⁺ T and NK cells. It can also reprogram CAFs and eventually promote the development of cancer. Furthermore, similar phenomena occur after the inactivation of tumor suppressor genes. For example, cancer cells with inactivated PTEN genes will secrete large amounts of IL-33 and LOX to recruit macrophages and induce TAMs. Cancer cells can secrete a variety of microRNAs into the tumor microenvironment after p53 dysregulation. These mircoRNAs can reprogram CAFs and lead to epithelial-mesenchymal transition. Finally, we summarize the reversing effects of therapeutic interventions targeting mutant oncogenes or tumor suppressor genes (such as KRAS inhibitors, overexpression of p53 by mRNA, PI3Kβ inhibitors) on the immunosuppressive tumor microenvironment. Some of the results of their synergistic effects in combination with immunotherapy are also listed. Compared with monotherapy, the combination of either KRAS inhibitor or p53 mRNA nanomedicine with αPD-1 therapy resulted in more durable and potent anti-tumor effects. In summary, this review elucidates the regulatory and remodeling effects of genetic alterations in tumor cells on the tumor immune microenvironment, and analyzes the great potential of gene alteration intervention combined with immunotherapy. We hope it can provide theoretical basis and development strategy for precise cancer immunotherapy.]]> 2025/9/18 12:01:30 TAN Shu-Yi and ZHANG Jian 91true via phosphorylation. Epigenetic mechanisms—including N6-methyladenosine (m6A) RNA modification and histone H3K18 lactylation—further stabilize glycolytic gene expression and reinforce metabolic reprogramming. These alterations form an integrated regulatory network that sustains high glycolytic flux in ectopic cells. Importantly, GMR profoundly affects the immune microenvironment. Lactate produced by glycolytic stromal cells promotes M2 macrophage polarization and impairs the function of cytotoxic T cells and dendritic cells, leading to immune evasion and chronic inflammation. Meanwhile, immune cells themselves undergo metabolic reprogramming, exhibiting increased dependence on glycolysis and diminished oxidative capacity. This bidirectional metabolic-immune feedback loop facilitates lesion persistence and disease progression. GMR is also closely linked to infertility in EM and AM. In the ovarian microenvironment, glycolytic imbalance leads to lactate accumulation in follicular fluid, negatively affecting oocyte quality and embryo development. In the endometrium, excessive glycolysis disrupts decidualization, angiogenesis, and immune tolerance—processes essential for implantation and pregnancy. Targeting glycolysis offers promising therapeutic potential. Small-molecule inhibitors such as dichloroacetate and meclozine target PDK and HK2, respectively. Natural compounds like cinnamic acid and protoberberine derivatives exhibit both anti-glycolytic and anti-inflammatory effects. Traditional Chinese medicine formulations, including Guizhi Fuling Wan, have shown efficacy in modulating metabolism, vascular remodeling, and fibrosis. Combination therapies, such as atorvastatin with resveratrol, may provide synergistic benefits by inhibiting both glucose uptake and lactate export. In conclusion, glycolytic metabolic reprogramming is a central mechanism linking inflammation, immune dysfunction, lesion progression, and reproductive failure in endometriotic diseases. Future research should focus on identifying metabolic subtypes, developing combined metabolic-immune therapies, and evaluating the safety of these treatments in reproductive-age women. These insights may pave the way toward personalized, mechanism-driven interventions for EM and AM.]]> 2025/8/5 20:03:27 DU Lin,WANG Mei-Ling,ZHOU Shuang-Shuang,FU Xian-Yun,SHI Wen-Jie,TAO Yi-Dan and ZHOU Hao-Xin 90true 1 150 mitochondrial proteins are encoded by nuclear genes (nDNA), and the two genomes cooperate to preserve cellular homeostasis and proper function. Mitochondrial proteins are localized to the outer mitochondrial membrane (OMM), intermembrane space (IMS), inner mitochondrial membrane (IMM) or matrix, participating in oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, fission-fusion dynamics, and other processes indispensable for mitochondrial integrity. Mitochondrial quality control (MQC) is exerted largely by mitochondrial proteases, which selectively modulate protein activity and degrade misfolded or superfluous proteins. Among them, a group of mitochondrial ATPases associated with diverse cellular activities (AAA+ proteases) couple ATP binding and hydrolysis to protein unfolding and proteolysis, thereby regulating fusion protein maturation, respiratory-chain assembly, and mtDNA replication/transcription. Mutations or aberrant expression of these mitochondrial AAA+ proteases cripple mitochondrial architecture and function, precipitating a spectrum of severe neurological disorders. This review summarizes current knowledge on three paradigmatic mitochondrial AAA+ proteases, LONP1, YME1L1, and AFG3L2. We highlight their conserved Walker A/B motifs in the ATPase domain and hexameric architecture, yet emphasize divergent sub-mitochondrial topologies: LONP1 is soluble in the matrix, whereas YME1L1 and AFG3L2 are embedded in the IMM with catalytic domains facing IMS and matrix, respectively. These positional differences translate into distinct substrates and proteolytic strategies, enabling a division of labor and mutual complementation that cooperatively safeguards mitochondrial proteostasis. Pathogenic mutations linked to neurological disorders are mapped predominantly to the ATPase and the hydrolase/peptidase domains. Substitutions of the amino acid within these core domains can directly abolish ATP hydrolysis, substrate engagement or peptide cleavage, thereby crippling local MQC networks. Additional variants may disturb transcriptional, translational or post-translational regulation, altering protease stoichiometry and impairing compartmental balance. The subsequent cascade, mtDNA instability, respiratory-chain dysfunction, and aberrant mitochondrial dynamics, propagates stress signals that culminate in neuronal dysfunction and/or neurodegeneration. The mutational and clinical heterogeneity observed across cell types, developmental stages, and genetic backgrounds underscores the context-dependent fine-tuning of these AAA+ proteases. Deciphering how disease-associated variants rewire domain structure, catalytic cycle, and network-level crosstalk will therefore illuminate pathophysiologic mechanisms and guide precision therapeutic strategies.]]> 2025/9/18 13:09:56 LI Ru-Ru,ZHANG Ye,WEI Tao-Tao and ZHU Li 89true via activation of pathways such as PPARα, ameliorates insulin resistance, and thus optimizes the metabolic environment of cardiomyocytes. In the context of cellular stress regulation, irisin exhibits potent antioxidant properties. It not only directly counteracts the accumulation of reactive oxygen species (ROS) to alleviate oxidative damage but also inhibits ferroptosis by upregulating the MITOL/MARCH5 signaling axis, thereby helping to maintain mitochondrial homeostasis. Regarding endoplasmic reticulum stress (ERS), irisin downregulates key proteins including GRP78 and PERK, thus mitigating ERS-induced cardiomyocyte apoptosis and fibrosis—a protective mechanism that has also been validated in other diseases such as pancreatitis and osteoporosis. In maintaining the balance between autophagy and cell death, irisin sustains cellular homeostasis by coordinating both mitochondrial-targeted autophagy and non-selective autophagy. It promotes FUNDC1-mediated mitophagy to support mitochondrial turnover and ensure proper organelle function. At the same time, it suppresses excessive autophagy-induced cell damage through pathways such as PI3K/AKT/mTOR. In terms of apoptosis regulation, irisin downregulates pro-inflammatory factors (e.g., TNF-α, IL-6) and apoptosis-related proteins such as Caspase-3, while upregulating the anti-apoptotic protein Bcl-2. It inhibits cardiomyocyte apoptosis through multiple signaling pathways, including AMPK/mTOR and miR-19b/PTEN. In summary, irisin plays a crucial protective role in improving metabolic disorders, reducing cellular stress damage, and regulating cell death in diabetic cardiomyopathy (DCM) through multi-target and multi-pathway synergistic mechanisms. Its diverse actions provide an important theoretical basis and potential therapeutic targets for the clinical prevention and treatment of DCM. However, further research is needed to clarify its systemic effects, the safety of clinical interventions, and optimal treatment strategies to fully realize its therapeutic potential.]]> 2025/9/23 11:17:28 YAN Xue-Ru,ZHANG Yue-Jun,LI Jia-Yue,ZHANG Hao-Da and HE En-Peng 88true etc. With the intensifying trends of global population growth and aging, the incidence of NDs continues to rise, yet no curative treatments are currently available. The blood-brain barrier (BBB) plays a crucial role in maintaining central nervous system (CNS) homeostasis by blocking harmful substances in the bloodstream from entering brain tissue. More than 98% of small-molecule drugs and nearly 100% of large-molecule therapeutics fail to cross the BBB and reach brain parenchyma. Ultrasound-targeted microbubble destruction (UTMD) is an emerging interdisciplinary technology integrating materials science and bioengineering, which combines the advantages of microbubble carriers with the physical properties of ultrasound. This innovative approach enables transient and reversible opening of the BBB, and enhancing drug delivery efficiency. Microbubbles (MB) are the core component of the UTMD system, consisting of two fundamental structural elements: a gaseous core and a biocompatible outer shell. The drug-loading capacity of MB has been significantly expanded, evolving from traditional chemotherapeutic agents to encompass nucleic acid drugs, macromolecular antibodies, and even traditional Chinese medicines. Concurrently, their drug-loading strategies have advanced from initial passive physical adsorption to active targeted delivery. UTMD possesses the following 4 biological advantages. (1) UTMD can transiently and reversibly enhance the permeability of cell membranes and blood vessels. The biocompatible shells commonly used in microbubbles can be metabolized by the body, posing no risk of long-term accumulation. (2) UTMD not only significantly improves drug delivery efficiency but also simultaneously serves as an ultrasound contrast agent and therapeutic carrier, achieving the integration of diagnosis and treatment. (3) UTMD technology offers dual advantages of spatial targeting and molecular targeting, allowing for precise drug delivery. (4) UTMD only requires conventional ultrasound equipment, and the raw materials for microbubble preparation are readily available with simple synthesis processes. Whether applied in diagnostics or treatment, the cost remains relatively low. The mechanism by which UTMD opens the BBB is primarily associated with cavitation effect and sonoporation effect. The cavitation effect induces mechanical stretching of both cellular membranes and capillary walls, creating transient, reversible channels that facilitate macromolecular drug passage, to enhance BBB permeability. Meanwhile, the sonoporation effect promotes drug penetration through dual mechanisms: (1) augmenting passive diffusion across biological barriers; (2) potentiating active transport processes. This synergistic action significantly elevates both local drug concentrations and therapeutic efficacy at target sites. The permeability of BBB is predominantly influenced by both microbubble characteristics and ultrasound parameters. Microbubble characteristics and ultrasound parameters are key factors affecting BBB permeability. By adjusting the composition of microbubbles and optimizing ultrasound parameters, effective BBB opening can be achieved while minimizing tissue damage, to regulate the dosage of drugs delivered to the brain parenchyma. Both preclinical investigations and clinical trials have consistently shown that UTMD holds significant therapeutic promise for NDs. This article outlines the fundamental properties of microbubbles and elucidates the potential mechanisms underlying UTMD mediated BBB opening. Furthermore, it systematically reviews recent advances in UTMD technology for the treatment of treating various NDs, aiming to provide a theoretical foundation and future directions for developing novel therapeutic strategies and drugs for NDs.]]> 2025/9/11 15:02:52 LI Ling-Yan,ZHENG Ruo-Quan,HU Huo-Jun,YOU Cheng-Cheng,YANG Yi,SHENG De-Qiao,ZHOU Jun and HUANG Yi-Ling 87true e.g., hallucinations), negative symptoms (e.g., social withdrawal), and cognitive impairments. Among these, cognitive impairment is a core feature that severely compromises patients’ social functioning and long-term prognosis. Antipsychotics, the first-line treatment for schizophrenia, are generally effective in managing positive symptoms. However, their efficacy in alleviating negative symptoms and cognitive deficits remains limited. Moreover, long-term use may lead to metabolic syndrome and extrapyramidal side effects. Consequently, non-pharmacological interventions have garnered increasing attention as alternative or adjunctive strategies for cognitive remediation in schizophrenia. In recent years, techniques grounded in neuroplasticity theory have advanced rapidly. These interventions aim to alleviate cognitive impairments by modulating neural circuits (e.g., enhancing prefrontal-hippocampal connectivity) and synaptic plasticity (e.g., modulating the BDNF/TrkB pathway) from multiple dimensions. Such approaches not only enhance cognitive function but also reduce medication-related adverse effects and improve treatment compliance. This article comprehensively reviews the clinical evidence and recent technological advances in non-pharmacological interventions targeting cognitive impairments in schizophrenia. The interventions discussed include cognitive remediation therapy (CRT), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), electro-acupuncture (EA), aerobic exercise (AE), and light therapy (LT). CRT, the most extensively studied and evidence-based intervention, uses structured cognitive training tasks to enhance neuroplasticity and has consistently demonstrated efficacy in improving executive function and social cognition. Both rTMS and tDCS are non-invasive brain stimulation techniques that modulate cortical excitability and neural network connectivity. While rTMS has shown promise in improving working memory and attention—particularly in patients with prominent negative symptoms—its clinical efficacy remains inconsistent, likely due to variability in stimulation parameters and patient heterogeneity. In contrast, tDCS has demonstrated encouraging effects on working memory and attention with a relatively rapid onset, although optimal stimulation protocols have yet to be standardized. EA, which combines traditional acupuncture with electrical stimulation, has been shown to improve memory function, possibly through upregulation of brain-derived neurotrophic factor (BDNF) and enhanced cerebral blood flow. It may be especially useful in treatment-resistant cases. AE is a low-cost and widely accessible intervention that promotes hippocampal neuroplasticity and BDNF expression, thereby improving memory and attention. It is recommended as a foundational adjunctive therapy, particularly for patients with chronic schizophrenia. LT, although still experimental, has yielded promising results in animal models by modulating neuroinflammation and enhancing neurogenesis via the BDNF/CREB signaling pathway. However, clinical evidence remains limited, necessitating further large-scale trials to validate its efficacy and safety. In addition to reviewing individual interventions, this article highlights the potential of combination strategies—such as CRT combined with AE or rTMS—to produce synergistic cognitive benefits. Future directions include the development of personalized treatment protocols, early intervention during neurodevelopmental windows (e.g., adolescence), and the integration of biomarkers and neuroimaging to guide therapeutic decisions. This synthesis aims to provide clinicians and researchers with a comprehensive framework for advancing non-pharmacological cognitive rehabilitation in schizophrenia.]]> 2025/7/24 7:29:57 FENG Jia-Xin,XIE Yan-Hong,LI Yi,LIN Fo-Xiang,HUANG Min-Fang,WANG Qin-Wen and WANG Zheng-Chun 86true GBA1, PRKN, PINK1, and SNCA dictate distinct molecular pathologies—including lysosomal dysfunction, impaired mitophagy, and α-synuclein aggregation—which necessitate tailored exercise regimens. For instance, patients with PRKN/PINK1 mutations may benefit from moderate-intensity endurance training to support mitochondrial biogenesis without exacerbating oxidative stress, whereas carriers of GBA1 mutations might require exercises focusing on enhancing lysosomal function and managing oxidative damage. Clinically, patients are stratified into tremor-dominant (TD) and postural instability/gait difficulty (PIGD) subtypes, which demand divergent exercise priorities: coordinative, rhythm-based activities like dance or Tai Chi for TD-PD to engage cerebellar circuits, versus targeted balance and strength training, potentially aided by virtual reality, for PIGD-PD to mitigate axial symptoms and fall risk. Furthermore, intervention strategies must evolve with disease progression: high-intensity exercise is prioritized in early stages to leverage neuroplasticity and potential disease modification, while mid- and late-stage management focuses on functional maintenance, fall prevention, and compensatory strategies, respectively. Critical to implementing this framework is the adoption of digital biomarkers via wearable technology (e.g., inertial sensors, smartwatches), which enables continuous, objective monitoring of gait, tremor, and physiological responses. This facilitates a closed-loop feedback system, allowing for the remote adjustment of exercise parameters (intensity, frequency, duration) in real-time, thus optimizing efficacy and ensuring safety. Finally, we detail how to configure exercise parameters through personalized adaptation (What), including exercise type, intensity, frequency and dose. Higher volumes of physical activity are associated with reduced PD risk and slower progression, though optimal thresholds remain incompletely defined. Aerobic exercise improves cardiovascular fitness and may aid clearance of pathogenic proteins; resistance training counters sarcopenia and bradykinesia; balance training reduces falls; and mind-body exercises (e.g., Tai Chi) integrate motor and cognitive components. Multimodal regimens are often most beneficial. High-intensity aerobic exercise appears particularly effective in early PD, enhancing neural connectivity and mitigating disease progression in randomized trials. Most evidence supports supervised sessions occurring 3-5 times per week, lasting 30-60 min, adapted to individual tolerance and disease stage. In conclusion, this narrative review outlines a comprehensive precision medicine framework for exercise intervention in PD, moving beyond symptomatic management towards targeting underlying pathophysiology. By stratifying patients based on genetic, phenotypic, and staging characteristics, and by leveraging digital technology for dynamic personalization, exercise therapy can be transformed into a more potent, individualized, and disease-modifying strategy. Future research must validate these biomarker-driven approaches in large-scale trials and establish definitive guidelines for translating precision exercise into clinical practice.]]> 2025/9/28 22:06:58 ZHOU Zi-Gui,YAN Min,WEN Xiao,WANG Hui,LIU Guo-Qiang and TIAN Xue-Wen 85true 2025/9/8 21:25:14 YUAN Chen-Man,SHI Xiu-Yan,LIU Jia and WANG Jing-Jing 84true e.g., FASTAptamer, AptaCLUSTER) to identify enriched sequences, and motif discovery algorithms (such as AptaTRACE and MPBind) that uncover conserved sequence-structure patterns associated with binding functionality. These approaches allow researchers to move beyond manual curation and extract meaningful candidates from complex selection rounds. Accurate prediction of secondary and tertiary structures is essential for understanding aptamer function and interaction mechanisms. Conventional tools, including RNAfold and Mfold, employ thermodynamics-based models to predict RNA folding, yet often struggle with pseudoknots and non-canonical pairs. Recent advances in deep learning—exemplified by SPOT-RNA, E2Efold, and UFold—have significantly improved prediction accuracy by leveraging neural networks trained on large structural datasets. For tertiary structure, methods range from fragment assembly (Rosetta FARFAR2) and homology modeling (RNAComposer) to deep learning-aided approaches such as AlphaFold-RNA and RoseTTAFoldNA. While these tools offer new insights, predicting structures for short, flexible aptamers remains non-trivial. Predicting aptamer-target interactions draws on both physics-based and data-driven approaches. Molecular docking programs—AutoDock Vina, ZDOCK, and MDockPP—provide initial binding poses, which can be refined using molecular dynamics simulations (with GROMACS, AMBER, or NAMD) and free energy perturbation techniques to estimate binding affinity. Complementarily, machine learning models are increasingly employed to predict interactions from sequence and structural features. Early efforts used hand-engineered features with classifiers like SVM and random forest, while contemporary deep learning models (AptaNet, AptaBERT, PAIR) utilize pre-trained language models to capture intricate sequence-binding relationships with superior generalization. Perhaps the most transformative development is the use of generative AI for de novo aptamer design. Conditional variational autoencoders (e.g., RaptGen), generative adversarial networks (e.g., AptaDesigner), and diffusion models (e.g., AptaDiff) can generate novel aptamer sequences conditioned on target properties or desired binding affinities. Reinforcement learning and evolutionary algorithms, including Monte Carlo tree search (Apta-MCTS) and NSGA-II, support multi-objective optimization toward high specificity, stability, and low immunogenicity. These approaches mark a paradigm shift from selective discovery to intentional design, greatly expanding the functional sequence space. Aptamers designed using these computational strategies are increasingly used across biomedical and environmental applications, including targeted therapeutics, diagnostic biosensors, and food-safety monitoring. Nonetheless, key challenges persist: data scarcity and heterogeneity, model interpretability, and experimental validation bottlenecks. Future progress will depend on standardized data sharing, improved explainable AI, and the integration of computational design with high-throughput experimental screening—ultimately enabling robust, clinically viable aptamer technologies.]]> 2025/9/25 16:23:48 LIU Shang-Hua,ZHANG Hong-Qi,LIU Ru-Ming,ZENG Hong-Juan,DENG Ke-Jun,YAN Dan,TANG Li-Xia and LIN Hao 83true Pisum sativum). However, the molecular bases underlying these traits have only come into sharp focus in recent years. Leveraging advances in traditional map-based cloning, TILLING, long-read resequencing, population genetics, and GWAS, this article synthesizes current knowledge of ten genes governing seven traits—plant height, seed shape, flower color, seed color, pod color, pod morphology, and flower position—by summarizing each gene’s identity, chromosomal localization, and functional pathway. For plant height, the classical Le locus corresponds to PsGA3ox1, which encodes a gibberellin 3β-hydroxylase. Mutations at Le impede the biosynthesis of the bioactive hormone GA₁, and the resulting deficiency leads to a dwarf or reduced-stature phenotype. Seed shape is determined by R, identified as PsSBEI (starch-branching enzyme I). Insertion of a transposable element into R restricts amylopectin synthesis, perturbing endosperm starch architecture and resulting in the wrinkled seeds noted by Mendel. Flower color is specified by the coordinated action of A (a bHLH transcription factor) and A2 (a WD40 scaffold). Together, they assemble the canonical MYB-bHLH-WD40 (MBW) regulatory complex, which co-activates structural genes in the anthocyanin pathway to determine pigment accumulation and floral hue. Seed color is governed by I, which encodes PsSGR (STAY-GREEN), a magnesium dechelatase that catalyzes a key step in chlorophyll catabolism. Loss-of-function alleles at I block chlorophyll degradation, yielding “stay-green” seeds in which chlorophyll persists beyond normal developmental stages. Pod coloration maps to Gp, corresponding to ChlG (chlorophyll synthase). Either direct loss of ChlG function or readthrough-fusion transcriptional interference caused by a large upstream deletion suppresses chlorophyll biosynthesis in developing pods, resulting in the yellow-pod phenotype. Pod morphology depends on two convergent regulatory pathways. The P gene, PsCLE41, signals through the P-PXY-WOX/NAC axis to promote vascular differentiation and secondary-wall programs, while V encodes PsMYB26, a transcription factor that drives secondary wall thickening in fiber cells. Acting in concert, these modules ensure robust secondary-wall deposition in the fiber layer lining the inner pod wall; disruption of either component compromises wall thickening and leads to pleated or wrinkled pods. Flower position (inflorescence determinacy at the shoot apex) is controlled by FA, identified as PsCIK, which participates in the CLAVATA-WUSCHEL (CLV-WUS) feedback circuit that maintains shoot apical meristem homeostasis. Mutations in FA destabilize this self-regulatory loop and promote terminal flowers at the apex. The expressivity of this determinacy phenotype is further modulated by a recessive modifier, Mfa, which fine-tunes the outcome in the fa background. Across these loci, convergent evidence highlights the central role of structural variation in generating the classical Mendelian phenotypes. Building on this clarified molecular landscape, we outline practical implications for quality improvement and the deliberate “design” of traits. Looking ahead, we envisage a next generation of legume genetic improvement anchored on three mutually reinforcing pillars: high-quality reference genomes to deliver contiguous, structurally faithful assemblies; comprehensive pan-genomes to capture presence/absence variation and structural polymorphism across germplasm; and precise gene editing to target coding, regulatory, and structural features alike. Together, these tools chart a path toward mechanism-based breeding, enabling purposeful, design-driven trait improvement in peas and, by extension, other legumes.]]> 2025/9/19 0:00:00 GUO Jia-He and LI Shao-Jun 82true 2025/7/10 11:17:28 WANG Hai-Zhu,HUANG Chun-Cui and LI Yan 81true via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF-κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.]]> 2025/7/30 16:18:19 YAN Si-Ru,CAI Ming-Yang,SUN Ya-Xuan,HUO Qing and DAI Xue-Ling 80true 2025/7/24 7:23:10 TANG Li,SHEN Yun-Long,PENG De-Jian,RAN Tian-Lu,PAN Zi-Heng,ZENG Xin-Yi and LIU Hui 79true e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β-catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.]]> 2025/8/7 11:27:33 CHENG Di,CHEN Yu-Hua,JIANG Xia-Ping,LI Lan-Yu,TAN Yi,LI Ming and MO Zhong-Cheng 78true via aberrant activation of signaling pathways. The ubiquitination/deubiquitination process mainly involves E3 ligases (E3s) that catalyze substrate ubiquitination, deubiquitinating enzymes (DUBs) that remove ubiquitin chains, and the 26S proteasome complex that degrades ubiquitinated substrates. Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumor-related proteins, thereby driving OSCC initiation and progression. Therefore, understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components. Here, we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway, Wnt/β-catenin pathway, Hippo pathway, and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways, along with potential drug targets. PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70% of OSCC cases. It is modulated by E3s (e.g., FBXW7 and NEDD4) and DUBs (e.g., USP7 and USP10): FBXW7 and USP10 inhibit signaling, while NEDD4 and USP7 potentiate it. Aberrant activation of the Wnt/β-catenin pathway leads to β-catenin nuclear translocation and induction of cell proliferation. This pathway is modulated by E3s (e.g., c-Cbl and RNF43) and DUBs (e.g., USP9X and USP20): c-Cbl and RNF43 inhibit signaling, while USP9X and USP20 potentiate it. Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis. This pathway is modulated by E3s (e.g., CRL4^DCAF1 and SIAH2) and DUBs (e.g., USP1 and USP21): CRL4^DCAF1 and SIAH2 inhibit signaling, while USP1 and USP21 potentiate it. Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance. This pathway is modulated by E3s (e.g., TRAF6 and LUBAC) and DUBs (e.g., A20 and CYLD): A20 and CYLD inhibit signaling, while TRAF6 and LUBAC potentiate it. Targeting these E3s and DUBs provides directions for OSCC drug research. Small-molecule inhibitors such as YCH2823 (a USP7 inhibitor), GSK2643943A (a USP20 inhibitor), and HOIPIN-8 (a LUBAC inhibitor) have shown promising antitumor activity in preclinical models; PROTAC molecules, by binding to surface sites of target proteins and recruiting E3s, achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors, for example, PU7-1-mediated USP7 degradation, offering new strategies to overcome traditional drug limitations. Currently, NX-1607 (a Cbl-b inhibitor) has entered phase I clinical trials, with preliminary results confirming its safety and antitumor activity. Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.]]> 2025/7/22 7:18:45 CHANG Han,ZHAO Meng-Xiang,JIN Xiao-Feng and YING Bin-Bin 77true via the PGC-1α/TFAM axis, and initiation of autophagy through the ULK1/mTOR pathway. Emerging mechanisms are also discussed, such as exercise-induced epigenetic modifications (e.g., histone acetylation and miRNA regulation), modulation of the gut microbiota, and metabolite-mediated immune programming (e.g., short-chain fatty acids (SCFAs), β-hydroxybutyrate). The effects of exercise on innate immunity vary considerably among individuals, depending on factors such as age, sex, and comorbidities. For example, adolescents exhibit enhanced NK cell mobilization, whereas older adults benefit from reduced chronic inflammation and immune aging. Sex hormones and metabolic conditions (e.g., obesity, diabetes, chronic obstructive pulmonary disease, cancer) further modulate the immune response to exercise. Based on these insights, we propose a personalized approach to exercise prescription guided by the FITT (frequency, intensity, time, and type) principle, aiming to optimize immune outcomes across diverse populations. Importantly, given the dual role of exercise in immune activation and regulation, caution is warranted: while moderate exercise enhances immune defense, excessive or high-intensity activity may induce transient immunosuppression. In pathological contexts such as infection, autoimmune diseases, or tissue injury, exercise intensity and timing must be carefully adjusted. This review provides practical guidelines for exercise-based immune modulation and underscores the need for dose-response studies and advancements in precision exercise medicine. In conclusion, exercise represents a safe and effective strategy for enhancing innate immune function and mitigating chronic inflammatory diseases.]]> 2025/8/4 8:30:48 ZHAO Shu-Yang,LI Xin,NING Ke and WANG Zhuo 76true 2+ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-α (PPAR-α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR-α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.]]> 2025/8/5 19:53:06 LIAO Fang-Lian,CHEN Xiao-Feng,XIANG Han-Yi,XIA Zhi and SHANG Hua-Yu 75true e.g., group size, response consistency), attributes of peers (e.g., familiarity, social status, distinctions between human and artificial agents), as well as individual differences such as confidence, personality traits, and developmental stage. The motivations driving social influence encompass three primary mechanisms: improving decision accuracy through informational influence, gaining social acceptance through normative influence, and maintaining positive self-concept. Recent computational approaches have employed diverse theoretical frameworks to provide valuable insights into the cognitive mechanisms underlying social influence in perceptual decision making. Reinforcement learning models demonstrate how social feedback shapes future choices through reward-based updating. Bayesian inference frameworks describe how individuals integrate personal beliefs with social information based on their respective reliabilities, dynamically updating beliefs to optimize decisions under uncertainty. Drift diffusion models offer powerful tools to decompose social influence into distinct cognitive components, allowing researchers to differentiate between changes in perceptual processing and shifts in decision criteria. Collectively, these models establish a comprehensive methodological foundation for disentangling the multiple pathways by which social context shapes perceptual decisions. Neuroimaging and electrophysiological studies provide converging evidence that social context influences perceptual decision making through multi-level neural mechanisms. At early perceptual processing stages, social influence modulates sensory evidence accumulation in parietal cortex and directly alters primary visual cortex activity, while guiding selective attention to stimulus features consistent with social norms through attentional alignment mechanisms. At higher cognitive levels, the reward system (ventral striatum, ventromedial prefrontal cortex) is activated during group-consistent decisions; emotion-processing networks (anterior cingulate cortex, insula, amygdala) regulate experiences of social acceptance and rejection; and mentalizing-related brain regions (dorsomedial prefrontal cortex, temporoparietal junction) support inference of others’ mental states and social information integration. These neural circuits work synergistically to achieve top-down multi-level modulation of perceptual decision making. Understanding the mechanisms by which social context shapes perceptual decision making has broad theoretical and practical implications. These insights inform the optimization of collective decision-making, the design of socially adaptive human-computer interaction systems, and interventions for cognitive disorders such as autism spectrum disorder and anorexia nervosa. Future studies should combine computational modeling and neuroimaging approaches to systematically investigate the multi-level and dynamic nature of social influences on perceptual decision making.]]> 2025/7/26 7:05:38 LIU Yu-Pei,WANG Yu-Shu,ZHAN Bin,WANG Rui and JIANG Yi 74true AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.]]> 2025/7/22 7:07:57 HOU Song,ZHANG Lin-Shan,HONG Xiu-Qin,ZHANG Chi,LIU Ying,ZHANG Cai-Li,ZHU Yan,LIN Hai-Jun,ZHANG Fu and YANG Yu-Xiang 73true e.g., humic acids, heme, indigo dyes), and often inadequate sensitivity for trace or degraded samples typical of crime scenes, thereby failing to meet the critical operational imperatives of forensic practice: rapidity, high specificity, sensitivity, portability, and robustness against interference. This review posits that CRISPR-Cas-based RNA detection technology provides a groundbreaking solution by leveraging the programmable, sequence-specific recognition conferred by the synergistic interaction between a designed guide RNA (gRNA) and Cas effector proteins (e.g., Cas12a, Cas13a, Cas14). Upon target RNA binding, specific Cas enzymes undergo conformational activation, exhibiting collateral cleavage activity―a unique catalytic amplification mechanism where the enzyme non-specifically cleaves surrounding reporter molecules, enabling ultra-high sensitivity. To further enhance detection limits, CRISPR-Cas systems are strategically integrated with isothermal pre-amplification techniques like recombinase polymerase amplification (RPA) or loop-mediated isothermal amplification (LAMP), which efficiently amplify target RNA at constant temperatures, eliminating the need for thermal cyclers. This powerful cascade―isothermal pre-amplification followed by CRISPR-mediated sequence-specific recognition and collateral signal amplification―achieves exceptional sensitivity, often down to the single-molecule (attomolar) level, while drastically reducing analysis time to potentially 30-60 min. Crucially, the compatibility of CRISPR-Cas detection with simple, equipment-free readout systems, such as lateral flow strips (LFS) for visual colorimetric results or portable fluorescence/electrochemical sensors, facilitates true point-of-need (PON) forensic analysis directly at crime scenes, morgues, or field labs. This enables rapid applications like specific body fluid identification (e.g., distinguishing menstrual blood via miRNA, identifying saliva via mRNA), post-mortem interval (PMI) estimation through RNA degradation/expression patterns, donor age inference via age-related RNA markers, tissue identification, and microbial forensics, thereby accelerating investigative leads, minimizing sample degradation risks, and optimizing resource allocation. However, significant challenges impede widespread adoption, including persistent environmental interference inhibiting enzymes, fluctuations in Cas/amplification enzyme activity affecting reproducibility, a critical lack of standardized protocols and validated quality assurance/quality control (QA/QC) frameworks essential for forensic reliability and court admissibility, and current limitations in multiplex detection capability. Consequently, future research must prioritize overcoming multiplexing bottlenecks for comprehensive analysis, enhancing system robustness through Cas protein engineering and optimized reagents, developing fully integrated, sample-to-answer microfluidic or lateral flow devices for user-friendly field deployment, and collaboratively establishing universally accepted validation guidelines, performance standards, and stringent QA/QC procedures. Furthermore, the urgent development of clear ethical guidelines governing the use of this highly sensitive technology, particularly concerning RNA data privacy and potential misuse, is imperative. This review systematically outlines the principles, forensic applications, current limitations, and future trajectories of CRISPR-RNA detection, with the authors’ conviction that focused efforts addressing these challenges will translate this technology into a cornerstone of next-generation forensic practice, driving unprecedented efficiency and innovation in field investigations and laboratory analysis to enhance justice delivery.]]> 2025/8/1 7:31:35 FANG Yun,WANG Xian-Miao,XIE Wei and SUN Qi-Fan 72true GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF-κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF-κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.]]> 2026/5/29 9:23:23 ZHAO Jia-Nan,LI Yu-Xuan,ZHU Jie,LI Hong and JIN Xiao-Feng 71true i.e., dietary lipid intake plans tailored to an individual’s unique microbiome profile) and targeted microbiome modulation therapies (such as next-generation probiotics, prebiotics, or specific metabolite supplements). Targeting the gut as a “reactor” to treat vascular wall lesions represents a promising direction for future cardiovascular medicine.]]> 2026/6/7 10:41:40 PAN Jin-Qian,LIU Wang,LI Zhao-Bing,LIU Shi-Yang and ZHOU Qin-Yi 70true 2026/5/31 17:03:39 ZHU Xiao-Yan,JIN Tao,ZHANG Yu,LIAN Lu-Lu and DU Wan-Li 69true in vivo spatial measurements of lysosomal functions, rational optimisation of combination therapy timings, and safety assessments in immunocompetent liver cancer models prior to clinical translation. Translation difficulties are also evident, such as insufficient tumour selectivity, pharmacokinetic limitations, compensatory lysosomal regeneration, toxicity to normal liver and immune cells, and a lack of validated predictive biomarkers. A new way will be found to use biomarkers to divide the patient group, optimize nanoparticles for better delivery, design specific schedules for combined treatments based on the problem they cause within the cell, etc., thereby overcoming drug resistance and reducing the harm patients suffer from toxic treatments. This system can help select biomarkers and rational drug pairs for the next round of lysosome-centred precision trials.]]> 2026/6/25 6:31:31 HUANG Chun-Ping,LI Yong-Zhuo and ZHOU Jing 68true 2026/5/31 22:40:09 KE Zhi-Fei,SONG Wen-Jing,DONG Yun-Feng and SHANG Hua-Yu 67true 2+) stands out due to its unique ability to simultaneously disrupt energy metabolism, damage mitochondria, degrade mutant p53, and activate antitumor immunity. Notably, tumor cells exhibit greater sensitivity to Zn²⁺ overload while normal cells maintain higher tolerance. This review systematically summarizes design strategies for achieving “zinc overload” using biodegradable zinc-based nanomaterials, focusing on two fundamental questions: how to specifically deliver Zn²⁺ to tumors (targeted delivery), and how to trigger controlled release at the tumor site (release strategies). Current challenges are critically analyzed and future perspectives are offered. For targeted delivery, the strategies are categorized into passive, active, and biomimetic approaches. Passive targeting relies on the enhanced permeability and retention (EPR) effect but suffers from poor enrichment efficiency and rapid clearance. Active targeting conjugates ligands (e.g., folic acid, hyaluronic acid) to recognize overexpressed receptors, significantly enhancing cellular uptake. It is emphasized that hyaluronic acid-modified ZIF-8 can co-deliver siRNA for GLUT1 silencing, achieving systematic energy exhaustion. Biomimetic delivery using cell membranes confers immune evasion, prolonged circulation, and homologous targeting, exhibiting the lowest off-target toxicity. This approach is considered to guide future nanocarrier design. For Zn²⁺ release, 4 mechanisms are discussed. Endogenous environment-responsive release exploits acidic pH to degrade materials like ZIF-8 or ZnO, causing mitochondrial dysfunction, reactive oxygen species (ROS) burst, and autophagic blockade. Incorporation of other ions (Ca²⁺, Mn²⁺, Ni²⁺) enables synergistic metabolic interference and immune activation. Exogenous responsive release using near-infrared light offers spatiotemporally precise activation. For example, a nanorobot combining black phosphorus with ZIF-8 accelerates Zn²⁺ release under dual acid and light stimuli. Ion exchange represents an elegant trigger: zinc complexes (e.g., Zn-carnosine) have higher affinity for Cu²⁺; competitive coordination releases Zn²⁺ while depleting Cu²⁺, dually inhibiting oxidative phosphorylation and glycolysis. This mechanism is proposed to hold promise for overcoming metabolic reprogramming. Finally, biological regulation—silencing the ZnT1 zinc transporter to block Zn²⁺ efflux—represents a paradigm shift from passive delivery to active homeostatic disruption. This “block and attack” strategy may prevent acquired resistance. The therapeutic consequences of zinc overload are multifaceted. Zn²⁺ causes lysosomal membrane permeabilization and impaired SNARE complex formation, blocking autophagic flux and inducing a distinct cell death termed “zincosis”. In mitochondria, Zn²⁺ inhibits glutathione reductase, causing oxidative stress and electron transport chain blockade. Meanwhile, Zn²⁺ suppresses glycolytic enzymes (GAPDH, LDHA), leading to ATP depletion and reversing drug resistance by downregulating P-glycoprotein. Moreover, zinc overload triggers immunogenic cell death, promoting dendritic cell maturation and CD8⁺ T cell infiltration. Combined with cGAS-STING activation, this reshapes the immunosuppressive tumor microenvironment and inhibits distant metastasis. These interconnected mechanisms endow zinc overload with a unique advantage over single-modality treatments. Despite remarkable preclinical efficacy, challenges remain: systemic toxicity from off-target release, potential zinc tolerance via metallothionein upregulation, and insufficient pharmacokinetic data. Future directions should prioritize: (1) intelligent stimuli-responsive materials; (2) combination with immune checkpoint inhibitors; (3) theragnostic integration; (4) deeper mechanistic studies; and (5) artificial intelligence-assisted screening. Zinc overload therapy is expected to become an indispensable component of integrated tumor treatment.]]> 2026/6/4 10:37:05 WANG Rong,ZHAO Lu,BAI Yun-Feng and FENG Feng 66true e.g., collagen and elastin), metabolic coenzymes (e.g., nicotinamide adenine dinucleotide), and pigments (e.g., melanin), together with exogenous cosmetic constituents like organic colorants, chemical sunscreens, and fragrances, often possess strong absorption and emission characteristics. When excited by lasers, these components produce a fluorescence background that can be 10⁶ to 10⁸ times stronger than the Raman scattering signals, effectively masking the inherently weak vibrational fingerprint information. In recent years, driven by the rapid development of optoelectronic hardware and artificial intelligence algorithms, fluorescence suppression strategies have evolved from isolated, single-method approaches into comprehensive, multi-level synergistic systems. These systems are categorized into three distinct tiers: sample preparation, signal acquisition, and data processing. At the sample preparation level, techniques such as photobleaching and surface-enhanced Raman spectroscopy (SERS) are employed to eliminate or bypass the generation of fluorescence at the source. At the signal acquisition level, instrumental improvements—including the use of long-wavelength near-infrared excitation (typically 785 nm or 1 064 nm), confocal spatial filtering, and shifted excitation Raman difference spectroscopy (SERDS)— are utilized to physically isolate Raman signals from the fluorescence background. Furthermore, at the data processing level, numerical baseline correction methods such as polynomial fitting, penalized least squares (e.g., airPLS, arPLS), wavelet transform, and derivative algorithms are increasingly integrated into the analytical pipeline to extract Raman spectral features from mixed signals without increasing hardware costs or acquisition time. This review provides a systematic categorization and critical evaluation of these fluorescence suppression methods, detailing their underlying principles, technical advantages, and inherent limitations in diverse experimental setups. By focusing on critical application scenarios—including skin barrier assessment, percutaneous absorption monitoring, the routine quality control of cosmetics, and the emerging field of portable on-site detection—this paper explores the current state of technique selection and optimization. Finally, the article discusses future development trends, emphasizing the necessity of constructing adaptive, tiered suppression strategies, developing intelligent and automated data processing algorithms, and promoting the integration of portable, multi-modal diagnostic devices. The objective of this review is to provide a comprehensive technical reference to facilitate the transition of Raman spectroscopy from a specialized laboratory tool into a routine, robust analytical platform for advancements in skin science and cosmetic research.]]> 2026/6/13 8:41:54 CHEN Yun-Xia,WANG Jia-Rong,ZHU Jian-Yu,LIN Shi-Wen,LIU Ya-Nan,MA Xiao-Yue,XI Guang-Cheng and LIU Juan 65true in situ structural biology.]]> 2026/4/9 22:42:21 QIN Chang-Dong,GUO Qiang and GAO Ning 64true via amide bond formation. This process proceeds spontaneously without requiring external enzymes, cofactors, or chemical reagents, granting inteins exceptional biocompatibility and traceless performance in protein engineering applications. Split inteins represent a specialized and versatile subclass whose splicing domains are encoded by two separate gene fragments rather than a single continuous open reading frame. These fragments, known as the N-terminal (IntN) and C-terminal (IntC) split inteins, associate through non-covalent interactions including hydrophobic forces, hydrogen bonds, and van der Waals forces to assemble into an active three-dimensional structure, which then drives efficient extein ligation and enables protein trans-splicing. Protein trans-splicing mediated by split inteins has become a cornerstone for traceless protein ligation owing to its high specificity and irreversibility, fundamentally reshaping strategies for protein modification, assembly, and functional regulation. Compared with traditional chemical ligation methods, split intein systems require no complex chemical derivatization of peptide fragments and can operate efficiently at micromolar concentrations under physiological conditions, thus avoiding structural and functional damage caused by organic reagents. In contrast to enzymatic ligation tools such as sortase, split inteins eliminate the need for additional enzymes or cofactors, simplifying reaction systems, reducing costs, and minimizing non-specific side products. These distinctive advantages render split inteins highly promising for applications in chemical biology, synthetic biology, and biopharmaceutical development. In recent years, deepened mechanistic understanding has established structure-guided rational design as the primary approach to overcoming key limitations of split inteins, including intrinsic aggregation propensity, strict extein sequence dependence, and limited splicing efficiency. Bioinformatic tools have been used to identify aggregation-prone regions in the IntN fragment, and site-directed mutagenesis of hydrophobic residues, relocation of split sites, or removal of misfolding-prone sequences has substantially reduced in vitro aggregation and improved soluble expression and assembly activity. Rational engineering of catalytic residues and adjacent flexible loops has relaxed strict amino acid preferences at extein junctions, enhancing sequence tolerance and reducing the risk of functional impairment in target proteins. Consensus design based on multiple sequence alignments has yielded ultra-fast splicing variants such as Cfa DnaE and Cat-TerL, which exhibit significantly accelerated kinetics and improved tolerance to denaturing conditions. Meanwhile, advances in structural biology have further clarified the conformational dynamics and catalytic mechanisms of splicing, supporting the precise design of high-performance intein modules. On this basis, electrostatic interaction tuning and metagenomic screening have yielded multiple mutually orthogonal split intein pairs, enabling selective multi-fragment protein ligation and providing new routes for the efficient synthesis of large multi-domain functional proteins. With these engineered split inteins offering continuously improved performance and expanded applicability, protein trans-splicing has been widely applied in numerous cutting-edge areas of protein research and biomedicine. In gene delivery, split intein-based systems overcome the packaging limit of adeno-associated viral vectors, enabling the accurate reconstitution of large therapeutic proteins and base editors in target cells, thereby enhancing the efficacy and scope of gene therapy for genetic diseases. In internal protein sequence editing, split inteins mediate precise sequence replacement and modification in flexible regions or loops of target proteins, without the need for complex multi-step ligation and protein refolding involved in traditional protein semisynthesis. In protein-protein interaction studies, intein-mediated splicing covalently captures transient and weak intracellular complexes, enabling sensitive, high-throughput interaction detection and drug screening. In synthetic biology, conditionally controllable splicing systems support the construction of diverse intracellular and cell-surface biological logic gates for the precise regulation of cellular behavior. In mechanistic biochemical research, split inteins enable photocatalytic proximity labeling and site-specific tagging, allowing the preparation of homogeneous protein samples carrying precise post-translational modifications such as ubiquitination and polyglutamylation for chromatin interactome analysis and epigenetic studies. Moreover, covalent trapping strategies using split inteins stabilize transient enzymatic intermediates, providing unprecedented insights into molecular mechanisms such as nucleosome ubiquitination that are difficult to elucidate using conventional methods. This review systematically summarizes key technological advances in split inteins over the past decade, highlighting engineering strategies, mechanistic insights, and the development of orthogonal components. It comprehensively surveys emerging applications at the frontiers of protein research, analyzes current core challenges, and proposes future directions, particularly emphasizing artificial intelligence-driven de novo design and novel splicing pathways to break existing technical bottlenecks. By enabling traceless, efficient, and versatile protein manipulation, split inteins continue to serve as indispensable tools that drive innovation in protein engineering and fundamental life science research.]]> 2026/4/23 12:10:19 GAN Jin-Qiu,DENG Xiang-Yu,WANG Xin-Yan and LI Jia-Bin 63true 2026/4/30 9:44:28 SHEN Zhuo-Qun,XU Xiao-Fei,WANG Yan-Qing,LI Jing-Xin,TIAN Lan,GUO Wei and XU Jing-Jing 62true e.g., skin tone, tissue thickness), and low AC signal to noise ratio. In contrast, DS—an advanced derivative of PPG—uses a differential principle to extract absorbance changes between systolic and diastolic peaks. This theoretically eliminates interference from static tissues (skin, bone, venous blood) and common mode noise (e.g., ambient light), positioning DS as a more robust framework for high precision Hb quantification. Beyond spectral methods, color analysis/RGB imaging offers a hardware minimalist approach. By analyzing images of vascular rich, thin tissues (e.g., conjunctiva, nail beds, palms), it enables Hb estimation using smartphone cameras. Recent advances have shifted from manual RGB feature extraction to deep learning models and spectral super resolution that reconstruct hyperspectral data from RGB inputs, significantly improving screening accuracy. Our academic perspective emphasizes critical and integrative analysis. We highlight persistent challenges that hinder clinical translation: profound individual biological variability (skin optics, microvascular architecture), sensitivity to measurement conditions (pressure, ambient light), and a lack of standardized validation protocols and multi center trials. A central thesis is that no single optical method is universally superior; each involves trade offs between accuracy, complexity, cost, and practicality. Looking forward, we posit that the next performance leap will come from multimodal information fusion—combining PPG, electrocardiogram (ECG), bioimpedance, or different optical modalities to compensate for individual differences and environmental noise. AI and deep learning are essential not only for image analysis but also for automated, end to end feature extraction from complex waveforms like PPG sequences. Advancing hardware (tunable lasers, quantum dot LEDs, novel sensor designs) is crucial to improve signal fidelity and portability. Finally, we advocate for clinical scenario specific optimization and rigorous standardized evaluation frameworks to gain regulatory approval (e.g., FDA, NMPA) and achieve widespread clinical acceptance. In conclusion, this review synthesizes a decade of progress. Optical non-invasive Hb detection has evolved from proof of concept studies to emerging products and validated screening tools, but the journey toward reliable, clinic ready quantitative devices continues. The convergence of smarter algorithms, fused sensing modalities, and focused clinical validation offers the most promising path to transform this potential into routine medical practice, ultimately enabling personalized, continuous, and accessible hematological management.]]> 2026/4/30 9:30:32 PENG Yao,WANG Xian-Long,LAN Bi-Tie and YU Jian-Hai 61true In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.]]> 2026/4/18 17:16:11 CHEN Yu-Ying,HUANG Chun-Mei,PAN Jin-Zhi,LIU De-Liang,ZHOU Yang,DAI Gui-Qin,ZHAO Peng-Fei,LU Hong-Zhou and ZHENG Ming-Bin 60true in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.]]> 2026/5/3 13:04:41 XU Meng,ZHU Long-Jiao,LI Jie,LEI Chong-Bin,ZHANG Yang-Zi,TIAN Hong-Tao and XU Wen-Tao 59true via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.]]> 2026/5/14 14:15:18 LIU Xu,LIU Si-Rui,MA Jia-Yu,MOU Yu-Ting,SHI Ting-Yu,HUANG Sheng and SONG Tian-Li 58true in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.]]> 2026/5/15 14:41:56 CHEN Ru-Long,XIE Ting-Fei,ZHANG Jin-Xin,CHEN Jia-Ting,LI Jie,ZHANG Peng-Fei,CHEN Ji-Hong and CAI Lin-Tao 57true in vitro and in vivo anticancer efficacy, as well as their pharmacological and toxicological characteristics. Anti-RON ADCs demonstrated favorable stability both in vitro and in vivo. In cellular models, anti-RON ADCs carrying different payloads all exhibited potent cytotoxic effects. In animal models, anti-RON ADCs have convincingly demonstrated significant anti-cancer activity, with stable pharmacological properties and manageable toxicity at therapeutic doses. Anti-RON ADCs have a number of distinct therapeutic advantages. Compared with ADCs targeting other RTKs, anti-RON ADCs have unique effects in regulating the immune microenvironment and can potentially provide additional therapeutic options for overcoming drug resistance. Compared with RON antibodies and small molecule inhibitors, anti-RON ADCs do not rely on the RON signaling pathways, thereby significantly enhancing therapeutic efficacy. Moreover, anti-RON ADCs show therapeutic potential for targeting RON variants. In summary, the results of basic researches indicated that anti-RON ADCs have favorable anti-cancer effects and show promising clinical translation prospects. In addition, this article analyzed the current limitations of anti-RON ADCs and emphatically discussed their future development directions. The payloads of the existing anti-RON ADCs are relatively limited, and the drug-to-antibody ratio (DAR) of each ADC is not uniform. There also remains considerable room for improvement in terms of endocytosis efficiency and drug combination strategies. Therefore, the development of the next-generation anti-RON ADCs should focus on the diversification of the payloads, and explore new types of ADCs, dual-load ADCs, etc. Additionally, the structure of antibodies or ADCs could be optimized to enhance the endocytosis efficiency and progressively overcome current limitations. At present, anti-RON ADCs are limited to basic research, and the current research outcomes and observations indicated their potential for clinical application. Therefore, the clinical translation of anti-RON ADCs will be an important objective for future development. To this end, it is necessary to carefully devise a rational clinical translation pathway for anti-RON ADCs, and comprehensively evaluate the potential challenges that may arise during the implementation, so as to accelerate the initiation of clinical trials. Ultimately, clinical application of anti-RON ADCs will be realized, providing more treatment options for cancer patients.]]> 2026/4/16 15:54:39 SUN Ting and YAO Hang-Ping 56true + T cells, thereby strengthening their ability to recognize and eliminate tumor cells and alleviate immune imbalance. On the other hand, aerobic exercise promotes tumor vascular normalization, improves vascular maturity, and stimulates the secretion of irisin and other anti-inflammatory myokines, thereby remodeling the TME and relieving its immunosuppressive state to delay tumor progression. However, psychological stress following a cancer diagnosis can not only act as an independent disruptive factor that exacerbates immune imbalance within the TME, but also amplify the effects of other detrimental factors, such as reduced treatment adherence, thereby further weakening the antagonistic effect of aerobic exercise on tumor growth. Psychological stress, as a chronic stressor, promotes the excessive secretion of emotion-related hormones, including glucocorticoids (GCs) and norepinephrine (NE), which further suppress the activation and effector functions of antitumor immune cells such as CD8⁺ T cells and natural killer (NK) cells, while facilitating the recruitment of protumor immune cells such as regulatory T cells (Tregs). These changes ultimately disrupt immune homeostasis in the TME, promote tumor immune evasion, accelerate tumor invasion and metastasis, and offset the beneficial effects of aerobic exercise on tumor control. In addition, psychological stress induces hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal excitation of the sympathetic nervous system (SNS), thereby maintaining elevated levels of GCs, NE, and related stress hormones, suppressing inflammatory chemokine expression and immune cell recruitment, and further disturbing immune homeostasis in the TME, which accelerates tumor progression. More importantly, prolonged psychological stress can also disrupt the homeostasis of central neurotransmitters, such as 5-hydroxytryptamine (5-HT) and glutamate (Glu). This not only directly inhibits the activation and effector functions of antitumor immune cells and promotes the establishment of an immunosuppressive microenvironment, but also impairs cellular energy metabolism and continuously provides energy for tumor cells through metabolic reprogramming, thereby sustaining rapid tumor growth and adaptation to a hostile TME. Ultimately, these alterations contribute to the dysregulation of “neuro-endocrine-immune” axis and weaken the protective effect of aerobic exercise against tumor progression. Therefore, this review focuses on the interaction between psychological stress and the “neuro-endocrine-immune” axis, with particular emphasis on the mechanisms by which psychological stress induces immune imbalance and weakens the antagonistic effect of aerobic exercise on tumor progression. We further highlight the important role of psychological stress in tumor progression and propose that combining psychotropic interventions, aerobic exercise, and clinical antitumor immunotherapy may help restore the tumor-killing capacity of the immune system. Such a multimodal strategy may exert synergistic effects at multiple levels, including psychological stress relief, neuroendocrine regulation, and reconstruction of immune homeostasis, thereby providing new perspectives for identifying therapeutic targets in solid tumors, enhancing the efficacy of cancer immunotherapy, and improving patient prognosis.]]> 2026/4/11 8:47:56 ZHOU Xin,ZHANG Hua,LIU Jing-Jing,PAN Hui-Xin,ZHANG Jing and WANG Qing-Lu 55true 2026/3/23 0:00:00 ZHENG Wen-Xian,XIONG Meng-Jie,JIA Shu-Ting and ZHOU Ruo-Yu 54true 6-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.]]> 2026/3/21 21:51:39 MENG Shi-Qi,LU Wen-Ting,CHENG Xu,YANG Fan,NIU Chang-Min and ZHEGN Ying 53true via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safe in vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.]]> 2026/4/3 11:59:32 JI Wei-Xiu,KU Bo-Wei-Cheng and ZHAO Yun-Gang 52true via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.]]> 2026/4/7 10:42:19 LI Meng-Wei,CAI Ji-Tang,WANG Jun-Jie,CAI Yi-Bo and TAN Meng-Ting 51true Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.]]> 2026/4/7 8:23:57 LIU Ruo-Can,WANG Yu-Qian,ZHANG Shuai,ZUO Shao-Zhi,WU Yun-Di and WU Xi-Long 50true 2026/4/3 0:00:00 WU Xiao-Qin,LIU Da-Wei,LI Bin-Yu,LIU Yang,CAO Yang and DAI Wen-Tao 49true 2026/4/3 11:19:39 ZHANG Kun-Peng,YE Zi-Hong and XUE Zhi-Chao 48true in vitro reconstitution and maturation of their catalytic centers, and the inefficiency and instability of the natural electron transfer pathways. To overcome these limitations and enhance the catalytic performance of hydrogenases, researchers have developed various strategies, among which enzyme molecular engineering, photo-driven modification, and enzyme immobilization techniques are the most common exploration directions. Particularly, enzyme immobilization technology is widely used to improve the reusability of hydrogenases, but traditional immobilization methods often come with disadvantages in practical applications, such as complex multi-step procedures and insufficient biocompatibility of the immobilization materials. In recent years, bioencapsulation technology has emerged as a promising alternative strategy to enhance the catalytic performance of hydrogenases. This method utilizes biologically derived encapsulation materials to construct physically confined and precisely defined chemical microenvironments around the enzyme molecules, offering simpler self-assembly processes and superior biocompatibility. With these biomimetic constructs, bioencapsulation technology not only provides better oxygen tolerance but also helps to create a local microenvironment conducive to sustained catalytic function. This article systematically reviews the latest research progress of two main bioencapsulation strategies for hydrogenases: one is the encapsulation technology based on protein-based nanocages; the other is the engineering strategy for whole-cell hydrogenase expression. In the nanocage-based systems, this article focuses on the structural and functional characteristics of virus-like capsids and carboxysome protein shells, which serve as efficient enzyme encapsulation scaffolds, not only providing a stable physical barrier to prevent oxygen diffusion but also enabling high-density enzyme loading, thereby promoting substrate channeling effects and electron transfer kinetics. This article also discusses whole-cell encapsulation systems, which achieve hydrogenase compartmentalization within engineered cellular structures or by using external natural polysaccharide-based encapsulation matrices to wrap whole-cell catalysts. Bioencapsulation strategies can bring multiple synergistic benefits: they can effectively protect hydrogenases from oxygen-mediated inactivation, significantly delay the decline of catalytic activity over time, and enhance the hydrogen production rate by increasing the local concentration of active enzyme molecules and optimizing the electron transfer efficiency from redox partners to the catalytic center.Despite the significant progress made, several technical challenges remain to be addressed. The main obstacles include limited enzyme loading and encapsulation efficiency, insufficient long-term stability of encapsulation materials under operating conditions, and the need to improve the matching of the photo-biological interface in systems integrating light-harvesting components with enzymatic catalysis. Future efforts can focus on the integration of multiple technological approaches, such as using computer-aided protein design to optimize encapsulation structures, developing engineered electron transfer pathways to enhance catalytic conversion efficiency, and designing composite multifunctional materials with both structural stability and functional adaptability. These directions collectively aim to achieve efficient, stable, and scalable hydrogen production applications of bioencapsulated hydrogenase systems.]]> 2026/4/7 8:30:49 XU Xiang and CAO Chang-Qian 47true via linewidth analysis of known structures (e.g., microtubules) or edge-spread function measurements, capturing the effects of photobleaching and sample-induced aberrations. A major paradigm shift is parameter-free resolution estimation based on decorrelation analysis. This method analyzes the autocorrelation decay of a single image’s Fourier spectrum to identify the cutoff spatial frequency without requiring dual datasets or user-defined thresholds. Its high efficiency and broad applicability have been validated across widefield, confocal, STED, SIM, and SMLM modalities. Optimized rendering strategies for SMLM data further enhance its accuracy, and it is emerging as a tool for real-time optimization of experimental parameters. The review also addresses the “gold standard” of resolution validation using well-defined nanostructures, such as DNA origami and nuclear pore complexes, which provide ground truth for verifying resolution claims and detecting artifacts. In the era of artificial intelligence, deep learning plays a dual role: it powerfully enhances image resolution but also introduces challenges, as models may generate “hallucinations” or false details. This underscores the need for new validation metrics to verify the physical fidelity of AI-generated content. Finally, we outline future directions: developing unified cross-modality standards, enabling real-time dynamic resolution monitoring for live-cell imaging, creating techniques for generating local resolution maps to capture sample heterogeneity, and integrating intelligent error correction to ensure data veracity. By providing a comprehensive overview of resolution assessment progress and challenges, this review aims to equip researchers with the knowledge to select appropriate tools, thereby fostering rigorous quantitative imaging in the life and material sciences.]]> 2026/3/6 8:29:29 FANG San-Hua,CHEN Jing-Yao,YANG Dan and LIU Li 46true in vivo antigen expression to enhance the persistence of immune responses. Moreover, the LNP delivery system not only protects mRNA from degradation and mediates endosomal escape but also synergizes with mRNA to optimize immune activation via self-adjuvant effects. Importantly, mRNA platforms circumvent the pre-existing immunity associated with viral vectors and the genomic integration risks of DNA vaccines, positioning them as a cornerstone for global pandemic preparedness. This review systematically delineates recent advances in mRNA technology for HIV-1 vaccine development, focusing on four pivotal research frontiers. First, mRNA innovations building upon the RV144 trial optimize antigens through codon modification and multivalent designs to induce more durable and broad-spectrum immunity. Second, particulate mRNA vaccine strategies, utilizing virus-like particles (VLPs) and ferritin nanoparticles, achieve in situ antigen self-assembly, significantly enhancing B cell activation and reducing infection risks in non-human primate models. Third, germline-targeting mRNA vaccines address the low-affinity barrier of broadly neutralizing antibody (bNAp) precursors, efficiently activating rare precursor B cells and promoting affinity maturation. Fourth, therapeutic mRNA vaccines offer unique advantages for an HIV functional cure; combining immunogens with mRNA-encoded adjuvants potentiates cellular immunity, while LNP-mediated “shock-and-kill” strategies specifically activate latent reservoirs to guide immune clearance. Comparative analyses with traditional platforms reveal that mRNA technology redefines antigen production and presentation, simulating chronic infection through sustained expression and enabling dual-pathway presentation via endogenous synthesis. Furthermore, we explore the mechanistic innovations of mRNA vaccines in inducing bNAps: sustained in vivo production prolongs the activation window for precursor B cells and maintains germinal center (GC) reactions; endogenously expressed antigens adopt native conformations to expose conserved epitopes; and self-adjuvanting effects modulate the functions of antigen-presenting cells (APCs) and follicular helper T cells (Tfh), driving somatic hypermutation and affinity maturation. We also address critical clinical translation challenges, including immune durability, adaptability to special populations, and large-scale LNP manufacturing, while proposing targeted optimization strategies. In conclusion, this review establishes a theoretical framework for utilizing mRNA technology to overcome HIV-1 immune escape, transitioning from a descriptive paradigm to a problem-solving-based synthesis of evidence. By integrating preclinical and early clinical data, we bridge the gap between basic design and translational verification. mRNA technology is poised to become a central pillar in HIV-1 prevention and therapy, providing a robust toolset to achieve the global goal of ending the AIDS pandemic and offering a blueprint for vaccine development against other recalcitrant infectious diseases.]]> 2026/3/4 12:32:18 LIU Pei,FANG Zhong-Yue,CHEN Xin-Xin,LI Shao-Wei and GU Ying 45true de novo sequencing technology. These strategies enable multi-level, high-precision characterization ranging from peptides and domains to intact antibody molecules. Unlike the shotgun strategy commonly used in routine proteomics, obtaining full sequences of all antibodies presents unique challenges. It requires specialized methodological adaptations to address issues related to dynamic range, sequence variation, and sample complexity. This review introduces the technical principles, methodological workflows, and recent applications of various mass spectrometry-based antibody repertoire sequencing (Ab-seq) strategies, with a focus on approaches designed to improve sequence coverage and identification accuracy. These include multi-enzyme digestion, hybrid fragmentation methods, and artificial intelligence-assisted de novo sequencing. By systematically comparing database-dependent techniques—such as bottom-up, middle-down, and top-down approaches—with database-independent de novo sequencing, this review outlines their respective advantages and limitations in terms of sample throughput, sequence coverage, post-translational modification characterization, and data analysis complexity. In addition, this review discusses emerging technological trends, including the integration of ion mobility separation, native mass spectrometry, and artificial intelligence-driven data interpretation, which are expected to enhance the depth and accuracy of antibody characterization. Although current methods continue to face challenges related to sample complexity, dynamic range, and unambiguous sequence variant assignment, we emphasize the importance of integrating BCR-seq and Ab-seq data to construct gene-protein association maps. These maps help validate sequence accuracy and facilitate epitope discovery. This dual-platform strategy helps bridge the gap between genotype and phenotype, thereby enhancing both the resolution and scope of antibody repertoire studies. Such an integrative approach also offers a valuable tool for therapeutic antibody development, structure-function analysis, and precise evaluation of vaccine efficacy.]]> 2026/3/6 22:33:44 LIU Sheng-Mei,XUE Peng and WANG Xiao-Jian 44true 2026/2/11 10:17:45 WANG Hui,ZHOU Zi-Gui,HAN Teng-Teng,YANG Chang-Zhi and TIAN Xue-Wen 43true 2026/3/1 21:28:47 LI Yang,WANG Ke and ZHAO Di 42true 2026/3/16 15:25:47 ZHANG Xin,DU Jie,LI Zhao-Huan and GAO Feng 41true de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.]]> 2026/3/10 22:07:40 JIA Meng,LI Fang-Hui,YAN Shi-Zhan,LI Ai-Ju,WANG Yi-Le,NI Pin-Shi,HE Jia-Han and LI Yin-Lu 40true de novo fatty acid synthesis, is subject to precise regulation at multiple levels, including transcriptional control, various post-translational modifications such as ubiquitination and phosphorylation, as well as modulation by diverse signaling pathways. Recent studies have revealed that FASN is aberrantly overexpressed in various malignant tumors and is closely associated with tumor progression and poor patient prognosis. FASN is a homodimer composed of seven functional domains that catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to generate saturated fatty acids, primarily palmitic acid. Its stability is regulated by multiple ubiquitin ligases and deubiquitinating enzymes. Additionally, FASN is subject to upstream regulation via neural precursor cell-expressed developmentally downregulated 8 (Nedd8) modification and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, thereby establishing a metabolic-signaling positive feedback loop. As a core executor of metabolic reprogramming, FASN promotes tumorigenesis through dual mechanisms. First, its fatty acid synthesis product, palmitate, participates in membrane phospholipid synthesis, lipid raft formation, and protein palmitoylation, thereby activating several key oncogenic signaling pathways, including PI3K/AKT/mTOR, wingless-type MMTV integration site family member (Wnt)/β-catenin, and signal transducer and activator of transcription 3 (STAT3)/matrix metalloproteinase (MMP), leading to tumor development and progression. Second, FASN plays a pivotal role in modulating the anti-tumor functions of immune cells and remodeling the tumor immune microenvironment. Specifically, FASN enhances immune checkpoint inhibition by inducing programmed death-ligand 1 (PD-L1) palmitoylation, suppresses the activation of cytotoxic T lymphocytes and natural killer cells, and promotes the polarization of M2-type macrophages, consequently facilitating tumor immune evasion and malignant progression. Precisely due to its significant overexpression in tumor cells, its critical functional role, and its differential expression compared to normal cells, FASN has emerged as a highly promising target for anti-tumor drug development. Highly selective small-molecule inhibitors, notably represented by TVB-2640, have advanced to clinical trial stages and demonstrated favorable anti-tumor activity. Furthermore, the combination of FASN inhibitors with other chemotherapeutic agents or targeted drugs can overcome the limitations of monotherapy through synergistic effects or by resensitizing tumor cells to conventional drugs, achieving a “1+1>2” therapeutic outcome. With the advancement of modern traditional Chinese medicine (TCM), numerous active ingredients derived from TCM have been confirmed to exert anti-tumor effects by modulating FASN-related pathways. This integrated approach leverages the precision of Western medicine while simultaneously harnessing the holistic regulatory benefits of TCM to alleviate the side effects of radiotherapy and chemotherapy. Despite the promising prospects of FASN-targeted therapies, challenges remain, including tumor cell metabolic plasticity, tumor context-dependent responses, and heterogeneity. This review systematically summarizes the molecular structure, physiological functions, and mechanisms of FASN in tumorigenesis, as well as recent advances in targeted therapies. Future directions—including the precise identification of responsive patient populations using spatial transcriptomics, the development of novel combination regimens, and the active exploration of integrative strategies combining traditional Chinese and Western medicine—will facilitate the clinical translation of FASN-targeted therapies and open new avenues for improving the quality of life and prognosis of cancer patients.]]> 2026/3/18 14:48:35 JIANG Wen-Jing,ZHANG Ruo-Xi,TAI Yu-Qing,SUN Ya-Wen,ZHANG Xi-Yu and LI Xiao 39true in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.]]> 2026/3/18 14:54:44 PAN Zhao-Tao,GAI Feng-Yu,CHEN Chen,LI Tong and QING Yan-Ping 38true via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs. (3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.]]> 2026/3/10 22:14:40 ZHOU Fa-Xiao,YU Di-Ping,TAN Si-Qi,DUAN Hong-Yu and WU Xiao-Ming 37true via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF-β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)-compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.]]> 2026/2/28 22:22:53 WANG Zi-Qi,WANG Jing,HUANG Yuan-Yu and LU Mei 36true 2026/2/9 16:44:19 ZHONG Jia-Bin,ZHANG Qing and QIAN Shuai-Wei 35true 2026/3/6 22:24:41 WANG Shu-Xian,Guo Fei-Fei and MA Guang-Qiang 34true 6), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF-κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.]]> 2026/2/4 21:05:53 LI Ao-Ning,LI Wen-Bo,LU Yu-Ying,ZHU Min-Hui,QIN Yu-Long,ZHAO Yong and ZHANG Zhao-Huan 33true via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.]]> 2026/1/17 20:34:39 YANG Pei-Wen,YUAN Meng-Meng,ZHOU Ying,LI Peng,QI Gui-Hong,YANG Ying,MAO Zhong-Yi,ZHOU Meng-Sha,MAO Xiao-Shuang,XIE Jian-Ping,YANG Yi-Nan and SUN Shi-Hao 32true 2026/1/28 20:26:52 TIAN Xin,ZHANG Zhen,LUO Fu-Cheng and Lü Tao 31true 2+, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.]]> 2026/1/11 23:07:00 LI Yan,LIU Tao,GU Yu-Biao,TIAN Hui-Qing,ZHANG Lei,BAI Bi-Hui,HE Zhi-Jun,CHEN Wen,LI Jin-Peng and LI Fei 30true e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.]]> 2026/2/3 17:21:13 DUAN Liang-Chen,HU Hao-Liang,WANG Shu-Zhi,YAN Jia-Long and CHEN Lin-Xi 29true CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors (e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.]]> 2026/2/3 10:00:41 LI Jia-Wen,CHEN Yang,WANG Jia-Qi,MA Yu-Kai and GUO Zhi-Yi 28true via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.]]> 2026/1/26 20:43:29 WU Yue-Yan,CHEN Xin,ZHOU Ce-Fan,TANG Jing-Feng and ZHANG Rui 27true in vivo pharmacokinetics and long-term toxicity of Au NCs is absent. To address this gap, it is crucial to develop advanced imaging methodologies and integrated theranostic platforms. Au NCs, serving as both a therapeutic core and a highly promising photoluminescent material, are key to constructing such platforms through integration with other agents. These multifunctional systems are designed to achieve optimal synergistic therapy by combining multiple treatment modalities. Finally, the investigation of Au NCs is still largely confined to preclinical cellular and animal studies. Progress necessitates comprehensive clinical research to rigorously assess their safety and efficacy across a range of human cancer models, thereby ensuring broad clinical applicability. In summary, Au NCs-based platforms hold immense promise for translation into clinical anticancer therapy.]]> 2026/1/26 20:50:17 Lü Jia,WANG Ruo-Ping,ZHU Lin-Lin and GAO Liang 26true de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ-selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.]]> 2026/1/29 15:43:38 XIAO Wen-Ping,MA Yang,GUAN Heng,WAN Sha,HAN Wen,LUO Bing-Bing,WANG Wu-Feng and LIU Fang 25true 2026/1/23 15:48:28 ABOD Kareem Salim and ABBAS Salma Abdulredha 24true e.g., interventional radiology) and medical diagnostics (e.g., CT scans). Crucially, individual susceptibility is modified by genetic background, age, and environmental co-factors, complicating risk assessment. Second, we critically examine the dose-effect relationship. Although the ICRP suggests a threshold of 0.5 Gy, emerging data challenge the traditional threshold model, with some studies advocating for a linear non-threshold (LNT) relationship. We further discuss the critical roles of radiation quality and dose rate. High linear energy transfer (LET) radiation demonstrates a significantly higher relative biological effectiveness (RBE) for cataractogenesis compared to low-LET radiation. Paradoxically, and unlike many other tissues, the lens may exhibit an “inverse dose-rate effect,” where fractionated or protracted exposures potentially enhance biological damage—a finding that challenges classical radiobiological paradigms. Third, drawing upon the “cataractogenic load” hypothesis and the unique physiological constraints of the lens, this review elucidates the multidimensional molecular mechanisms driving radiation-induced opacification. Key mechanisms include four aspects. (1) DNA damage and repair: IR induces DNA double-strand breaks (DSBs) that, due to the lens’ limited repair capacity (modulated by genes such as ATM, Ptch1, and Ercc2), lead to the accumulation of damage. (2) Antioxidant defense system: dysfunction of the Nrf2/HO-1 antioxidant axis results in redox imbalances, triggering NF-κB-mediated inflammation and protein aggregation. (3) Cell proliferation and senescence: IR disrupts cell cycle regulation, causing a dichotomy of effects—driving premature senescence in some cell populations (evidenced by ATM nuclear foci) while inducing aberrant proliferation via growth factor upregulation (FGF2, TGFβ) in others. (4) Cell migration and adhesion: activation of the Wnt/β-catenin pathway and alterations in the E-cadherin complex promote the abnormal migration of epithelial cells to the posterior capsule, a hallmark of radiation-induced cataracts. In conclusion, radiation-induced cataractogenesis is a multifactorial process in which genetic susceptibility and environmental stressors converge to overwhelm the lens’ homeostatic thresholds. Future research must prioritize longitudinal cohort studies to refine dose thresholds and employ multi-omics approaches to map the crosstalk between DNA damage responses and matrix remodeling. Establishing a robust mechanistic model is essential for developing targeted radioprotective strategies and optimizing radiation protection standards for occupational and medical safety.]]> 2026/2/5 20:29:51 HU Cheng-Hao,REN Shao-Han,ZHANG Hai-Tao and ZHAN Jing-Ming 23true . Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.]]> 2025/12/26 21:25:35 WEI Hai-Jun,WANG He-Ming,CHEN Shu-Jing,WANG Shu-Zhi and CHEN Lin-Xi 22true in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ development in vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.]]> 2026/1/11 11:26:47 LIU Rui-Xia,ZHANG Jing,LI Xiao,LIU Yi,HUANG Long and HOU Hong-Wei 21true cis-acting element level, it elaborates on how components such as riboswitches, RNA thermometers, and Toehold switches achieve precise gene expression regulation by responding to specific ligands, temperatures, or trigger RNAs through conformational changes. Concerning trans-acting elements, it delves into the molecular mechanisms of miRNA-mediated gene silencing, the high stability and “sponge-like adsorption” function conferred by the closed-loop structure of circRNA, the targeting role of siRNA within the RNAi pathway, and the targeting specificity of sgRNA within the CRISPR system. The paper emphasizes that rational design, sequence optimization, and chemical modifications can significantly enhance the performance and orthogonality of these natural elements. Secondly, the paper focuses on the design and optimization strategies for synthetic RNA regulatory modules. Taking miRNA-responsive circRNA switches as an example, it elucidates the principles of customized miRNA responsiveness. The engineering applications of circRNA are explored, introducing strategies for constructing functional RNA nanostructures via siRNA self-assembly. Building upon this, the paper emphasizes synthetic genetic circuits: from logical operations to resource allocation, enabling advanced cellular logic and functional regulation. For instance, by combining transcriptional cascade switches or utilizing the CRISPR-Cas13a system, an AND logic gate responsive to multiple miRNAs (such as miRNA-155 and miRNA-21) was constructed, significantly enhancing the specificity of disease diagnosis. Addressing the challenges of resource competition and expression noise faced by synthetic circuits within cells, this paper introduces computational models such as MIRELLA, with particular emphasis on the design of endogenous miRNA-based iFFLs. These advanced circuits, illustrated in this paper, have been successfully applied to real-time monitoring of cellular differentiation states and regulation of stem cell-directed differentiation. For cellular state detection and dynamic regulation, miRNA switches can be integrated with fluorescent systems to track differentiation statuses in real time via fluorescent signal changes. Synthetic genetic circuits, meanwhile, utilize endogenous miRNA logic integration alongside miSFITs technology to achieve state-specific protein regulation in human pluripotent stem cells, laying the groundwork for customized cellular control. This approach ingeniously harnesses intrinsic cellular regulatory mechanisms to buffer gene expression burdens, thereby enhancing circuit robustness. These advanced circuits, illustrated schematically herein, have been successfully applied to real-time monitoring of cellular differentiation states and regulation of stem cell-directed differentiation. At the therapeutic translation level, the paper systematically reviews application strategies for RNA technologies across multiple fields, including cancer, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, regenerative medicine engineering, immunotherapy, and vaccine applications. For instance, in cancer treatment, specific killing of tumor cells is achieved by embedding targets for miRNAs specific to healthy cells within the genomes of oncolytic viruses (such as Zika virus). Within metabolic and degenerative diseases, LNP-delivered mRNA therapeutics and antisense oligonucleotide (ASO) technologies have demonstrated significant clinical progress. Finally, this paper highlights ongoing challenges in the field, including limited programmability of RNA elements, low in vivo delivery efficiency, and inadequate off-target risk assessment systems. It advocates for future integration of epigenomics and computational modelling to optimize element functionality, establishing an integrated “element-circuit-delivery” platform. Furthermore, leveraging single-cell sequencing and organoid technologies to develop a multidimensional safety assessment system is proposed to advance the deep integration and translation of RNA synthetic biology in personalized medicine. Consequently, RNA engineering has transcended single-dimensional regulation, evolving towards multi-layered, dynamic, and intelligent synthetic biological systems. Its deep integration with clinical needs will reshape disease diagnosis and treatment paradigms.]]> 2026/1/8 10:50:13 DAI Yi-Han 20true MPC1/2, HSP27, and SIRT6 or knockout of Bax, Apaf1, and IGF-1R—have demonstrated significant improvements in cell viability and product yield. The combination of multi-omics metabolic modeling with artificial intelligence (AI)-based prediction offers new opportunities for building self-regulating CHO systems capable of dynamic adaptation to environmental stress. Regarding glycosylation uniformity, which determines therapeutic efficacy and immunogenicity, gene editing-based glycoengineering (e.g., FUT8 knockdown or ST6Gal1 overexpression) has enabled the humanization of CHO glycan profiles, minimizing non-human sugar residues and enhancing drug stability. Process-level strategies such as galactose or manganese co-feeding and fine control of temperature or osmolarity further allow rational regulation of glycosyltransferase activity. Additionally, in vitro chemoenzymatic remodeling provides a complementary route to construct human-type glycans with defined structures, though industrial applications remain constrained by cost and scalability. The integration of model-driven process design and AI feedback control is expected to enable real-time prediction and correction of glycosylation deviations, ensuring batch-to-batch consistency in continuous biomanufacturing. Long-term expression stability, another critical challenge, is often impaired by promoter silencing, chromatin condensation, and random genomic integration. Molecular optimization—such as the use of improved promoters (CMV, EF-1α, or CHO endogenous promoters), Kozak and signal peptide refinement, and incorporation of chromatin-opening elements (UCOE, MAR, STAR)—helps maintain durable transcriptional activity, while site-specific integration systems including Cre/loxP, Flp/FRT, φC31, and CRISPR/Cas9 can enable single-copy, position-independent gene insertion at genomic safe-harbor loci, ensuring stable, predictable expression. Collectively, this review highlights a paradigm shift in CHO system optimization driven by the convergence of genome editing, synthetic biology, and artificial intelligence. The transition from empirical optimization to rational, data-driven design will facilitate the development of programmable CHO platforms capable of autonomous regulation of metabolic flux, glycosylation fidelity, and transcriptional activity. Such intelligent cell factories are expected to accelerate the transformation from laboratory-scale research to industrial-scale, high-consistency, and economically sustainable biopharmaceutical manufacturing, thereby supporting the next generation of efficient and customizable biologics manufacturing.]]> 2025/10/22 8:20:52 ZHANG Rui-Ming,LI Meng-Lin,ZHU Hong-Wei and ZHANG Xing-Xiao 19true 2025/12/13 13:51:47 YUE Wen-Tian,HE Shu-Rong,AN Qin,ZOU Yun-Xia,DONG Wen-Wen,MENG Qing-Yong and ZHANG Ya-Li 18true 2025/12/15 15:39:45 XIANG Qiong,YANG Li-Chang,LI Zan and LING Yun 17true 2025/12/29 15:01:22 DUAN Hao-Qing,GOU Yu-Qi,LI Ya-Wen,HU Li and Lü Xue-Jing 16true 2026/1/5 14:44:54 WANG Chun-Yu and LIU Yan-Xia 15true via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.]]> 2025/12/10 9:34:40 SHI Zhi-Chao,TIAN Xu-Ping,CHEN Si-Yi and LIU Shi-Guo 14true via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.]]> 2025/12/13 14:04:01 ZHENG Hong,MO Zhong-Cheng,LIU Hang,PAN Xi-Zhang and WEI Bing 13true via low pH; and class III proteins, which combine α-helices and β-structures, with mechanisms involving internal fusion loop insertion and membrane remodeling. It is evident that a comprehensive understanding of the mechanisms underlying viral membrane fusion is crucial for developing effective stabilization strategies for the prefusion conformation of these proteins. This paper presents several such methods that have been successfully employed in this endeavor, including: disulfide bond formation to stabilize domain-domain interactions; hydrophobic cavity filling to enhance core stability; proline substitution to restrict structural transitions in hinge regions; and multimer domains stabilizing the trimeric conformation. The stabilization strategies summarized and discussed herein have been validated in studies of multiple viral membrane fusion proteins and further applied in the design of vaccine antigens. Moreover, this paper highlights the potential applications of novel techniques, such as time-resolved cryo-EM, in capturing conformational intermediates and resolving dynamic transition processes. Such stabilization efforts, informed by structural insights, have yielded promising outcomes—for instance, prefusion-stabilized RSV F antigens that elicit potent neutralizing antibodies in clinical trials. Looking ahead, integrating computational modeling, such as AlphaFold predictions, with experimental data will further refine these approaches. Ultimately, these innovations promise to enable structure-guided therapeutics to combat emerging viral threats. This review provides a theoretical foundation for developing stable viral membrane fusion proteins, offering crucial insights for understanding viral membrane fusion mechanisms and advancing next-generation vaccines and antiviral drugs.]]> 2025/10/31 11:58:04 XIE Chen-Yi,DONG Xiang-Ge,ZHAN Jiu-Yu,ZHU Hong-Wei,YU Xin,LIU Yang,YU Jia-Yu and ZHANG Xing-Xiao 12true 2025/11/17 16:06:04 BAI Guang-Ye,CHEN Deng-Jin,ZHANG Lei,ZHANG Qian,LIU Kai-Dong,HAO Hai-Yu,LI Peng,YI Fu-De,LI Jing-Lin,CHEN Shan and HAO Xiao-Jing 11true -), suppresses glutathione (GSH) synthesis, and impairs GPX4-mediated detoxification of lipid peroxides, leading to uncontrolled lipid peroxidation and oxidative stress that ultimately trigger ferroptotic cell death. This iron-driven cell death exhibits distinct morphological and biochemical characteristics compared with other forms of cell death. Ferroptosis contributes to AD pathogenesis through multiple mechanisms and is closely associated with disease onset and progression. Iron overload can affect early amyloid precursor protein processing, accelerate Aβ production and plaque deposition, reduce Tau protein solubility, and promote Tau hyperphosphorylation and aggregation into NFTs. Therapeutic strategies targeting ferroptosis—such as iron chelation with deferoxamine to reduce labile iron levels and inhibit Fenton reaction-driven oxidative damage, supplementation with antioxidants such as α-tocopherol or α-lipoic acid to neutralize ROS and scavenge lipid radicals, and administration of selenium or activators of the Nrf2-SLC7A11-GPX4 axis and the SIRT1/Nrf2 signaling pathway to restore glutathione-GPX4 function—can effectively block lipid peroxidation and suppress iron-dependent cell death. By modulating iron metabolism, enhancing antioxidant defenses, and inhibiting lipid peroxidation, these approaches hold promise for mitigating ferroptosis-related neuronal injury. These interventions collectively aim to modulate iron metabolism, strengthen antioxidant defenses, and suppress lipid peroxidation, thereby mitigating neuronal injury and delaying cognitive deterioration. Ferroptosis represents a pivotal intersection of iron metabolism, oxidative stress, and neurodegeneration in AD. Exploring ferroptotic mechanisms not only deepens our understanding of AD pathophysiology but also opens new avenues for therapeutic intervention. This review aims to comprehensively summarize the molecular basis of ferroptosis, elucidate its pathological roles in AD, and propose ferroptosis-centered therapeutic strategies, thereby providing a theoretical framework for future research and drug development in AD.]]> 2025/10/16 16:27:34 LEI Bin,YING Jia-Qin,CHEN Shi-Yu,LIN Zhi-Cheng,LI Wan-Yi,LIU Zhi-Tao,HUANG Yu-Han,YE Zhi-Tao,CHEN Lu-Yi,ZHOU Chen-Xuan,JIANG Yi,CHEN Hui,YANG ZI-YU and LI Li-Ping 10true 2025/11/21 11:54:38 LIU Xiao-Qian,Lü Meng-Lin and KOU Xian-Juan 9true +-dependent sirtuins. Histone deacetylase inhibitors (HDACi) exert significant neuroprotective effects following ischemic stroke through a multi-target, multi-pathway synergistic mechanism. The core mechanisms include inhibition of neuronal apoptosis, regulation of neuroinflammation, protection of the blood-brain barrier (BBB), and improvement of cognitive impairments (PSCI). HDACi regulate gene expression epigenetically by upregulating genes such as p21/CIP1, leading to cell cycle arrest, while also modulating apoptosis-related proteins by inhibiting pro-apoptotic signaling pathways, thereby reducing neuronal cell death. In terms of neuroinflammation, HDACi suppress NF-κB and activate Nrf2 pathways, decreasing the release of pro-inflammatory cytokines and preventing the pro-inflammatory polarization of microglia and macrophages, thus modulating the inflammatory response. Regarding BBB protection, HDACi regulate the expression and restoration of tight junction proteins such as occludin and claudin-5, while inhibiting the release of destructive factors like MMP-9, alleviating vasogenic edema, and maintaining BBB integrity. Furthermore, HDACi promote the transcription of neurotrophic factors and synaptic-associated genes, enhancing neuroplasticity and repairing neuronal networks, ultimately improving cognitive functions. Therefore, HDACi demonstrate great potential as a multifaceted therapeutic strategy for ischemic stroke. HDACis represent a powerful multi-target therapeutic approach that transcends the limitations of traditional thrombolytic therapies. HDACis represent a powerful multi-target therapeutic approach that transcends the limitations of traditional thrombolytic therapies, which are hampered by a narrow time window and risks of reperfusion injury. Histone acetylation is increased by HDACis, which relaxes chromatin and reactivates protective gene transcription. Their selectivity and chemical structure are used to classify them. Trichostatin A (TSA) and sodium butyrate (SB), a short-chain fatty acid, are examples of broad-spectrum inhibitors that are effective in lowering infarct volume and reducing neuroinflammation. More selective inhibitors, including Tubastatin A (HDAC6-selective) and Entinostat (class I-selective), may have fewer adverse effects while increasing efficacy. By suppressing apoptosis by modifying the p53, Bcl-2, and JNK pathways, reducing neuroinflammation by blocking NF-κB and NLRP3 activation, preserving the integrity of the blood-brain barrier by strengthening tight junction proteins, and promoting synaptic plasticity, neurogenesis, and the expression of neurotrophic factors like BDNF, these inhibitors provide neuroprotection through a variety of interrelated mechanisms.Despite their great potential, HDACis’ clinical translation is fraught with difficulties, mostly because of non-selective inhibition-related adverse effects such as hepatotoxicity and gastrointestinal problems with valproic acid (VPA). In order to accomplish targeted delivery to the brain, future research is consequently shifting toward the development of highly selective inhibitors, refining dosing regimes, and utilizing cutting-edge drug delivery technologies like nanoparticles. In summary, the development of effective neuroprotective and neurorestorative treatments for IS may be greatly aided by a nuanced, spatiotemporally accurate understanding of HDAC activities and the judicious use of subtype-selective HDACis.]]> 2025/11/27 14:05:38 PAN Feng-Yuan,XU Yi-Wei,ZOU Xin-Yu and CHEN Jing 8true +-dependent deacetylases, play a central role in critical biological processes such as cellular metabolism regulation, immune homeostasis maintenance, and stress injury repair, and have been identified as potential intervention targets for neurological diseases. This review systematically summarizes the cellular localization and core biological functions of each member of the Sirtuins family, with a focus on their regulatory roles and molecular mechanisms in the pathological process of SCI: SIRT1, 3, 5, and 6 inhibit the excessive activation of the NF-κB pathway and block NLRP3 inflammasome assembly through deacetylation modification, thereby participating in the regulation of neuroinflammation after SCI; meanwhile, they alleviate oxidative stress injury in spinal cord tissues by activating the Nrf2 antioxidant pathway and enhancing the activity of antioxidant enzymes such as SOD and NADPH, forming a “anti-inflammatory-antioxidant” synergistic protective effect. SIRT7 delays neuronal apoptosis by promoting DNA damage repair and inhibiting apoptotic signaling pathways. SIRT3 and SIRT5 target mitochondrial function, improve mitochondrial energy metabolism by regulating the modification status of enzymes involved in the tricarboxylic acid cycle and oxidative phosphorylation, and restore autophagic homeostasis by modulating the acetylation levels of FOXO3a and AMPK, providing metabolic support for neural repair. We summarize that a variety of natural Chinese herbal components (e.g., resveratrol, matrine) and synthetic compounds (e.g., SRT1720, AGK2) can influence the pathological progression of SCI by targeting and regulating members of the Sirtuins family. We propose that Sirtuins-targeted combined therapeutic strategies (e.g., combined with stem cell transplantation, neurotrophic factor supplementation, or antioxidant intervention) are expected to break through the limitations of single therapies and enhance the repair effect of SCI through multi-mechanism synergistic actions. In conclusion, the Sirtuins family exhibits critical mechanisms of action and potential intervention value in the pathophysiological process of SCI. This review summarizes and prospects novel Sirtuins-targeted therapeutic strategies, aiming to provide new insights for basic research and clinical translation in this field.]]> 2025/11/21 10:59:06 DU Hai-Lin,ZHANG Jian,LI Hong-Ru,CUI Yin-Jie and ZHENG Chen-Guang 7true -/- fibroblasts in vitro is preceded by stochastic ALT induction, indicating that stochastic recombination at dysfunctional telomeres can overcome senescence barriers and initiate malignant transformation. Consistent with this model, whole-genome sequencing of ALT-positive tumors frequently identifies early driver mutations in TP53, ATRX, and DAXX, which disable replicative-senescence checkpoints while simultaneously enhancing telomeric HDR. Here, we synthesize the convergent molecular features of ALT tumors and senescent cells, highlighting:(1) replication stress as a common initiating cue, (2) SUMO-dependent phase separation as a platform for telomere-templated recombination, and (3) epigenetic erosion of ATRX/DAXX-mediated heterochromatin as a rate-limiting step. Finally, we discuss therapeutic implications: (1) pharmacological inhibition of SUMO E1/E2 enzymes to prevent APB scaffold nucleation, (2) synthetic-lethal exploitation of replication stress via ATR/CHK1 inhibitors, and (3) immune-microenvironment-targeting strategies that remodel the senescence-associated secretory phenotype (SASP). Collectively, this review elucidates the mechanisms by which ALT regulates cellular senescence and tumorigenesis, offering druggable vulnerabilities and translational strategies for the clinical management of telomerase-negative tumors.]]> 2025/11/17 15:52:58 JIA Tong-Xin,XIONG Meng-Jie,HOU Kai-Long,LIU Jia-Hua,ZHANG Hao-Nan,JIA Shu-Ting and LIU Jing 6true e.g., theta-, beta-, or gamma-band stimulation), their endogenous neural rhythms tend to align with the exogenous signal and, consequently, with each other. This alignment effectively instantiates principles of the communication through coherence (CTC) framework, which posits that coherent oscillations optimize information exchange by synchronizing periods of excitability across neural populations. Meanwhile, transcranial direct current stimulation (tDCS) exerts its influence by altering the excitability of targeted cortical regions in a polarity-dependent manner, thereby tuning the computational readiness of social-cognitive hubs such as the temporoparietal junction, superior temporal cortex, or inferior frontal gyrus. A growing body of empirical evidence demonstrates that such manipulations yield robust behavioral effects. In joint motor tasks, in-phase tACS enhances interpersonal coordination by aligning motor preparation dynamics, reducing temporal variability, and enabling individuals to anticipate each other’s actions more effectively. In communication and social learning contexts, MBS targeting high-order integrative regions promotes conceptual alignment, accelerates knowledge transfer, and supports more efficient encoding of shared representations. Notably, the effects of MBS often persist beyond the stimulation period, suggesting short-term plasticity in cross-brain networks. Post-stimulation improvements in synchronization and coordination indicate that MBS may temporarily recalibrate the neural architecture underlying social interaction. However, these benefits exhibit strong parameter specificity—precise phase relationships (e.g., 0° in-phase versus 180° anti-phase) and frequency matching are essential for generating reliable behavioral outcomes. Taken together, MBS represents a transformative step toward establishing the causal principles of human sociality and offers a new avenue for probing how multiple brains become functionally aligned during interaction.]]> 2025/12/10 9:19:59 CHEN Han-Lin,LI Qi,LI Yuan-Yuan and PAN Ya-Feng 5true 2025/12/31 10:44:26 TANG Yu-Ting,LI Yong-Hui,SHEN Xun-Bing and DONG Xin-Wen 4true e.g., PI3K-Akt, mTOR, Wnt) and core nodes such as NFKBIA and CXCL12 that may mediate the protective effects of exercise. The review further discusses the potential of exercise-mediated biomarkers as objective indicators for diagnosis, dynamic monitoring of therapeutic efficacy and patient stratification. Multi-gene diagnostic models based on peripheral samples (e.g., hair follicles, blood) demonstrate how biomarker panels can distinguish non-recovered, almost-recovered and healthy individuals, providing a molecular basis for staging METH use disorder and evaluating the impact of exercise interventions. The temporal dynamics of biomarker changes before and after exercise are highlighted, underscoring the value of longitudinal monitoring of factors such as BDNF, immune-related genes and circulating microRNAs to capture treatment-relevant windows of plasticity. In addition, the underlying molecular basis of exercise as an adjunct therapy and gene-targeted exercise strategies that leverage individual biomarker and gene expression profiles to optimize exercise prescriptions are summarized. Current conceptual and technical challenges are outlined, including heterogeneity of biomarker responses, individual variability, assay sensitivity and specificity, and gaps between preclinical findings and clinical application, together with future directions for integrating exercise with multi-omics, artificial intelligence-assisted biomarker discovery and, prospectively, gene-editing-based interventions. Particular emphasis is placed on the need to standardize exercise protocols, incorporate stage-specific and sex-sensitive designs, and combine exercise with pharmacotherapy and psychosocial rehabilitation in real-world clinical settings across diverse healthcare systems. Overall, this review aims to provide a comprehensive and integrated mechanistic framework and updated theoretical support for the application of exercise-mediated biomarkers in the diagnosis, therapeutic effect monitoring and personalized intervention of METH addiction, and to offer new and clinically relevant insights into the development of precision medicine strategies for substance use disorders.]]> 2025/12/4 14:20:54 HE Jin-Ke,ZHANG Xue-Jie,XU Ji-Sheng and LI Xue 3true e.g., carvedilol) and ACE inhibitors/ARBs have shown protective effects on LVEF in some randomized trials, though results remain inconsistent and require larger confirmatory studies. (3) Metabolic targeted interventions: animal experiments indicate that activation of PPARα or supplementation with L carnitine restores fatty acid oxidation and improves ATP generation, suggesting metabolic modulators as promising cardioprotective candidates. (4) Lifestyle modifications: regular aerobic exercise up regulates mitochondrial biogenesis genes (PGC-1α) and reduces reactive oxygen species (ROS) production; small clinical studies have demonstrated a potential benefit in attenuating cTnT elevation. However, DOX-induced cardiotoxicity has not been effectively controlled, indicating that the core mechanism underlying DOX-related cardiac toxicity remains unidentified. Cardiomyocytes are high energy demand cells, and metabolic dysregulation is considered a central component of DOX induced cardiotoxicity. DOX disrupts myocardial metabolic balance through several interrelated pathways. (1) Oxidative stress and mitochondrial damage: DOX generates abundant ROS within cells, leading to mitochondrial membrane potential loss, lipid peroxidation, and iron accumulation, which suppress electron transport chain activity and markedly reduce ATP synthesis efficiency. (2) Autophagy dysregulation: DOX interferes with autophagic flux, preventing the clearance of damaged mitochondria and further aggravating apoptosis and inflammatory responses. (3) Inflammation and cytokine release: oxidative stress activates NF-κB, up-regulating pro inflammatory cytokines such as TNF-α and IL-6, creating a chronic inflammatory microenvironment that weakens myocardial contractility. (4) Epigenetic modifications: studies have shown that DOX alters DNA methylation and histone acetylation patterns in cardiomyocytes, affecting the expression of key metabolic genes (e.g., PGC-1α, CPT-1) and further inhibiting fatty acid β oxidation. These mechanisms collectively lead to suppressed fatty acid oxidation and compensatory up regulation of glycolysis, manifested by an elevated lactate/pyruvate ratio, accumulation of medium chain acyl carnitines, and a pronounced decline in ATP production. The resulting energy deficit precipitates left ventricular contractile dysfunction and, ultimately, heart failure. Despite extensive basic and clinical research on DOX cardiotoxicity, a unified risk assessment model and precise interventions targeting metabolic disturbances remain lacking. This review systematically summarizes recent progress on DOX induced cardiotoxicity and highlights that impairment of myocardial energy metabolism is a central mechanism of injury, thereby deepened our understanding of how impaired myocardial energy metabolism drives DOX induced injury, we can move toward safer chemotherapy protocols that achieve “cure cancer without harming the heart”.]]> 2025/11/21 8:04:12 LIU Jia-Wei,JIA Tong-Xin,WU Jia-Zhen,SU Wen-Hua,GU Dan and DAN Ju-Hua 2true in vivo and possess pharmacokinetic characteristics marked by a long terminal elimination half-life. Symmetric IgG-like bispecific antibodies feature a symmetric structure and are bivalent for each target antigen. During production, since the two heavy chains carrying the Fc region are identical, issues related to chain mispairing do not arise, thereby simplifying the manufacturing and purification processes. Moreover, the pairing of two identical natural Fc chains allows for correct disulfide bond formation, resulting in a more stable structure. Glycosylation of the Fc region remains in its natural state, preserving Fc-mediated functions. However, as the variable regions of the two antigen-binding sites are linked to the same heavy chain, the design must account for potential steric hindrance when the antibody binds both antigens simultaneously. In contrast, asymmetric IgG-like bispecific antibodies consist of two different heavy chains, each carrying antigen-binding domains that recognize distinct antigens or epitopes, offering greater structural design flexibility. Their development, however, requires addressing challenges related to heavy chain and light chain pairing. Strategies to prevent heavy chain mispairing include engineering the spatial configuration of the Fc region, facilitating Fab arm exchange, applying IgG-IgA chain exchange techniques, and introducing charge modifications in the Fc domain. To ensure correct light chain-heavy chain pairing, approaches such as introducing electrostatic interactions or novel disulfide bonds between the chains, swapping the CH1 and CL domains, or replacing the CH1-CL module with a T-cell receptor-derived structure have been employed. Non-IgG-like bispecific antibodies lack an Fc region. They are characterized by their small size and low molecular mass, which confer enhanced tissue penetration, rapid systemic clearance, and high structural versatility. Unlike IgG-based formats, they do not bind Fc receptors or activate the complement system directly. Different bispecific antibodies exert therapeutic effects through distinct mechanisms, which are largely determined by their structural design and target specificity. Currently recognized mechanisms of action include T cell redirection, dual signaling pathway blockade, immune checkpoint inhibition, formation of ternary complexes by binding two molecules, neutralization of soluble ligands, and acting as cofactors to mimic or enhance biological processes. Bispecific antibodies are extensively applied in cancer therapy. Beyond oncology, they are also being developed for the treatment of autoimmune diseases, infectious diseases, hematological disorders, and other conditions. Different structural designs offer unique advantages across therapeutic areas. This article elaborates on the structural designs of various types of bispecific antibodies and reviews their mechanisms of action and applications in therapeutics.]]> 2025/10/31 15:52:08 ZHANG Ding,ZHENG Yue-Ting and ZHANG Wei 1true