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Stable non-synonymous substitutions on NS gene (NS1 and NS2 proteins) of.Qinghai lake H5N1 inf.uenza virus (Clade 2.2) af.er successive passages in Muscovy ducks

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Science China(Lif. Sciences) 2009年第9期52卷 847-853页

作者： gao george f. Key Laboratory of.Pathogenic Microbiology and Immunology of.CAS (CASPMI) Institute of Microbiology Chinese Academy of Sciences (CAS) China-Japan Joint Laboratory of.Molecular Immunology and Molecular Microbiology Institute of Microbiology Chinese Academy of Sciences Graduate University of.Chinese Academy of.Sciences Beijing Institutes of.Lif. Science Chinese Academy of Sciences

Although worldwide concern has been raised since the large-scale outbreak of.highly pathogenic avian inf.uenza in wild birds at Qinghai Lake,China in 2005,the f.ctors responsible f.r the ability to kill waterf.wl remain unclear. The why and how questions of.the H5N1 virus species-jump into its reservoir host need to be answered. In this report we test the pathogenicity and adaptation of.Qinghai Lake (Clade 2.2) isolate to Muscovy ducks f.r f.rther understanding of.this virus. The isolate was highly pathogenic in ducks and retained its high pathogenicity even af.er 20 generations of.passage in ducks. During the process of.serial passages,only the NS gene developed non-synonymous substitutions,which caused two mutations in NS1 protein (Val23Ala and Leu207Pro) and one in NS2 (Phe55Leu). These mutations persisted immutably through all subsequent passages and the pathogenicity remained high,implying that highly pathogenic H5N1 virus remains stable in aquatic birds through oral transmission. Although the exact f.nctions of.these mutations are not known,our results provide an important f.undation f.r f.rther understanding the characteristics of.the Qinghai Lake isolates.

关键词： avian inf.uenza virus H5N1 mutation NS1/2 serial passages

Ribavirin is ef.ective against drug-resistant H7N9 inf.uenza virus inf.ctions

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Protein & Cell 2016年第8期7卷 611-614页

作者： Bi, Yuhai Wong, Gary Liu, Yingxia Liu, Lei gao, george f. Shi, Yi Chinese Acad Sci Inst Microbiol CAS Key Lab Pathogen Microbiol & Immunol Beijing 100101 Peoples R China Shenzhen Third Peoples Hosp Shenzhen Key Lab Pathogen & Immun State Key Discipline Infect Dis Shenzhen 518112 Peoples R China Chinese Acad Sci Ctr Influenza Res & Early Warning CASCIRE Beijing 100101 Peoples R China Chinese Acad Sci Beijing Inst Life Sci RNIH Beijing 100101 Peoples R China Zhejiang Univ Collaborat Innovat Ctr Diag & Treatment Infect Di Hangzhou 310003 Zhejiang Peoples R China

Dear Editor, In f.bruary and March 2013, a novel inf.uenza A （H7N9） virus emerged in China, causing an acute respiratory distress syndrome and occasionally multiple organ f.ilure with high f.tality rates in humans （Li et al., 2014）. A total of.681 laboratory-conf.rmed cases and 275 deaths have been reported as of.November 13th,

关键词： H7N9 Virus Oseltamivir Zanamivir Inf.uenza Virus Inf.ction H7N9 Inf.ction

The new emerging H7N9 inf.uenza virus indicates poultry as new mixing vessels

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Science China(Lif. Sciences) 2014年第7期57卷 731-732页

作者： LIU Di gao george f. Key Laboratory of.Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences Network Inf.rmation Center Institute of MicrobiologyChinese Academy of Sciences Beijing Institutes of.Lif. Science Chinese Academy of Sciences Of.ice of.Director-General Chinese Center for Disease Control and Prevention

Since 30 March 2013,the Chinese Center f.r Disease Control and Prevention(China CDC)has reported the f.rst laboratory-conf.rmed cases of.inf.uenza A H7N9 virus human *** new pathogen caused 144 human inf.ctions with 47 f.tal cases in year 2013,and continued to bring another wave in 2014,caused another 273 inf.ctions with 108deaths as of.27th *** H7N9 inf.uenza virus has again raised the global concerns of.the potential *** of.the origin and evolution of.this virus revealed that the novel H7N9 inf.uenza virus was reassorted f.om H7,N9and H9N2 subtypes of.inf.uenza viruses f.om domestic ducks,wild waterf.wls and poultry,respectively;and the processes of.genetic reassortments were sequential and dynamic[1?3].

关键词：甲型流感病毒中国疾病预防控制中心混合容器家禽 H9N2亚型人类感染全球性问题野生水禽

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以T细胞受体为基础的免疫疗法研究进展

生物工程学报 2023年第10期39卷 4004-4028页

作者：陈缘高福谭曙光广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心广西南宁530021 中国科学院微生物研究所病原微生物与免疫学重点实验室北京100101 中国科学院大学存济医学院北京100049

T细胞是机体抗肿瘤免疫的核心,以T细胞功能调控为基础的免疫检查点疗法已经在多种肿瘤的临床治疗中取得了重大突破,以基因工程化T细胞为基础的过继性免疫细胞疗法在血液瘤治疗中取得了重要进展,免疫治疗已经对肿瘤的临床治疗产生了深刻... 详细信息

T细胞是机体抗肿瘤免疫的核心,以T细胞功能调控为基础的免疫检查点疗法已经在多种肿瘤的临床治疗中取得了重大突破,以基因工程化T细胞为基础的过继性免疫细胞疗法在血液瘤治疗中取得了重要进展,免疫治疗已经对肿瘤的临床治疗产生了深刻变革,成为肿瘤临床治疗策略的重要组成部分。T细胞受体(T cell receptor, TCR)赋予了T细胞识别肿瘤抗原的特异性,能够识别由主要组织相容性复合体(major histocompatibility complex, MHC)呈递的包括胞内抗原在内的广泛肿瘤抗原,具有高度的抗原敏感性,因而具有广泛的抗肿瘤应用前景。2022年第一款TCR药物的上市开启了TCR药物开发的新纪元,多项TCR药物临床研究表现出潜在的肿瘤治疗价值。本文综述了以TCR为基础的免疫治疗策略研究进展,包括T细胞受体工程化T细胞(Tcell receptor-engineered T cell, TCR-T)和TCR蛋白药物,以及基于TCR信号的其他免疫细胞疗法,以期为以TCR为基础的免疫治疗策略开发提供参考。

关键词： T细胞受体免疫治疗 T细胞受体工程化T细胞 T细胞衔接器

Diversif.ed anchoring f.atures the peptide presentation of.DLA-88*50801: f.rst structural insight into domestic dog MHC class I

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Diversified anchoring features the peptide presentation of D...

Onf.actional(g,f.n′,m)-Critical Covered Graphs

第十一届全国免疫学学术大会

作者： Xiao Jin Wang Ming Liu William J. gao george f. Key Laboratory of.Veterinary Bioproduction and Chemical Medicine of.the Ministry of.Agriculture Zhongmu Institutes of China Animal Husbandry Industry Co.Ltd National Institute f.r Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention

Background:Canines represent a crucial animal model f.r studying human diseases and organ transplantation,as well as the evolution of.domestic *** histocompatibility complexes(MHCs),with a central role in cellular immunity,are commonly used in the study of.dog population genetics and genome ***,the molecular basis f.r the peptide presentation of.dog MHC remains largely unknown.

关键词： domestic animal canine MHC I peptide

来源： cnki会议评论

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Journal of.the Operations Research Society of.China 2024年第2期12卷 446-460页

作者： Wei gao Wei-f.n Wang School of.Inf.rmation Science and Technology Yunnan Normal UniversityKunming 650500YunnanChina Department of.Mathematics Zhejiang Normal UniversityJinhua 321004ZhejiangChina

The main contribution in this article is threef.ld:(1)we show the necessary and suf.icient condition f.r graphs to be f.actional(g,f.-covered which can be expressed in dif.erent f.rms,and extended to f.actional(g,f.m)-covered graphs;(2)the concept of.f.actional-critical covered graph is put f.rward and its necessary and suf.icient condition is given;(3)we present the degree condition f.r a graph to be f.actional(g,f.n′,m)-critical covered,and show that degree bound is sharp when m is ***,the related result in f.actional((a,b,n′,m)-critical covered setting is also verif.ed.

关键词： Network f.actional f.ctor Data transmission f.actional covered graph f.actional critical covered graph

f.rster resonance energy transf.r reveals phillygenin and swertiamarin concurrently target AKT on dif.erent binding domains to increase the anti-inf.ammatory ef.ect

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Chinese Chemical Letters 2024年第5期35卷 207-212页

作者： Xiaoyao Ma Jinling Zhang Ge f.ng He gao Jie gao Li f. Yuanyuan Hou Gang Bai State Key Laboratory of.Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300000China College of.Lif. Health Dalian UniversityDalian 116622China Dalian f.sheng Pharmaceutical Co. Ltd.Dalian 116000China

The clinical benef.t of.combination therapy is signif.cant,but it is not easy to def.ne the mechanism of.complexity and *** studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of.protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of.***,the combined synergistic ef.ect of.relieving the inf.ammatory response has yet to be *** on high sensitivity,specif.city and f.st-responsibility f.uorescent sensors,the f.rster resonance energy transf.r(f.ET)technique of.ers a route to provide clear insights into physiological and pathological *** the study,molecular docking,the f.uorescent probes of.Phi and Swe f.r f.ET were designed and *** analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of.AKT,*** combination of.Swe and Phi signif.cantly increased the heat stability of.AKT and decreased protease-induced *** lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear f.ctor kappa-B(Nf.κB)phosphorylation,and the expression of.tumor necrosis f.ctor-α(TNf.α),interleukin(IL)-6 and *** conclusion,f.ET revealed Phi and Swe concurrently targeted AKT on dif.erent domains and the combination of.Phi and Swe enhanced the anti-inf.ammatory ef.ect.

关键词： f.ET Swertiamarin Phillygenin AKT Anti-inf.ammation Combinatorial drug

Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant f.rmulated subunit vaccine

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Signal Transduction and Targeted Therapy 2024年第1期9卷 47-50页

作者： Mengyu Guo Mingjing Cao Jiuf.ng Sun Ziwei Chen Xin Wang Lianpan Dai george f.gao Yuliang Zhao Yaling Wang Chunying Chen CAS Key Laboratory f.r Biomedical Ef.ects of.Nanomaterials and Nanosaf.ty&CAS Center f.r Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijingChina Guangdong Provincial Institute of.Public Health Guangdong Provincial Center for Disease Control and PreventionGuangzhouChina CAS Key Laboratory of.Pathogen Microbiology and Immunology Institute of MicrobiologyBeijingChina

Dear editor,Vaccines are the most ef.icient and ef.ective means to prevent inf.ctious diseases,but improving the long-term protective ef.icacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversif.cation of.the pathogen and the number of.booster doses.1 Strategies to overcome this warrant is using adjuvants that amplif. the immune response,and drive the production of.memory B and T cells or long-lived plasma cells that recognize the pathogen f.r durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of.global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of.adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen f.rmulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the inf.ction of.severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of.MnARK f.r subunit vaccine development,we f.rther explored the durable immune regulation abilities of.MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine Zf.001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surf.ce and epitope can be well preserved(Supplementary f.g.1a).The size and zeta potential of.MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary f.g.1b,c).

关键词： manganese immunity protective

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H7N9亚型禽流感病毒的T细胞免疫研究

病毒学报 2018年第6期34卷 911-919页

作者：赵敏舒刘梅高福刘军中国科学院北京生命科学研究院北京100101 中国疾病预防控制中心病毒病预防控制所北京102206

2013年春季,我国首次出现人感染H7N9亚型禽流感疫情,随后H7N9禽流感病毒相继引发了五波流行,在病人中导致较多的重症感染,死亡率接近40%,成为近来的关注热点之一。本文对H7N9亚型禽流感病毒感染的T细胞免疫特征进行了系统综述,尤其是对H... 详细信息

2013年春季,我国首次出现人感染H7N9亚型禽流感疫情,随后H7N9禽流感病毒相继引发了五波流行,在病人中导致较多的重症感染,死亡率接近40%,成为近来的关注热点之一。本文对H7N9亚型禽流感病毒感染的T细胞免疫特征进行了系统综述,尤其是对H7N9禽流感患者在感染急性期及康复后的T细胞免疫特征、健康人群对H7N9的预存T细胞免疫、以及H7N9禽流感病毒与季节性流感病毒的交叉T细胞免疫特点等方面相关研究进展进行了总结。为了解禽流感病毒的T细胞免疫特征和研发新型流感疫苗提供科学参考。

关键词：流感病毒 H7N9 感染患者 T细胞免疫交叉免疫