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Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

animal models and Experimental Medicine 2024年第3期7卷 347-361页

作者： Yanju Gong Mingfeng Li Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang iNHC key laboratory of human disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInternational Center for Technology and lnnovation of Animal ModelComparative Medicine CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PuMC)BeijingChina Changping National laboratory(CPNL) BeijingChina

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD ***,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain ***:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD *** in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were *** addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD ***:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive *** mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal ***,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and *** expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also ***:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces co

关键词： 5xFAD mice Alzheimer's disease ApoE4 allele depression like

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Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

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Zoological Research 2024年第2期45卷 429-438页

作者： Hong Zhou Ren-Rong Tian Xiu-Rong Wang Jin-Xuan Yang Yun-Xiao Wang Ming-Liang Zhao Xu-Dong Zhang Yu-Hua Ma Long-Bao Lv Edward CHolmes Yong-Tang Zheng Wei-Feng Shi School of Clinical and Basic Medical sciences Shandong First Medical University&Shandong Academy of Medical SciencesJi’nanShandong 250117China key laboratory of Emerging Infectious diseases in Universities of Shandong Shandong First Medical University and Shandong Academy of Medical SciencesTaianShandong 271000China key laboratory of animal models and human disease mechanisms of the chinese academy of sciences/key laboratory of Bioactive Peptides of yunnan province KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China School of Public Health Shandong First Medical University&Shandong Academy of Medical SciencesJi’nanShandong 250117China National Resource Center for Non-human Primates Kunming Primate Research CenterKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Sydney Institute for Infectious diseases School of Medical SciencesThe University of SydneySydneyNew South Wales 2006Australia Department of Infectious diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute of Virology Shanghai Jiao Tong University School of MedicineShanghai 200025China

The chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic *** similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health ***,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic *** total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and ***,the presence of rotavirus was recorded in tree shrews for the first *** viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(ndicating ***,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral *** analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel *** findings provide insights into the diverse viral spectrum present in captive chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

关键词： Tree shrew(Tupaia belangeri chinensis) Meta-transcriptomic sequencing Mammalian viruses Genomic analysis

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DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang Ceshi Chen Affiliated Hospital of Guangdong Medical University Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China key laboratory of animal models and human disease mechanisms of the chinese academy of sciences and yunnan province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research Center of Guizhou Medical University GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China yunnan Cancer Hospital and the Third Affiliated Hospital of Kunming Medical University and yunnan Cancer Center KunmingYunnan 650500China academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina key laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina key laboratory of animal models and human disease mechanisms of the chinese academy of sciences&yunnan province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing key laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological Research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs Marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou key laboratory of Genetic Evolution and animal models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National Research Facility for Phenotypic&Genetic Analysis of Model animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint laboratory of Bioresources and Molecular Research in Common diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health Center and Psychiatric laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical Medical Research Center for Mental Disorders ChengduSichuan 610044China German Primate Center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State key laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary animal diseases Center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering Research Center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC key laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina key laboratory of animal models and human disease mechanisms of the chinese academy of sciences and yunnan province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State key laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State key laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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A booming field of large animal model research

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Zoological Research 2024年第2期45卷 311-313页

作者： Xiao-Jiang Li Liangxue Lai Guangdong key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhouGuangdong 510632China CAS key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China

animal models are integral to the study of fundamental biological processes and the etiology of human *** animal models,especially those involving mice,have yielded abundant and significant insights,greatly enhancing ... 详细信息

关键词： mechanisms insight field

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The 3rd Symposium on animal models of Primates——The Application of Non-human Primates to Basic Research and Translational Medicine

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Journal of Genetics and Genomics 2015年第6期42卷 339-341页

作者： Yong-Gang Yao Yong-Bin Chen Bin Liang key laboratory of animal models and human disease mechanisms of the chinese academy of sciences & yunnan province and Kunming Primate Research CenterKunming Institute of ZoologyChinese Academy of Sciences

In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues：（1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.

关键词： The 3rd Symposium on animal models of Primates The Application of Non-human Primates to Basic Research and Translational Medicine

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animal secretory endolysosome channel discovery

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Zoological Research 2021年第2期42卷 141-152页

作者： Yun Zhang Qi-Quan Wang Zhong Zhao Cheng-Jie Deng key laboratory of animal models and human disease mechanisms of the chinese academy of sciences&yunnan province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Center for Excellence in animal Evolution and Genetics Chinese Academy of SciencesKunmingYunnan 650223China

Secretory pore-forming proteins(PFPs) have been identified in organisms from all kingdoms of life. Our studies with the toad species Bombina maxima found an interaction network among aerolysin family PFPs(af-PFPs) and trefoil factors(TFFs). As a toad af-PFP, Bm ALP1 can be reversibly regulated between active and inactive forms, with its paralog Bm ALP3 acting as a negative regulator. Bm ALP1 interacts with Bm TFF3 to form a cellular active complex called βγ-CAT. This PFP complex is characterized by acting on endocytic pathways and forming pores on endolysosomes, including stimulating cell macropinocytosis. In addition, cell exocytosis can be induced and/or modulated in the presence of βγ-CAT. Depending on cell contexts and surroundings, these effects can facilitate the toad in material uptake and vesicular transport, while maintaining mucosal barrier function as well as immune defense. Based on experimental evidence,we hereby propose a secretory endolysosome channel(SELC) pathway conducted by a secreted PFP in cell endocytic and exocytic systems, with βγ-CAT being the first example of a SELC protein. With essential roles in cell interactions and environmental adaptations, the proposed SELC protein pathway should be conserved in other living organisms.

关键词： Pore-forming protein Secretory endolysosome channel(SELC) Endocytosis Exocytosis Vesicular transport

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Formation of membrane pores by gasdermin-N causes pyroptosis

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Science China(Life sciences) 2016年第10期59卷 1071-1073页

作者： Xiaopeng Qi key laboratory of animal models and human disease mechanisms Kunming Institute of Zoology Chinese Academy of Sciences

Pyroptosis, a lytic, highly inflammatory form of pro- grammed cell death, plays an important role in the defense against microbial infections and danger signals. However, excessive pyroptosis can be detrimental to host defense. Pyroptosis is uniquely dependent on inflammatory caspases such as caspase-1, murine caspase-ll, and its human hom- ologs caspases-4 and -5. Caspase-1 is a central component of canonical NLRP3, NLRC4, AIM2,

关键词：细胞程序性死亡 caspase 膜孔宿主防御微生物感染半胱天冬酶组成部分炎症

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