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Exploration of a Sequential Gp140-Gp145 Immunization Regimen with Heterologous Envs to Induce a Protective Cross-Reactive HIV Neutralizing Antibody Response In Non-human Primates

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Virologica Sinica 2021年第4期36卷 784-795页

作者： Xiangqing Ding Kangli Cao Jing Wang Yanmin Wan Qinyun Chen Yanqin Ren Yongtang Zheng Mingzhao Zhu Renrong Tian Wenjun Wang Chen Zhao Xiaoyan Zhang Jianqing Xu shanghai public health clinical center and institutes of biomedical sciences Key Laboratory of Medical Molecular VirologyShanghai Medical CollegeFudan UniversityShanghai 201508China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China University of Chinese Academy of sciences Beijing 100049China Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijing 100101China College of Life sciences University of the Chinese Academy of SciencesBeijing 100101China

Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine *** this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this *** exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost *** first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in ***,when examined in rhesus macaque,this modality showed little *** improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click *** resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week ***,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV ***,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.

关键词： Human immunodeficiency virus type 1(HIV-1) Vaccine Broadly neutralizing antibodies(bnAbs) Sequential immunization Native-like Env trimers Nanoparticle

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Neutralization of five SARS-CoV-2 variants of concern by convalescent and BBIBP-CorV vaccinee serum

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Virologica Sinica 2022年第6期37卷 831-841页

作者： Yuqi Zhu Xinyi Yang Jingna Xun Jun Liu Qing Wen Yixiao Lin Xiaoting Shen Jun Chen Songhua Yuan Xiaying Zhao Jing Wang Hanyu Pan Jinlong Yang Zhiming Liang Yue Liang Qinru Lin Huitong Liang Min Li Jianping Liu Yinzhong Shen Xiaoyan Zhang Pengfei Wang Daru Lu Chunhua Yin Jianqing Xu Shibo Jiang Hongzhou Lu Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesFudan UniversityShanghai200438China Scientific Research center Shanghai Public Health Clinical CenterFudan UniversityShanghai201508China Fubio(Suzhou)biomedical Technology Co. LtdSuzou215300China Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghai201508China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesFudan UniversityShanghai200032China Department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People's Hospital of ShenzhenShenzhen518112China

The prevalence of SARS-CoV-2 variants of concern(VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients’ sera and convalescent sera against all VOCs,including B.1.1.7(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta), and B.1.1.529(Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain(WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100%(30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90%(18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.

关键词： SARS-CoV-2 Variants of concern(VOCs) Convalescent BBIBP-CorV vaccine Neutralization

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Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5727-5768页

作者： Yongchao Zhao Weidong Xiong Chaofu Li Ranzun Zhao Hao Lu Shuai Song You Zhou Yiqing Hu Bei Shi Junbo Ge Department of Cardiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Key Laboratory of Viral Heart Diseases National Health CommissionShanghai 200032China Key Laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghai 200032China National clinical Research center for Interventional Medicine Shanghai 200032China shanghai clinical Research center for Interventional Medicine Shanghai 200032China institutes of biomedical sciences Fudan UniversityShanghai 200032China

Hypoxia,characterized by reduced oxygen concentration,is a significant stressor that affects the survival of aerobic species and plays a prominent role in cardiovascular *** the research history and milestone events related to hypoxia in cardiovascular development and diseases,The"hypoxia-inducible factors(HIFs)switch"can be observed from both temporal and spatial perspectives,encompassing the occurrence and progression of hypoxia(gradual decline in oxygen concentration),the acute and chronic manifestations of hypoxia,and the geographical characteristics of hypoxia(natural selection at high altitudes).Furthermore,hypoxia signaling pathways are associated with natural rhythms,such as diurnal and hibernation *** addition to innate factors and natural selection,it has been found that epigenetics,as a postnatal factor,profoundly influences the hypoxic response and progression within the cardiovascular *** this intricate process,interactions between different tissues and organs within the cardiovascular system and other systems in the context of hypoxia signaling pathways have been ***,it is the time to summarize and to construct a multi-level regulatory framework of hypoxia signaling and mechanisms in cardiovascular diseases for developing more therapeutic targets and make reasonable advancements in clinical research,including FDA-approved drugs and ongoing clinical trials,to guide future clinical practice in the field of hypoxia signaling in cardiovascular diseases.

关键词： cardiovascular therapeutic organs

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Endovascular embolization by a magnetic microfiberbot

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National Science Review 2024年第5期11卷 95-96页

作者： Shuning Zhang Wenlong Yang Junbo Ge Department of Cardiology Zhongshan HospitalFudan University Shanghai Institute of Cardiovascular Diseases Key Laboratory of Viral Heart Diseases National Health Commission Key Laboratory of Viral Heart Diseases Chinese Academy of Medical Sciences National clinical Research center for Interventional Medicine institutes of biomedical sciences Fudan University

The evolving landscape of embolization therapy for treating cerebral aneurysms and brain tumors represents a pivotal stride towards enhancing the efficacy and safety of minimally invasive treatments [1]. Conventional endovascular embolization methods [2], characterized by the manual maneuvering of catheters through the vascular system, present notable limitations in steerability and precision, compounded by the potential health risks associated with prolonged exposure to radiation for surgeons.

关键词： embolization endovascular magnetic microfiberbot

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Kinase-substrate Edge Biomarkers Provide a More Accurate Prognostic Prediction in ER-negative Breast Cancer

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Genomics, Proteomics & Bioinformatics 2020年第5期18卷 525-538页

作者： Yidi Sun Chen Li Shichao Pang Qianlan Yao Luonan Chen Yixue Li Rong Zeng CAS Key Laboratory of Systems Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China University of Chinese Academy of sciences Shanghai 200031China Deptartment of Statistics School of Mathematical SciencesShanghai Jiao Tong UniversityShanghai 200240China School of Life sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Department of Life sciences ShanghaiTech UniversityShanghai 201210China CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China Bio-Med Big Data center Key Laboratory of Computational BiologyCAS-MPG Partner Institute for Computational BiologyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Collaborative Innovation center for Genetics and Development Fudan UniversityShanghai 200032China shanghai center for Bioinformation Technology Shanghai Academy of Science&TechnologyShanghai 201203China center for Single-Cell Omics School of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China

The estrogen receptor(ER)-negative breast cancer subtype is aggressive with few treatment options *** identify specific prognostic factors for ER-negative breast cancer,this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance,Epidemiology,and End Results(SEER)and The Cancer Genome Atlas(TCGA)databases,*** identify key differential kinase-substrate node and edge biomarkers between ER-negative and ERpositive breast cancer patients,we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory *** analysis of the clinical and molecular data revealed the significant prognostic power of kinase-substrate node and edge features for both subtypes of breast *** promising kinase-substrate edge features,CSNK1A1-NFATC3 and SRC-OCLN,were identified for more accurate prognostic prediction in ERnegative breast cancer patients.

关键词： ER-negative breast cancer Edge biomarkers Kinase Substrate Prognostic prediction

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Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States(1992–2015)

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biomedical and Environmental sciences 2021年第2期34卷 152-162页

作者： WU Jing JI Yi Bing TANG Bi Wei BROWN Matthew WANG Bao Hua DU Chen Lei DU Jian Shu WANG Xue Mei CAI Li Jun WU Guo Yi ZHOU Yan National center for Chronic and Non-communicable Diseases Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100050China Inner Mongolia Medical University Hohhot 010110Inner MongoliaChina National Cancer Insitiute National Institutes of HealthBethesda 20892MarylandUnited States shanghai Topgen Biopharm Technology Co. LtdShanghai 201203China Scientific Research center Shanghai Public Health Clinical CenterFudan UniversityShanghai 201508China State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 200433China shanghai-MOST Key Laboratory of health and Disease Genomics Chinese National Human Genome Center at ShanghaiShanghai 200000China

Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly *** The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of *** Black males were diagnosed at a later stage, more commonly with local or distant *** incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting *** Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

关键词： Testicular cancer Germ cell tumor Race Survival rate Survival analysis

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Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2581-2592页

作者： Jin-Tao Li Hai Yang Ming-Zhu Lei Wei-Ping Zhu Ying Su Kai-Yue Li Wen-Ying Zhu Jian Wang Lei Zhang Jia Qu Lei Lv Hao-Jie Lu Zheng-Jun Chen Lu Wang Miao Yin Qun-Ying Lei Fudan University shanghai Cancer center&institutes of biomedical sciences Cancer institutes Key Laboratory of Breast Cancer in shanghai shanghai Key Laboratory of Radiation Oncology the Shanghai Key Laboratory of Medical EpigeneticsDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032People’s Republic of China Department of Hepatic Surgery Fudan University Shanghai Cancer CenterShanghai Medical CollegeFudan UniversityShanghai 200032People’s Republic of China

Folic acid,served as dietary supplement,is closely linked to one-carbon metabolism and methionine *** clinical evidence indicated that folic acid supplementation displays dual effect on cancer development,promoting or suppressing tumor formation and ***,the underlying mechanism remains to be ***,we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma(HCC)induced by DEN/high-fat diet(HFD),simultaneously with increased expression of methionine adenosyltransferase 2A(gene name,MAT2A;protein name,MATIIα),the key enzyme in methionine metabolism,and acceleration of methionine cycle in cancer *** contrast,folate-free diet reduces MATIIαexpression and impedes HFD-induced HCC ***,methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein(VCIP135)which functions as a deubiquitylating enzyme to bind and stabilize MATIIαin response to folic acid ***,upregulation of MATIIαexpression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent ***,liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC,demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on ***,folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a ***,folate promotes the integration of methionine and one-carbon metabolism,contributing to HCC development via hijacking MATIIαmetabolic *** study provides insight into folate-promoted cancer development,strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIαexpression.

关键词： metabolism cancer methionine

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Profiling B and T cell immune responses to co-infection of Mycobacterium tuberculosis and hookworm in humans

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Infectious Diseases of Poverty 2015年第1期4卷 133-142页

作者： Xin-Xu Li Jia-Xu Chen Li-Xia Wang Jun Sun Shao-Hong Chen Jun-Hu Chen Xiao-Yan Zhang Xiao-Nong Zhou National Institute of Parasitic Diseases Chinese Center for Disease Control and PreventionKey Laboratory of Parasite and Vector BiologyMinistry of HealthWHO Collaborating Centre for MalariaSchistosomiasis and Filariasis207 Rui Jin Er RoadHuangpu DistrictShanghai 200025PR China(PRC) National center for Tuberculosis Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206PR China shanghai public health clinical center Key Laboratory of Medical Molecular Virology of Ministry of EducationInstitutes of Biomedical SciencesFudan UniversityShanghai 201508PR China

Background:Humoral and cellular immune responses play protective roles against Mycobacterium tuberculosis(MTB)***,hookworm infection decreases the immune response to hookworm and bystander ***,immune responses to co-infection of MTB and hookworm are still unknown,although co-infection has been one of the public health problems in co-endemic areas of pulmonary tuberculosis(PTB)and hookworm ***,it is essential to evaluate B and T cell immune responses to the ***:Seventeen PTB cases co-infected with hookworm,26 PTB cases,15 patients with hookworm infection,and 24 healthy controls without PTB or hookworm infection were enrolled in the *** of CD3,CD4,CD8,CD10,CD19,CD20,CD21,CD25,CD27,CD38,FoxP3,and PD-1 were assessed on B and T cell subsets using multicolor flow ***:For the B cell(CD19+)subsets,naïve B cells(CD10−CD27−CD21+CD20+),plasma cells(CD10−CD27+CD21−CD20−),and tissue-like memory B cells(CD10−CD27−CD21−CD20+)had higher proportions,whilst resting memory B cells(CD10−CD27+CD21+CD20+)had lower proportions in the group co-infected with MTB and hookworm as compared to other *** of activated memory B cells(CD10−CD27+CD21−CD20+)did not differ among the four *** the T cell(CD3+)subsets,frequencies of regulatory T cells(CD4+CD25+Foxp3+)and exhausted CD4+and CD8+T cells(CD4+PD-1+and CD8+PD-1+)were higher,and frequencies of activated CD4+and CD8+T cells(CD4+CD38+and CD8+CD38+)were lower in the co-infected group as compared to the other ***:The change patterns of the cell profile of circulating lymphocytes were indentified in human co-infection of MTB and hookworm,which might indicate that the humoral and cellular immune responses are more suppressed.

关键词： Co-infection Mycobacterium tuberculosis Hookworm Immune response

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Mutually exclusive epigenetic modification on SIX6 with hypermethylation for precancerous stage and metastasis emergence tracing

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2683-2686页

作者： Shihua Dong Zhicong Yang Peng Xu Wanxiang Zheng Baolong Zhang Fangqiu Fu Zhanrui Mao Jianlin Yuan Haiquan Chen Wenqiang Yu shanghai Epiprobe Biotechnology Co. LtdShanghaiChina shanghai public health clinical center&Department of General Surgery Huashan Hospital&Cancer Metastasis Institute&Institutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghaiChina Department of Urology Xijing HospitalAir Force Medical UniversityXi’anShaanxiChina Department of Thoracic Surgery Fudan University Shanghai Cancer Center&Institute of Thoracic Oncology&State Key Laboratory of Genetic EngineeringFudan UniversityShanghaiChina

Dear Editor,Aberrant DNA methylation gets involved in cancer initiation,progression,and recurrence,which in turn makes it an ideal cancer *** methylation markers or their panels have been developed in diverse cancer ***,the model-constructing based marker mining strategy and incompatibility of application have greatly impeded their ways to ***,single methylation marker applicable to all/most cancer types and multiple clinical scenarios is desperately *** hope came from the unexpected observation that HIST1H4F was universally hypermethylated in all 17 cancer types;thus,we raised the concept of“Universal Cancer Only Marker(UCOM)”and established a paradigm for discovery and clinical application of UCOM.1 Recently,a novel UCOM,hypermethylated PCDHGB7,was identified and found to advance cervical cancer(CC)screening to the precancerous stage.2 During the screening of UCOM,we discerned a bunch of cancer cell-differentially methylated regions.1 Among them,sine oculis(SIX)homeobox family of transcription factors,which were found to function as tumorigenesis regulator by promoting epithelial-to-mesenchymal transition and metastasis recently in addition to their traditional roles in tissue formation and organogenesis,3 sparked our special ***,we interrogate whether SIX6 methylation could serve as a novel UCOM and its potential applications.

关键词： metastasis precancerous raised

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Climate Change and Temperature-related Mortality:Implications for health-related Climate Policy

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biomedical and Environmental sciences 2021年第5期34卷 379-386页

作者： TONG Shi Lu Jom Olsen Patrick L.Kinney shanghai Children’s Medical center Shanghai Jiao Tong University School of MedicineShanghai 200127China School of public health Institute of Environment and Population HealthAnhui Medical UniversityHefei 230032AnhuiChina center for Global health School of Public HealthNanjing Medical UniversityNanjing 210029JiangsuChina School of public health and Social Work Queensland University of TechnologyBrisbane 4059Australia Department of clinical Epidemiology University of AarhusAarhus 8000Denmark Department of Environmental health Boston University School of Public HealthBoston MA02215USA

It is widely recognized that climate change is one of the greatest challenges humanity faces in the 21st century[1,2].As the leading authority for the assessment of climate change,the Intergovernmental Panel on Climate Change (IPCC),in its special report on global warming of 1.5℃,has concluded that human activities have caused approximately 1.0℃ of global warming above preindustrial levels,with a likely increase of 1.5℃ between 2030 and 2052[3].Climate-related risks for natural and human systems are projected to increase with global warming of 1.5℃,and increase further with 2℃ or *** risks depend on the magnitude and rate of warming,geographic location,levels of development and vulnerability,and on the choices and implementation of adaptation and mitigation options.

关键词： warming magnitude likely

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