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A four-compartment model for the COVID-19 infection—implications on infection kinetics,control measures,and lockdown exit strategies

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Precision Clinical Medicine 2020年第2期3卷 104-112页

作者： Tianbing Wang Yanqiu Wu Johnson Yiu-Nam Lau Yingqi Yu Liyu Liu Jing Li Kang Zhang Weiwei Tong Baoguo Jiang Peking University People’s Hospital Beijing 100044China Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijing 100044China Department of Applied Biology and Chemical Technology Hong Kong Polytechnic UniversityHong KongChina Gennlife(Beijing)Technology Co Ltd BeijingChina School of Medicine Hangzhou Normal UniversityHangzhou 311121China center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacaoChina

Objective:To analyse the impact and repercussions of the surge in healthcare demand in response to the COVID-19 pandemic,assess the potential effectiveness of various infection/disease control measures,and make projections on the best approach to exit from the current ***:A four-compartment model was constructed for SARS-CoV-2 infection based on the Wuhan data and validated with data collected in Italy,the UK,and the *** model captures the effectiveness of various disease suppression measures in three modifiable factors:(a)the per capita contact rate(β)that can be lowered by means of social distancing,(b)infection probability upon contacting infectious individuals that can be lowered by wearing facemasks,personal hygiene,etc.,and(c)the population of infectious individuals in contact with the susceptible population,which can be lowered by *** model was used to make projections on the best approach to exit from the current ***:The model was applied to evaluate the epidemiological data and hospital burden in Italy,the UK,and the *** control measures were identified as the key drivers for the observed epidemiological data through sensitivity *** the different lockdown exit strategies showed that a lockdown exit strategy with a combination of social separation/general facemask use may work,but this needs to be supported by intense monitoring whichwould allowre-introduction/tightening of the controlmeasures if the number of newinfected subjects increases *** and relevance:Governments should act early in a swift and decisive manner for containment *** lockdown exit will need to be monitored closely,with regards to the potential of lockdown *** mathematical model provides a framework for major pandemics in the future.

关键词： COVID-19 exit strategy population infection rates control measures

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ARTICLE OPEN Viral dynamics and antibody responses in people with asymptomatic SARS-CoV-2 infection

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1788-1794页

作者： Zhiwei Sui Xinhua Dai Qingbin Lu Yulan Zhang Min Huang Shufen Li Tao Peng Jie Xie Yongzhuo Zhang Chunchen Wu Jianbo Xia Lianhua Dong Jiayi Yang Wenfeng Huang Siyuan Liu Ziquan Wang Ke Li Qingfang Yang Xi Zhou Ying Wu Wei Liu Xiang Fang Ke Peng center for Advanced Measurement Science National Institute of MetrologyBeijingChina Department of Laboratorial Science and Technology School of Public HealthPeking UniversityBeijingChina State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhanHubeiChina Joint Laboratory of infectious diseases and Health Wuhan Institute of Virology and Wuhan Jinyintan HospitalWuhanChina Department of Laboratory Medicine Huazhong University of Science and TechnologyTongji HospitalTongji Medical CollegeHUSTWuhanHubeiChina Department of Laboratory Medicine Maternal and Child Health Hospital of Hubei ProvinceTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Shenzhen Mindray Bio-Medical Electronics Co. Ltd.ShenzhenChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Virology/Institute of Medical Virology and School of Basic Medical Sciences Wuhan UniversityWuhanChina Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijingChina

Over 40% of the coronavirus disease 2019(COVID-19)COVID-19 patients were asymptomatically infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the immune responses of these asymptomatic individuals is a critical factor for developing the strategy to contain the COVID-19 ***,we determined the viral dynamics and antibody responses among 143 asymptomatic individuals identified in a massive screening of more than 5 million people in eight districts of Wuhan in May *** individuals were admitted to the government-designated centralized sites in accordance with *** incidence rate of asymptomatic infection is〜2.92/100,*** individuals had low viral copy numbers(peaked at 315 copies/mL)and short-lived antibody responses with the estimated diminish time of 69 *** antibody responses in individuals with persistent SARS-CoV-2 infection is much longer with the estimated diminish time of 257 *** results imply that the immune responses in the asymptomatic individuals are not potent enough for preventing SARS-CoV-2 re-infection,which has recently been reported in recovered COVID-19 *** casts doubt on the efficacy of forming"herd-immunity"through natural SARS-CoV-2 infection and urges for the development of safe and effective vaccines.

关键词： asymptomatic admitted immunity

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Mechanism of Cordyceps sinensis in atherosclerosis treatment based on network pharmacology and molecular docking analysis

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Precision Medicine research 2023年第2期5卷 43-50页

作者： Jin-Rong Lang Yue Hao Ping Li Zi-Yu Cui Qi-Qing Cheng Shi Wang School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China Hubei Engineering research center of Traditional Chinese Medicine of South Hubei Province Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100China

Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(***)in treating atherosclerosis by combining network pharmacology and molecular docking ***:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of *** and the corresponding *** String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the ***-active components-targets of action-disease *** databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of *** to identify the potential therapeutic *** String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID ***,the core components of *** and the targets of action were confirmed via molecular docking on AutoDock Vina and ***:In total,7 bioactive ingredients of *** were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with *** core targets involved in AS treatment with *** included MAPK1,SRC,PIK3R1,AKT1,and *** enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and ***,through molecular docking,it was found that the active ingredients of *** presented with strong binding capacities with their corresponding targets,a

关键词： Cordyceps sinensis atherosclerosis network pharmacology molecular docking

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The ubiquitin ligase Pelil inhibits ICOS and thereby Tfh-mediated immunity

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Cellular & Molecular Immunology 2021年第4期18卷 969-978页

作者： Xinfang Huang Shumeng Hao Junli Liu Yuanyuan Huang Manman Liu Chunyuan Xiao Yan Wang Siyu Pei Tao Yu Jing Xu Haikun Wang Dongfang Dai Xiao Su Yichuan Xiao Department of Rheumatology Shanghai East Hospital Tongji UnrversitySchool of MedicineShanghai Giina CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina CAS Key Laboratory of Molecular Virology&Immunology Unit of Respiratory Infection and ImmunityInstitut Pasteur of ShanghaiChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghaiChina Department of Radiation Oncology The Affiliated Cancer Hospital of Nanjing M4edical University(Jiangsu Cancer Hospital)and Jiangsu Institute of Cancer ResearchNanjingJiangsuChina

T follicular helper(Tfh)cells are crucial for regulating autoimmune inflammation and protective immunity against viral ***,the molecular mechanism controlling Tfh cell differentiation is poorly ***,through two mixed bone marrow chimeric experiments,we identified Peli1,a T cell-enriched E3 ubiquitin ligase,as an intrinsic regulator that inhibits Tfh cell ***1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator(ICOS)expression,and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4^(+)T ***,increased ICOS expression on Peli1-KO CD4^(+)T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2,a transcription factor that inhibits Tfh ***,reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO *** a consequence,Peli1-deficient CD4^(+)T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse ***,our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfhrelated autoimmunity or infectious diseases.

关键词： T follicular helper cells Peli1 ICOS

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Ethylene-auxin crosstalk regulates postharvest fruit ripening process in apple

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Fruit research 2021年第1期1卷 116-128页

作者： Nicola Busatto Alice Tadiello Marco Moretto Brian Farneti Francesca Populin Urska Vrhovsek Mauro Commisso Elisa Sartori Paolo Sonego Franco Biasioli Guglielmo Costa Flavia Guzzo Paolo Fontana Kristof Engelen Fabrizio Costa research and Innovation Centre Fondazione Edmund Machvia Mach 138098 San Michele all'AdigeTrentoItaly Department of Biotechnology University of VeronaStrada le Grazie 15CàVignal 137134 VeronaItaly Department of Agricultural Science University of BolognaVia Fanin 4640127BolognaItaly center Agriculture Food Environment C3A University of TrentoVia Mach 138098 San Michele all'AdigeTrentoItaly

The ripening of climacteric fruits,such as apple,is represented by a series of genetically programmed events orchestrated by the action of several *** this study,we investigated the existence of a hormonal crosstalk between ethylene and auxin during the post-harvest ripening of three internationally known apple cultivars:‘Golden Delicious',‘Granny Smith'and‘Fuji'.The normal climacteric ripening was impaired by the exogenous application of 1-methylcyclopropene(1-MCP)that affected the production of ethylene and the physiological behaviour of specific ethylene-related quality traits,such as fruit texture and the production of volatile organic *** application of 1-MCP induced,moreover,a de-novo accumulation of *** RNA-Seq wide-transcriptome analysis evidenced as the competition at the level of the ethylene receptors induced a cultivar-dependent transcriptional *** DEGs annotation carried out through the KEGG database identified as most genes were assigned to the plant hormone signaling transduction category,and specifically related to auxin and *** interplay between these two hormones was further assessed through a candidate gene analysis that highlighted a specific activation of GH3 and ILL genes,encoding key steps in the process of the auxin homeostasis *** results showed that a compromised ethylene metabolism at the onset of the climacteric ripening in apple can stimulate,in a cultivar-dependent fashion,an initial de-novo synthesis and de-conjugation of auxin as a tentative to restore a normal ripening progression.

关键词： crosstalk cultivar process

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Emerging therapeutics in the management of COVID-19

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World Journal of Virology 2021年第1期10卷 1-29页

作者： Asim Kichloo Michael Albosta Akshay Kumar Michael Aljadah Mohamed Mohamed Zain El-Amir Farah Wani Shakeel Jamal Jagmeet Singh Akif Kichloo Department of Internal Medicine Samaritan Medical CenterWatertownNY 13601United States Department of Internal Medicine Central Michigan UniversitySaginawMI 48602United States Department of Cardiothoracic Surgery University of PittsburghPittsburghPA 15260United States Deparment of Internal Medicine Medical College of WisconsinMilwaukeeWI 53226United States Department of Family Medicine Samaritan Medical CenterWatertownNY 13601United States Department of Transplant Nephrology Geisinger Commonwealth School of MedicineSayrePA 18510United States Department of Anesthesiology and Critical Care Saraswathi Institue of Medical SciencesUttar Pradesh 245304India

Abstract The severe acute respiratory syndrome coronavirus 2(coronavirus disease 2019,COVID-19)pandemic has placed a tremendous burden on healthcare systems *** for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical ***,there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19.A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 *** used PubMed,Google Scholar,and *** to search for articles relative to the topic of *** used the following keywords:“COVID-19”,“therapeutics”,“clinical trials”,“treatment”,“FDA”,“ICU”,“mortality”,and“management”.In addition,searches through the references of retrieved articles was also *** this paper,we have elaborated on the therapeutic strategies that have been hypothesized or trialed todate,the mechanism of action of each therapeutic,the clinical trials finished or inprocess that support the use of each therapeutic,and the adverse effects associated with each ***,there is no treatment that has been proven to provide significant benefit in reducing morbidity and *** are many clinical trials for numerous different therapeutic agents currently *** looking back and measuring successful strategies from previous pandemics in addition to carrying out ongoing research,we provide ourselves with the greatest opportunity to find treatments that are beneficial.

关键词： COVID-19 Therapeutics infectious disease SARS-CoV-2 Pharmacology Virology

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Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal

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Cell Regeneration 2022年第1期11卷 399-412页

作者： Fanlu Meng Congcong Shen Li Yang Chao Ni Jianyong Huang Kaijun Lin Zanxia Cao Shicai Xu Wanling Cui Xiaoxin Wang Bailing Zhou Chunyang Xiong Jihua Wang Bing Zhao Shandong Key Laboratory of Biophysics Institute of BiophysicsDezhou UniversityDezhou 253023China Department of Mechanics and Engineering Science College of EngineeringPeking UniversityBeijing 100871China State Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Beijing Innovation center for Engineering Science and Advanced Technology College of EngineeringPeking UniversityBeijing 100871China Wenzhou Institute University of Chinese Academy of SciencesOujiang LaboratoryWenzhou 325000ZhejiangChina

Intestinal organoids,derived from intestinal stem cell self-organization,recapitulate the tissue structures and behav-iors of the intestinal epithelium,which hold great potential for the study of developmental biology,disease modeling,and regenerative *** intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut ***,the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological ***,we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem ***,mechanical stretching stimulates the expansion of SOX9+progenitors by activating the Wnt/β-Catenin *** data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells,thus benefiting organoid *** findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors,paving the way for the application of mechanical forces in organoid-based models.

关键词： Mechanical stretching Intestinal organoid Lgr5+stem cell Regeneration Wnt/β-catenin signaling

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Alzheimer's disease with the Comorbidity of Depression:A Unique Role of Phosphodiesterase-4(PDE4)-Mediated cAMP signaling

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神经药理学报 2019年第Z1期 76-77页

作者： WANG Hao FU Hua-rong ZHANG Fang-fang CHEN Ying ZHOU Yan-meng XU Ying James M. O'Donnell ZHANG Han-ting Institute of Pharmacology Shandong First Medical University Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical SciencesUniversity at Buffalothe State University of New York Departments of Behavioral Medicine & Psychiatry and Physiology Pharmacology & Neurosciencethe Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center

Depression is highly correlated with Alzheimer’s disease(AD),but treatment for the comorbidity of both is lacking. Phosphodiesterase-4(PDE4),an enzyme that catalyzes the hydrolysis of cyclic AMP(cAMP),has been considered as a promising target for treatment of both memory loss in AD and depression. Using mouse models of AD,potent PDE4 inhibitors,and PDE4-subtype knockout mice,we demonstrated that PDE4,in particular the PDE4 D isoform,plays an important role in the comorbidity of memory loss and depression in AD. Treatment with the PDE4 inhibitor rolipram or roflumilast reversed memory deficits in novel object recognition and Morris water-maze tests in APP/PS1 double transgenic and 3 xTg-AD mice,which are widely used models for AD. Similarly,in the tail-suspension and forced-swimming tests,the PDE4 inhibitors reversed the decreased immobility in AD mice,suggesting antidepressant-like effects. The effects of PDE4 inhibitors were mimicked in the tests using mice deficient in PDE4 D,which displayed memory-enhancing and antidepressant-like effects,relative to the WT mice microinfused with beta-amyloid peptide 1-42 into the hippocampus. In addition,the PDE4 inhibitor treatment reversed the decreased ratio of Bcl-2/BAX and inhibited the increased expression of PDE4 D in the cerebral cortex and hippocampus of AD mice. Further,the PDE4 inhibitors reversed the decreased levels of cAMP and expression of phosphorylated cAMP response element-binding protein(CREB) and brain derived neurotrophic factor(BDNF) in AD mice. These were mimicked by PDE4 D deficiency and treatment with a PDE4 D relatively selective inhibitor. In conclusions,these results suggest that PDE4 is an important target for the comorbidity of memory loss and depression in AD,which appears to be mediated by PDE4 D-cAMP signaling.

关键词： Alzheimer’s disease PDE4 inhibitor cAMP signaling Alzheimer’s disease model memory depression

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Role of platelet-rich plasma in ischemic heart disease: An update on the latest evidence

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World Journal of Cardiology 2015年第10期7卷 665-670页

作者： Eleftherios Spartalis Periklis Tomos Demetrios Moris Antonios Athanasiou Charalampos Markakis Michael D Spartalis Theodore Troupis Dimitrios Dimitroulis Despina Perrea Second Department of Propedeutic Surgery Athens University Medical School "Laiko" Hospital Department of Cardiology Onassis Cardiac Surgery Center Department of Anatomy Medical School University of Athens Laboratory of Experimental Surgery and Surgical research "N.S.Christeas" Medical School University of Athens

Myocardial infarction is the most common cause of congestive heart failure. Novel strategies such as directly reprogramming cardiac fibroblasts into cardiomyocytes are an exciting area of investigation for repair of injured myocardial tissue. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. Cell-based myocardial restoration, however, has not penetrated broad clinical practice yet. Plateletrich plasma, an autologous fractionation of whole blood containing high concentrations of growth factors, has been shown to safely and effectively enhance healing and angiogenesis primarily by reparative cell signaling. In this review, we collected all recent advances in novel therapies as well as experimental evidence demonstrating the role of platelet-rich plasma in ischemic heart disease, focusing on aspects that might be important for future successful clinical application.

关键词： Platelet-rich plasma Ischemic heart disease Myocar

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肺结核患者与健康人群肠道菌群差异及其生物标志物的比较研究

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中华结核和呼吸杂志 2021年第11期44卷 939-946页

作者：卢映宏史文佩胡屹夏凡宁柱吴妹英陈诚胡越徐飚复旦大学公共卫生学院流行病学教研室上海200032 解放军海军第九〇五医院结核病科上海200050 自贡市疾病预防控制中心结核病防治所四川643000 苏州大学附属第五人民医院临床检验科 215007 江苏省疾病预防控制中心慢性传染性疾病科南京320106 center for Translational Microbiome research(CTMR) Department of MicrobiologyTumor and Cell BiologyKarolinska InstitutetStockholmSweden

目的分析活动性肺结核患者与健康对照者肠道菌群在物种组成、丰度上的差异,识别并评估特定菌群作为生物标志物区分两组人群的潜能。方法以2017年9月至2019年9月在四川、江苏、上海3个市区级结核病定点医疗机构收治的活动性肺结核患者88... 详细信息

目的分析活动性肺结核患者与健康对照者肠道菌群在物种组成、丰度上的差异,识别并评估特定菌群作为生物标志物区分两组人群的潜能。方法以2017年9月至2019年9月在四川、江苏、上海3个市区级结核病定点医疗机构收治的活动性肺结核患者88例为病例组,其中男65例,女20例,年龄(44.2±15.7)岁。同期在当地体检人群中招募无结核病史的健康人62名为对照组,其中男33名,女29名,年龄(41.4±11.9)岁。采用16S rRNA基因测序技术检测两组人群的粪便样本,分析两组研究对象肠道菌群的多样性差异,以及门和属水平上的物种组成和丰度差异,采用随机森林方法构建预测模型,探索特定菌群是否可以作为区分结核病患者和健康人群的生物标志物。结果α多样性分析结果表明,病例组肠道菌群物种丰富度和均匀度低于对照组,差异有统计学意义(P<0.001),两组人群的肠道菌群整体构成差异有统计学意义(基于Bray-Curtis距离,P<0.001)。与对照组相比,病例组肠道菌群中机会致病菌相对富集,而部分产生短链脂肪酸的有益菌丰度较少,由毛螺菌属(Lachnospira)、毛螺菌科ND3007组(Lachnospiraceae ND3007 group)、罗斯拜瑞菌属(Roseburia)3个菌属训练的随机森林分类器判别两组人群的准确率为76.67%,曲线下面积(AUC)=75.29%(95%CI:0.661~0.845)。结论活动性肺结核患者与健康人群的肠道菌群存在差异,特定菌群有作为生物标志物区分两组人群的潜能。

关键词：结核,肺肠道菌群生物标志物

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