+Advanced Search

  • Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, 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.
    Citation
    YIN Han, LI Yu, FAN Yu-Chuan, GUO Shuai, HUANG Yuan-Yu, LI Yong, WENG Yu-Hua.Nucleic Acid-driven Protein Degradation: Frontiers of Lysosomal Targeted Degradation Technology[J].,2025,52(1):5-19.Export: BibTex EndNote
  • Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, 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.
    Citation
    ZHU Gui-Zhen, YE Qiao, LUO Yuan, PENG Jie, WANG Lu, YANG Zhao-Ting, DUAN Feng-Sen, GUO Bing-Qian, MEI Zhu-Song, WANG Guang-Yun.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance[J].,2025,52(1):20-31.Export: BibTex EndNote
  • With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects: (1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation; (3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.
    Citation
    ZHANG Yu, CHI Hong-Xia, YANG Wu-Ri-Tu, ZUO Yong-Chun, XING Yong-Qiang.Alternative Polyadenylation in Mammalian[J].,2025,52(1):32-49.Export: BibTex EndNote
  • Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, 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.
    Citation
    CHEN Lin-Fang, ZHANG Jia-Fan, GUO Ye-Ning, HUANG Hui-Zhong, HU Kang-Hong, YAO Chen-Guang.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides[J].,2025,52(1):50-60.Export: BibTex EndNote
  • Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D1-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.
    Citation
    GAO Bo, LAI Yi-Ning, GE Yi-Tong, CHEN Wei.Erk Signaling Pathway in Striatal D2-MSNs: an Essential Pathway for Exercise-induced Improvement in Parkinson’s Disease[J].,2025,52(1):61-71.Export: BibTex EndNote
  • Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α-synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.
    Citation
    LI Yu-Meng, LIU Jing-Kai, CHEN Zi-Xuan, DENG Yu-Lin.Insights on Peripheral Blood Biomarkers for Parkinson’s Disease[J].,2025,52(1):72-87.Export: BibTex EndNote
  • Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an 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.
    Citation
    HOU Li-Juan, GENG Ya-Xuan, LI Ke, HUANG Zhao-Yang, MAO Lan-Qun.Research on The Role of Dopamine in Regulating Sleep and Wakefulness Through Exercise[J].,2025,52(1):88-98.Export: BibTex EndNote
  • Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Among them, rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of the brain neural population and being intimately tied to cognitive and behavioral states. Conversely, aperiodic fluctuations exhibit a power-law decaying spectral trend, unveiling the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in the study of brain aperiodic dynamics. These studies demonstrate that aperiodic activity bears significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. It serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent emerges as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with neural activities at the levels of individual neurons, neuronal ensembles, and neural networks each expletively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic activities. Currently, aperiodic dynamics boasts broad application prospects, not only providing a fresh perspective for investigating brain neural dynamics but also holding immense potential as neural markers in neuromodulation technologies or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, comparatively analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and finally, based on these findings, elaborates on the research prospects of aperiodic dynamics.
    Citation
    HU Zhi-Cai, ZHANG Zhen, WANG Jiang, LI Gui-Ping, LIU Shan, YU Hai-Tao.Brain Aperiodic Dynamics[J].,2025,52(1):99-118.Export: BibTex EndNote
  • Circadian rhythm is an endogenous biological clock mechanism that organisms adapt to the earth"s alternation of day and night, and has a fundamental role in regulating the maintenance of physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body"s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin"s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as 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.
    Citation
    ZHAO Ya-Qi, ZHANG Lin-Lin, MA Xiao-Meng, JIN Zhen-Kai, LI Kun, WANG Min.The Role and Mechanism of Circadian Rhythm Regulation in Skin Tissue Regeneration[J]..Export: BibTex EndNote
  • Parkinson’s disease (PD) is a common neurodegenerative disorder that significantly impacts patients" independence and quality of life, imposing a substantial burden on both individuals and society. Although dopaminergic replacement therapies provide temporary relief from various symptoms, their long-term use often leads to motor complications, limiting overall effectiveness. In recent years, non-invasive deep brain stimulation (DBS) techniques have emerged as promising therapeutic alternatives for PD, offering a means to modulate deep brain regions with high precision without invasive procedures. These techniques include temporal interference stimulation (TIs), low-intensity transcranial focused ultrasound stimulation (LITFUS), transcranial magneto-acoustic stimulation (TMAS), non-invasive optogenetic modulation, and non-invasive magnetoelectric stimulation. They have demonstrated significant potential in alleviating various PD symptoms by modulating neural activity within specific deep brain structures affected by the disease. Among these approaches, TIs and LITFUS have received considerable attention. TIs generate low-frequency interference by applying two slightly different high-frequency electric fields, targeting specific brain areas to alleviate symptoms such as tremors and bradykinesia. LITFUS, on the other hand, uses low-intensity focused ultrasound to non-invasively stimulate deep brain structures, showing promise in improving both motor function and cognition in PD patients. The other three techniques, while still in early research stages, also hold significant promise for deep brain modulation and broader clinical applications, potentially complementing existing treatment strategies. Despite these promising findings, significant challenges remain in translating these techniques into clinical practice. The heterogeneous nature of PD, characterized by variable disease progression and individualized treatment responses, necessitates flexible protocols tailored to each patient"s unique needs. Additionally, a comprehensive understanding of the mechanisms underlying these treatments is crucial for refining protocols and maximizing their therapeutic potential. Personalized medicine approaches, such as the integration of neuroimaging and biomarkers, will be pivotal in customizing stimulation parameters to optimize efficacy. Furthermore, while early-stage clinical trials have reported improvements in certain symptoms, long-term efficacy and safety data are limited. To validate these techniques, large-scale, multi-center, randomized controlled trials are essential. Parallel advancements in device design, including the development of portable and cost-effective systems, will improve patient access and adherence to treatment protocols. Combining non-invasive DBS with other interventions, such as pharmacological treatments and physical therapy, could also provide a more comprehensive and synergistic approach to managing PD. In conclusion, non-invasive deep brain stimulation techniques represent a promising frontier in the treatment of Parkinson"s disease. While they have demonstrated considerable potential in improving symptoms and restoring neural function, further research is needed to refine protocols, validate long-term outcomes, and optimize clinical applications. With ongoing technological and scientific advancements, these methods could offer PD patients safer, more effective, and personalized treatment options, ultimately improving their quality of life and reducing the societal burden of the disease.
    Citation
    ZHANG Yu-Feng, WANG Wei, LU Zi-Jun, Lü Jiao-Jiao, LIU Yu.Application of Non-invasive Deep Brain Stimulation in Parkinson’s Disease Treatment[J]..Export: BibTex EndNote
  • The plasma membrane (PM) plays an essential role in maintaining cell homeostasis, therefore, timely and effective repair of damage to the PM by causes such as mechanical rupture, pore-forming toxins, or pore-forming proteins, is essential for cell survival. PM damage induces cell membrane rupture and stimulates an immune response. However, PM damage caused by regulated cell death processes, including pyroptosis, ferroptosis, and necroptosis, cannot be repaired by simple sealing mechanisms, thus, necessitates specialized repair machinery. Recent research has revealed a PM repair mechanism of regulated cell death injury, mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Here, we review research progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury, with particular focus on processes related to regulated cell death. This overview, and continued work in this field, can provide novel insights into treatment targets for diseases caused by dysregulation of regulated cell death pathways.
    Citation
    FENG Tian-Yang, DENG Le, XU Gou, LI Li, GUO Miao-Miao.ESCRT Mechanism-mediated Repair of Damage Induced by Regulatory Cell Death and Plasma Membrane Damage[J]..Export: BibTex EndNote
  • PANoptosis is a form of programmed cell death that integrates features of pyroptosis, apoptosis, and necroptosis. The core mechanism underlying PANoptosis involves the assembly and activation of the PANoptosome, a multi-protein complex. This process is regulated by key upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), and is influenced by various organelle functions. Targeting the regulatory mechanisms of PANoptosis represents a promising therapeutic approach for modulating this form of cell death. Inflammation is known to play a pivotal role in cardiovascular diseases. Given the highly pro-inflammatory nature of PANoptosis, investigating its contribution to cardiovascular pathophysiology is of great importance. This review summarizes the existing evidence on PANoptosis in cardiovascular diseases, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury. Understanding the role of PANoptosis in these conditions is crucial for advancing clinical knowledge and developing therapeutic strategies for cardiovascular disease pathophysiology.
    Citation
    CHEN Xin-Nong, YANG Ying-Xi, GUO Xiao-Chen, ZHANG Jun-Ping, LIU Na-Wen.PANoptosis: A New Target for Cardiovascular Diseases[J]..Export: BibTex EndNote
  • Objective This study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects.Methods LoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions.Results Confocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126.Conclusion The underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.
    Citation
    CHENG Ya-Jie, ZHOU Xue-Tong, WANG Rui, FANG Jin.Promotion of Angiogenesis by Colorectal Cancer Cell LoVo Derived-exosomes Through Transferring pEGFR[J]..Export: BibTex EndNote
  • Objective As a second messenger in intracellular signal transduction, Ca2+ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca2+ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca2+ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca2+ flux on the electrotaxis of Dictyostelium discoideum.Methods The electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca2+ chelator EGTA, Ca2+-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca2+ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca2+ release was explored using mutants.Results Dictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca2+ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca2+ influx and intracellular Ca2+ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca2+ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca2+ release mediated by caffeine restored the electrotaxis of the Gα2-, Gβ-, and Erk2- mutant cells partially or completely, but did not restore electrotaxis in the - mutant cells.Conclusion Ca2+ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.
    Citation
    WANG Yi-Fan, YUAN Shu-Qin, GAO Run-Chi, ZHAO San-Jun.Ca2+ Release From The Endoplasmic Reticulum Mediates Electric Field Guided Cell Migration of Dictyostelium discoideum[J]..Export: BibTex EndNote
  • Alzheimer"s disease (AD) is one of the most common and severe dementias, severely affecting the physical and mental health and quality of life of patients and imposing a heavy burden on society. Recently, transcranial electrical stimulation (tES) has shown great potential for improving cognitive function in AD. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are the two main forms of tES. The present review mainly summarizes the neuromolecular mechanisms of tDCS and tACS for the improvement of AD. Both techniques show similarities in exerting neuroprotective effects, improving cerebral blood flow to alleviate cerebrovascular dysfunction, affecting the state and function of astrocytes, affecting the levels of amyloid β protein (Aβ) and phosphorylated tau (p-tau) proteins, and affecting neuroplasticity. Specifically, tDCS improves neuronal status, inhibits neuronal apoptosis, improves cholinergic neurons and reduces oxidative stress, 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.
    Citation
    YUAN Yuan, CHEN Zhuang-Fei, FU Yu.Neuromolecular Mechanisms of Transcranial Electrical Stimulation for The Improvement of Alzheimer’s Disease[J]..Export: BibTex EndNote
  • Hypothalamic neural stem cells (htNSCs) are a type of glial-like neural stem cell located in the hypothalamus. They possess the ability to proliferate, differentiate, and migrate into the hypothalamic parenchyma, where they develop into neurons and integrate into neural circuits. HtNSCs play a crucial role in regulating various physiological processes within the adult hypothalamus, including the formation of the blood-hypothalamic barrier (BHB), facilitating the diffusion of small molecules between the blood, cerebrospinal fluid, and hypothalamic parenchyma, sensing blood glucose levels, and regulating neuropeptide release. The aging of htNSCs significantly impacts energy metabolism, sex hormone secretion, and overall hypothalamic function. Transplanting younger htNSCs has been shown to alleviate neurological and skeletal muscle dysfunction associated with aging. In recent years, htNSCs have garnered widespread attention from researchers due to their roles in energy metabolism and their influence on the aging process. This article briefly discusses the classification of htNSCs, the effects of htNSC aging on bodily functions, their association with related diseases, and the regulatory mechanisms that promote htNSC regeneration. Certain interventions that enhance htNSC regeneration and mitigate their aging appear to influence the overall aging phenotype of organisms. In-depth research on htNSC aging may provide valuable insights into the hypothalamus"s role in systemic aging, the gender differences in aging, and offer new approaches and therapeutic targets for managing energy metabolism disorders and treating diseases related to gonadal hormone abnormalities.
    Citation
    ZHANG Yu, ZHANG Xiu-Feng.Aging of Hypothalamic Neural Stem Cells[J]..Export: BibTex EndNote
  • Objective To investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior.Methods Forty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min 85%–90% Smax+1 min 50%–55% Smax, 3–5 cycles, Smax is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sugar-water preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs).Results 4-week HIIT intervention significantly increased the sugar-water preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group.Conclusion The 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.
    Citation
    HAN Yu-Mei, BAO Chun-Hui, ZHANG Zi-Wei, LIANG Jia-Ren, XIANG Huan, TIAN Jun-Sheng, ZHOU Shi, WU Shuang-Shuang.4 Weeks of HIIT Modulates Metabolic Homeostasis of Hippocampal Pyruvate-lactate Axis in CUMS Rats Improving Their Depression-like Behavior[J]..Export: BibTex EndNote
  • In the process of maintaining the steady state of bone tissue, the transcription network and signal pathway of the body play a vital role. These complex regulatory mechanisms need precise coordination to ensure the balance between bone formation and bone absorption. Once this balance is broken, it may lead to pathological changes of bone and cartilage, and then lead to various bone diseases. Therefore, it is of great significance to understand these regulatory mechanisms for the prevention and treatment of bone diseases. In recent years, with the deepening of research, more and more lncRNA has been found to be closely related to bone health. Among them, nuclear accessory spot assembly transcript 1 (NEAT1), as an extremely abundant RNA molecule in mammalian nuclei, has attracted extensive attention. NEAT1 is mainly transcribed from a specific site in human chromosome 11 by RNA polymerase II (RNaseP), which can form two different subtypes NEAT1_1 and NEAT1_2. These two subtypes are different in intracellular distribution and function, but they participate in many biological processes together. Studies have shown that NEAT1 plays a specific role in the process of cell growth and stress response. For example, it can regulate the development of osteoblasts (OB), osteoclasts (OC) and chondrocytes by balancing the differentiation of bone marrow mesenchymal stem cells (BMSCs), thus maintaining the steady state of bone metabolism. This discovery reveals the important role of NEAT1 in bone development and remodeling. In addition, NEAT1 is closely related to a variety of bone diseases. In patients with bone diseases such as osteoporosis (OP), osteoarthritis (OA) and osteosarcoma (OS), the expression level of NEAT1 is different. These differential expressions may be closely related to the pathogenesis and progression of bone diseases. By regulating the level of NEAT1, it can affect a variety of signal transduction pathways, and then affect the development of bone diseases. For example, some studies show that by regulating the expression level of NEAT1, the activity of osteoclasts can be inhibited, and the proliferation and differentiation of osteoblasts can be promoted, thus improving the symptoms of osteoporosis. It is worth noting that NEAT1 can also be used as a key sensor for the prevention and treatment of bone diseases. When exercising or receiving some natural products, the expression level of NEAT1 will change, thus reflecting the response of bones to external stimuli. This feature makes NEAT1 an important target for studying the prevention and treatment strategies of bone diseases. However, although the role of NEAT1 in bone biology and bone diseases has been initially recognized, its specific mechanism and regulatory relationship are still controversial. For example, the expression level, mode of action and interaction with other molecules of NEAT1 in different bone diseases still need further in-depth study. This paper reviews the role of NEAT1 in maintaining bone and cartilage metabolism, and discusses its expression and function in various bone diseases. By combing the existing research results and controversial points, this paper aims to provide new perspectives and ideas for the prevention and treatment of bone diseases, and provide useful reference and enlightenment for future research.
    Citation
    WEN Rui-Ming, HUANG Rui-Qi, CHANG Yi-Xing, XU Ke, YI Xue-Jie.The Role of NEAT1 in Bone and Cartilage Metabolism and Bone Diseases[J]..Export: BibTex EndNote
  • The E2F family consists of transcription factors that mediate the induction of the E2 gene by adenovirus E1a and play a vital role in regulating cell cycle progression, cell proliferation, and cell apoptosis. Given its primary functions in cell proliferation and differentiation, early studies on the E2F family focused on its relationship with cancer. However, as research has expanded, the E2F family has been found to play an independent role in the development of the musculoskeletal system and the mechanisms of related diseases. The E2F family can influence the progression of musculoskeletal diseases by regulating the cell cycle and proliferation of stem cells, osteoblasts, osteoclasts, chondrocytes, and myoblasts, acting as a target gene for various downstream pathways and microRNAs. This review is divided into two parts: the first elaborates on the physiological roles of the E2F family in bone metabolism, skeletal muscle, and cartilage development, while the second summarizes its roles in the pathological processes of osteosarcoma, rheumatoid arthritis, osteoporosis, and muscle-related diseases. During musculoskeletal system development, the E2F family affects bone metabolism by regulating stem cell differentiation, promoting osteoclast differentiation and metabolism, and increasing osteoblast activity or inhibiting osteoblast differentiation. It also regulates mitosis in cartilage, influencing chondrocyte proliferation and differentiation. Additionally, the E2F family is essential for skeletal muscle development, controlling muscle differentiation and myogenesis. In the pathological mechanisms of musculoskeletal diseases, most E2F family members act as downstream targets of various microRNAs, regulating osteosarcoma progression. Some members function independently through their ability to control cell proliferation. The E2F family also contributes to osteoporosis progression by promoting pathological increases in osteoclast activity and affecting osteoblast function. In rheumatoid arthritis and osteoarthritis, E2F family members aggravate inflammation by increasing inflammatory factors through multiple pathways. Moreover, the E2F family plays a crucial role in muscle-related diseases, influencing skeletal muscle regeneration after injury and affecting symptoms of muscular dystrophies. This review provides a comprehensive overview of the physiological roles of the E2F family in the musculoskeletal system and its mechanisms of action in related diseases. By offering a systematic summary and analysis, this article aims to provide a foundation for future research as well as insights for disease diagnosis and treatment.Key words E2F family,bone,muscle,osteosarcoma,osteoarthritis
    Citation
    WANG Shu-Wan, WANG Zhuo.Effects of E2F Family on Musculoskeletal System Development and Related Diseases[J]..Export: BibTex EndNote
  • Objective Gliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm.Methods This retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed.Results Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Postoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%).Conclusion We have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.
    Citation
    MA Qiang, YU Song-Lin, ZHAO Chu-Yue, WANG Xi-Jie, LIN Song, ZUO Zhen-Tao, YU Tao.High-risk Glioma Leading to Changes in The Morphology of Cerebral-spinal Tract Predicts Postoperative Motor Function[J]..Export: BibTex EndNote
  • Objective To investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development, and immune mechanisms of psoriasis-like inflammation in mice.Methods Healthy C57BL/6 mice aged 6–8 weeks were selected and randomly divided into 3 groups: control group(Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues.Results Compared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues.Conclusion RGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
    Citation
    XU Fan, ZHANF Xin-Rui, XIA Yang-Chen, LI Wen-Ting, CHEN Hao, QIN An-Qi, ZHANG Ai-Hong, ZHU Yi-Ran, TIAN Feng, ZHENG Quan-Hui.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Th17[J]..Export: BibTex EndNote
  • Disorders of consciousness (DOC) are pathological conditions characterized by severely suppressed brain function and the persistent interruption or loss of consciousness. Accurate diagnosis and evaluation of DOC are prerequisites for precise treatment. Traditional assessment methods are primarily based on behavioral scales, which are inherently subjective and rely on observable behaviors. Moreover, traditional methods have a high misdiagnosis rate, particularly in distinguishing minimally conscious state (MCS) from vegetative state/unresponsive wakefulness syndrome (VS/UWS). This diagnostic uncertainty has driven the exploration of objective, reliable, and efficient assessment tools. Among these tools, electroencephalography (EEG) has garnered significant attention for its non-invasive nature, portability, and ability to capture real-time neurodynamics. This paper systematically reviews the application of EEG biomarkers in DOC assessment. These biomarkers are categorized into 3 main types: resting-state EEG features, task-related EEG features, and features derived from transcranial magnetic stimulation-EEG (TMS-EEG). Resting-state EEG biomarkers include features based on spectrum, microstates, nonlinear dynamics, and brain network metrics. These biomarkers provide baseline representations of brain activity in DOC patients. Studies have shown their ability to distinguish different levels of consciousness and predict clinical outcomes. However, because they are not task-specific, they are challenging to directly associate with specific brain functions or cognitive processes. Strengthening the correlation between resting-state EEG features and consciousness-related networks could offer more direct evidence for the pathophysiological mechanisms of DOC. Task-related EEG features include event-related potentials, event-related spectral modulations, and phase-related features. These features reveal the brain"s responses to external stimuli and provide dynamic information about residual cognitive functions, reflecting neurophysiological changes associated with specific cognitive, sensory, or behavioral tasks. Although these biomarkers demonstrate substantial value, their effectiveness rely on patient cooperation and task design. Developing experimental paradigms that are more effective at eliciting specific EEG features or creating composite paradigms capable of simultaneously inducing multiple features may more effectively capture the brain activity characteristics of DOC patients, thereby supporting clinical applications. TMS-EEG is a technique for probing the neurodynamics within thalamocortical networks without involving sensory, motor, or cognitive functions. Parameters such as the perturbational complexity index (PCI) have been proposed as reliable indicators of consciousness, providing objective quantification of cortical dynamics. However, despite its high sensitivity and objectivity compared to traditional EEG methods, TMS-EEG is constrained by physiological artifacts, operational complexity, and variability in stimulation parameters and targets across individuals. Future research should aim to standardize experimental protocols, optimize stimulation parameters, and develop automated analysis techniques to improve the feasibility of TMS-EEG in clinical applications. Our analysis suggests that no single EEG biomarker currently achieves an ideal balance between accuracy, robustness, and generalizability. Progress is constrained by inconsistencies in analysis methods, parameter settings, and experimental conditions. Additionally, the heterogeneity of DOC etiologies and dynamic changes in brain function add to the complexity of assessment. Future research should focus on the standardization of EEG biomarker research, integrating features from resting-state, task-related, and TMS-EEG paradigms to construct multimodal diagnostic models that enhance evaluation efficiency and accuracy. Multimodal data integration (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.
    Citation
    WANG Zhong-Peng, LIU Jia, CHEN Long, XU Min-Peng, MING Dong.Applications of EEG Biomarkers in The Assessment of Disorders of Consciousness[J]..Export: BibTex EndNote
  • Polyketides(PKs) and non-ribosomal peptides are the most important drug-leads for human, animal, and plant diseases. The conserved modular architectures and biosynthetic assembly line of polyketide synthases (PKS) and non-ribosomal peptide synthases (NRPS) endow PKs and NRPs with extremely diverse structures and activities and bring infinite possibilities to edit and modify the backbone structure of PKs and NRPs by adding, removing, inactivating and replacing PKS/NRPS modules or domains. The biosynthetic machinery of microbial polyketide natural products has evolved delicately with specific recognition and efficient catalysis of upstream intermediates by downstream enzymes/domains. Therefore, manipulations of PKS/NRPS and their related tailoring enzymes usually lead to attenuated production or abolished accumulation of intermediates with modified structures. As the terminal domain of most PKS and NRPS, thioesterases (TEs) play crucial roles in substrate selection during the chain release of these bioactive natural products, serving as pivotal bottleneck steps in their late-stage biosynthesis. TEs mainly perform chain hydrolysis or ester transfer reactions by nucleophilic attack of foreign nucleophiles such as H2O. 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 thioesterases (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 thioesterase was identified in the chain release of polyether backbones, such as monensin and nanchangmycin. Since 2001, more than twenty 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 thioesterases, which further promotes the understanding of the chain release mechanism of natural products and better served the rational design of thioesterases. Previous articles have systematically reviewed the structure, function, and regulatory mechanism of different thioesterase 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 thioesterases, 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 thioesterases, 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 thioesterases, as well as its rational design for improved chain release of unnatural products.
    Citation
    ZHOU Yu-Cong, SHI Ting, LU Chen-Yang, Liu Hao, BAI Lin-Quan.Structural Elucidation and Catalytic Mechanisms of PKS and NRPS Thioesterase Domains[J]..Export: BibTex EndNote
  • Epilepsy is a chronic neurological disease caused by abnormal synchronous discharge of the brain, which is characterized by recurrent and transient neurological abnormalities, mainly manifested as loss of consciousness and limb convulsions, and can occur in people of all ages. At present, anti-epileptic drugs (AEDs) are still the main means of treatment, but their efficacy is limited by the problem of drug resistance, and long-term use can cause serious side effects, such as cognitive dysfunction and vital organ damage. Although surgical resection of epileptic lesions has achieved certain results in some patients, the high cost and potential risk of neurological damage limit its scope of application. Therefore, the development of safe, accurate and personalized non-invasive treatment strategies has become one of the key directions of epilepsy research. In recent years, photobiomodulation (PBM) has gained significant attention as a promising non-invasive therapeutic approach. PBM uses light of specific wavelengths to penetrate tissues and interact with photosensitive molecules within cells, thereby modulating cellular metabolic processes. Research has shown that PBM can enhance mitochondrial function, promote ATP production, improve meningeal lymphatic drainage, reduce neuroinflammation, and stimulate the growth of neurons and synapses. These biological effects suggest that PBM not only holds the potential to reduce the frequency of seizures but also to improve the metabolic state and network function of neurons, providing a novel therapeutic avenue for epilepsy treatment. Compared to traditional treatment methods, PBM is non-invasive and avoids the risks associated with surgical interventions. Its low risk of significant side effects makes it particularly suitable for patients with drug-resistant epilepsy, offering new therapeutic options for those who have not responded to conventional treatments. Furthermore, PBM"s multi-target mechanism enables it to address a variety of complex etiologies of epilepsy, demonstrating its potential in precision medicine. In contrast to therapies targeting a single pathological mechanism, PBM"s multifaceted approach makes it highly adaptable to different types of epilepsy, positioning it as a promising supplementary or alternative treatment. Although animal studies and preliminary clinical trials have shown positive outcomes with PBM, its clinical application remains in the exploratory phase. Future research should aim to elucidate the precise mechanisms of PBM, optimize light parameters, such as wavelength, dose, and frequency, and investigate potential synergistic effects with other therapeutic modalities. These efforts will be crucial for enhancing the therapeutic efficacy of PBM and ensuring its safety and consistency in clinical settings. This review summarizes the types of epilepsy, diagnostic biomarkers, the advantages of PBM, and its mechanisms and potential applications in epilepsy treatment. The unique value of PBM lies not only in its multi-target therapeutic effects but also in its adaptability to the diverse etiologies of epilepsy. The combination of PBM with traditional treatments, such as pharmacotherapy and neuroregulatory techniques, holds promise for developing a more comprehensive and multidimensional treatment strategy, ultimately alleviating the treatment burden on patients. PBM has also shown beneficial effects on neural network plasticity in various neurodegenerative diseases. The dynamic remodeling of neural networks plays a critical role in the pathogenesis and treatment of epilepsy, and PBM"s multi-target mechanism may promote brain function recovery by facilitating neural network remodeling. In this context, optimizing optical parameters remains a key area of research. By adjusting parameters such as wavelength, dose, and frequency, researchers aim to further enhance the therapeutic effects of PBM while maintaining its safety and stability. Looking forward, interdisciplinary collaboration—particularly in the fields of neuroscience, optical engineering, and clinical medicine—will drive the development of PBM technology and facilitate its transition from laboratory research to clinical application. With the advancement of portable devices, PBM is expected to provide safer and more effective treatments for epilepsy patients and make a significant contribution to personalized medicine, positioning it as a critical component of precision therapeutic strategies.
    Citation
    LI Ao-Yun, LU Zhan-Chuang, CAO Li, CHEN Si, JIANG Hui, CHEN Chang-Chun, CHEN Lei.The Adoption of Non-invasive Photobiomodulation in The Treatment of Epilepsy[J]..Export: BibTex EndNote
  • The 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 Hnf3α (hepatocyte nuclear factor 3α), 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, the 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.
    Citation
    WANG Jing-Han, YANG Li-Xin.The Function of FoxA Gene in Evolution, Development, and Disease[J]..Export: BibTex EndNote
  • Cell models can simulate a variety of life states and disease development, including single-cell, 2D cell, 3D multicellular spheroids and organoids. They are important tools for resolving complex biochemical problems. Using cell as an experimental model, mass spectrometry technology combined with morphological analysis can obtain quantitative changes and spatial distribution changes of a variety of life substances at the spatio-temporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, metals, etc. It is possible to investigate cell-cell interaction, microenvironment of tumor cell and cell bio-information heterogeneity. In this review, we summarize the research of cell imaging based on mass spectrometry technology, including the selection and preparation of cell models, cell model morphological analysis, mass spectrometry spatial omics technology, mass cytometry and applications. We also propose the difficult problems and prospect the future development in this filed.
    Citation
    ZHOU Peng, WANG Xin, LUO Qian, ZHAO Chao.Mass Spectrometry-based Cell Imaging[J]..Export: BibTex EndNote
  • Objective This study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes.Methods Structural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments.Results The collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments.Conclusion The antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.
    Citation
    ZHU Zheng, CHEN Zheng-Shan, ZHANG Guan-Ying, FANG Ting, FAN Pu, BI Lei, CUI Yue, LI Ze-Ya, SU Chun-Yi, CHI Xiang-Yang, YU Chang-Ming.Structural and Spatial Analysis of The Recognition Relationship Between Influenza A Virus Neuraminidase Antigenic Epitopes and Antibodies[J]..Export: BibTex EndNote
  • Objective Molecular property prediction plays a crucial role in drug development, especially in virtual screening and compound optimization. The advancement of artificial intelligence (AI) technologies has led to the emergence of numerous deep learning-based methods, which have demonstrated significant potential in improving molecular property prediction. Nonetheless, acquiring labeled molecular data can be both costly and time-consuming. The scarcity of labeled data poses a substantial challenge for supervised machine learning models to effectively generalize across the vast chemical space.Methods In order to overcome the above limitations, in this work, we proposed a novel Bert and GCN-based Multimodal Fusion method (called BGMF) to predict molecular property. BGMF can extract comprehensive molecular representation from atomic sequences, molecular fingerprint sequences, and molecular graph data and combine them through pre-training and fine-tuning. Specifically, our method consists of the following three main parts. (1) Molecular feature extraction; (2) Bert-GCN based pre-training; (3) fine-tuning. During molecular feature extraction, the Morgan algorithm is employed to generate the molecular fingerprints, transforming input SMILES strings of drugs into molecular fingerprint sentences. Simultaneously, atom sentences are created based on the atom indices within the molecule, Consequently, drug molecule are represented as both molecular fingerprint sentences and atom sentences. In the pre-training section, BGMF utilizes a self-supervised learning strategy, specifically masked molecular fingerprint and masked atom recovery, on a large dataset of unlabeled data using the Bert model. Here, molecular graph data is incorporated by merging graph convolutional neural networks with the Bert model, effectively combining the global "word" features of drug molecules with the local topological features of molecular graphs. We have also developed a dual decoder for atomic and molecular fingerprints to amplify molecular feature expression. Finally, in the fine-tuning stage, the addition of a pooling layer and task-specific fully connected neural networks allows the pre-trained module to be applied to a variety of downstream tasks for molecular property prediction.Results To validate the effectiveness of our BGMF, we conduct several experiments on 43 molecular attribute prediction tasks across 5 datasets. In comparison with other recent state-of-the-art methods, our BGMF achieves the best results in terms of area under the ROC curve (AUC). We also verified the generalization performance of the BGMF model by constructing independent test dataset, show that the BGMF model has the best generalization performance. Additionally, we conduct the ablation studies to demonstrate the effect of atomic sequence, molecular fingerprint sequence, GCN based molecular graph module, and pre-training module on the overall performance of the model.Conclusion In this paper, we propose a novelmethod for drug molecular attribute prediction named BGMF which integrating the molecular graph data into tasks of molecular fingerprint recovery and masked atom recovery by combining graph convolutional neural network with the Bert model. The molecular fingerprint representations generated by BGMF were visualized using t-SNE, revealing that the BGMF model effectively captures the intrinsic structure and features of molecular fingerprints.
    Citation
    YAN Xiao-Ying, JIN Yan-Chun, FENG Yue-Hua, ZHANG Shao-Wu.A Multimodal Fusion Drug Molecular Attribute Prediction Method Based on Bert and GCN[J]..Export: BibTex EndNote
  • RNA-binding proteins (RBPs) are ubiquitous components within cells, fulfilling essential functions in a myriad of biological processes. These proteins interact with RNA molecules to regulate gene expression at various levels, including transcription, splicing, transport, localization, translation, and degradation. Understanding the intricate network of RBP-RNA interactions is crucial for deciphering the complex regulatory mechanisms that govern cellular function and organismal development. UV Cross-linking and Immunoprecipitation (CLIP) stands out as a powerful approach designed to map the precise locations where RBPs bind to RNA. By using ultraviolet (UV) light to create covalent bonds between proteins and RNA, followed by immunoprecipitation to isolate the protein-RNA complexes, researchers can identify the direct targets of specific RBPs. The advent of high-throughput sequencing technologies has revolutionized CLIP, enabling the identification of not only the types but also the exact sequences of RNA bound by RBPs on a genome-wide scale. The evolution of CLIP has led to the development of specialized variants, each with unique features that address specific challenges and expand the scope of what can be studied. High-throughput sequencing CLIP (HITS-CLIP) was one of the first advancements, significantly increasing the throughput and resolution of RNA-protein interaction mapping. Photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) introduced the use of photoactivatable ribonucleosides to enhance cross-linking efficiency and specificity, reducing background noise and improving the detection of low-abundance RNA-protein interactions. Individual-nucleotide resolution CLIP (iCLIP) further refined the technique, achieving unprecedented precision by resolving individual nucleotides involved in RBP binding, which is particularly valuable for studying the fine details of RNA structure and function. Despite the remarkable progress, there remains room for improvement in CLIP technology. Researchers continue to seek methods to increase sensitivity, reduce technical variability, and improve the reproducibility of results. Advances in sample preparation, data analysis algorithms, and computational tools are critical for addressing these challenges. Moreover, the application of CLIP to more diverse biological systems, including non-model organisms and clinical samples, requires the development of tailored protocols and the optimization of existing ones. Looking forward, the field of RNA biology is poised to benefit greatly from ongoing innovations in CLIP technology. The exploration of non-canonical RNA-protein interactions, such as those involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), promises to reveal new layers of cellular regulation and may lead to the discovery of novel therapeutic targets. Furthermore, integrating CLIP data with other omics approaches, such as proteomics and metabolomics, will provide a more comprehensive understanding of the dynamic interplay between RNA and its binding partners within the cell. In conclusion, the continuous refinement and expansion of CLIP techniques have not only deepened our knowledge of RNA biology but have also opened up new avenues for investigating the molecular underpinnings of health and disease. As the technology matures, it is expected to play an increasingly pivotal role in both basic and applied research, contributing to the advancement of medical science and biotechnology.
    Citation
    ZHAO Jia-Min, LU Cheng-Jiang, YANG Ming, Buhe Nashun, WANG Gang.The Refinement and Innovation of The UV Cross-linking and Immunoprecipitation[J]..Export: BibTex EndNote
  • Objective In the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by The Internal Transcribed Spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms.Methods ITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while Analysis of Similarities (ANOSIM) and Permutational Multivariate Analysis of Variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using LEfSe (Linear Discriminant Analysis Effect Size) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples.Results Among the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted.Conclusion Significant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.
    Citation
    ZHANG Wen-Jun, FENG Yao-Sen, PENG Jia-Jin, FENG Kai, Deng Ye, KANG Ke-Lai, WANG Le.Geographical Inference Study of Dust Samples From Four Cities in China Based on ITS2 Sequencing[J]..Export: BibTex EndNote
  • The somatosensory system, including modalities such as touch, temperature, and pain, is essential for perceiving and interacting with the environment. When individuals encounter different somatosensory modalities, they interact through a process called multimodal somatosensory integration. This integration is essential for accurate perception, motor coordination, pain management, and adaptive behavior. Disruptions in this process can lead to a variety of sensory disorders and complicate rehabilitation efforts. However, research on the behavioral patterns and neural mechanisms underlying multimodal somatosensory integration remains limited. According to previous studies, multimodal somatosensory integration can result in facilitative or inhibitory effects depending on factors like stimulus type, intensity, and spatial proximity. Facilitative effects are observed primarily when stimuli from the same sensory modality (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.
    Citation
    ZHANG Yu, ZHANG Ming, KONG Ya-Zhuo.The Effects of Facilitation and Inhibition During Multimodal Somatosensory Integration[J]..Export: BibTex EndNote
  • Objective Obesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer"s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved.Methods A total of sixty 6-week-old male C57BL/6 mice, weighing between 20–30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totaling 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axons, dendrites, dendritic spines, c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1 beta (IL-1β), and major histocompatibility complex II (MHC-II) positive cells.Results Mice with high-fat diet-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the high-fat diet-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the high-fat diet-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the high-fat diet-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the high-fat diet-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of high-fat diet-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a high-fat diet.Conclusion Treadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in high-fat diet-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against high-fat diet-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.
    Citation
    YANG Meng-Si, SHU Lin-Jie, WANG Chao-Ge, CHENG Ran, MU Lian-Wei, LIAO Jing-Wen.Treadmill Exercise Alleviates Memory Impairment by Enhancing Hippocampal Neuronal Structural Plasticity and Neurogenesis in High-fat Diet-induced Obese Mice[J]..Export: BibTex EndNote
  • Objective To investigate whether 2,3,5,4"-Tetrahydroxystilbene-2-O-β-glucoside (TSG) ameliorated polycystic ovary syndrome (PCOS)-like characteristics by inhibiting inflammation.Methods PCOS models were established by injecting subcutaneously with dehydroepiandrosterone into female Sprague-Dawley rats, followed by receiving intraperitoneal injection of TSG. The granular cells (GCs) KGN were transfected with small interfering RNAs (si-NC and si-CYP19A1). The cells were preincubated with lipopolysaccharide (LPS) and then treated with or without TSG. The estrous cycle was monitored using vaginal exfoliated cells. The morphology of ovarian follicles was analyzed by H&E staining. ELISA was used to analyze estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), IL-6, TNF-α, AGEs, CRP and Omentin-1 levels in serum. Immunohistochemistry was performed to analyze PCNA and CYP19A1 expressions in the GCs of ovaries. Tunel staining was executed to detect the apoptosis of GCs. qPCR and Western blot were implemented to measure the expression of CYP19A1 in the ovaries and transfected cells. qPCR was used to analyzed the expression of IL-6 and TNF-α in the transfected cells treated with LPS and TSG.Results The estrous cycles were restored in TSG-treated PCOS. Compared with PCOS, the sinus follicles were reduced and corpus luteums were increased in TSG-treated PCOS. TSG-treated PCOS showed increased E2, and decreased T and LH compared with PCOS. Pro-inflammatory factors (IL-6, TNF-α, CRP and AGEs) were decreased, and anti-inflammatory factor (Omentin-1) was increased in TSG-treated PCOS compared with those in PCOS. TSG could partially inhibit decrease of PNCA-positive GCs and increase of Tunel-positive GCs caused by PCOS. The CYP19A1 expression of GCs in TSG-treated PCOS was upregulated compared with PCOS. The expressions of IL-6 and TNF-α in si-CYP19A1 cells were increased compared with si-NC cells. Compared with cells (si-NC and si-CYP19A1) treated without LPS, the expressions of IL-6 and TNF-α cells were increased, and the expression of CYP19A1 was downregulated in LPS-preincubated cells. Compared with cells treated with LPS, the expression of IL-6 and TNF-α were decreased, and the expression of CYP19A1 was increased in cells treated with LPS and TSG. Compared with si-NC cells treated with LPS and TSG, the expressions of IL-6 and TNF-α cells were increased in the si-CYP19A1 cells treated with LPS and TSG.Conclusion TSG could alleviate PCOS-like characteristics by inhibiting inflammatory response via increasing the expression of CYP19A1 in GCs.
    Citation
    YAO Jian-Feng, XU Bo, LIU Pin-Yue, CHENG Di, WEI Le, PAN Xin-Yun, MO Zhong-Cheng, LI Ming.2,3,5,4"-Tetrahydroxystilbene-2-O-β-glucoside Alleviates PCOS-like Characteristics by Inhibiting Inflammatory Response via Increasing The Expression of CYP19A1 in Granular Cells of Sinus Follicles[J]..Export: BibTex EndNote
  • In recent years, due to the development of radiotherapy technology and nuclear energy, people have paid more and more attention to the various effects of ionizing radiation on organisms. Ionizing radiation can induce protein, DNA and other biological macromolecules to damage, resulting in apoptosis, senescence, cancer and a series of changes. For a long time, it has been believed that the main target of ionizing radiation damage is DNA in the nucleus. However, it has been reported in recent years that ionizing radiation has both direct and indirect effects, and the theory of ROS damage in the indirect effects believes that ionizing radiation has target uncertainty, so it is not comprehensive enough to evaluate only the DNA damage in the nucleus. It has been reported that ionizing radiation can cause damage to organelles as well as damage to cells. Mitochondria are important damaged organelles because mitochondria occupy as much as 30% of the entire cell volume in the cytoplasm, which contains DNA and related enzymes that are closely related to cellular ATP synthesis, aerobic respiration and other life activities. What is more noteworthy is that mitochondria are the only organelles in which DNA exists in the human body, which makes researchers pay attention to various damage to mitochondrial DNA caused by ionizing radiation (such as double-strand breaks, base mismatching, and fragment loss). Although these damages also occur in the nucleus, mitochondrial DNA is more severely damaged than nuclear DNA due to its lack of histone protection, so mitochondria are important targets of ionizing radiation damage in addition to the nucleus. Mitochondrial DNA is not protected by histones and has little repair ability. When exposed to ionizing radiation, common deletions occur at an increased frequency and are passed on to offspring. For large-scale mitochondrial DNA damage, mitochondria indirectly compensate for the amount of damaged DNA by increasing the number of DNA copies and maintaining the normal function of mitochondrial DNA. Mitochondria are in a state of oxidative stress after exposure to ionizing radiation, and this oxidative stress will promote the change in mitochondrial function. When mitochondria are damaged, the activity of proteins related to aerobic respiration decreases, and oxidative respiration is inhibited to a certain extent. At the same time, a large amount of active superoxide anions are continuously produced to stimulate mitochondrial oxidative stress, and the signal of such damage is transmitted to the surrounding mitochondria, resulting in a cascade of damage reaction, which further activates the signalling pathway between mitochondria and nucleus. The cell nucleus is also in a state of oxidative stress, and finally, the level of free radicals is high, causing secondary damage to the genetic material DNA of mitochondria and the nucleus. In this paper, the damage effects of ionizing radiation on mitochondria are reviewed, to provide a new idea for radiation protection.
    Citation
    TIAN Lian-Chen, YUAN Ya-Yi, DANG Xu-Hong.Mitochondria: The Target of Ionizing Radiation Damage[J]..Export: BibTex EndNote
  • Objective To characterize transmembrane protein (TMEM68) in an alternative triacylglycerol (TAG) biosynthesis pathway, and determine the interplay between TMEM68 and the canonical TAG synthase acyl-CoA:diacylglycerol acyltransferase (DGAT).Methods Effects of exogenous fatty acid and monoacylglycerol on TAG synthesis and lipid droplet (LD) formation in TMEM68 overexpression and knockout cells treated with DGAT inhibitor or not were investigated by comparing LD morphology, Oil Red O staining area, and TAG levels. LDs were stained with fluorescence dye and observed by confocal fluorescence microscopy. TAG levels were determined with an enzyme-based triglyceride assay kit. Colocalization of TMEM68 and DGAT1 was detected by co-expression and confocal fluorescence microscopy and their interaction was determined by co-immunoprecipitation. RT-qPCR and immunoblotting assay were used to detect the expression of DGAT1.Results The synthesis of TAG catalyzed by TMEM68 was independent of DGAT activity. Surplus exogenous fatty acids and monoacylglycerol promoted TAG synthesis mainly through DGAT in human neuroblastoma cells. The LDs formed by TMEM68 were different in morphology from those by DGAT. In addition, TMEM68 and DGAT1 colocalized in the same endoplasmic reticulum (ER) compartment but did not interact physically. TMEM68 overexpression reduced the expression of DGAT1, the major DGAT enzyme involved in TAG synthesis, while TMEM68 knockout had little impact.Conclusion The TMEM68-mediated TAG synthesis pathway has distinct features from the canonical DGAT pathway, however TMEM68 and DGAT may coregulate intracellular TAG levels.
    Citation
    YU Qing, FU Yang-Yang, ZENG Fan-Si, Pang Hui-Min, Huang Fei-Fei, Chang Ping-An.Contribution of Transmembrane Protein 68 to Triglyceride Synthesis and Lipid Droplet Formation Differs From Diacylglycerol Acyltransferase[J]..Export: BibTex EndNote
  • The pathogenesis of cardiovascular diseases (CVD) is complex, and dynamic imbalances in protein acylation modification are significantly associated with the development of CVD. In recent years, most studies on exercise-regulated protein acylation modifications to improve cardiovascular function have focused on acetylation and lactylation. Protein acylation modifications are usually affected by exercise intensity. High-intensity exercise directly affects oxidative stress and cellular energy supply, such as changes in ATP and NAD+ levels; moderate-intensity exercise is often accompanied by improvements in aerobic metabolism, such as fatty acid β-oxidation and TCA cycle, which modulate mitochondrial biogenesis. The above processes may affect the acylation status of relevant regulatory enzymes and functional proteins, thereby altering their function and activity and triggering signaling cascades to adapt to exercise"s metabolic demands and stresses. Exercise regulates the levels of acylation modifications of H3K9, H3K14, H3K18, and H3K23, which are involved in regulating the transcriptional expression of genes involved in oxidative stress, glycolysis, inflammation, and hypertrophic response by altering chromatin structure and function. Exercise can regulate the acylation modification of non-histone-specific sites in the cardiovascular system involved in mitochondrial function, glycolipid metabolism, fibrosis, protein synthesis, and other biological processes, and participates in the regulation of protein activity and function by altering the stability, localization, and interaction of proteins, and ultimately works together to achieve the improvement of cardiovascular phenotypes and biological functions. Exercise affects acyl donor concentration, acyltransferase, and deacetylase expression and activity by influencing acyl donor concentration, acyltransferase, and deacetylase. Exercise regulates the abundance of acyl donors such as acetyl coenzyme A, propionyl coenzyme A, butyryl coenzyme A, succinyl coenzyme A, and lactoyl coenzyme A by promoting glucose and lipid metabolism and improving intestinal bacterial flora, which in turn affects protein acylation modification, accelerates oxidative decarboxylation of pyruvic acid in the body, and activates the energy-sensing molecule, adenosine monophosphate-activated protein kinase (AMPK), to improve cardiovascular function. Exercise may affect protein acylation modifications in the cardiovascular system by regulating the activity and expression of adenoviral E1A binding protein of 300 kDa (p300)/cyclic adenosine monophosphate response element-binding protein (CBP), general control nonderepressible 5-related N-acetyltransferases (GNAT), and alanyl-transfer t-RNA synthetase (AARS) , which in turn improves cardiovascular function. The relationship between exercise and cardiovascular deacetylases has attracted much attention, with SIRT1 and SIRT3 of the silence information regulator (SIRT) family of proteins being the most studied. Exercise may exert transient or long-term stable cardiovascular protective benefits by promoting the enzymatic activity and expression of SIRT1, SIRT3, and HDAC2, inhibiting the enzymatic activity and expression of HDAC4, and mediating the deacylation of metabolic regulation-related enzymes, cytokines, and molecules of signaling pathways. This review introduces the role of protein acylation modification on CVD and the effect of exercise-mediated protein acylation modification on CVD. Based on the existing studies, it analyzes the possible mechanisms of exercise-regulated protein acylation modification to improve CVD from the perspectives of acylation modification donors, acyltransferases, and deacetylases. Deciphering the regulation of cardiovascular protein acylation and modification by exercise and exploring the essential clues to improve cardiovascular disease can enrich the theoretical basis for exercise to promote cardiovascular health. However, it is also significant for developing new cardiovascular disease prevention and treatment targets.
    Citation
    LI Feng-Yi, HUANG Wen-Hua, ZHANG Jing.Exercise Regulates Protein Acylation Modifications to Enhance Cardiovascular Diseases Outcomes[J]..Export: BibTex EndNote
  • Objective To construct a multiplex amplification system based on the capillary electrophoresis platform for simultaneous detection of saliva, semen, and vaginal secretions using tissue-specific RNA markers. The aim is to identify the tissue origin of suspicious body fluid stains found at crime scenes and determine whether the body fluid stains at the crime scene are one or several types among saliva, semen, and vaginal secretions.Methods Thirty saliva samples, forty semen samples, and forty vaginal secretion samples (half from 2015 and half from 2024) were collected from healthy adult volunteers. Through primer designing, system formulation, and PCR condition optimization, a multiplex fluorescent amplification system was constructed. The specificity, sensitivity, and detection ability for mixed samples of this system were investigated, and it was tested using real crime scene materials. In the primer design stage, to reduce the requirements for RNA template quality, the amplification products were set within 80–300 bp. In the system formulation stage, dominant and subordinate primers were mainly considered. By reducing the concentration of dominant primers and increasing that of subordinate primers, a capillary electrophoresis spectrum with an appropriate peak height ratio was finally obtained. Additionally, gradient experiments were designed to adjust the concentrations of PCR reagents and PCR amplification conditions, and multiple versions of DNA amplification enzymes were optimized to achieve the best experimental results.Results Through statistical analysis, there was no significant difference in the capillary electrophoresis of the 3 types of body fluid samples from the two years (2015 and 2024), demonstrating that the sample preservation method in this study can preserve samples for a relatively long time. The composite amplification system constructed in this study exhibited high specificity for all 3 types of body fluid, with no cross-reactions between the markers of each type of body fluid. The minimum detection thresholds for the three types of body fluid reached 0.002 9 ng/μl, 0.001 5 ng/μl, and 0.42 ng/μl, respectively. This system also had a high degree of discrimination for mixed samples, especially for semen-saliva mixtures, where each body fluid marker could still be successfully detected when the concentration ratio of semen to saliva was 100:1. Meanwhile, in the two actual cases presented in this article, the application of this composite amplification system performed outstandingly.Conclusion The composite amplification detection system constructed in this study can achieve the correct screening of saliva, semen, and vaginal secretions, overcoming the problems such as low specificity and sensitivity of marker tests and unbalanced RFU values of each marker in previous studies. The specificity and sensitivity meet the practical work requirements, and the operation is simple. It provides an analytical and identification method for body fluid stains in actual case and is applicable to the identification of the tissue origin of biological evidence at crime scenes involving sexual assault, indecent assault, and other criminal acts. In the future, more types of body fluid markers will be screened to expand the types of body fluids detected by the system, and body fluid-specific cSNP and cInDel genetic markers will be introduced to infer the sources (individuals and types) of mixed and complex stains more accurately.
    Citation
    BAI Yi-Fan, ZHAO He-Miao, CHEN Jing, LIU Hong-Di, YANG Rui-Qin, WANG Chong.Research on The Construction and Application of Multiple Fluorescence Amplification System for Three Kinds of Stains[J]..Export: BibTex EndNote
  • Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression—phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and type 2 diabetes. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.
    Citation
    WANG Yong-Lang, CHEN Si-Si, LI Qi-Long, Gong Yu, DUAN Xin-Yue, DUAN Ye-Hui, GUO Qiu-Ping, LI Feng-Na.Heterogeneity of Adipose Tissue From The Perspective of Single-cell Transcriptomics[J]..Export: BibTex EndNote
  • Ferroptosis, a programmed cell death modality discovered and defined in the last decade, mainly induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compunds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--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 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 (MOF) 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.
    Citation
    WANG Xin-Die, FENG Da-Li, CUI-Xiang, ZHOU Su, ZHANG Peng-Fei, GAO Zhi-Qiang, ZOU Li-Li, WANG Jun.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer[J]..Export: BibTex EndNote
  • Objective The aim of this study was to investigate the prophylactic effects of caloric restriction (CR) on lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) and to elucidate the mechanisms underlying the cardioprotective actions of CR. This research aims to provide innovative strategies and theoretical support for the prevention of SCM.Methods A total of forty-eight 8-week-old male C57BL/6 mice, weighing between 20–25 g, were randomly assigned to 4 distinct groups, each consisting of 12 mice. The groups were designated as follows: CON (control), LPS, CR, and CR+LPS. Prior to the initiation of the CR protocol, the CR and CR+LPS groups underwent a 2-week acclimatization period during which individual food consumption was measured. The initial week of CR intervention was set at 80% of the baseline intake, followed by a reduction to 60% for the subsequent 5 weeks. After 6-week CR intervention, all 4 groups received an intraperitoneal injection of either normal saline or LPS (10 mg/kg). Twelve hours post-injection, heart function was assessed, and subsequently, heart and blood samples were collected. Serum inflammatory markers were quantified using enzyme-linked immunosorbent assay (ELISA). The serum myocardial enzyme spectrum was analyzed using an automated biochemical instrument. Myocardial tissue sections underwent hematoxylin and eosin (HE) staining and immunofluorescence (IF) staining. Western blot analysis was used to detect the expression of protein in myocardial tissue, including inflammatory markers (TNF-α, IL-9, IL-18), oxidative stress markers (iNOS, SOD2), pro-apoptotic markers (Bax/Bcl-2 ratio, CASP3), and SIRT3/SIRT6.Results 12 hours after LPS injection, there was a significant decrease in ejection fraction (EF) and fractional shortening (FS) ratios, along with a notable increase in left ventricular end-systolic diameter (LVESD). Morphological and serum indicators (AST, LDH, CK, and CK-MB) indicated that LPS injection could induce myocardial structural disorders and myocardial injury. Furthermore, 6-week CR effectively prevented the myocardial injury. LPS injection also significantly increased the circulating inflammatory levels (IL-1β, TNF-α) in mice. IF and Western blot analyses revealed that LPS injection significantly up-regulating the expression of inflammatory-related proteins (TNF-α, IL-9, IL-18), oxidative stress-related proteins (iNOS, SOD2) and apoptotic proteins (Bax/Bcl-2 ratio, CASP3) in myocardial tissue. 6-week CR intervention significantly reduced circulating inflammatory levels and downregulated the expression of inflammatory, oxidative stress-related proteins and pro-apoptotic level in myocardial tissue. Additionally, LPS injection significantly downregulated the expression of SIRT3 and SIRT6 proteins in myocardial tissue, and CR intervention could restore the expression of SIRT3 proteins.Conclusion A 6-week CR could prevent LPS-induced septic cardiomyopathy, including cardiac function decline, myocardial structural damage, inflammation, oxidative stress, and apoptosis. The mechanism may be associated with the regulation of SIRT3 expression in myocardial tissue.
    Citation
    ZHANG Ming-Chen, ZHANG Hui, LI Ting-Ting, CHEN Ming-Hua, WANG Xiao-Wen, SUN Zhong-Guang.6-Week Caloric Restriction Improves Lipopolysaccharide-induced Septic Cardiomyopathy by Modulating SIRT3[J]..Export: BibTex EndNote
  • Transmembrane proteins (TMEM) are a type of membrane protein. Most proteins in this family are located in the phospholipid bilayer of the cell membrane, while a smaller portion is found in the membranes of cellular organelles. Transmembrane protein 43 (TMEM43) is a member of the TMEM protein family and is encoded by the 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.
    Citation
    CUI Rong-Jie, WEI Jing-Ru, LI Yun-Long.The Current Status of Research on The TMEM43 Gene and Its Association With Hearing Loss[J]..Export: BibTex EndNote
  • Depression, also known as major depressive disorder (MDD), is an emotional disorder characterized by low mood, decreased interest, and lack of energy, which imposes a heavy burden on families and society. Neuromodulation technology has made significant progress in improving depressive symptoms by using invasive or non-invasive methods, such as electricity and magnetism, to regulate neural activity in specific areas of the brain. Determining objective evaluation indicators can provide reliable basis for the development of neural regulation strategies and efficacy evaluation in MDD. This article systematically reviews the latest application progress of non-invasive neural regulation techniques such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (TES), and transcranial ultrasound stimulation (TUS), as well as invasive neural regulation techniques such as deep brain stimulation (DBS), optogenetics, and chemical genetics in MDD. The focus is on exploring behavioral, neuroimaging, and neurophysiological evaluation indicators of neural regulation, providing direction for the development of precise and personalized neural regulation schemes and assessment tools for MDD in the future.
    Citation
    LI Yu-Qing, JIE Hui-Cong, GUOJIANG Zi-Hui, LIU Tiao-Tiao, ZHENG Xu-Yuan.Application and Evaluation of Neuromodulation in Major Depressive Disorder[J]..Export: BibTex EndNote
  • Drug addiction is a worldwide issue that threaten social stability and development. It has been proved to be a chronic, relapsing disease that results from the prolonged effects of drugs on the various neural networks. Over time, plenty of attention has been paid to find new approaches to enhance the sensitivity and accuracy of assessment on addiction. In recent years, researchers found that the expression of neurotransmitters and their receptors in some peripheral blood immunocyte may reflect their expression in the brain. By analyzing the changes of addiction-related neural biomarkers in peripheral blood immunocyte, it is potential to enhance the accuracy and the susceptibility of assessments on addiction and treatment effectiveness, and in turn help to reduce drug relapse. In this review, we summarize the potential biomarkers related to addiction in peripheral blood immunocyte and changing trend of their mRNA expression level in patients using different types of drugs and with different addiction states, and discuss their application prospects and future research directions. Previous studies have found various types of potential addiction biomarkers, including neurotransmitter receptor proteins, hormones, small molecule metabolites, ΔFosB microRNA and other transcriptional (post) regulators. Considering the correlation with addiction and the richness of existing research, this article mainly introduces neurotransmitter receptor proteins closely related to addiction, including dopamine receptors, opioid receptors, cannabinoid receptors, and N-methyl-D-aspartate (NMDA) receptors. The expression levels of these potential biomarkers often change correspondingly at different stages. For example, mRNA expression of dopamine D3 receptor was increased in opioid addicted and methadone-maintained patients, but no change was observed in the heroin abstinent group. In addition, changing patterns of the biomarkers induced by different types of drugs were also various. Although both opioid addiction and alcohol addiction could induce the change of mRNA expression of dopamine D4 receptor, it was decreased in the opioid addiction patients while increased in the alcohol addiction patients. On the basis of the available evidence, dopamine receptors (especially D4 receptors) are most potent at the indicative action across drugs and stages, while cannabinoid receptors mainly specifically reflect different stages of cannabis addiction status. In addition, the mRNA level of the GluN3B subunit showed a steady increase in different stages of opioid addiction and showed a decreased response to methadone treatment, suggesting that it has high potential as a biomarker of heroin addiction. Besides, the mRNA level of D4 receptor showed a clear reverse trend in the stage of alcohol addiction and alcohol withdrawal, which also reflected the potential of D4 receptor mRNA in the state of alcohol addiction. Considering evidences about serum levels changing in patients with drug addiction, immune response induced by drugs may be one possible mechanism of changes in the expression levels of transmitter receptors in the peripheral blood of drug addiction patients. Finally, the current research on biomarkers in peripheral blood for addiction is still relatively fragmented, and lack systematic mechanism exploration. Future studies could further combine animal studies and clinical studies to systematically demonstrate the role of relevant biomarkers and underlying mechanisms. In addition, there are often interactions between multiple biomarker proteins in mediating drug addiction, especially in the process of addiction development. Thus, the overall observation of the dynamic changing of different biomarkers in the addiction process may be helpful to enhance the accuracy of assessment of addiction states. At the same time, when applying peripheral blood biomarkers, corresponding standards should be formulated based on experimental evidences, so as to enhance the pertinence and effectiveness of peripheral blood biomarkers in the diagnosis and treatment of addiction.
    Citation
    WU Mei-Lin, WANG Yi-Fan, DUAN Wen-Jing, DANG Wang-Jie, HAN Jing, REN Wei, DUAN Hai-Jun.Potential Addiction Biomarkers in Peripheral Blood Immunocyte and Their Quantification Analysis of mRNA[J]..Export: BibTex EndNote
  • Tripartite motif-containing protein 13 (TRIM13) is a crucial member of the TRIM protein family, distinguished by its unique transmembrane domain that anchors it to the endoplasmic reticulum (ER). As an E3 ubiquitin ligase, TRIM13 influences multiple key signaling pathways through ubiquitination regulation, playing significant roles in modulating ER function, immune responses, metabolic disorders, inflammatory diseases, and tumor suppression. TRIM13 possesses the common RING, B-box, and coiled-coil domains of the TRIM family, along with its distinctive transmembrane domain. Its E3 ubiquitin ligase activity serves as the structural basis for its diverse biological functions. TRIM13 acts as a non-canonical ER-phagy receptor to participate in regulating ER stress responses, recruiting LC3 through interaction with SQSTM1/p62 to initiate autophagy-mediated degradation of damaged ER, which is crucial for maintaining ER homeostasis and cellular function under stress conditions. TRIM13 is involved in inflammatory and antiviral immune responses by modulating key molecules in signaling pathways such as MDA5, NF-κB, and STING, highlighting its potential in regulating innate immunity and inflammatory. TRIM13 is associated with various pathological conditions, particularly in cancer and metabolic diseases. In multiple cancers, including non-small cell lung cancer, hepatocellular carcinoma, and acute myeloid leukemia, TRIM13 exhibits tumor-suppressive effects, with its expression levels closely associated with patient prognosis, suggesting its potential as a biomarker or therapeutic target in oncology. In diabetic nephropathy, TRIM13 improves renal function by promoting CHOP ubiquitination and inhibiting interstitial collagen synthesis, demonstrating its protective role in kidney disease. In atherosclerosis, TRIM13 is involved in regulating cholesterol metabolism and inflammatory pathways, indicating its significance in cardiovascular disorders. Recent studies have also implicated TRIM13 in neurodegenerative disorders and metabolic syndromes, with its role in regulating protein quality control and ER stress responses suggesting potential involvement in diseases characterized by protein misfolding and aggregation, such as Alzheimer"s and Parkinson"s diseases. Additionally, TRIM13"s participation in lipid metabolism and insulin signaling pathways points to its possible influence on obesity and diabetes. Despite significant advancements in TRIM13 research, the precise molecular mechanisms underlying its functions in various physiological and pathological processes remain to be elucidated. In this article, we review the structural characteristics and functions of TRIM13 protein, with particular emphasis on its roles in ER-phagy, inflammatory responses, and tumor suppression, as well as its potential significance in various diseases. Future studies should focus on revealing the specific core mechanisms of TRIM13 function and exploring its unique role in ER function regulation. A deeper understanding of TRIM13 protein and its regulatory mechanisms in development of diseases may provide novel targets and strategies for disease diagnosis and treatment.
    Citation
    JIANG Miao, JIANG Li-Na, DONG Yue-Hong, YAO Yong-Ming, ZHAO Zi-Gang, NIU Chun-Yu.The Biological Characteristics and Functions of TRIM13 and Its Relationship With The Development of Diseases[J]..Export: BibTex EndNote
  • In recent years, tumor-infiltrating B lymphocytes (TIL-B) play a complex and important role in tumorigenesis and tumor development. TIL-B contains various subpopulations, which can be broadly classified into subpopulations of tumor-suppressing B cells, such as antigen-presenting B cells and plasma cells; and subpopulations of tumor-promoting B cells, such as regulatory B cells (Bregs). The anti-tumor mechanisms of TIL-B contain many aspects, including the secretion of specific antibodies such as IgG and IgA; activation of T cells through antigen presentation; release of cytokines that affect tumor cell growth; direct killing of target cells through the Fas/FasL and perforin pathways; and enhancement of anti-tumor immunity through interactions with T cells. The pro-tumor mechanism of TIL-B also includes many aspects, such as Bregs can inhibit anti-tumor immunity by secreting cytokines, inducing the production of regulatory T cells (Tregs), and inhibiting the interaction between T cells and antigen presenting cells (APCs), etc. Atypical memory (AtM) B cells and leucine-tRNA-synthase-2 (LARS2) -expressing B cells (LARS B) subpopulations can also promote tumor progression by secreting cytokines such as TNF-α and TGF-β. Based on the above mechanisms, a variety of tumor therapies are now available. Firstly, the anti-tumor effect of TIL-B can be enhanced. Immune checkpoint blockade therapy is a classical immunotherapy method, and TIM-1 is a key checkpoint and has achieved certain efficacy. In addition, the development of suitable novel antibodies, safe and effective TIL-B vaccines are also promising therapeutic methods. Adoptive metastatic B-cell therapy, direct activation of B-cells, chemotherapy and targeted drugs is limited because of the high technical requirements, high toxicity and uncertainty of efficacy. In the future, it is expected that further research will gradually expand the scope of its application to achieve more effective treatment for tumor patients. Selective depletion of B cells is an immunotherapy based on the inhibition of Bregs subpopulations to achieve anti-tumor effects. The next step is to develop more efficacious targeted drugs by understanding the phenotypic and functional differences of Bregs. Finally, TIL-B can be involved in the treatment and prognosis of tumors as a predictive tumor immune marker. The efficacy of treatment can be simply assessed by observing TIL-B distribution and density in tumor. Stress-responsive memory B cells and tumor-associated atypical B cells (TAAB) have clearly shown to be associated with shorter and longer survival in cancer patients, thus be used as biomarkers of immunotherapeutic response in human cancers. This paper reviews the current status of TIL-B research, summarizes its mechanism of action in tumor immunity, analyses current therapeutic strategies and prognostic assessment methods. Future focus on understanding the functional heterogeneity and molecular regulatory mechanisms of TIL-B is essential for optimising tumor immunotherapy strategies. The systematic study of TIL-B characteristics and mechanisms of action in different tumor types can help provide a theoretical basis and potential targets for the development of new tumor therapeutic strategies.
    Citation
    HUANG Ming, CHEN Jin-Xiu, ZHANG Yu-Le, DONG XIANG, Cao Chun-Yu, WU Hong-Yan.Tumor-infiltrating B Lymphocytes[J]..Export: BibTex EndNote
  • Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by progressive demyelination and neuroinflammation, leading to axonal damage and neuronal degeneration. It is the most prevalent non-traumatic cause of neurological disability in young adults, affecting millions of people worldwide. MS manifests with a wide range of symptoms, including motor dysfunction, sensory deficits, and cognitive impairment, which can severely impact the quality of life. Despite extensive research, the exact pathogenesis of MS remains unclear, and currently available treatments primarily focus on reducing inflammation and relapse rates rather than reversing neurological damage. Thus, one of the major therapeutic challenges is to develop strategies that can not only suppress the aberrant immune response but also enhance endogenous myelin regeneration and neurorepair, ultimately halting or even reversing disease progression. Recent studies have highlighted the critical role of chondroitin sulfate proteoglycans (CSPGs), a family of inhibitory extracellular matrix (ECM) molecules, in regulating CNS repair processes. CSPGs accumulate at the sites of demyelinated lesions and form a dense, inhibitory matrix that impedes the migration and differentiation of oligodendrocyte precursor cells (OPCs), thereby preventing effective myelin regeneration. CSPGs exert their inhibitory effects through several cell surface receptors, including leukocyte common antigen-related receptor (LAR), Nogo receptors (NgR1 and NgR3), and protein tyrosine phosphatase σ (PTPσ). Among these, PTPσ is a predominant receptor that mediates the biological activities of CSPGs 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 inhibitor 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.
    Citation
    WANG Jing-Tong, LUO Fu-Cheng, CHEN Wen-Li.Targeting CSPGs/PTPσ: a Novel Approach for Multiple Sclerosis Treatment[J]..Export: BibTex EndNote
  • Objective Cancer is a global public health issue that has attracted much attention. Detecting and treating cancer at an earlier time point is the key to improving cancer survival rates. However, due to factors such as high equipment cost, slow detection speed, and poor detection accuracy, the promotion of early cancer screening is limited. Therefore, this paper proposes a high-precision and high-speed bioimpedance spectroscopy detection method for tumor identification based on multi-frequency synchronous bioimpedance spectroscopy technology.Methods First, based on the multi-frequency synchronization technology, this paper built a multi-frequency synchronous bioimpedance spectrum detection system, realized the high-speed detection of bioimpedance spectrum, designed concentric circle sensors to reduce the influence of biological tissue anisotropy on impedance detection, and improved the discrimination of bioimpedance spectrum between different tissues. Secondly, a gastric wall tissue model was established, and the degree of anisotropy influence on traditional four-electrode sensors and concentric circle sensors was studied through simulation. Finally, through pork tissue detection experiments and clinical gastric cancer tissue detection experiments, it was verified that the multi-frequency synchronous bioimpedance spectroscopy detection system using concentric circle sensors has higher detection accuracy.Results The experimental results show that when using concentric circle sensors, the average overlap rate of detection results is 13.4%, which is 41.7% lower than that of traditional electrodes, and the average discrete coefficient Cv is 7.6%, which is 54.0% lower than that of traditional electrodes. The multi-frequency synchronous bioimpedance spectrum detection system takes about 20 ms to perform a detection, and the detection method proposed in this paper has higher detection accuracy and detection speed. Finally, the concentric circle electrodes were selected to conduct clinical experiments on human gastric cancer tissue, and normal tissue and tumor tissue were successfully distinguished.Conclusion The high-precision and high-speed bioimpedance spectroscopy detection method for tumor identification proposed in this paper can effectively reduce the influence of anisotropy of biological tissues and obtain higher-precision and higher-speed detection results.
    Citation
    WANG Zhong-Wei, LIU Kai, HU Song-Pei, ZOU Bin, PAN Min-Hong, YAO Jia-Feng.Research on High-precision and High-speed Bioimpedance Spectroscopy Detection Method for Tumour Identification[J]..Export: BibTex EndNote
  • Transcranial Focused Ultrasound (tFUS) technology achieves precise stimulation or treatment of the area of interest in the head by directing ultrasound beams to penetrate the human skull to form an intracranial focal point, with the advantages of eliminating the need for craniotomy and the absence of ionizing radiation. High-intensity tFUS treats brain diseases such as essential tremor or brain tumors through thermal effects, while low-intensity tFUS can safely and reversibly open the blood-brain barrier or conduct neuromodulation studies through mechanical effects. However, in practical applications, ultrasound waves undergo strong phase distortion and energy attenuation due to the strong acoustic attenuation properties and inhomogeneous structure of the skull. Acoustic simulation models the interaction between ultrasound and media based on acoustic fluctuation equations to predict the propagation properties of sound waves in different media. Therefore, acoustic simulation is commonly used to predict the intracranial acoustic field for single-element tFUS or to perform phase correction for each element of multi-element tFUS to ensure accurate focusing of intracranial ultrasound. According to the different methods of solving the acoustic fluctuation equations, the commonly used acoustic simulation methods in tFUS can be categorized into numerical and semi-analytical methods. The numerical methods include k-space pseudo-spectral method, time-domain finite difference method and finite element method, 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.
    Citation
    CHEN Guo-Wei, WANG Xue, HE Feng, ZHANG Hao, XU Min-Peng, MING Dong.Research and Application of Transcranial Focused Ultrasound Simulation Methods[J]..Export: BibTex EndNote
  • As the aging population in China continues to grow, the country’s public health sector faces an urgent need to address the significant social challenges posed by Alzheimer’s disease (AD). The available clinical treatments for AD are extremely limited, and the effectiveness of these drugs often diminishes after a period of use. Despite substantial global investment in drug research and development, the progress of clinical trials for AD treatments has been exceedingly slow. Over the past 30 years, only seven AD drugs have been approved by the U.S. Food and Drug Administration (FDA). Traditional drug therapies are expensive and can only slow the progression of AD, without halting the progressive degeneration of neurons. Therefore, exploring and developing emerging treatment methods for AD is imperative. Photobiomodulation (PBM) is a non-invasive therapeutic approach that uses red or near-infrared light to stimulate cellular metabolism and biological responses. PBM has the potential to improve brain metabolism and blood circulation, repair damaged neurons in the brain, and stimulate dendritic and neuronal growth, making it a promising non-invasive neurotherapeutic method that could complement drug treatments. This paper discusses the pathological characteristics and pathogenic mechanisms of AD, as well as the challenges faced by existing treatment strategies. It also reviews the research on PBM treatment in AD cellular and animal models and clinical studies, summarizes the history of phototherapy and the current state of advanced PBM phototherapy device development, and finally offers a perspective on the future development of advanced photonic technologies and therapeutic devices for PBM treatment of AD.
    Citation
    GUO Yan-Guang, WEI Shuang-Hong, WANG Yun-Le, CHEN Si, HOSSEIN Chamkouri, CHEN Peng, SI Jian-Min, NIU Chao-Shi, CHEN Lei.Non-invasive Photobiomodulation Therapy Techniques in Alzheimer’s Disease[J]..Export: BibTex EndNote
  • The two-component system (TCS) is a signaling mechanism extensively found in prokaryotes, playing a pivotal role in bacterial environmental sensing and adaptive responses. Comprising histidine kinase (HK) and response regulator (RR) components, TCS ensures appropriate bacterial reactions to various stimuli. Understanding its structural composition, signal transduction mechanisms, and applications in synthetic biology underscores its significance in both basic research and biotechnological applications. At its core, TCS operates through a sequence of events initiated by the detection of environmental cues. When the HK senses specific signals such as temperature changes, osmolarity shifts, or the presence of ligands, it undergoes autophosphorylation at a conserved histidine residue within its kinase domain. Subsequently, this phosphoryl group is transferred to a conserved aspartate residue on the RR’s receiver domain. This phosphotransfer event activates the RR, inducing a conformational change that alters its activity, often leading to changes in gene expression or other cellular responses. The specificity and fidelity of signal transduction in TCS are critical for bacteria to differentiate between various environmental cues and mount appropriate responses. This specificity is achieved through mechanisms such as unique signal molecule recognition by HKs and precise phosphotransfer from HKs to RRs. Moreover, the directional transfer of phosphoryl groups ensures tightly regulated signaling cascades, contributing to the overall robustness of bacterial response systems. Beyond its natural role, the versatility of TCS has been harnessed by engineers in synthetic biology to create tools like biosensors. By integrating TCS components into synthetic circuits, researchers can develop customized biosensors capable of highly sensitive and specific detection of environmental signals or biomolecules. These engineered biosensors find applications across diverse fields including environmental monitoring, medical diagnostics, and industrial biotechnology. The robustness of TCS-driven biosensors is particularly advantageous in synthetic biology. The modular design of TCS allows for the construction of sensor systems sensitive to a broad range of signals, adaptable to different cellular contexts. This adaptability is crucial for optimizing sensor performance under varying conditions, ensuring reliable and reproducible results. Safety considerations are paramount in synthetic biology, where TCS-based systems offer inherent safety features due to their reliance on natural signaling pathways and components. Well-characterized interactions between HKs and RRs minimize risks such as unintended cross-talk or interference with endogenous cellular processes, enhancing reliability in bioengineering applications requiring predictable and controllable cellular responses. Looking ahead, ongoing research aims to expand the capabilities of TCS-based biosensors through innovative engineering approaches. Advances in synthetic biology techniques, including genome editing and high-throughput screening, facilitate rapid design and optimization of novel sensor systems. These efforts promise next-generation biosensors with enhanced functionalities such as multiplexed sensing and real-time monitoring in complex biological environments. In summary, the TCS stands as a cornerstone of bacterial signal transduction, facilitating precise environmental sensing and adaptive responses. Its structural simplicity, coupled with robust signaling mechanisms and programmability, underpins its utility in synthetic biology for developing advanced biosensors and other bioengineering applications. By leveraging these capabilities, researchers are poised to address critical challenges in healthcare, environmental sustainability, and industrial biotechnology, shaping the future of biologically inspired technologies.
    Citation
    LUO Bo-Yu, TENG Yue.Structural Characteristics and Signal Transduction Mechanisms of Bacterial Two-component Systems[J]..Export: BibTex EndNote
  • Objective The aim of this study was to investigate the effect and mechanism of quercetin on lipid droplet formation in foam cells induced by oxidized low-density lipoprotein (ox-LDL).Methods Mouse RAW264.7 cells were induced by 50 mg/L ox-LDL to construct a foam cell model. After different quercetin concentrations were treated for different time, the optimal quercetin concentration and time were screened by CCK8 assay. Based on the constructed foam cell model, the formation of fat droplets was observed by oil red O staining after quercetin treatment with or without AS1842856 (FOXO1 inhibitor). Apoptosis was detected by flow cytometry. The protein expression of FOXO1 in each group was detected by Western blot. Autophagosome formation was observed by acridine orange staining. The mRNA and protein expression levels of Beclin1, LC3II and P62 were detected by qRT-PCR and Western blot.Results After being treated with 100 μmol/L quercetin for 12 h, the formation of fat droplets and apoptosis of foam cells were inhibited (P<0.05). Compared with control group, there was an increase in fat droplet formation and apoptosis (P<0.05), a decrease in autophagosome (P<0.05), a decrease in FOXO1 protein expression (P<0.05), a decrease in Beclin1 and LC3II protein and mRNA expression levels (P<0.05), and the expression levels of P62 protein and mRNA were found to be increased (P<0.05) in model group. Compared with model group, quercetin treatment up-regulated FOXO1 protein expression (P<0.05), induced autophagosome formation (P<0.05), promoted the protein and mRNA expression levels of Beclin1 and LC3II (P<0.05), and inhibited the protein and mRNA expression levels of P62 (P<0.05). In addition, treatment with the FOXO1 inhibitor AS1842856 reversed quercetin’s effect on OX-LDL-induced foam cells.Conclusion Quercetin induced autophagy by upregulating FOXO1 expression and inhibited fat droplet formation induced by OX-LDL.
    Citation
    ZENG jiang-Qin, SUN Qin-Guo, XU Hong-Jie, DING Xiao-Ming, MOU Yan-Jie, JIANG Yue-Wen.Quercetin Inhibits Lipid Droplet Formation in ox-LDL-induced Foam Cells Through FOXO1-mediated Autophagy[J]..Export: BibTex EndNote
  • Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.
    Citation
    SHANG Peng, LIU Jun-Yu, WANG Sheng-Hang, YANG Jian-Cheng, ZHANG Zhe-Yuan, LI An-Lin, ZHANG Hao, ZENG Yu-Hong.Translational Research of Electromagnetic Fields on Diseases Related With Bone Remodeling: Review and Prospects[J]..Export: BibTex EndNote
  • In recent years, it has been discovered that innate immunity also exhibits immune memory characteristics, referred to as trained immunity. This refers to the ability of innate immune cells to acquire a memory-like capacity after being attacked by pathogens, thereby demonstrating enhanced reactivity upon secondary stimulation from the same or different stimuli. Existing research indicates that high-fat diet stimulates innate immune cells to undergo trained immunity, thereby significantly boosting their immune response to secondary metabolic disorders. This process serves as a crucial mechanism underlying the development of insulin resistance-associated metabolic diseases. Breaking the vicious cycle between insulin resistance and trained immunity by inducing innate immune cells to establish immune tolerance and inhibiting excessive inflammatory reactions caused by various secondary metabolic disorders of insulin resistance represents a novel strategy for early prevention and treatment of related metabolic diseases. As is widely known, exercise intervention serves as an effective means to improve insulin resistance-related metabolic diseases. It promotes metabolic homeostasis by exerting anti-inflammatory effects, yet the underlying mechanism of these anti-inflammatory effects remains unclear. Numerous studies suggest that after a high-fat diet generates innate immune memory, exercise intervention may alleviate excessive inflammatory reactions caused by secondary metabolic disorders due to insulin resistance by inducing immune tolerance in innate immune cells, and promote early prevention and treatment of related metabolic diseases. Therefore, targeting innate immune cell immune tolerance to explore the anti-inflammatory mechanism of exercise intervention in insulin resistance holds exciting and vast prospects. Metabolic reprogramming refers to the process in which cells undergo systematic adjustments and transformations in their energy requirements and metabolic patterns to adapt to changes in the external environment and meet their own needs for proliferation and differentiation under specific physiological and pathological conditions. Numerous studies have shown that metabolic reprogramming plays a crucial role in tumor biology, immunology, stem cell research, and the occurrence and development of various diseases. Increasing evidence suggests that metabolic reprogramming is also a key mechanism for innate immune cells to respond to external stimuli and perform immune functions. The process of immune tolerance is also driven by metabolic reprogramming. Studying the mechanisms of innate immune cell immune tolerance from the perspective of metabolic reprogramming is expected to provide new directions for the prevention and treatment of chronic inflammation and related metabolic diseases. Meanwhile, exercise has been proven to regulate metabolic reprogramming in various cells. It may induce immune tolerance in activated innate immune cells by inhibiting glycolysis and enhancing their oxidative phosphorylation levels, thereby mitigating excessive inflammatory reactions and achieving early prevention and treatment of insulin resistance-related metabolic diseases. Itaconate, an intermediate product of the tricarboxylic acid cycle, represents a newly discovered central regulatory point for balancing the trained immunity and immunity tolerance in innate immune cells. Additionally, exercise modulates IRG1/Itaconate signaling. Therefore, conducting an in-depth exploration of the interrelationships between trained immunity, immunity tolerance, metabolic reprogramming, and IRG1/Itaconate signaling in exercise intervention for insulin resistance, as well as summarizing the immune tolerance mechanism of exercise in improving insulin resistance, can provide theoretical support for the preventive and therapeutic effects of exercise in insulin resistance and related metabolic diseases. This can also offer new insights for the development of simulated drugs tailored for individuals with exercise intolerance.
    Citation
    LUO Wei, GAO Wen-Yue, WANG Yu-Hang, LIU Yan-Song, AI Lei.The Emerged Perspective on Improving Insulin Resistance Through Exercise: Metabolic Reprogramming Induces Trained Immunity Tolerance[J]..Export: BibTex EndNote
  • Aging has been identified as one of the risk factors for chronic disease, and the onset and development of many chronic diseases are closely related to gut immune dysfunction in the elderly. Aging profoundly affects the intestinal immune system and the homeostasis of intestinal flora. We have reviewed the changes in intestinal mucosal immune function that occur with aging, including Toll-like receptors (TLRs), T cells, B cells and inflammatory cytokines such as IL-6, TNF-α and IFN-γ. Age-related changes in typical gut microbiota and their metabolites were discussed. Aging leads to changes in the composition and diversity of the gut microbiota. Age-related changes occur in intestinal bacteria such as Bacteroides, Bifidobacterium and Clostridium butyricum. The metabolites of gut flora, including short chain fatty acids (SCFAs), bile, indole and indole derivatives, decrease and the homeostasis of the gut flora becomes unbalanced. 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.
    Citation
    GUO Wen-Wen, QI Li-Li, WANG Meng-Ting, KE Zhi-Jian, MAO Hai-Guang, WANG Jin-Bo.The Relationship Between Intestinal Flora and Intestinal Mucosal Immune Senescence[J]..Export: BibTex EndNote
  • Alzheimer’s disease (AD) is the most common form of dementia, and its prevalence is rapidly increasing with the aging population. Among the growing number of genetic risk factors, apolipoprotein E (ApoE) is the most prevalent and strongest risk factor, accounting for nearly three-quarters of AD cases. ApoE is a key protein involved in lipids and cholesterol metabolism in the central nervous system. There are three subtypes of ApoE: ApoE2, ApoE3, and ApoE4, among which ApoE4 is a high-risk factor for the incidence of AD. ApoE4 not only affects lipid efflux and distribution in glial cells, but also affects the lipid metabolism in neurons, resulting in the imbalance of lipid homeostasis. ApoE plays a role in the processing of amyloid precursor protein (APP), which is associated with the early production of amyloidβ-(Aβ) protein and plaque deposition. ApoE4 also reduces the solubility of Tau protein, which contributes to promoting the aberrant phosphorylation and the aggregation of Tau, and resulting in neurofibrillary tangles (NFTs). Moreover, brain regions expressing ApoE4 are more susceptible to Tau diffusion. Furthermore, ApoE4 has been demonstrated to activate the NF-κB inflammatory pathway, convert microglia and astrocytes into the pro-inflammatory phenotypes, secrete pro-inflammatory factors and oxidative mediators, and induce neuroinflammation. Altogether, ApoE participates in AD neuropathology through multiple pathways such as Aβ plaque, Tau pathology, neuroinflammation, neuroplasticity and blood-brain barrier, which all jointly promotes the progression of the disease. It has been demonstrated that anti-ApoE4 antibodies can reduce the formation of Aβ plaques and neuroinflammation. The repurposing of metformin, rapamycin, enoxaparin, DHA, and tamoxifen have been shown to reduce the expression of ApoE4 protein and ameliorate AD pathology. Gene therapies utilising antisense oligonucleotides (ASO) and double-stranded interfering small RNA (siRNA) has been proved to be effective technologies to reduce ApoE4 expression and mitigate AD pathology. Adeno-associated virus (AAV)-mediated ApoE2 has been demonstrated to neutralize the negative effects of ApoE4 by expressing ApoE2 in the ventricular membrane. Traditional Chinese medicine resveratrol and waterside delivered by ApoE-modified liposome nanodrug delivery system can improve the BBB penetration of drugs and provid a new method for the treatment of AD. In addition, targeting the interaction of ApoE with low-density lipoprotein receptor (LDLR) and low density lipoprotein-related protein 1 (LRP1) receptors can indirectly regulate the expression level of ApoE, which provids a new perspective for the treatment of AD. This article aims to elucidate the roles of ApoE and its isoforms in the pathogenesis of AD and summarize the potential therapeutic strategies against ApoE with the hope of providing novel insights for the ApoE-based therapies combat AD.
    Citation
    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, LI Li-Ping.Apolipoprotein E and Alzheimer’s Disease: Risk, Mechanisms, and Treatment[J]..Export: BibTex EndNote
  • Objective Electroencephalography (EEG) serves as a non-invasive electrophysiological monitoring technique employed to record brain electrical activity. Nonetheless, traditional EEG electrodes are susceptible to reference activation influences and exhibit limited spatial resolution. Laplacian electrodes, devoid of reference dependencies, possess the potential to amplify the spatial resolution of EEG recordings. Anchored in the utilization of bipolar concentric ring Laplacian electrodes, this study delves into the autonomous referencing attributes intrinsic to Laplacian electrodes. Furthermore, it conducts a comparison of spatial resolution disparities between Laplacian electrodes and their conventional counterparts.Methods A three-dimensional (3D) hemispherical tank experiment was conducted utilizing 21 Ag/AgCl bipolar concentric ring Laplacian electrodes to simulate whole-brain signal acquisitions. A sinusoidal signal with an amplitude of 400 mVpp@13 Hz was employed for detection. The positions of the ground electrodes in the Laplacian electrode array were varied, alongside the reference electrode positions in the case of the traditional electrodes. Subsequently, the spatial distribution of the 13 Hz source frequency component was extracted and subjected to comprehensive analysis.Results With varying ground electrode positions, the spatial distribution of the signal-to-noise ratio (SNR) among Laplacian electrodes maintains remarkable consistency, yielding a correlation coefficient of 0.94. In contrast, for traditional electrodes, the correlation coefficient for SNR distribution under distinct reference electrode positions barely reaches 0.07. While Laplacian electrodes exhibit independence from reference electrodes, traditional counterparts display a notable susceptibility to changes in reference electrode positions. Comparing amplitude"s 3 dB attenuation area ratio, Laplacian electrodes showcase a mere 2.1% reduction, a significantly favorable outcome when juxtaposed with the 6.9% reduction evident in traditional electrodes. Similarly, the SNR"s 3 dB attenuation area ratio for Laplacian electrodes is a mere 1.0%, contrasting with the considerably higher figure of 30.1% for traditional electrodes.Conclusion Laplacian electrodes remain impervious to reference electrode influence, displaying distinctive reference-independent attributes, in addition to boasting a heightened spatial resolution. These characteristics imbue them with the capacity to achieve heightened precision in localizing brain electrical activities, thus constituting a cornerstone for the integration of Laplacian electrodes into brain-computer interfaces (BCIs).
    Citation
    ZHENG Chun-Hou, HE Feng, SHI Tian-Ning, XUE Jia-Xing, YING Bing-Jie, XU Min-Peng.EEG Study Based on Bipolar Concentric Ring Laplacian Electrodes[J]..Export: BibTex EndNote
  • Objective Photoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected.Methods The advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively.Results In the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice.Conclusion This work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.
    Citation
    XIE Zhuo-Jun, ZHONG Hong-Wen, LIU Run-Xiang, WANG Bo.A Fitting Method for Photoacoustic Pump-probe Imaging Based on Phase Correction[J]..Export: BibTex EndNote
  • Objective Stroke is a leading cause of death and disability worldwide, with ischemic stroke accounting for 80%-85% of cases. Despite the prevalence, effective treatments remain scarce. The compelling evidence suggest that high concentrations of ATP in the brain post-stroke can trigger irreversible neuronal damage and necrosis, contributing to a range of neurocellular dysfunctions. Pyroptosis, a recently identified form of programmed cell death, is characterized by caspase-1 activation and the action of the Gasdermin D (GSDMD) protein family, leading to cell perforation and inflammatory death.Methods In this study, human neuroblastoma SH-SY5Y cells were used to investigate the mechanisms of ATP-induced neurotoxicity and the protective effects of hydrogen sulfide (H2S) against this toxicity through the antagonization of pyroptosis. We employed CCK-8 and LDH assays to assess cell viability. YO-PRO-1 fluorescent dyes and flow cytometry were conducted for detecting changes in cell membrane permeability. Western blot analysis was used to measure protein levels associated with cellular dysfunction.Results Our results indicate that high concentrations of ATP enhance cytotoxicity and increase cell membrane permeability in SH-SY5Y cells, effects that are mitigated by the H2S donor NaHS. Furthermore, ATP was found to promote the activation of the NOD-like receptor pyrin domain containing 1 (NLRP-1), caspase-1, and the cleavage of GSDMD, with NaHS significantly attenuating these effects.Conclusion Our research suggests that H2S protects SH-SY5Y cells from ATP-induced neurotoxicity through a mechanism mediated by the NLRP1, caspase-1, and GSDMD pathway.
    Citation
    REN Yan-Kai, LI Ying-Hong, LI Man-Li, YANG Kun-Li, FAN Zhi-Ru, ZHANG Si-Yu, LI Dong-Liang.Hydrogen Sulfide Prevents ATP-induced Neurotoxicity via Inhibiting The NLRP1/caspase-1/ Gasdermin D-mediated Pyroptosis Pathway[J]..Export: BibTex EndNote
  • Objective Tomatoes are one of the highest-yielding and most widely cultivated economic crops globally, playing a crucial role in agricultural production and providing significant economic benefits to farmers and related industries. However, early blight in tomatoes is known for its rapid infection, widespread transmission, and severe destructiveness, which significantly impacts both the yield and quality of tomatoes, leading to substantial economic losses for farmers. Therefore, accurately identifying early symptoms of tomato early blight is essential for the scientific prevention and control of this disease. Additionally, visualizing affected areas can provide precise guidance for farmers, effectively reducing economic losses.Methods This study combines hyperspectral imaging technology with machine learning algorithms to develop a model for the early identification of symptoms of tomato early blight, facilitating early detection of the disease and visual localization of affected areas. To address noise interference present in hyperspectral images, robust principal component analysis (RPCA) is employed for effective denoising, enhancing the accuracy of subsequent analyses. To avoid insufficient information representation caused by the subjective selection of regions of interest, the Otsu’s thresholding method is utilized to extract tomato leaves effectively from the background, with the average spectrum of the entire leaf taken as the primary object of study. Furthermore, a comprehensive spectral preprocessing workflow is established by integrating multivariate scatter correction (MSC) and standardization methods, ensuring the reliability and effectiveness of the data. Based on the processed spectral data, a discriminant model utilizing a linear kernel function support vector machine (SVM) is constructed, focusing on characteristic wavelengths to improve the model"s discriminative capability.Results Compared to full-spectrum modeling, this approach results in an 8.33% increase in accuracy on the test set. After optimizing the parameters of the SVM model, when C=1.64, the accuracies of the training set and test set reach 91.67% and 94.44%, respectively, demonstrating a 1.19% increase in training set accuracy compared to the unoptimized model, while maintaining the same accuracy on the test set, effectively alleviating issues of underfitting.Conclusion This study successfully establishes an early discriminant model for tomato early blight using hyperspectral imaging and achieves visualization of early symptoms. Experimental results indicate that the SVM discriminant model based on characteristic wavelengths and a linear kernel function can effectively identify early symptoms of tomato early blight. Visualization of these symptoms in terms of disease probability allows for a more intuitive detection of early diseases and timely implementation of corresponding control measures. This visual analysis not only enhances the efficiency of disease identification but also provides farmers with more straightforward and practical information, aiding them in formulating more reasonable prevention strategies. These research findings provide valuable references for the early identification and visualization of plant diseases, holding significant practical implications for monitoring, identifying, and scientifically preventing crop diseases. Future research could further explore how to apply this model to disease detection in other crops and how to integrate IoT technology to create intelligent disease monitoring systems, enhancing the scientific and efficient management of crops.
    Citation
    BAO Hao, HUANG Li, ZHANG Yan, PANG Hao.Early Identification and Visualization of Tomato Early Blight Using Hyperspectral Imagery[J]..Export: BibTex EndNote
  • Electroencephalography (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (‘source’) and negative values indicating current flow from the scalp to the brain (‘sink’). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.
    Citation
    LUO Rui-Xin, GUO Si-Ying, LI Xin-Yi, ZHAO Yu-He, ZHENG Chun-Hou, XU Min-Peng, MING Dong.Research and Application of Scalp Surface Laplacian Technique[J]..Export: BibTex EndNote
  • Objective To explore the mechanisms of exercise intervention to improve autism-like behaviors in rats induced by Shank3 knockout (Shank3-/-) through 8-week swimming exercise intervention in an autism spectrum disorder (ASD) rat model based on the cellular autophagy perspective.Methods According to the genotype identification and exercise intervention, rats were divided into wild control group (WC group), Shank3-/- group (KC group), wild swimming group (WS group), and Shank3-/- swimming group (KS group), with 15 rats in each group. 8 weeks of swimming exercise were performed in the KS group and the WS group, with the exercise being performed for 5 d per week, and then progressively increased to 40 min per session and maintained. Behavioral tests were performed 24 h after the swimming exercise intervention, including: self-grooming test, buried bead test, and hole test. Sampling was performed 12 h after the behavioral test, and the number of autophagosomes in the striatal region was observed by transmission electron microscopy, the protein expression level of microtubule-associated protein 1 light chain 3 (LC3) protein and selective autophagy junction protein (p62) protein was observed by immunofluorescence staining, and the protein expression level of B-cell lymphoma protein 2 interactions protein 1 (BECLIN1), LC3, p62, autophagy-associated protein 5 (Atg5), autophagy-associated 16-like protein 1 (Atg16L), and lysosome-associated protein 1 (LAMP1) in striatal tissues was detected by qPCR and Western blot.Results Compared with the WC group, rats in the KC group had a significant increase in the number and time of self-grooming (P<0.05), the number of buried beads (P<0.01), and the number of hole explorations and the number of single hole explorations (P<0.05), and after 8 weeks of swimming exercise, rats in the KS group showed a significant decrease in the time of self-grooming, the number of bead burials, and the number of single hole explorations, compared with those of rats in the KC group. In addition, rats in the KC group had a large number of autophagosomes formed in the striatal region compared with the WC group, while the expression of autophagy-related proteins and mRNAs (Atg5, Atg16L, p62, and microtubule-associated protein 1 light chain 3 II/I (LC3II/LC3I)) increased significantly (P<0.05), Beclin1 protein increased significantly (P<0.05), and LAMP1 protein and mRNA Expression of autophagy-related proteins and mRNAs (Atg5, Atg16L, p62, LC3II/LC3I) were significantly decreased (P<0.05), BECLIN1 protein was significantly decreased (P<0.05), and LAMP1 protein and mRNA expression was significantly increased in the KS group rats compared to the KC group rats after 8 weeks of swimming exercise (P<0.05).Conclusion Early swimming at 8 weeks could alleviate stereotyped behavior in Shank3-/- rats by enhancing the function of striatal cell autophagy proteins.
    Citation
    XUE Ya-Qi, LIU Niu, WANG Shi-Jiao, BA Yi, ZHEN Zhi-Ping.Early Swimming Alleviates Stereotypic Behavior in Shank3 Knockout Rats by Enhancing Striatal Cell Autophagy Protein Function[J]..Export: BibTex EndNote
  • “Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner"s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.
    Citation
    WANG Yun-Teng, LIANG Jia-Qi, SU Wan-Tang, ZHAO Li, LI Yan.The Neurobiological Mechanisms of Runner’s High[J]..Export: BibTex EndNote
  • Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, 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 and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, which 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.
    Citation
    XIA Yong-Hang, DENG Hao, HU Li-Ling, LIU Wei, TAN Xiao.Role of SPINK in Dermatologic Diseases and Potential Therapeutic Targets[J]..Export: BibTex EndNote
  • GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was mainly expressed in the muscular and skeletal systems; with the deepening of research, it has been found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interaction. GPR126 has a typical seven-transmembrane helix structure of aGPCRs, which can mediate transmembrane signal transduction and participate in the regulation of cell proliferation, differentiation and migration. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still need to be further studied. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126 to provide ideas and references for future research on GPR126.
    Citation
    WU Ting-Ting, JIA Si-Qi, CAO Shu-Zhu, ZHU De-Xin, TANG Guo-Chao, SUN Zhi-Hua, DENG Xing-Mei, ZHANG Hui.Structure and Function of GPR126/ADGRG6[J]..Export: BibTex EndNote
  • Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, 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. Applications, focusing on the use of animal disease models to explore the effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometrium (TE), chronic endometritis (CE), in vivo regeneration of bone tissue, cardiovascular disease, breast cancer (BC), and anti-ageing, and there are studies proving that the effects of mechanism of action of recombinant collagen in the treatment of FPFD and CE, and also elaborated the clinical therapeutic effects of recombinant collagen in skin burns, skin wounds, dermatitis, acne, and genitourinary syndromes of menopause (GSM). 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 facing 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.
    Citation
    HU Huan, LI Yun-Lan, ZHANG Hong, WANG Jian, WANG Li-Wen, LIU Qian, CHENG Ning-Wen, ZHANG Xin-Yue.Application of Recombinant Collagen in Biomedicine[J]..Export: BibTex EndNote
  • Objective At present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin, methylene blue, etc., in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors.Methods In this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sative japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 μmol/L singlet oxygen probe of SOSG and 5 μmol/L superoxide anion probe of DHE after fixed to A445=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 μmol·m-2·s-1.Results The results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 μmol·m-2·s-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of ROS by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress.Conclusion LovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.
    Citation
    XU Shuang, WAN Ben, SHA Na, ZHAO Kai-Hong.Cytotoxicity Studies of Light-oxygen-voltage (LOV) Domain Photosensitizers[J]..Export: BibTex EndNote
  • Lactate, with a chemical formula of C3H6O3, 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.
    Citation
    MA Jing, BU Shu-Min, CHENG Yang.The Role and Mechanism of Lactate Produced by Exercise in The Nervous System[J]..Export: BibTex EndNote
  • Diabetes mellitus type 2 (T2DM) is one of the most common metabolic diseases in the world and has a significant impact on the health of patients. As a key factor in cellular mechanical transduction, Piezo1 protein plays a crucial role in regulating the basic life activities of the body. By participating in energy metabolism, it not only promotes the improvement of basic metabolic rate, but also helps to maintain the stability of the internal environment of the body. The activation of Piezo1 pathway has a significant effect on the release of insulin by islet beta cells, and also plays an important role in the production of adipose tissue after food intake. This study explores the effects of exercise intervention on the expression and function of Piezo1 protein, as well as its role in metabolic regulation and insulin level regulation in T2DM patients. The study showed that a modest exercise intervention activated Piezo1 signaling pathway, which improved insulin sensitivity and improved sugar metabolism. In addition, the activation of Piezo1 pathway is closely related to the metabolic regulation of adipose tissue, helping to regulate the differentiation and maturation of adipose cells, thereby affecting the metabolic function of adipose tissue. Based on a comprehensive analysis of existing literature, Piezo1 pathway is found to play a complex role in the pathogenesis of T2DM. Exercise intervention, as a non-drug therapy, provides a new strategy for the treatment of T2DM by activating Piezo1 signaling pathway. However, the exact mechanism of action of Piezo1 pathway in T2DM still needs further investigation. Future studies should focus on the interaction between the Piezo1 pathway and T2DM, and how to regulate the Piezo1 pathway to optimize treatment for T2DM. The effects of exercise intervention on Piezo1 protein and its role in metabolic regulation and insulin level regulation of T2DM patients were comprehensively analyzed in this paper, aiming to provide a new perspective for further research and development of therapeutic strategies for metabolic diseases such as diabetes and obesity.
    Citation
    DONG Zi-Xuan, MA Zhan-Ke.The Ameliorate Effect of Piezo1 Signaling Pathway on Diabetes Mellitus Type 2 in Exercise Intervention[J]..Export: BibTex EndNote
  • Objective To investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons.Methods Twenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it.Results Compared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior.Conclusion CRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.
    Citation
    CHEN Jing, CHEN Cong-Cong, ZHANG Kai-Na, LAI Yu-Lin, ZOU Yang.Exercise Ameliorates Chronic Restraint Stress-induced Anxiety via PVN CRH Neurons[J]..Export: BibTex EndNote
  • Objective Chemotherapy is one of the important therapeutic approaches for cancer treatment. However, the emergence of multidrug resistance and side effects during chemotherapy seriously limit its application. Therefore chemotherapy is often combined with other drugs or therapies. Among the 13 human fucosyltransferases (FUTs) that have been identified, FUT8 (alpha-(1,6)-fucosyltransferase) is the only enzyme responsible for core fucosylation. Core fucosylation plays an important role in the occurrence, metastasis and chemotherapy resistance of cancer, and suppression of FUT8 is a potential method of reversing multidrug resistance. This study aims to explore the feasibility of using the small molecule 2FF inhibitor 2-deoxy-2-fluoro-L-fucose (2FF) of FUT8 and the clinical chemotherapeutic drug doxorubicin (DOX) to treat malignant tumors in combination.Methods Human hepatocellular carcinoma cell line HepG2 and mouse colon cancer cell line CT26 cells were treated with 2FF, DOX or their combination and the core fucosylation levels of tumor cells were detected by Lectin Blot. We treated HepG2 and CT26 cells with 50 μmol/L 2FF for a duration of 72 h, followed by exposure to a gradient concentration of DOX for 24 h. Then cell viability and IC50 values were determined using the CCK-8 assay. Transwell invasion assays were used to investigate the effect of 2FF combined with DOX on the invasion ability of HepG2. Flow cytometry was performed to analyse the effect of 2FF, DOX and their combination on the membrane PD-L1 expression of HepG2 cells. To explore the inhibitory effect of 2FF combined with DOX on tumor growth in vivo, 6 to 8 week old female BALB/c mice weighing approximately 20-25 g, were subcutaneously injected with 1×106 CT26 cells in the right axilla (four groups, six mice in each group). After the average tumor volume reached 100 mm3, DOX or 2FF or DOX combined with 2FF was then injected into mice every other day. In DOX group, each mice was intraperitoneally injected with 2 mg/kg DOX; in 2FF group, each mice was intravenously injected with 5 mg/kg 2FF; in 2FF combined with DOX group, each mice was intraperitoneally injected with 2 mg/kg DOX and intravenously injected with 5 mg/kg 2FF; in mock group, each mice was injected with the same volume of saline as in the experimental group. These mice were observed daily and the tumor size was measured and recorded every other day using a vernier caliper.Results In this study, we found that DOX upregulates the core fucosylation level of HepG2 and CT26 cells,while 2FF effectively inhibits the tumor cell core fucosylation levels-induced by COX. 2FF effectively enhances the sensitivity of HepG2 and CT26 cells to DOX. In addition, 2FF combined with DOX synergistically inhibits the invasion ability of HepG2 cells, enhances the anti-tumor efficacy of CT26 subcutaneous tumor model in BALB/c mice. However the combination leads to weight loss in mice. In addition, DOX upregulates the cell surface PD-L1 expression of HepG2 cells, and 2FF inhibits this effect-induced by DOX.Conclusion The FUT8 inhibitor 2FF effectively suppresses the upregulation of core fucosylation and PD-L1 levels-induced by DOX in tumor cells, and 2FF synergistically enhances the anticancer efficacy of DOX.
    Citation
    XIE Zhi-Dong, ZHANG Xiao-Lian.Synergistic Effect and Mechanism of FUT8 Inhibitor 2FF With DOX for Cancer Treatment[J]..Export: BibTex EndNote
  • Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Owing to its high inter-tumor and intra-tumor heterogeneity, it poses significant obstacles to the implementation of personalized diagnosis and treatment for TNBC. Alongside the advancement of clustered regular interspaced short palindromic repeats (CRISPR) system, it has profoundly enhanced our comprehension of the structure and function of the TNBC genome, offering a straightforward and promising instrument for investigating the occurrence and development of diseases. In this review, we zero in on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We initially deliberate on the unique attributes of TNBC and the constraints of current diagnostic and treatment approaches: conventional diagnostic methods have a restricted understanding of TNBC; conventional chemotherapy drugs have limited efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNA (gRNA) to initiate the selective degradation of exogenous nucleic acids, has emerged as a potent tool for TNBC research, providing precise gene editing capabilities. CRISPR technology enables a comprehensive grasp of the heterogeneity of TNBC by marking and tracking different TNBC cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes associated with TNBC growth, metastasis, and drug resistance, furnishing new targets and strategies for treatment. The application of CRISPR/Cas in TNBC diagnostics encompasses the development of molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA), providing sensitive and specific diagnoses. In precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR screening has facilitated the discovery of potential therapeutic targets, and the gene-editing capabilities of the system have been applied to develop combination therapies with traditional chemotherapy drugs, enhancing their efficacy. The clinical translation of CRISPR/Cas technology is still in its nascent stage, with several clinical trials currently underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. While the applications of CRISPR/Cas in TNBC therapy hold great promise, challenges such as off-target effects, editing efficiency, and delivery methods need to be tackled. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is anticipated to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and costs decline, the establishment of clinical relevance and the translation of CRISPR/Cas system data into clinical applications will clear the path for the optimal diagnosis and treatment strategies for TNBC patients. Nevertheless, the journey ahead is accompanied by technical challenges and ethical considerations that require further research and regulation to ensure safety and efficacy.
    Citation
    LIN Hui-Ling, OUYANG Yu-Xin, TANG Wan-Ying, HU Mi, PENG Mao, HE Ping-Ping, OUYANG Xin-Ping.Application of CRISPR/Cas System in Precision Medicine for Triple-negative Breast Cancer[J]..Export: BibTex EndNote
  • Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β-amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β-secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
    Citation
    ZHANG Yu-Meng, TIAN Yu-Shan, LI Jie, MOU Wen-Jun, YIN Chang-Feng, CHEN Huan, HOU Hong-Wei.The Mechanisms of Quercetin in Improving Alzheimer’s Disease[J]..Export: BibTex EndNote
  • Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as 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.
    Citation
    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, LI Li-Ping.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease[J]..Export: BibTex EndNote
  • Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, 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.
    Citation
    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, GONG Wei-Li.Enzyme-directed Immobilization Strategies for Biosensor Applications[J]..Export: BibTex EndNote
  • Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.
    Citation
    WANG Si-Wen, YIN Xiao-Xiao, GAO Lin-Lin, GUI Wen-Jun, HU Qiao-Xia, LOU Qiong, WANG Qin-Wen.The Use of Speech in Screening for Cognitive Decline in Older Adults[J]..Export: BibTex EndNote
  • Objective For prepubertal and urgently treated malignant tumor patients, ovarian tissue cryopreservation and transplantation represent more appropriate fertility preservation methods. Current clinical practices often involve freezing ovarian tissue with high concentrations of cryoprotectants (CPAs) and thawing with water baths. These processes lead to varying degrees of toxicity and devitrification damage to ovarian tissue. Therefore, this paper proposes optimized methods for vitrification of ovarian tissues based on sodium alginate hydrogel encapsulation and magnetic induction nanowarming technology.Methods Firstly, the study investigated the effects of sodium alginate concentration, the sequence of hydrogel encapsulation and CPAs loading on vitrification efficiency of encapsulated ovarian tissue. Additionally, the capability of sodium alginate hydrogel encapsulation to reduce the required concentration of CPAs was validated. Secondly, a platform combining water bath and magnetic induction nanowarming was established to rewarm ovarian tissue under various concentrations of magnetic nanoparticles and magnetic field strengths. The post-warming follicle survival rate, antioxidant capacity, and ovarian tissue integrity were evaluated to assess the efficacy of the method.Results The study found that ovarian tissue encapsulated with 2% sodium alginate hydrogel exhibited the highest follicle survival rate after vitrification. The method of loading CPAs prior to encapsulation proved more suitable for ovarian tissue cryopreservation, effectively reducing the required concentration of CPAs by 50%. A combination of 8 g/L Fe3O4 nanoparticles and an alternating magnetic field of 300 Gs showed optimal warming effectiveness for ovarian tissue. Combining water bath rewarming with magnetic induction nanowarming yielded the highest follicle survival rate, enhanced antioxidant capacity, and preserved tissue morphology.Conclusion Sodium alginate hydrogel encapsulation of ovarian tissue reduces the concentration of CPAs required during the freezing process. The combination of magnetic induction nanowarming with water bath provides an efficient method ovarian tissue rewarming. This study offers novel approaches to optimize ovarian tissues vitrification.
    Citation
    CAO Yu-Kun, YE Na, ZHOU Xin-Li.Optimization of Ovarian Tissue Vitrification Using Hydrogel Encapsulation and Magnetic Induction Nanowarming[J]..Export: BibTex EndNote
Journal Information
Sponsored by:Institute of Biophysics, The Chinese Academy of Sciences; Biophysical Society of China Edited by: Editorial Office of Progress in Biochemistry and Biophysics Published by:Editorial Office of PIBB Editor-in-Chief:HE Rong-Qiao Adress:15 Datun Road, Chaoyang District,Beijing 100101,China Telephone:86-10-64888459 Email:prog@ibp.ac.cn Journal inclusion:SCI, CA, Scopus, AJ ISSN    1000-3282 CN    11-2161/Q Current Issue
External Links
Chinese Academy of SciencesInstitute of Biophysics, Chinese Academy of SciencesBiophysical Society of China