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Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han xiaoyun Wang Chunmei Wang Xinxin Yan wenwen Lei Ke Xu Jianjie Zhou Jianxun Qi Ruiwen fan Guizhen Wu wen.xia tian.george f.gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

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The persistent prevalence and evolution of cross-family recombinant coronavirus GCCDC1 among a bat population:a two-year follow-up

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Science China(Life Sciences) 2017年第12期60卷 1357-1363页

作者： Joseph O.Obameso Hong Li Hao Jia Min Han Shiyan Zhu Canping Huang Yuhui Zhao Min Zhao Yu Bai fei Yuan Honglan Zhao xia Peng wen Xu wenjie Tan Yingze Zhao Kwok-Yung Yuen William J.Liu Lin Lu george f.gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Yunnan Provincial Center for Disease Control and Prevention Kunming 650022China University of Chinese Academy of Sciences Beijing 100049China College of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China Key Laboratory of Medical Virology and Viral Diseases Ministry of Health of People's Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China State Key Laboratory of Emerging Infectious Diseases The University of Hong KongHong Kong Special Administrative RegionHong KongChina

Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.

关键词： coronavirus bat population evolution

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Existence of Positive Solutions for Singular fourth Order Coupled System with Sign Changing Nonlinear Terms

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Communications in Mathematical Research 2013年第2期29卷 167-178页

作者： xia tian gao Jing-lu Cao Chun-ling gao wen-jie School of Mathematics Jilin University

This paper deals with the existence of positive solutions to a singular fourth order coupled system with integral boundary conditions. Since the nonlinear terms f, g may change sign or be singular at t = 0 or t = 1, the authors make a priori estimates to overcome some difficulties and apply Cuo-Krasnoselskii fixed point theorem to prove the existence of solutions of the system under suitable assumptions. finally, some examples to illustrate the main results are given.

关键词： fixed point theorem positive solution integral boundary condition,

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Non-fused medium bandgap electron acceptors for efficient organic photovoltaics

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Journal of Energy Chemistry 2022年第7期31卷 576-582,I0014页

作者： tian-Jiao wen Jiale xiang Nakul Jain Zhi-Xi Liu Zeng Chen Xinxin xia Xinhui Lu Haiming Zhu feng gao Chang-Zhi Li State Key Laboratory of Silicon Materials MOE Key Laboratory of Macromolecular Synthesis and FunctionalizationDepartment of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027ZhejiangChina Department of Physics Chemistry and Biology(IfM) Link?ping UniversityLinköping SE-58183Sweden Department of Chemistry Zhejiang UniversityHangzhou 310027ZhejiangChina Department of Physics The Chinese University of Hong KongNew TerritoriesHong Kong 999077China

The cost-effective organic semiconductors are strongly needed in organic photovoltaics(OPVs). Herein,two medium bandgap(MBG) electron acceptors, TPT4f and TPT4Cl are developed via the new design of multi-noncovalent interaction assisted unfused core, flanked with two electron withdrawing end groups. These fullly non-fused MBG acceptors adapt the planar and rigid conformation in solid, therefore exhibiting the ordered face-on stacking and strong photoluminescence in films. As results, TPT4Cl^(-)based OPVs, upon blending with the PBDB-Tf polymer donor, have achieved a power conversion efficiency of 10.16% with a low non-radiative loss of 0.27 e V, representing one of the best fullly non-fused medium bandgap acceptors with desirable cost-efficiency balance.

关键词： Organic photovoltaic Medium bandgap Electron withdrawing unit Non-covalent interaction

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A review on the extraction and separation of andrographolide from Andrographis paniculata:extraction selectivity,current challenges and strategies

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Traditional Medicine Research 2023年第7期8卷 11-23页

作者： Di Liang Wei-Mei Zhang Xu Liang Hong-Yue tian Xue-Min Zhang xia Li wen-Yuan gao tianjin Key Laboratory for Advanced Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300193China Key Laboratory of Advanced Chinese Medicine Resources Research Enterprises Tianjin 300402China College of Pharmacy Qinghai Minzu UniversityQinghai 810007China

Andrographolide is the main active ingredient of Andrographis paniculata(Burm.f.)Nees,known as“natural antibiotic”.Here,for the purpose of discovering a more efficient,low-cost extraction and separation method,the research status of andrographolide was *** present,researches only take extraction rate as the only index to optimize extraction parameters,but ignores the importance of extraction *** is usually meaningless to blindly pursue the extraction rate without considering the difficulty and cost of subsequent ***,factors affecting extraction selectivity such as solvent choice,temperature and physicochemical effects caused by extraction technique itself,are first *** extraction techniques for andrographolide were discussed by comparing the selectivity,efficiency and cost of *** separation procedures of andrographolide such as decolorization,impurity removal,crystallization,membrane separation,solid-phase extraction and partition chromatography and their challenges and possible strategies are also *** is hoped that this review can provide guidance for researchers who are committed to advancing the field of andrographolide extraction and purification.

关键词： andrographolide extraction techniques extraction selectivity separation

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CASCIRE surveillance network and work on avian influenza viruses

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Science China(Life Sciences) 2017年第12期60卷 1386-1391页

作者： Yuhai Bi Weifeng Shi Jianjun Chen Quanjiao Chen Zhenghai Ma Gary Wong wenxia tian Renfu Yin Guanghua fu Yongchun Yang William J.Liu Chuansong Quan Qianli Wang Shenghu He xiangdong Li Qianfeng xia Lixin Wang Zhaohui Pan Laixing Li Hong Li wen Xu Ying Luo Hui Zeng Lianpan Dai Haixia xiao Kirill Sharshov Alexander Shestopalov Yi Shi Jinghua Yan Xuebing Li Yingxia Liu fumin Lei wenjun Liu george f.gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Collaborative Innovation Center for Diagnosis and Treatment ofInfectious DiseaseInstitute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)Chinese Academy of SciencesBeijing 100101China Shenzhen Key Laboratory of Pathogen and Immunity State Key Discipline of Infectious DiseaseShenzhen Third People's HospitalShenzhen 518112China Shandong Universities Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases Taishan Medical CollegeTai'an 271016China CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China College of Life Science and Technology Xinjiang UniversityUrumchi 830046China College of Animal Science and Veterinary Medicine Shanxi Agricultural UniversityTaigu 030801China Department of Veterinary Preventive Medicine College of Veterinary MedicineJilin UniversityJilin 130062China Institute of Animal Husbandry and Veterinary Medicine Fujian Academy of Agricultural SciencesFuzhou 350013China Center of Excellence for Animal Health Inspection College of Animal Science and TechnologyZhejiang Agriculture and Forestry UniversityZhejiang 311300China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Key Laboratory of Public Health Safety Ministry of EducationSchool of Public HealthFudan UniversityShanghai 200032China Laboratory of Clinical Veterinary Medicine College of AgricultureNingxia UniversityYinchuan 750021China National Research Center for Veterinary Medicine Luoyang 471003China Laboratory of Tropical Biomedicine and Biotechnology and Faculty of Tropical Medicine and Laboratory MedicineImmunology DepartmentSchool of Basic Medicine and Life ScienceHainan Medical UniversityHaikou 571101China Xizang Agriculture and Animal Husbandry College Linzhi 860000China Key Laboratory of Adaptation and Evolution of Plateau Biota N

Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).

关键词： CASCIRE surveillance network work on avian influenza viruses

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Identification of the miniature pig inbred line by skin allograft

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Journal of Integrative Agriculture 2015年第7期14卷 1376-1382页

作者： MU Yu-lian LIU Lan fENG Shu-tang WU tian-wen LI Kui LI Jun-you HE Wei gao Qian ZHOU wen-fang WEI Jing-liang TANG fang YANG Shu-lin WU Zhi-gu xia Ying SUN Tong-zhu Key Laboratory of farm Animal Genetic Resources and Utilization Ministry of Agriculture/Institute of Animal Sciences Chinese Academy of Agricultural Sciences Key Laboratory of Wound Repair the General Hospital of the People's Liberation Army

Skin grafting has been used as one of the most reliable tests to determine the genetic stability of laboratory animal such as mice and rats inbred line, but no identification of swine inbred lines by skin grafting has been reported. At present, Wuzhishan miniature pig （WZSP） inbred line has acquired the f24 individuals in China. In order to verify whether WZSP inbred line had D^en cultivated successfully, allogeneic skin grafts and related research were performed on f20 individuals of WZSP inbreeding population, compared with a control group of autologous transplantation. We observed the transplant recipients＇ wounds, detected peripheral blood-related indicators interleukin-2, 4 and 10, CD4~ and CD8~ lymphocytes, and conducted hematoxylin-eosin （HE） and Masson＇s staining of skin to judge whether the immune rejection reactions occurred within 28 days after transplantation. Chr. 7 genomic heterozygosity of 48 WZSP individuals from f20 to f22 was analyzed by high-density single nucleotide polymorphism （SNP） chips （60 000 SNPs）. The result showed that there were no significant differences in graft skin, the plasma interleukin-2, 4, 10, CD4~ and CD8~, HE and Masson＇s staining results between the allograft and autograft groups, and no immune rejection occurred on the allograft group. We found that 11 genes in Chr. 7 of major histocompatibility complex （MHC） I and MHC II were homozygous which confirmed that immune antibody of the allograft and autograft groups were highly identical and also provided a theoretical basis to no immune rejection occurred on the allograft in the inbred WZSP. The result proved that the WZSP inbred line had been cultivated successfully for the first time in the world. The test methods also provide a scientific basis for the identification of swine and mammal inbred lines.

关键词： Wuzhishan miniature pigs inbred line skin allograft immune rejection

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Genetic Analysis and Preliminary Mapping of a Highly Male-Sterile Gene in foxtail Millet(Setaria italica ***.) Using SSR Markers

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Journal of Integrative Agriculture 2013年第12期12卷 2143-2148页

作者： WANG Jun WANG Zhi-lan YANG Hui-qing YUAN feng GUO Er-hu tian Gang AN Yuan-huai LI Hui-xia WANG Yu-wen DIAO xian-min GUO Ping-yi College of Agriculture Shanxi Agricultural University Millet Research Institute Shanxi Academy of Agricultural Sciences Institute of Crop Sciences Chinese Academy of Agricultural Sciences

Breeding of male-sterile lines has become the mainstream for the heterosis utilization in foxtail millet,but the genetic basis of most male-sterile lines used for the hybrid is still an area to be *** this study,a highly male-sterile line gao146A was *** analysis indicated that the highly male-sterile phenotype was controlled by a single recessive gene a single recessive *** f 2 population derived from cross gao146A/K103,one gene controlling the highly male- sterility,tentatively named as ms1,which linked to SSR marker b234 with genetic distance of 16.7 cM,was mapped on the chromosome *** results not only laid the foundation for fine mapping of this highly male-sterile gene,but also helped to accelerate the improvement of highly male-sterile lines by using molecular marker assisted breeding method.

关键词： foxtail millet(Setaria italic L.Beauv.) highly male-sterility gene mapping SSR marker

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Mouse model for pangolin-origin coronavirus GX/P2V/2017 infection and cross-protection from COVID-19 Zf2001 subunit vaccine

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hLife 2023年第1期1卷 35-43页

作者： xiao Qu Yunfei Jia Na Jia Huahao fan Anqi Zheng Luoyuan xia Zhenfei Wang Di tian Sheng Niu Yu Hu wenxia tian Zhihai Chen Yigang Tong Yuwei gao Wuchun Cao Qihui Wang george fu gao CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina College of Veterinary Medicine Shanxi Agricultural UniversityShanxiChina State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijingChina Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and TechnologyBeijing University of Chemical TechnologyBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Center of Infectious Disease Beijing Ditan HospitalCapital Medical UniversityBeijingChina School of Life Sciences University of Science and Technology of ChinaAnhuiChina Institute of Military Veterinary Medicine Academy of Military Medical SciencesJilinChina

Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human ***,it remains unclear whether the currently available vaccines are effective against these ***,we constructed a wild-type mouse model to evaluate pathogenicity of the SARS-CoV-2-related pangolin coronavirus GX/P2V/2017 and neutralization efficacy of the approved tandemrepeat SARS-CoV-2 spike receptor-binding domain(RBD)vaccine *** found that Zf2001-induced cross-reactive and cross-neutralizing antibodies against GX/P2V/2017,and the vaccination alleviated the pathological lung damage caused by GX/P2V/2017 in *** results indicate that RBD may work as a promising candidate for pan-coronavirus vaccine development.

关键词： Zf2001 pangolin-origin coronavirus mouse model vaccine protection

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由超拍电子伏特加速器产生的超高能伽马射线气泡

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Science Bulletin 2024年第4期69卷 449-457页

作者： LHAASO Collaboration Zhen Cao Chuandong gao Cong Li Ruo-Yu Liu Ruizhi Yang 不详 Key Laboratory of Particle Astrophyics&Experimental Physics Division&Computing Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China tianfU Cosmic Ray Research Center ChengduChina Institute of frontier and Interdisciplinary Science Shandong UniversityQingdao 266237China School of Astronomy and Space Science Nanjing UniversityNanjing 210023China University of Science and Technology of China Hefei 230026China

We report the detection of aγ-ray bubble spanning at least 100deg2 in ultra-high energy(UHE)up to a few PeV in the direction of the star-forming region Cygnus X,implying the presence super PeVatron(s)accelerating protons to at least 10 PeV.A log-parabola form with the photon indexΓ(E)=(2.71±0.02)+(0.11±0.02)×log10(E/10 TeV)is found fitting the gamma-ray energy spectrum of the bubble *** sources,“hot spots”correlated with very massive molecular clouds,and a quasi-spherical amorphousγ-ray emitter with a sharp central brightening are observed in the *** the core of~0.5°,spatially associating with a region containing massive OB association(Cygnus OB2)and a microquasar(Cygnus X-3),as well as previously reported multi-TeV sources,an enhanced concentration of UHEγ-rays is observed with 2 photons at energies above 1 *** general feature of the bubble,the morphology,and the energy spectrum,are reasonably reproduced by the assumption of a particle accelerator in the core,continuously injecting protons into the ambient medium.

关键词： Cosmic rays γ-rays Interstellar medium Star cluster

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