Abstract:Chemical modifications of RNA bases play essential roles in finetuning the functions of the modified RNA species. The m⁶A 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.

Abstract:Oncolytic viruses are a class of viruses that are naturally or genetically engineered to replicate specifically in tumor cells and exert anti-tumor effects. The anti-tumor effect of oncolytic virus is mainly achieved through the following two aspects: (1) direct oncolytic effect, such as inducing apoptosis of tumor cells and promoting cell lysis; (2) as a drug that activates immunity, oncolytic viruses induce the body to produce strong anti-tumor immunity and achieve the purpose of clearing tumors. As an important branch of immunotherapy, oncolytic viral therapy has become a research hotspot in this field due to its tumor specificity and convenient genetic modification. Until now, only four products have been approved for marketing, despite more than 100 cases of oncolytic viral therapies in the recruitment and completion stages of clinical trials. There continue to be many challenges in the application of oncolytic therapy in oncology treatment. Therefore, a systematic review of oncolytic virus modification strategies and an in-depth understanding of the biological processes of oncolytic viruses are all the more necessary. Viruses are host-dependent in their replication and proliferation processes, and their biological processes are closely related to the metabolic state of the host. The hallmark feature of tumors is metabolic reprogramming, the process by which tumor cells reconsider their metabolic networks to meet the demands of exponential growth and proliferation and to prevent oxidative stress. This typically includes enhanced glycolysis and glutaminolysis, as well as changes in mitochondrial function and redox homeostasis.The replication of oncolytic viruses requires the synthesis of biological macromolecules, such as amino acids, lipids, nucleotides, etc. Viruses themselves do not encode relevant enzymes, so they often need to use the metabolic pathways of their host cells to synthesize the substances they need. Enhancing the replication and oncolytic ability of oncolytic viruses by targeting host metabolic reprogramming is a promising direction. It has been shown that lipid metabolism and intermediates are one of the ways in which viruses engage in dialogue with their hosts, and lipid rafts are essential components for oncolytic viruses to perform their infection and replication functions. Cholesterol depletion in host cells has shown conflicting results, presumably related to the type of virus. For example, the dependence of envelope and non-envelope viruses on lipid synthesis may differ, although this needs more literature support. The idea that enhanced glycolytic levels in host cells promote the infection, replication, and anti-tumor effects of oncolytic viruses is equally controversial. Oncolytic viruses replicate to a degree comparable to that of proliferative tumor cells, and both rely on glutamine metabolism to participate in the synthesis of biological macromolecules. Adenoviruses and VSV are significantly less able to replicate in states where the glutamine metabolic pathway is suppressed. Similarly, the level of host nucleotide metabolism is closely related to the replication capacity of oncolytic viruses, and enhancing RNA reductase (RR) activity can promote HSV replication in tumors. Therefore, the use of oncolytic viruses to regulate host metabolic reprogramming, or in combination with drugs that can regulate host metabolism, is one of the directions to further improve oncolytic virus anti-tumor efficacy.

Abstract:Can emotional information be unconsciously processed by the brain? The subliminal affective priming effect provides rigorous evidence for this question. With the visual masking and continuous flash suppression paradigms, the subliminal affective priming effect has been found in tasks on attention and memory, social evaluation and even behavior preference when invisibly facial expressions are employed as primes. It has also been shown that the participants’ skin conductance level and cardiovascular reactivity are enhanced in these tasks. The findings from studies that aimed to explore neural mechanisms suggest that unconsciously perceived facial expressions have an influence on the early perceptual processing and late emotional meaning analysis of the target stimuli, in which the amygdala plays an important role. The affective primacy hypothesis and the feelings-as-information theory are proposed to explain the mechanism of the subliminal affective priming effect from the perspectives of domain specificity of affective system and affective attribution. Finally, potential directions for future studies are suggested.

Abstract:Glucocorticoid (GC) was the final effect hormone in hypothalamic-pituitary adrenal (HPA) axis. Pain, disease, and stress can trigger increased GC expression. Depending on the peripheral area innervated by the nerve, the type of pain, and the stress stimulus, GC has been shown to be both injury-promoting and injury-resisting in chronic pain. In the context of chronic pain, GC induces the structural plasticity of neurons, schwann cells, microglia, oligodendrocytes and astrocytes through its interaction with glucocorticoid receptors (GR), which participate in the apoptosis, excitation and memory of neurons and immune cells of the nervous system, causing pain behavior to decrease or increase. GC is mainly expressed at a relatively high baseline in the central neuronal system, especially the hippocampus, cortex and spinal cord, under stress or non-stressconditions. However, the plasticity of neurons or immune cells induced by stress is usually poor. Meanwhile, the induced GC overexpression induces and enhances chronic pain through different signaling pathways, and associated with neuropsychiatric diseases such as depression. In addition, understanding the dual analgesic or pain-inducing mechanisms of GC in chronic pain should focus on determining how GC acts on different cell types in the peripheral and central nervous systems. At the same time, further research on the dual mechanism of GC in the central nervous system will undoubtedly contribute to the treatment of chronic pain and have obvious clinical significance.

Abstract:Metabolism is fundamental to survive and perpetuation of the species. Organisms regulate metabolism through behavior and a series of physiological change. Negative energy balance (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.

Abstract:In the past studies, lactate has been regarded as a product of glycolysis, namely an undesirable metabolic by-product. In recent 30 years, studies have proved that lactate can be used as an energy substrate, and it can also participate in neural activity by affecting signal pathways. Lactate can play a role in spatial memory, fear memory and addiction memory. Lactate generated in astrocytes and oligodendrocytes is transported to neurons, so as to provide energy for neurons and affect memory. Lactate can not only directly act on lactate receptor, but also indirectly promote neurogenesis, synaptic plasticity and immediate early gene expression by enhancing the activity of N-methyl-D-aspartic acid receptor, and induce the expression of brain-derived neurotrophic factor, thus affecting memory. Lactate is also a potential therapeutic target for neurological diseases related to memory, such as Alzheimer’s disease. This paper reviews the effects of lactate production on different memory, the effects of different neurotransmitters regulating lactate production on memory, the neural mechanism of lactate affecting memory, and the role of lactate in neurodegenerative diseases related to memory. Through combing the above aspects, it is hoped to further provide new ideas for the study on the role of lactate in memory and the role of lactate in nervous system.

Abstract:Piezo1 is a newly discovered mechanosensitive ion channel in mammals, which plays important functions in different tissues and organs, including bone, urinary tract, eyeball, and artery. However, abnormal Piezo1 mechanical transmission can cause a variety of diseases and promote the course of disease. Fibrotic disease can occur in almost any tissue and organ, and its main feature is excessive cross-linking and accumulation of collagen and other extracellular matrix components, which eventually leads to increased stiffness of tissues and organs and affected physiological functions. At present, more and more studies have shown that Piezo1 plays an important regulatory role in the occurrence and development of fibrotic diseases, which is closely related to the change of matrix mechanical state. This paper describes the structure and activation mechanism of Piezo1, and systematically summarizes the research progress of Piezo1 in fibrotic diseases of the heart, kidney, pancreas, liver and other organs, in order to provide a new perspective and strategy for the treatment of fibrotic diseases.

Abstract:Obesity is an important risk factor for the development and progression of chronic metabolic diseases such as diabetes, fatty liver and cardiovascular diseases. Endocrine factor fibroblast growth factor 21 (FGF21), which has multiple beneficial effects on energy homeostasis and glucose and lipid metabolism, serves as a promising therapeutic target for obesity and related metabolic diseases. FGF21 relies on high-affinity interaction with β-klotho (KLB) for recruitment and localization to the cell surface, where it engages FGF receptors (FGFRs). Obesity has been demonstrated as a FGF21 resistant state, in which circulating FGF21 levels are elevated while its downstream signaling and action are impaired. This may be caused by the decreased expression of KLB and FGFRs. Improving FGF21 resistance emerges as a new therapeutic strategy for obesity and its associated diseases. Exercise has long been considered as a cornerstone for the prevention and treatment of obesity and its related metabolic diseases. Evidence is mounting that FGF21 plays an important role in exercise-mediated health promotion. Exercise not only increases the expression of FGF21 in adipose tissue, skeletal muscle and heart, but also stimulates the expression of FGFRs and KLB to sensitize the effect of FGF21 and improve FGF21 resistance in target tissues such as adipose tissue. Knockout experiments confirmed FGF21 as a key mediator of exercise-induced improvements in obesity and related metabolic diseases. There are many issues that need further study. Circulating FGF21 is mainly derived from the liver. However, uncertainty about the long-term effects of exercise on liver FGF21 expression still remains. In most research, a single pharmacological dose of FGF21 was used to determine FGF21 sensitivity. Whether exercise improves the physiological effects and the long-term effects of FGF21 also needs further investigation. Clariying these issues has important implications for our understanding of how exercise ameliorates obesity and its related metabolic diseases through FGF21 signaling.

Abstract:Marine macroalgae (including brown algae, red algae, and green algae) exhibit several features of an excellent feedstock for biorefinery, such as high yield of biomass, no occupation of arable land, and no requirement of fresh water. In 2021, the production of brown algae in China was 1.9 million tons, which was much higher than other economic algae. It is worth noting that the carbohydrate content of brown algae is as high as 60%, and three sugars, including alginate, fucoidan and laminarin are unique to brown algae. Amongst them, alginate is a linear anionic polysaccharide which consists of 1,4-linked C-5-epimers β-D-mannuronic acid (M) and α-L-guluronic acid (G). The decomposition of alginate is catalyzed by alginate lyases 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.

Abstract:Phthalate (2-ethylhexyl) ester (DEHP) is a synthetic plasticizer of organic compounds, which is widely used in personal care, medical devices, food packaging, and plastic manufacturing due to its excellent flexibility, plasticity, and durability. DEHP is widespread in soil, water, atmosphere, and other environments. As DEHP is a common endocrine disruptor with reproductive toxicity, immunotoxicity, and neurotoxicity, it not only poses a threat to the ecological environment, but also enters the human body through the food chain to bring harm to health. Therefore, removing DEHP from the environment has attracted great attention. The biodegradation of DEHP is considered to be greenest and environmentally friendly degradation method, and many researches on the biodegradation of DEHP have been reported. In this paper, the harm of DEHP pollution, current situation of bacterial biodegradation, complete degradation pathway (including ester bond hydrolysis, β oxidation, protocatechuic acid degradation, benzoic acid degradation, and tricarboxylic acid cycle), and molecular mechanism are reviewed, and problems existing in the biodegradation of DEHP are summarized and prospected, which are listed below. (1) At present,the research on the biodegradation of DEHP mainly focuses on the domestication screening of degrading bacteria and the analysis of degradation properties, but the research on the functional genes of degradation is not deep enough. Therefore, more research on the functional genes of the degrading strains should be conducted while screening strains. (2) Although several biodegradation pathways of DEHP have been reported, the molecular mechanisms of the side chain β-oxidation of DEHP and the anaerobic degradation pathway of PA have been less studied and not yet understood, so revealing the mechanisms of these specific degradation pathways at the genetic level is necessary. (3) Most DEHP-degrading enzymes are derived from culturable microorganisms. Using metagenomic technology, all of the genetic resources in the environment can be mined in the future to obtain more novel DEHP-degrading enzymes. (4) The majority of research on DEHP biodegradation is still in the laboratory stage, and few researchers have applied it to the remediation of actual environmental pollution. Considering the significant difference between the laboratory and the actual environment, how to apply the research results obtained in the laboratory to the remediation of DEHP pollution in the natural environment and the resolution of practical issues is a problem that researchers need to consider and solve further. This review will provide a reference for effective biodegradation of DEHP in the environment.

Abstract:The complex tumor microenvironment leads to the inefficient intra-tumor delivery of antitumor drugs severely restrict the therapeutic effect of drugs on superficial tumors. At present, the main treatment methods for superficial tumors are surgical resection, chemotherapy, radiotherapy. These therapies can destroy tumor tissue or inhibit the growth of cancer cells in the short term, but the long-term treatment results are not satisfactory. With the research of anti-tumor treatment, chemotherapy , photodynamic therapy (PDT), photothermal therapy (PTT), gene therapy and immunotherapy and other new combined treatment strategies have the advantages of good therapeutic effect, small invasion, and low toxic and side effects, and have shown great potential for the treatment of superficial tumors. In order to achieve good therapeutic efficacy, it is necessary to effectively deliver therapeutic drugs (photosensitizers, photothermal agents, chemotherapeutic drugs, etc.) to the tumor site to exert anti-tumor effect. Based on the major drawbacks of the traditional administration strategy, such as low bioavailability of oral administration, pain, poor targeting, and systemic toxicity caused by subcutaneous/intravenous administration. It is important to develop safe and effective anticancer drug delivery strategies to promote novel cancer therapies. The transdermal delivery system (TDS) can deliver the drug through the stratum corneum of skin into the dermis and through capillaries into the bloodstream, effectively overcoming low bioavailability associated with oral administration. In addition, subcutaneous/intravenous administration often causes pain sensation defects, TDS can significantly improving patient medication compliance. However, due to the presence of a cuticle barrier on the skin that hinders drug penetration, there is a significant reduction in drug delivery efficiency, limiting its further application. The emergence of biocompatible transdermal microneedles presents a promising solution for enhancing drug penetration in TDS. These microneedles are composed of biodegradable components, such as polymers and polysaccharides, serving as matrix materials that encapsulate drugs. This innovative approach represents a minimally invasive local drug delivery system with the dual functionality of subcutaneous injection and transdermal drug administration. The biocompatible transdermal microneedles with high rigidity can effectively puncture the skin cuticle and deliver agents within the microneedle to superficial tumor tissues via controlled drug release, which would significantly improve drug bioavailability and avoid toxicity to livers/kidneys compared with conventional drug intravenous/oral administration. The biodegradable polymer material of microneedles avoids the safety risks and reduces the risk of cross infection, which is caused by the metal materials of solid microneedles or non-degradable polymers. In addition, biocompatible transdermal microneedles can overcome the shortcomings of low-dose hollow coated microneedles by encapsulating the drug into the entire tip for efficient drug loading. Meanwhile, the height and volume of the needle tip can be adjusted by changing the mold structure in order to meet the needs of different depth and dosage of the drug. Here, the design of biocompatible transdermal microneedles for cancer chemotherapy, PDT and PTT, immunotherapy, adoptive cell therapy and gene therapy in introduced. We also summarize the challenges of biocompatible transdermal microneedles-mediated superficial tumor therapy, to help promote potential translational superficial tumor applications of microneedles.

Abstract:Under the background of precision medicine and personalized medicine, molecular diagnosis is more and more widely applied in pathogen detection, tumor diagnosis, eugenics and fertility, environmental protection, food safety and other fields, and continues to develop in the direction of molecular point-of-care testing (POCT) with advantages of fast and accurate, low-cost, simple operation. Ultra-fast pulse-controlled PCR (upPCR) is an extension and upgrade of real-time quantitative PCR (qPCR) technology, which uses energy pulses to control metal heating elements (mainly gold nanoparticles) in amplification reactions to complete the rapid heating of the local microenvironment of the solution within a few hundred microseconds, and realize the melting and denaturation of template DNA; after stopping heating, the reaction microenvironment can be rapidly cooled by the surrounding solution down to the extension temperature of the polymerase to achieve amplification of template DNA. A single denaturation-amplification cycle of upPCR is only 1.5-5 s, which is much faster than traditional PCR (about 90 s per cycle), and can thus greatly speed up the PCR reaction. On the basis of retaining the advantages of traditional qPCR such as high sensitivity, high specificity and multiplex detection, ultra-fast pulse control PCR technology adds new advantages such as ultra-fast reaction time (less than 15 min) and simple operation, which is very suitable for molecular POCT scenarios such as home detection and community screening. This paper mainly reviews the principle, core raw materials, equipments and applications of upPCR technology in molecular diagnosis, and discusses the advantages and disadvantages of this technology, as well as future technology development and application trends.

Abstract:Microscopy technology has undergone rapid development and has surpassed the limits of optical diffraction. Currently, it mainly includes stimulated emission depletion microscopy (STED), structured illumination microscopy (SIM), photoactivation localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), minimal photon fluxes (MINFLUX) based on the localization of the minimum number of photons, and a variant of MINFLUX technology combining structured illumination microscopy (SIMFLUX). STORM technology has superiority, and on top of it, there are six multi-color imaging technologies currently available. This article introduces the latest multi-color imaging technology and a three-channel imaging technique implemented using spectral imaging. However, three-channel imaging using spectral imaging has issues such as spectral crosstalk and channel alignment errors. Therefore, relevant optimization algorithm principles are introduced. The article also demonstrates the imaging of COS-7 cells on a three-channel STORM microscopy platform, showcasing the superiority of three-channel STORM microscopy.

Abstract:Quorum sensing (QS) is a bacterial communication system that depends on bacterial density and is closely related to bacterial pathogenicity and drug resistance. QS signal molecules are an important substance basis for QS system to regulate various cellular processes of microorganisms. The identification and detection of QS signal molecules is an indispensable link in the exploration of the regulatory mechanism of bacterial QS system. It is of important reference significance for the interaction, efficient detection and mechanism analysis of microorganisms such as bacteria in the fields of life science and pharmacy. It is illustrated that the photoelectric sensing detection is of great potential for the real-time detection of QS signal molecules with its high sensitivity and diversity of methods. Combining with molecular imprinting, biological receptor recognition, magnetic separation and so on, photoelectric sensor could provide more efficient means of detection. In this paper, the types of QS signal molecules and common QS systems were briefly introduced, and then the photoelectric detection methods and technologies of QS signal molecules were summarized. The sensitive media, sensing interface, sensing mechanism and testing effect of photoelectric sensing detection were discussed in details. The optical analysis techniques were of a wide range of applications in the detection of QS signal molecule in biological samples. Fluorescence detection method has high sensitivity in quantification of signal molecules, and fluorescence imaging method can provide real-time in situ observation of bacterial QS process. Surface enhanced Raman scattering (SERS) spectral analysis technique could provide molecular fingerprint information of targets in the QS process of some biological samples. Electrochemical detection techniques could dynamically monitor QS signal molecules through the changes of electrochemical signals. Meanwhile, much more attention had been paid to microfluidic analysis technology, because it was taken as a favorable platform for the in-situ monitoring of bacterial QS signal molecules and QS process by the way of combining the photoelectric sensors and microfluidic control.

Abstract:Objective Recently, single-atom nanozyme (SAN) has been widely studied due to its high atom utilization and various enzyme-mimicking activities. However, most of the SANs present low metal-atom densities, which restrict their further application and development. The aim of this study is to prepare SAN with high atomic loading and to systematically investigate its enzyme-like activities, in the hope of providing ideas for the preparation of highly loaded SANs and theoretical support for the application of SANs in a wider range of fields.Methods In this work, high-loading Cu SAN with metal contents up to 7.66% (w/w) was prepared using in-situ anchoring strategy. The metal salt precursors were confined into the carbon carriers consisting of aminated graphene quantum dots, and then urea was introduced to provide a rich N-coordination environment for Cu atoms. The chemical bond between Cu atoms and the carrier was further stabilized by pyrolysis under the protection of Ar gas. The low-loading Cu SAN used for comparison was prepared according to traditional metal organic framework (MOFs) anchoring method. Then, the peroxidase (POD)-like, oxidase (OXD)-like and superoxide dismutase (SOD)-like catalytic activities of high/low-loading Cu SAN were tested and compared with 3,3",5,5"- tetramethylbenzidine (TMB) and nitrotetrazolium blue chloride (NBT) as chromogenic substrates. The catalase (CAT)-like catalytic activities of high/low-loading Cu SAN were assessed by monitoring the decomposition rate of hydrogen peroxide (H₂O₂).Results The results suggested that the high-loading Cu SAN possesses the improved catalytic activity and selectivity towards POD-like and SOD-like activities, showing 3.4-fold and 8.88-fold higher than low-loading Cu SAN, respectively.Conclusion This work provides a strategy to synthesize SAN with high metal-atom density. And the results show that atomic regulation can be achieved by adjusting preparation methods which assist to obtain SAN with different catalytic selectivity, and lay foundation for the development and application of SAN in detection and sensing, diseases treatment and environmental protection.

Abstract:Objective OxLDL can increase Plin2 expression, then promote the formation of foam cells. LOX1 was a scavenger receptor for oxLDL. Here, we investigate the relationship between Plin2 and LOX1 in the progress of atherosclerosis.Methods The data GSE43292 from GEO database were analyzed for Plin2 and LOX1 expressions and the correlation between Plin2, LOX1 and NF-κB pathway. RAW264.7 cells stimulated by oxLDL served as a cellular model of atherosclerosis. The Plin2, LOX1 and p-p65 expressions were analyzed by immunoblotting, the intracellular lipids were detected by BODIPY 493/503 staining.Results The Plin2 and LOX1 expressions in atheroma plaques were significantly higher than that in adjacent carotid tissues by analyzing GSE43292. The expressions of Plin2 and LOX1, the lipid droplets were increased obviously in RAW264.7 cells after treated with oxLDL for 24 h. And Plin2 overexpression significantly increased the expression of LOX1. This change was more obvious after oxLDL incubation. But knockdown Plin2 maked no difference on LOX1 when without oxLDL treatment. Furthermore, the GSEA plot showed that the expressions of Plin2 and LOX1 were positively related with NF-κB activation in atherosclerosis. Meanwhile, although oxLDL incubation, NF-κB inhibitor JSH-23 pretreatment significantly reduced Plin2 and LOX1 expressions and the amounts of intracellular lipids. In addition, the expressions of Plin2 and LOX1 were significantly inhibited by JSH-23 in spite of Plin2 overexpression plus oxLDL incubation.Conclusion Altogether, Plin2 can promote the intracellular lipids accumulation and may participate in pathophysiological process of atherosclerosis by increasing the expression of LOX1, which at least partly through the activation of NF-κB pathway.

Abstract:Objective To illustrate the interaction process and mechanism of chemokine CCL11 with receptor CCR3 and glycosaminoglycans (GAGs) and shade light on the regulation mechanism of CCL11-GAGs-CCR3.Methods A stably transfected CCR3-EGFP CHO cell line with single-molecule expression level was constructed using genetic engineering. The interaction between GAGs and CCL11 under different in vitro solution was studied by total internal reflection fluorescence (TIRF) and isothermal titration calorimetry (ITC) technique. The regulation of GAGs-CCL11 on chemotactic behavior of CCR3-EGFP stable cells and the effect of CCR3-EGFP aggregation on cell membrane were investigated by chemotactic assay and living cell monomolecular imaging assay.Results With the increase of chondroitin sulfate chain length, the binding heat release of chondroitin and CCL11 increased, indicating that the interaction force was enhanced and the promotion effect of CCL11 aggregation was enhanced. Single molecule fluorescence imaging technology combined with chemotactic test showed that different types and proportions of GAGs could affect the interaction between CCL11 and CCR3. The addition of GAGs inhibited the chemotactic effect of CCL11 on CCR3-EGFP stable cells and promoted the aggregation ability of CCR3-EGFP. With the increase of molecular mass of chondroitin sulfate, the inhibitory effect was significantly enhanced.Conclusion GAGs can affect the aggregation state of CCL11 and its interaction with receptor CCR3. Our study provides a theoretical basis for further elucidating the interaction between CCL11-GAGs-CCR3.

Abstract:Objective Aging is an increasingly serious social problem. The cognitive function of the elderly, such as attention, shows a significant decline. Investigating the deficits of visual attention regulatory network caused by aging will further our understanding of the neural mechanism of cognition declines of the elderly, and providing us the theoretical basis to find potential intervention methods.Methods In the study, we used a classical two-target attention task. Subjects were asked to keep their gaze on the central fixation cross, a pair of spots appeared separately located on left and right 13.5° from the cross. After 800-1 200 ms fixation, one of the two spots randomly changed its form or both remained unchanged. We recorded neural activity of young adults and old adults during the attention task using electroencephalogram (EEG).Results Through comparing the differences of EEG activity under visual stimuli changed and unchanged conditions, we found that neural activity of channels in frontal, parietal and temporal areas of young adults significantly changed with the change of stimuli, while neural activity of old adults didn’t follow the change of stimuli.Conclusion These results demonstrated that brain network of the elderly could not effectively react to the change of external visual information load in the attention task. Aging is accompanied by the functional decline of the visual attention regulatory network. Besides, decline of this brain network also showed sex difference. Our research provided new evidence for the decline of visual attention regulatory network of the elderly.

Abstract:Objective The cochlear microphonic (CM) signal produced by the bat cochlear outer auditory hair cells contains information related to the movement of the cochlear basilar membrane. The aim of this study was to investigate the mechanism of bat cochlear nerve influence on echolocation by analyzing the relationship between frequency modulation (FM) bat CM signals and their received acoustic frequencies.Methods The CM signals of FM bats (Eptesicus and Pipistrellus) were recorded and analyzed in response to pure acoustic (tone burst) stimulation by placing a set of metal electrodes in the ventral cochlear nucleus.Results Two different species of FM bats (Eptesicus and Pipistrellus) exhibited CM mean frequency response curves during high sound pressure stimulation with a distinct concavity in the narrower specific frequency band vocalization. For Eptesicus, the CM RMS frequency response curves showed significant troughs on both sides of the terminal frequency (TF) of the first and second harmonics; moreover, these troughs were repeated at 15 kHz intervals from 15 kHz onwards; for Pipistrellus, the CM RMS frequency response curves showed significant troughs only on both sides of the first harmonic. The valleys are evident on both sides.Conclusion The relationship between the inhibition exhibited by the CM signal and the FM bat’s first and second harmonic TF reflects the fact that the cochlear nerve produces inhibition for specific frequencies, and this inhibition helps the bat to extract target localization information modulated to the vicinity of the TF.

Abstract:Objective East Asia harbors a vast territory, with many populations and a diversity of languages. China has 34 provincial-level administrative districts which distributed in seven geographical divisions, mainly populated by seven linguistic family-speaking populations. Previous studies have focused on the genetic history of origin, migration and fusion of East Asia populations. We collected and analyzed high-density SNP data of 5 147 individuals in the world, studied the genetic relationship and structure between East Asia populations, especially Chinese populations and other world populations from the perspective of geography and language.Methods We collected and carried out quality control of high-density SNP data of 5 147 individuals in the world. We studied the genetic structure of Chinese population. The final obtained 32 789 SNPs were statistically tested by allele frequency difference analysis. Meanwhile, we employed principal component analysis, phylogenetic tree, ancestry component analysis and D-test statistics to explore the genetic relationship between East Asia populations and other populations in the world, as well as the genetic relationship and structure of Chinese populations.Results We found that there were significant differences among East Asian, African, American and European. Chinese population can be divided into seven subgroups. The genetic clustering in different populations has a strong correlation with their geographical distribution, linguistic families and ethnic origin history.Conclusion We studied the genetic relationship and differences between Chinese population and world population, and systematically studied the genetic substructure of Chinese population. This will enrich the research foundation of population genetics and forensic genetics of East Asia population and provide data support for individualized medical work.

Abstract:Objective The high density SNP genotype data were obtained by whole genome sequencing (WGS), the accuracy of genotype was evaluated, and this study is intended to establish the method of using whole genome sequencing data for SNP kinship relationship prediction.Methods The samples were sequenced at a depth of 30× through the MGISEQ-200RS sequencing platform, and 645 199 autosomal SNP in the Wegene GSA DNA microarray were extracted from the sequencing data. After quality control and filtering, the prediction relationship was calculated and predicted by IBS/IBD algorithm, and the ancestry of the samples was analyzed.Results The coincidence rate between SNP genotype extracted from sequencing data and Wegene GSA genotype is more than 99.62%.The SNP genotype obtained by sequencing can predict kinship from level 1 to level 4 by using IBS algorithm, and confidence interval accuracy of level 4 kinship prediction is 100%. Using IBD algorithm, the confidence interval accuracy of level 1 to 7 kinship prediction is 100%. The pedigree inference ability of SNP obtained from high-depth whole genome sequence data is not significantly different from that of DNA microarray prediction.At the same time, the use of whole genome sequencing data for ancestry inference is consistent with the survey results.Conclusion The whole genome resequencing technique can be applied to SNP genealogy inference to provide clues for case detection.

Abstract:Objective Based on bioelectrical impedance spectroscopy (BIS), we propose a label-free method for real-time detection of biological cell activity. The method determines whether the cells are active or not based on the differences in electrical properties of the cells at different concentrations, physiological and pathological states. It is used to assist physicians to quickly and precisely locate the scalded tissues in patients and achieve effective excision during clinical surgery.Methods Active zebrafish embryonic stem cells were used to simulate human scalded tissues, and bioimpedance spectroscopy was used to identify the physiological state of the cellular tissues.Results There were significant differences in the impedance amplitude changes of the cells in different states, from which it could be found that the impedance amplitude of the active cells at the same concentration was on average 17.25% higher than that of the dead cells, and the relaxation frequency of the active cells occurred 25% earlier than that of the dead cells.Conclusion The experimental data showed that the bioimpedance spectroscopy method can effectively distinguish two types of physiological states of embryonic cells; according to the clustering region, it can be seen that the BIS assay has obvious ability to distinguish cell activity and concentration, which can quickly assist physicians to complete the detection of scalded tissues of patients theoretically.