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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State Key laboratory of Virology and Department of medical microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province Key laboratory of Allergy&Immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years ago.Among these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of schizophrenia.Additionally,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia.Here,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated pathways.Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal controls.Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia.Studies indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce ferroptosis.Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities.Moreover,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by ERVW-1.In conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

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Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An Department of microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

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Isoform of Vascular Endothelial Cell Growth Inhibitor (VEGI72-251) Increases Interleukin-2 Production by Activation of T Lymphocytes

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Acta Biochimica et Biophysica Sinica 2006年第4期38卷 249-253页

作者： Jing-Juan YAO~1 Min ZHANG~1 Xiao-Hui MIAO~2 Ping ZHAO~1 Shi-Ying ZHU~1 Hui DING~1 Zhong-Tian QI~1 1 Key laboratory for medical microbiology,PLA,Department of microbiology,Second Military medical University,Shanghai 200433,China 2 Department of Infectious Diseases,Changzheng Hospital,Second Military medical University Shanghai 200433,China Key laboratory for medical microbiology PLA Department of Microbiology Second Military Medical UniversityShanghai 200433 China Department of Infectious Diseases Changzheng Hospital Second Military Medical UniversityShanghai 200433 China

The objective of this study is to investigate the characteristics of the recombinant variant ofhuman vascular endothelial cell growth inhibitor,VEGI72-251,and compare its biological activities with that ofits prototype VEGI24-174,The recombinant plasmid containing the variant VEGI72-251gene was constructedand expressed in Escherichia coli.The effects of the expressed VEGI72-251on cell proliferations were checkedin the human umbilical vein endothelial cell line and certain tumor cell lines （ECV304 and B 16）.The inhibitionof VEGI72-251on angiogenesis was detected in the chorioallantoic membrane of chick embryos.In comparisonwith VEGI24-174,the recombinant human VEGI72-251seems to have no effect on the proliferation of endothelialcells and the angiogenesis of the chorioallantoic membrane in vitro.An enzyme-linked immunosorbent assay-based method was used for the measurement of interleukin-2 （IL-2） production by peripheral blood monocytes（PBMCs） treated with VEGI72-251.PBMCs were pretreated with VEGI72-251（1.25-12.50μg/ml） for 24 h invitro,and the IL-2 concentration in PBMC medium was increased from 354 pg/ml to 1256 pg/ml.It can beconcluded that VEGI72-251is able to increase the level of human IL-2 production by the activation of Tlymphocytes.Differing from VEGI24-174on anti-angiogenesis,VEGI72-251may serve as an anti-cancer factorthrough its activation of T lymphocytes.

关键词： vascular endothelial cell growth inhibitor biological activity interleukin-2

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Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key laboratory of Applied microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

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Naturally occurring PA^(E206K)point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures

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Virologica Sinica 2024年第1期39卷 71-80页

作者： Mengmeng Cao Qiannan Jia Jinghua Li Lili Zhao Li zhu Yufan Zhang Shan Li Tao Deng National Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100730China CAS Key laboratory of Pathogen microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century.In this study,we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients.Sequence comparison of the three main protein subunits(PB2,PB1,and PA)of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution(E206K)was responsible for the observed impaired replication phenotype.Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus’s pathogenicity in vivo.Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1–PA complex to the nucleus at high temperature(39.5℃).Hence,this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.

关键词： H1N1 Influenza A virus Polymerase acidic protein Point mutation Viral replication

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Selenium-oxidizing Agrobacterium sp.T3F4 decreases arsenic uptake by Brassica rapa L.under a native polluted soil

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Journal of Environmental Sciences 2024年第4期138卷 506-515页

作者： Lijin An Chunzhi Zhou Lipeng Zhao Ao Wei Yiting Wang Huimin Cui Shixue Zheng State Key laboratory of Agricultural microbiology College of Life Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China

Toxic arsenic(As)and trace element selenium(Se)are transformed by microorganisms but their complex interactions in soil-plant systems have not been fully understood.An Asand Se-oxidizing bacterium,Agrobacterium sp.T3F4,was applied to a native seleniferous As-polluted soil to investigate As/Se uptake by the vegetable Brassica rapa L.and As-Se interaction as mediated by strain T3F4.The Se content in the aboveground plants was significantly enhanced by 34.1%,but the As content was significantly decreased by 20.5% in the T3F4-inoculated pot culture compared to the control(P<0.05).Similar result was shown in treatment with additional 5 mg/kg of Se(IV)in soil.In addition,the As contents in roots were significantly decreased by more than 35% under T3F4 or Se(IV)treatments(P<0.05).Analysis of As-Se-bacterium interaction in a soil simulation experiment showed that the bioavailability of Se significantly increased and As was immobilized with the addition of the T3F4strain(P<0.05).Furthermore,an As/Se co-exposure hydroponic experiment demonstrated that As uptake and accumulation in plants was reduced by increasing Se(IV)concentrations.The 50% growth inhibition concentration(IC50)values for As in plants were increased about one-fold and two-fold under co-exposure with 5 and 10μmol/L Se(IV),respectively.In conclusion,strain T3F4 improves Se uptake but decreases As uptake by plants via oxidation of As and Se,resulting in decrease of soil As bioavailability and As/Se competitive absorption by plants.This provides a potential bioremediation strategy for Se biofortification and As immobilization in As-polluted soil.

关键词： Selenium oxidation Selenium biofortification Arsenite-oxidizing bacteria Arsenic immobilization Brassica rapa L

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key laboratory of Virology and Department of medical microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key laboratory of medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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Effects of COVID-19 pandemic on human fertility:A scientometric and visualized evaluation

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Genes & Diseases 2024年第4期11卷 113-115页

作者： Xiangxiu Wang Yifan Rao Lili Tan Ziqiu Hu Lin Wen Weixi Qin Bingyi Li Keqiao He Tieying Yin Juhui Qiu Yuming Wang Yaokai Chen Xiancai Rao Guixue Wang Key laboratory of Biorheological and Technology of the Ministry of Education State and Local Joint Engineering LaboratoryforVascular ImplantsModern LifeScience Experiment Teaching Center at Bioengineering College of Chongqing UniversityChongqing 400030China Department of microbiology College of Basic Medical SciencesKey Laboratory of Microbial Engineering Under the Educational Committee in ChongqingArmy Medical University(Third Military Medical University)Chongqing 400038China Jinfeng laboratory Chongqing 401329China Division of Infectious Diseases Chongqing Public Health Medical CenterChongqing 400036China

CovID-19,also known as coronavirus disease 2019,is a novel coronavirus disease with high infectivity,strong heterogeneity,and long incubation period(generally 3-14 days).Its main symptoms and signs include fever,dry cough,nasal congestion,fatigue,disorientation,lymphopenia,and dyspnea.The short-term and long-term impacts of covID-19 on human health,particularly its effects on human reproduction and offspring development,continue to receive significant concerns,as they may lead to potential sequelae for several decades or even centuries.

关键词： nasal fertility fever

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Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 115-127页

作者： Yang Yi Wenzhe Li Kefang Liu Heng Xue Rong Yu Meng Zhang Yang-Oujie Bao Xinyuan Lai Jingjing Fan Yuxi Huang Jing Wang Xiaomeng Shi Junhua Li Hongping Wei Kuanhui Xiang Linjie Li Rong Zhang Xin Zhao Xue Qiao Hang Yang Min Ye State Key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing100191China Yunnan Baiyao International medical Research Center Peking UniversityBeijing100191China CAS Key laboratory of Pathogen microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS Key laboratory of Special Pathogens and Biosafety Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China Department of microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing100191China Hubei Jiangxia laboratory Wuhan430000China Shenzhen Children's Hospital ShenzhenGuangdong518036China

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

关键词： COVID-19 Inflammation Licorice-saponin A3 Receptor-binding domain(RBD) SARS-CoV-2

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From dichotomy to diversity:deciphering the multifaceted roles of tumor-associated macrophages in cancer progression and therapy

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Cancer Biology & Medicine 2024年第2期21卷 132-138页

作者： Xiumei Wang Jun Chen Guangshuai Jia Department of Immunology and microbiology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Jinfeng laboratory Chongqing 401329China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510182China

Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.

关键词： immunity homeostasis tumor

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