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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to ***,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD *** several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on *** this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different *** results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD ***,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological *** the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the ***,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild *** summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced *** models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU Department of Hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China Department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

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Zoological research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State Key Laboratory of Genetic Evolution&Animal models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource center for Non-Human primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Transferrin Is Up-Regulated by Microbes and Acts as a Negative Regulator of Immunity to Induce Intestinal Immunotolerance

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research 2024年第3期7卷 761-774页

作者： Xiaopeng Tang Mingqian Fang Ruomei Cheng Junkun Niu Xiaoshan Huang Kuanhong Xu Gan Wang Yang Sun Zhiyi Liao Zhiye Zhang James Mwangi Qiumin Lu Aili Wang Longbao Lv Chao Liu Yinglei Miao Ren Lai Engineering Laboratory of Peptides of Chinese Academy of Sciences Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)and Sino-African Joint Research CenterNew Cornerstone Science InstituteKunming Institute of Zoologythe Chinese Academy of SciencesNo.17 Longxin RoadKunmingYunnan650201China School of Basic Medicine Qingdao UniversityQingdao 266071ShandongChina. Department of Gastroenterology First Affiliated Hospital of Kunming Medical UniversityYunnan Institute of Digestive DiseaseKunming 650032YunnanChina yunnan Province Clinical research center for Digestive diseases Kunming 650032YunnanChina Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204YunnanChina Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences University of Science and Technology of ChinaHefei 230027AnhuiChina center for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhou 511458GuangdongChina.

Cross-talks (e.g., host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes) regulate immunotolerance and intestinal homeostasis. However, underlying mechanisms that regulate the cross-talks remain poorly understood. Here, we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14 (CD14) to inhibit pattern recognition receptor (PRR) signaling and induce host immunotolerance. Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis, which are characterized by impaired intestinal immunotolerance. Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism, suggesting an association between microbial commensalism, transferrin, and host immunotolerance. Mouse colitis models show that transferrin shortage impairs host’s tolerogenic responses, while its supplementation promotes immunotolerance. Designed peptide blocking transferrin–CD14 interaction inhibits immunosuppressive effects of transferrin. In monkeys with idiopathic chronic diarrhea, transferrin shows comparable or even better therapeutic effects than hydrocortisone. Our findings reveal that by up-regulating host transferrin to silence PRR signaling, commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.

关键词： impaired immunity tolerance

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Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of primate Biomedical research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China yunnan Key Laboratory of primate Biomedical research Kunming 650500China Faculty of Life Science and Technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology ***,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical ***,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus ***,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in *** cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed *** also found expression of signaling pathways components that may increase the potential for chimera *** for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in *** engineered cells retained embryonic and extra-embryonic developmental ***,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living *** study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

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Obituary:*** Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

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Zoological research 2024年第1期45卷 230-232页

作者： Wenhui Lee Ren Lai the Key Laboratory of Bioactive Peptides of yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

*** Zhang was born on 9 July 1963 in Kunming,yunnan,China,during a tumultuous period which he often *** his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human *** educational journey was marked by frequent changes in schools due to his parents’occupational ***,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in *** remained an active and loyal member of the School of Biotechnology at the university.

关键词： admitted harbor mechanisms

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The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

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Journal of Genetics and Genomics 2024年第7期51卷 735-748页

作者： Tongyu Zhang Yingxi Zhu Xiaochen Wang Danyang Chong Haiquan Wang Dandan Bu Mengfei Zhao Lei Fang Chaojun Li Ministry of Education Key Laboratory of model Animals for disease Study Model Animal Research CenterMedical School of Nanjing UniversityNational Resource Center for Mutant MiceNanjingJiangsu 210093China State Key Laboratory of Reproductive Medicine and Offspring Health China International Joint Research Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthGusu SchoolNanjing Medical UniversityNanjingJiangsu 211166China

In mammals,the neonatal heart can regenerate upon injury within a short time after birth,while adults lose this *** reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal ***,we reveal that cardiac metabolic reprogramming could be regulated by altering global protein *** performing 4D label-free proteomics and lysine lactylation(Kla)omics analyses in mouse hearts at postnatal days 1,5,and 7,2297 Kla sites from 980 proteins are identified,among which 1262 Kla sites from 409 proteins are *** clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic *** expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid ***,we verify the Kla levels of several differentially modified proteins,including ACAT1,ACADL,ACADVL,PFKM,PKM,and ***,our study reports a comprehensive Kla map in the neonatal mouse heart,which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

关键词： Lactylation Metabolicrep rogramming Postnatal heart regeneration Cell proliferation

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TMEM63B regulates postnatal development of cochlear sensory epithelia via thyroid hormone signaling

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Journal of Genetics and Genomics 2024年第6期51卷 673-676页

作者： Chang Ye Tian-Zi Zhang Yan-Yu Zang Yun Stone Shi Guoqiang Wan State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of model Animal for disease Study Model Animal Research CenterMedical SchoolNanjing UniversityNanjingJiangsu 210032China Guangdong Institute of Intelligence Science and Technology ZhuhaiGuangdong 519031China

Sound transmission occurs in the cochlea,a complex and ingenious subdivision in the inner *** structure of the cochlea develops structurally and functionally by the time before two postnatal weeks(the time of hearing onset)in mice(Geal-Dor et al.,1993).Greater epithelial ridge(GER,also known as Kolliker's organ)is a transient cochlear structure containing a group of columnar epithelial supporting cells surrounding the inner hair cells(IHCs).

关键词： cochlear al. supporting

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Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential

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Zoological research 2024年第5期45卷 1001-1012页

作者： Li-Na Cha Juan Yang Jin-Ai Gao Xin Lu Xiao-Long Chang Rebecca Caroline Thuku Qi Liu Qiu-Min Lu Dong-Sheng Li Ren Lai Ming-Qian Fang Engineering Laboratory of Peptides of Chinese Academy of Sciences Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Key Laboratory of Genetic Evolution&Animal ModelsSino-African Joint Research Centerand New Cornerstone Science LaboratoryKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650201China School of Molecular Medicine Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China First Affiliated Hospital of Kunming Medical University KunmingYunnan 650032China

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic *** contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic *** this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin ***,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,*** vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin *** murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral ***,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion ***,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical *** conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

关键词： PK FXIIa Anti-thromboinflammation Ischemic stroke therapies Oligopeptide

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Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR–Stat3/Akt pathway

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Journal of Molecular Cell Biology 2024年第1期16卷 29-42页

作者： Qiyao Liu Manyun Li Minli Sun Ruyue Xin Yushu Wang Qin Chen Xiang Gao Zhaoyu Lin MOE Key Laboratory of model Animals for disease Study State Key Laboratory of Pharmaceutical BiotechnologyJiangsu Key Laboratory of Molecular MedicineModel Animal Research CenterNational Resource Center for Mutant Mice of ChinaNanjing Drum Tower HospitalSchool of MedicineNanjing UniversityNanjing 210061China Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200240China

Homeostasis of the skin barrier is essential for maintaining normal skin *** A(GSDMA)is highly expressed in the skin and associated with many skin diseases,such as melanoma and *** mice,GSDMA is encoded by three gene homologues,namely Gsdma1,Gsdma2,and *** Gsdma3 gain-of-function mutations cause hair loss and skin inflammation,Gsdma3-deficient mice do not show any visible phenotypes in skin and hair *** explore the physiological function of GSDMA,we generated conventional Gsdma1/2/3 knockout(KO)*** mice showed significantly alleviated epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate(PMA).Furthermore,the alleviation of epidermal hyperplasia depended on the expression of Gsdma1/2/3 specifically in ***,Gsdma1/2/3 depletion downregulated epidermal growth factor receptor(EGFR)ligands,leading to the decreased EGFR–Stat3/Akt *** results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR–Stat3/Akt pathway.

关键词： GSDMA epidermal hyperplasia PMA Hb-egf EGFR Stat3 Akt

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