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Infection with SARS-CoV-2 can cause pancreatic impairment

Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng linlin Bao Zhiqi Song ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong li Jiangning liu Qi Lv Xujian liang fengdi li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key Laboratory of 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 Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key Laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key Laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National Laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

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Ficolin A exacerbates severe H1N1 influenza virus infection-induced acute lung immunopathological injury via excessive complement activation

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Cellular & Molecular Immunology 2021年第9期18卷 2278-2280页

作者： Xu Wu linlin Bao Ziqi Hu Duoduo Yao fengdi li Hui li Xiaoxue Xu Yunqing An Xi Wang Bin Cao Xulong Zhang Department of Immunology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Department of Respiratory Medicine Hunan Provincial People’s Hospital(The First Affiliated Hospital of Hunan Normal University)ChangshaChina NHC Key Laboratory of Human Disease Comparative Medicine(The Institute of Laboratory Animal Sciences CAMS&PUMC)Beijing Key Laboratory for Animal Models of Emerging and Reemerging InfectionBeijingChina China-Japan Friendship Hospital National Clinical Research Center for Respiratory DiseasesClinical Center for Pulmonary InfectionsCapital Medical UniversityBeijingChina Department of Core Facility Center Capital Medical UniversityBeijingChina Institute of Respiratory Medicine Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina Tsinghua UniversityPeking University Joint Center for life Sciences BeijingChina

Severe pandemic influenza A(H1N1)2009 virus(pH1N1)infection causes significant morbidity and *** and other groups have reported that immunopathological damage induced by excessive pulmonary inflammation plays a critical role in the pathogenesis of severe pneumonia and provides novel strategies for the treatment of severe influenza infection[1–3].The complement system plays critical roles in both innate and adaptive immunity by activating the classical,alternative and lectin pathways[4].

关键词： influenza infection immunity

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盖挖逆作地铁车站侧墙施工缝工艺优化研究

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广东土木与建筑 2024年第5期31卷 84-87页

作者：李冯缔邵光强陆天福苏守一中国建筑第二工程局有限公司北京100160 中建南方投资有限公司深圳518101

在盖挖逆作车站的侧墙施工中,板墙逆做节点的施工缝工艺是防止渗水病害的关键问题。侧墙施工缝斜坡面底部采用变厚度粗砂支撑,常因压实度不足造成施工缝附近的混凝土质量差,存在渗漏风险。针对盖挖逆作车站侧墙施工缝工艺进行了优化研究... 详细信息

在盖挖逆作车站的侧墙施工中,板墙逆做节点的施工缝工艺是防止渗水病害的关键问题。侧墙施工缝斜坡面底部采用变厚度粗砂支撑,常因压实度不足造成施工缝附近的混凝土质量差,存在渗漏风险。针对盖挖逆作车站侧墙施工缝工艺进行了优化研究,提出了侧墙下预埋预制梯形块的方法,其具有材料轻质、裁剪方便、耐腐蚀等优点,利于后期侧墙混凝土浇筑的密实性,提高施工质量。优化工艺成功应用于深惠城际某车站工程中,为同类型工程提供依据。

关键词：盖挖逆作地铁车站侧墙施工缝防水设计

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Sequentially immune-induced antibodies could cross-neutralize SARS-CoV-2 variants

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Animal Models and Experimental Medicine 2022年第1期5卷 89-93页

作者： Qi Lv Shasha Zhou Feifei Qi Yaqing Zhang fengdi li Mingya liu linlin Bao Beijing Key Laboratory for Animal Models of Emerging and Reemerging 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 National Center of Technology Innovation for Animal Model BeijingChina

Background:The Omicron(B.1.1.529)SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike *** the vaccine-induced neutralizing antibody targets are the spike protein,this may lead to the possibility of vaccine-induced hu-moral immunity ***:We measured the neutralizing activity in vitro for Omicron and compared this with wild type(WH-09)and Delta variants in human and monkey sera from different types of *** monkey sera samples were collected at 1 and 3 months post three-dose inactivated(PiCoVacc)and recombinant protein(ZF2001)*** sera were collected from 1 month post three-dose inactivated ***:In inactivated vaccine sera,at 1/3 months post three-dose,geometric mean titers(GMTs)of neutralization antibody(NAb)against the Omicron variant were 4.9/5.2-fold lower than those of the wild *** recombinant protein vaccine sera,GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild *** human sera,at 1 month post three-dose inactivated vaccination,GMTs of NAb against Omicron were 3.1-fold lower than those of the wild ***:This study demonstrated that despite a reduction in neutralization titers,cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.

关键词： cross-neutralize Omicron SARS-CoV-2 sequentially immune

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Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro

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Animal Models and Experimental Medicine 2023年第1期6卷 51-56页

作者： Yaqing Zhang Qi Lv Feifei Qi fengdi li Ran Deng Xujian liang Mingya liu Yiwei Yan linlin Bao Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina National Center of Technology Innovation for Animal Model BeijingChina

Background:New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and *** pathogenicity has changed from that of wild-type(WH-09)and Omicron variants have over time become globally *** spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants,which is likely to cause immune es-cape and the reduction of the protective effect of the *** study addresses the above issues and provides a basis for formulating relevant prevention and control ***:We collected cellular supernatant and cell lysates and measured the viral titers,viral RNA loads,and E subgenomic RNA(E sgRNA)loads in different Omicron subvariants grown in Vero E6 cells,using WH-09 and Delta variants as a ***,we evaluated the in vitro neutralizing activity of different Omicron sub-variants and compared it to the WH-09 and Delta variants using macaque sera with different types of ***:As the SARS-CoV-2 evolved into Omicron BA.1,the replication ability in vitro began to *** with the emergence of new subvariants,the replication ability gradually recovered and became stable in the BA.4 and BA.5 *** WH-09-inactivated vaccine sera,geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against *** Delta-inactivated vaccine sera,geometric mean titers of neutrali-zation antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against ***:According to the findings of this research,the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants,and was lower in BA.1 than in other Omicron *** two doses of inactivated(WH-09 or Delta)vaccine,cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.

关键词： cross-neutralize Omicron replication SARS-CoV-2

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Therapeutic efficacy of Pudilan Xiaoyan Oral liquid(PDL)for COVID-19 in vitro and in vivo

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1875-1877页

作者： Wei Deng Yanfeng Xu Qi Kong Jing Xue Pin Yu Jiangning liu Qi Lv fengdi li Qiang Wei linlin Bao 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 CollegeBeijingChina

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed *** now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 *** medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.

关键词： vivo fir COV

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Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

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Science China(life Sciences) 2022年第12期65卷 2517-2526页

作者： Zhe Chen linlin Bao Bin Zhu Hua Fu Shuangli Zhu Tianjiao Ji Ying Xue Chuan liu Xurong Wang fengdi li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong liu Qi Jin MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China 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 CollegeBeijing 100021China School of Computer Science and Engineering Hunan University of Science and TechnologyXiangtan 411201China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua UniversityBeijing 100084China Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityChangsha 410081China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310058China

Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to ***,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are ***,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in *** cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of *** a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic *** particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.

关键词： enterovirus A71 antibody mouse models cryo-electron microscopy

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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

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Sequential immunizations confer cross-protection against variants of SARS-CoV-2,including Omicron in Rhesus macaques

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1746-1755页

作者： Wei Deng Qi Lv fengdi li Jiangning liu Zhiqi Song Feifei Qi Qiang Wei Pin Yu Mingya liu Shasha Zhou Yaqing Zhang Hong Gao Nan Wang Zijing Jia Kai Gao Jiayi liu Chong Xiao Haiquan Shang Xiangxi Wang linlin Bao 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 CollegeBeijing 100021China National Center of Technology Innovation for Animal Model BeijingChina CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Department of Radiology Beijing Anzhen HospitalCapital Medical UniversityBeijingChina

Variants of concern(VOCs)like Delta and Omicron,harbor a high number of mutations,which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies(NAbs).In this study,Rhesus macaques immunized with 2-dose inactivated vaccines(Coronavac)were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine,or a bivalent inactivated vaccine(Beta and Delta)to determine the effectiveness of sequential *** booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type.

关键词： neutral harbor Omi

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Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients

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Signal Transduction and Targeted Therapy 2022年第2期7卷 560-572页

作者： Zhiqi Song linlin Bao Wei Deng Jiangning liu Erjun Ren Qi Lv Mingya liu Feifei Qi Ting Chen Ran Deng fengdi li Yunpeng liu Qiang Wei Hong Gao Pin Yu Yunlin Han Wenjie Zhao Junjun Zheng Xujian liang Fuhe Yang Chuan Qin 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 CollegeBeijingChina Shi Jia Zhuang Academy Of Agricultural And Forestry Sciences ShijiazhuangChina Institute of Special Animal and Plant Sciences of CAAS ChangchunChina Chinese Academy of Agricultural Sciences(CAAS) BeijingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many ***,the systemic pathological features of SARS-CoV-2-infected minks are mostly ***,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune *** viral protein partially co-localized with activated Mac-2+macrophages throughout the ***,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal ***,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune *** kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage ***,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted *** data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers.

关键词： patients alterations vitamin

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