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Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian Li Xueer Liu Zelin Zhang Xiaoxuan Chen Weiqiang Chen Kangsheng Li Jiangtao Sheng Department of Microbiology and Immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina Department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system *** neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types ***-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related ***,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain *** this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from *** found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 *** VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical *** findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological ***,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents

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The Current State and Progress of Mpox Vaccine Research

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China CDC weekly 2024年第7期6卷 118-125页

作者： Xinlong Wang Zhixia Gu Shugui Sheng Rui Song Ronghua Jin beijing key laboratory of emerging infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijingChina National Center for infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina

On July 23,2022,the World Health Organization(WHO)declared the monkeypox(mpox)outbreak a“Public Health Emergency of International Concern.”Since 2022,outbreaks of mpox in many countries around the world have primarily resulted in fatalities among immunocompromised individuals,such as untreated HIV/AIDS *** the eradication of smallpox was declared by the WHO in 1980,the global vaccination against smallpox has been gradually *** also stopped routine smallpox vaccination in *** protective effect of the smallpox vaccine has decreased over time due to aging and declining immunity in those who were *** individuals,timely vaccination against smallpox is an effective means of protection against ***,due to safety concerns with the smallpox vaccine and the limitations of current mpox vaccines,there is no vaccine that is safe,effective,and has low side effects applied in clinical *** article provides a comprehensive review of the development of mpox virus(MPXV)vaccines,their application in special populations,and the current state of vaccine research,considering the etiology,transmission,and prevention of the ***,as an effective method of epidemic prevention,can provide long-term immune protection and effectively reduce the severity of ***,as there is no licensed specific MPXV vaccine available globally,the vaccines currently used for mpox prevention are mostly smallpox *** smallpox vaccines can offer some degree of protection against mpox by activating cross-protection in the body.

关键词： prevention routine protective

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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GPA: A Microbial Genetic Polymorphisms Assignments Tool in Metagenomic Analysis by Bayesian Estimation

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 106-117页

作者： Jiarui Li Pengcheng Du Adam Yongxin Ye Yuanyuan Zhang Chuan Song Hui Zeng Chen Chen beijing key laboratory of emerging infectious diseases Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Center for Bioinformatics State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Peking University

Identifying antimicrobial resistant(AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing(NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations(CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments(GPA). Simulation results showed that GPA has reduced the false discovery rate(FDR) and mean absolute error(MAE) in CNV and single nucleotide variant(SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://***/IID-DTH/GPA-package.

关键词： Next-generation sequencing Pool-seq Bayesian model Metagenomics Genetic polymorphisms

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Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the trace

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Frontiers of Medicine 2018年第1期12卷 23-33页

作者： Biao Kan Haijian Zhou Pengcheng Du Wen Zhang Xin Lu Tian Qin Jianguo Xu State key laboratory of infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China Collaborative Innovation Center for Diagnosis and Treatment of infectious diseases Hangzhou 310003 China beijing key laboratory of emerging infectious diseases Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Beijing 100015 China

Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.

关键词： genome sequencing genomic epidemiotogy bacteria surveillance infectious diseases

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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State key laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State key laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University College of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University Department of Cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Efficient Humoral and Cellular Immune Responses Induced by a Chimeric Virus-like Particle Displaying the Epitope of EV71 without Adjuvant

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Biomedical and Environmental Sciences 2018年第5期31卷 343-350页

作者： LIANG Pu YI Yao SU Qiu Dong QIU Feng FAN Xue Ting LU Xue Xin BI Sheng Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Institute of infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijing Key Laboratory of Emerging Infectious DiseasesBeijing 100015China

Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71（SP70） without *** evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without *** The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in ***,and purified through ion exchange chromatography and density gradient *** were immunized with the VLPs and sera were collected *** specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal ***-γ and IL-4 secreted by splenocytes were tested by ELISPOT *** HBc-SP70 proteins can self-assemble into empty *** immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal *** was no significant difference for the immune efficacy whether the aluminum adjuvant was added or *** specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and *** The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without *** the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum ***,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.

关键词： Virus-like particles Enterovirus 71 Neutralizing antibody Humoral and cellular immunity Adjuvant Vaccine

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Co-immunoprecipitation for identifying protein–protein interaction on lipid droplets

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Biophysics Reports 2024年第2期10卷 102-110页

作者： Xiaochuan Fu Shuyan Zhang Pingsheng Liu Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences Institute of infectious diseases Beijing Key Laboratory of Emerging Infectious Diseases Beijing Ditan HospitalCapital Medical University beijing Institute of infectious diseases

The lipid droplet(LD) is a conserved organelle that exists in almost all organisms, ranging from bacteria to mammals. Dysfunctions in LDs are linked to a range of human metabolic syndromes. The formation of protein complexes on LDs is crucial for maintaining their function. Investigating how proteins interact on LDs is essential for understanding the role of LDs. We have developed an effective method to uncover protein–protein interactions and protein complexes specifically on LDs. In this method, we conduct co-immunoprecipitation(co-IP) experiments using LD proteins extracted directly from isolated LDs, rather than utilizing proteins from cell lysates. To elaborate, we begin by purifying LDs with high-quality and extracting LD-associated proteins. Subsequently, the co-IP experiment is performed on these LD-associated proteins directly, which would enhance the co-IP experiment specificity of LDassociated proteins. This method enables researchers to directly unveil protein complexes on LDs and gain deeper insights into the functional roles of proteins associated with LDs.

关键词： Lipid droplet Co-immunoprecipitation Protein interaction

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Knowledge,Attitude,and Practice Towards Mpox and Associated Factors Among HIV-Infected Individuals—beijing Municipality,China,2023

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China CDC weekly 2024年第7期6卷 109-117,I0001,I0002页

作者： Yue Gu Ruiqi Ren Jing Han Wenqing Bai Yuanyuan Zhang Haoliang Liu Zhaohe Li Chao Li Rui Song Lei Zhou Chinese Center for Disease Control and Prevention BeijingChina National Center for infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijingChina beijing key laboratory of emerging infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijingChina Nanjing Medical University Nanjing CityJiangsu ProvinceChina

Summary What is already known about this topic?Approximately 50%of patients with mpox are human immunodeficiency virus(HIV)-infected *** have shown that individuals with advanced HIV infection tend to have more severe... 详细信息

关键词： mortality Infect clinical

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Molecular dissection of phage lysin PlySs2: integrity of the catalytic and cell wall binding domains is essential for its broad lytic activity

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Virologica Sinica 2015年第1期30卷 45-51页

作者： Yanling Huang Hang Yang Junping Yu Hongping Wei key laboratory of Special Pathogens and Biosafety Center for Emerging Infectious Diseases Wuhan Institute of Virology Chinese Academy of Sciences

The novel phage lysin PlySs2, is reported to be highly active against various bacteria, including staphylococci, streptococci and Listeria. However, the molecular mechanisms underlying its broad lytic spectrum remain to be established. In the present study, the lytic activity of the catalytic domain(CD, PlySc) and binding specificity of the cell wall binding domain(CBD, PlySb) of PlySs2 were examined. Our results showed that PlySc alone maintains very limited lytic activity. Enhanced green fluorescent protein(EGFP)-fused PlySb displayed high binding affinity to the streptococcal strains tested, including ***, ***, and ***, but not staphylococci, supporting its utility as a good CBD donor for streptococcal-targeted lysin engineering. EGFP-fused intact PlySs2 similarly displayed high affinity for streptococci, but not staphylococci. Notably, four truncated PlySb fragments showed no binding capacity. These findings collectively indicate that integrity of the PlySc and PlySb domains is an essential determinant of the broad lytic activity of PlySs2.

关键词： streptococci lysin cell wall binding domain catalytic domain bacterial resistance

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