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SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterolincreased endosomal pH of alveolar macrophages

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Cellular & Molecular Immunology 2022年第2期19卷 210-221页

作者： Zhenfeng Wang Jiadi Lv Pin Yu yajin qu Yabo Zhou Li Zhou Qiangqiang Zhu Shunshun Li Jiangping Song Wei Deng Ran Gao Yuying Liu Jiangning Liu Wei-Min Tong Chuan Qin Bo Huang Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesCAMS and Peking Union Medical CollegeBeijingChina Department of Pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising ***,we show that ACE2-overexpressing A549 cell-derived microparticles(AO-MPs)are a potential therapeutic agent against SARS-CoV-2 *** administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages(AMs).Then,AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs,thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for *** pH regulation is attributable to oxidized cholesterol,which is enriched in AO-MPs and translocated to endosomal membranes,thus interfering with proton pumps and impairing endosomal *** addition to promoting viral degradation,AO-MPs also inhibit the proinflammatory phenotype of AMs,leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side *** findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.

关键词： SARS-CoV-2 microparticles Alveolar macrophages Endosomes Lysosomes

Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and covaccination as an effective method of prevention of COVID-19 and influenza

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1876-1883页

作者： Linlin Bao Wei Deng Feifei Qi Qi Lv Zhiqi Song Jiangning Liu Hong Gao Qiang Wei Pin Yu Yanfeng Xu yajin qu Fengdi Li Jing Xue Shuran Gong Mingya Liu Guanpeng Wang Shunyi Wang Binbin Zhao Bin Cong Chuan Qin Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Hebei Medical University ShijiazhuangChina

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus,leading to more serious respiratory diseases during this ***,the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains *** a mammalian model,sequential infection was performed in ferrets and in K18-MCE2 mice,with SARS-CoV-2 infection following *** found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19,and enhanced pulmonary damage,but reduced viral shedding of throat swabs and viral loads in the lungs of ***,mortality was increased in sequentially infected mice compared with single-infection *** with singlevaccine inoculation,co-inoculation of PiCoVacc(a SARS-CoV-2 vaccine)and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune *** immunization effectively protected K18-MCE2 mice against both H1N1 and SARS-CoV-2 *** findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2,which together notably enhanced pneumonia in ferrets and mice,as well as demonstrated that simultaneous vaccination against HINT and SARS-CoV-2 may be an effective prevention strategy for the coming winter.

关键词： prevention H1N1 influenza

Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques

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Protein & Cell 2022年第12期13卷 920-939页

作者： Chun-Chun Gao Man Li Wei Deng Chun-Hui Ma Yu-Sheng Chen Yong-Qiao Sun Tingfu Du Qian-Lan Liu Wen-Jie Li Bing Zhang Lihong Sun Si-Meng Liu Fengli Li Feifei Qi yajin qu Xinyang Ge Jiangning Liu Peng Wang Yamei Niu Zhiyong Liang Yong-Liang Zhao Bo Huang Xiao-Zhong Peng Ying Yang Chuan Qin Wei-Min Tong Yun-Gui Yang CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentCollege of Future TechnologyBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100000China Department of Pathology Institute of Basic Medical SciencesMolecular Pathology Research CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeKunming 650031China Center for Experimental Animal Research Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Pathology Peking Union Medical College HospitalMolecular Pathology Research CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Clinical Immunology Center Chinese Academy of Medical SciencesBeijing 100005China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Med

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries,how-ever,the underlying mechanism,in particular immune responses in different organs,remains *** this study,comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were *** to normal controls,SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs,with drastic transcriptomic changes in cerebral cortex and right ***,cerebral cortex exhibited a hyperinflammatory state evidenced by sig-nificant upregulation of inflammation response-related ***,expressions of coagulation,angio-genesis and fibrosis factors were also up-regulated in cerebral *** on our findings,neuropilin 1(NRP1),a receptor of SARS-CoV-2,was significantly elevated in cerebral cortex post infection,accompanied by active immune response releasing inflammatory factors and signal transmission among tissues,which enhanced infection of the central nervous system(CNS)in a positive feedback way,leading to viral ***,our study depicts a multi-tissue/organ tran-scriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2,and provides important insights into the mechanistic basis for COVID-19-asso-ciated clinical complications.

关键词： SARS-CoV-2 NRP1 inflammation central nervous system viral encephalitis rhesus macaque

SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice

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Animal Models and Experimental Medicine 2021年第1期4卷 2-15页

作者： Yuanwu Ma Dan Lu Linlin Bao yajin qu Jiangning Liu Xiaolong Qi Lei Yu Xu Zhang Feifei Qi Qi Lv Yunpeng Liu Xudong Shi Caixian Sun Jing Li Jie Wang Yunlin Han Kai Gao Wei Dong Ning Liu Shan Gao Jing Xue Qiang Wei Sidan Pan Hong Gao Lianfeng Zhang Chuan Qin Key Laboratory of Human Disease Comparative Medicine National Health Commission of China(NHC)Institute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Institute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina

Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of ***,how SARS-CoV-2 alters the progression of chronic diseases remain ***:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in ***-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology ***:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 *** infection increased fasting blood glucose and reduced insulin response in DM *** mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR ***:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic ***-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing *** work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.

关键词： Cardiovascular disease COVID-19 diabetes mellitus mouse model SARS-CoV-2

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高等级生物安全实验室风险分析与发展建议

实验室研究与探索 2023年第9期42卷 288-292页

作者：屈亚锦宋晓宇李泉霖孙洪磊韩军中国农业大学动物医学院北京100193

随着国际化进程的加快促使传染病传播方式和扩散途径呈多样化和快速化,病原微生物的跨物种感染和跨地域传播风险加剧,全球生物安全形势日趋复杂严峻。高等级生物安全实验室是从事高致病性病原微生物科学研究的重要技术平台,是保护实验... 详细信息

随着国际化进程的加快促使传染病传播方式和扩散途径呈多样化和快速化,病原微生物的跨物种感染和跨地域传播风险加剧,全球生物安全形势日趋复杂严峻。高等级生物安全实验室是从事高致病性病原微生物科学研究的重要技术平台,是保护实验室工作人员不被感染、外界环境不受污染的关键防护屏障。生物安全是国家安全的重要防线,建设布局完善的高等级生物安全实验室体系是国家安全的重要支撑保障。介绍了高等级生物安全实验室的发展历史、风险分析并归纳总结了实验室管理运行中存在的问题,并提出了今后高等级生物安全实验室的发展建议,为促进我国高等级生物安全实验室平稳健康发展提供参考。

关键词：高等级生物安全实验室生物安全动物疫病风险分析发展规划

麦哲伦企鹅曲霉菌病的组织病理学观察和病原分离鉴定

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中国兽医学报 2021年第10期41卷 2003-2008,2014页

作者：宋志琦孙艳明苏磊屈亚锦赵文杰韩云林秦川中国医学科学院医学实验动物研究所北京协和医学院比较医学中心国家卫生健康委员会人类疾病比较医学重点实验室北京市人类重大疾病实验动物模型工程技术研究中心北京100021 北京海洋馆北京100081

对病死的麦哲伦企鹅进行剖检、大体病变检查、组织病理学检验以及病原的分离与鉴定,为企鹅的临床诊断和饲养管理提供数据支持。采集死亡麦哲伦企鹅的各脏器,应用石蜡切片及HE染色、六胺银染色和PAS染色,结合组织切片扫描系统,对各脏器... 详细信息

对病死的麦哲伦企鹅进行剖检、大体病变检查、组织病理学检验以及病原的分离与鉴定,为企鹅的临床诊断和饲养管理提供数据支持。采集死亡麦哲伦企鹅的各脏器,应用石蜡切片及HE染色、六胺银染色和PAS染色,结合组织切片扫描系统,对各脏器进行组织病理学观察并进一步对病料进行病原分离和鉴定。通过大体病变观察,可见企鹅胸腔内部沿着气管两侧、肺脏和气囊周围散布大量浅黄色粟粒至杏核大小结节;肺脏呈现散在的大小不一的典型特异性肉芽肿结构,病变累及消化系统等其他脏器。肉芽肿结节中心为坏死区域,经六胺银染色和PAS染色,可在坏死区域分别观察到深褐色和紫红色的真菌菌丝样结构。从企鹅肺部病灶共分离12株真菌,对分离菌株的ITS序列进行测序并进行BLAST比对鉴定,基于ITS序列构建系统发育树,结合形态学特征,将这些菌株分别鉴定为6个种,其中烟曲霉菌分离频率最高,占分离菌株的33%;经高通量测序,获得270个操作分类单元,其中烟曲霉菌的相对丰度为91%,因此可进一步确定该病灶主要由曲霉菌引起。

关键词：麦哲伦企鹅曲霉菌病组织病理学分离鉴定

新型H3N3亚型禽流感病毒对鸡致病性与传播性研究

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中国农业大学学报 2023年第7期28卷 99-107页

作者：孙洪磊佟琪余海莉韩琪祺李涵常昊宇屈亚锦徐杰刘思当刘金华中国农业大学动物医学院/农业农村部禽流感等家禽重大疾病防控重点实验室北京100193 山东农业大学动物科技学院山东泰安271018

新型禽流感病毒对家禽养殖业可造成严重经济损失,及时发现和阻断其传播具有重要意义。2022—2023年,本实验室在我国发病鸡群中监测到新型H3N3亚型禽流感病毒的出现和传播。本研究对发病鸡群开展了临床发病情况调查,对分离病毒进行了全... 详细信息

新型禽流感病毒对家禽养殖业可造成严重经济损失,及时发现和阻断其传播具有重要意义。2022—2023年,本实验室在我国发病鸡群中监测到新型H3N3亚型禽流感病毒的出现和传播。本研究对发病鸡群开展了临床发病情况调查,对分离病毒进行了全基因组演化分析,并对分离的代表性病毒进行了鸡致病性以及空气传播性试验。结果表明:(1)H3N3最早于2022年12月在华东地区发生产蛋下降的蛋鸡群出现,随后陆续在华东、华北、东北等多个地区的鸡群中监测到,发病群体主要为产蛋鸡,鸡群发病率高,死亡率低(1%~5%),主要引起产蛋率急性下降(10%~40%)。(2)病毒全基因组序列分析显示,H3N3病毒为新型重排病毒,由鸡群中流行的H3N8病毒与H10N3病毒重排产生,6个内部基因来源于H9N2病毒。(3)与H3N8病毒类似,新型H3N3病毒对鸡群高度易感,可在鸡鼻甲、气管、肺等呼吸器官中高效复制并排毒,引起呼吸系统严重病理损伤。(4)空气传播性结果表明,新型H3N3病毒可在鸡群之间空气传播,而H3N8病毒不能在鸡群间空气传播。综上,新型H3N3禽流感病毒对鸡具有较强的致病性和传播性,有可能成为新的优势流行病毒,对我国家禽养殖业威胁较大,需要开展进一步的防控研究。

关键词： H3N3 禽流感病毒鸡致病性空气传播性

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Animal Models and Experimental Medicine 2020年第1期3卷 93-97页

作者： Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song yajin qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDCBeijingChina Department of Radiology Bejing Anzhen HospitalCapital Medical UniversityBeijingChina Institute of Pathogen Biology Chinese Academy of Medical SciencesBeijingChina Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChina

Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international *** high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate ***:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune ***:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 *** developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial *** antigens were detected mainly in alveolar epithelial cells and ***:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young *** macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.

关键词： pathogenicity pneumonia rhesus macaque model SARS-CoV-2

某规模化猪场猪瘟和伪狂犬病净化的实施及成效分析

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养猪 2013年第1期 100-102页

作者：任庆海胡东方刘月月李超屈亚锦刘立涛刘思当山东农业大学动物科技学院山东泰安271000

针对当前规模化猪场猪瘟病毒及伪狂犬病病毒感染的严峻状况,选取山东省某规模化猪场核心种猪群开展猪瘟及伪狂犬病的净化工作。结合血清学、分子生物学诊断方法,在系统研究了该场两种疫病的流行病学、带毒状况及疫苗免疫状态的基础上,... 详细信息

针对当前规模化猪场猪瘟病毒及伪狂犬病病毒感染的严峻状况,选取山东省某规模化猪场核心种猪群开展猪瘟及伪狂犬病的净化工作。结合血清学、分子生物学诊断方法,在系统研究了该场两种疫病的流行病学、带毒状况及疫苗免疫状态的基础上,对种猪群进行为期约一年的猪瘟及伪狂犬病净化工作,在良好的卫生防疫措施的基础上,精选疫苗、制定合理的免疫程序,淘汰带毒猪及抗体阴性猪。结果显示:经过两次净化,种猪群的猪瘟病毒带毒率下降到3.03%,伪狂犬病病毒带毒率下降到3.23%,生产成绩得到明显改善,达到了净化之目的。

关键词：猪瘟伪狂犬病规模猪场抗体监测净化