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Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects

Signal Transduction and Targeted Therapy 2024年第6期9卷 2655-2668页

作者： Rao Fu Ruoyao Qi Hualong Xiong Xing Lei Yao Jiang Jinhang He Feng Chen Liang Zhang Dekui Qiu Yiyi Chen Meifeng Nie Xueran Guo Yuhe Zhu Jinlei Zhang Mingxi Yue Jiali Cao Guosong Wang Yuqiong Que Mujing Fang Yingbin Wang Yixin Chen Tong Cheng Shengxiang Ge Jun Zhang Quan Yuan Tianying Zhang Ningshao Xia State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryDepartment of Laboratory MedicineSchool of Public Health&School of Life SciencesXiamen UniversityXiamen 361102 FujianChina National Institute of Diagnostics and Vaccine Development in Infectious Diseases Xiamen 361102 FujianChina

Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years,but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used *** this study,an oncolytic virus(rVSV-LCMVG)that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T *** transforming the immunosuppressive tumor microenvironment into an immunosensitive one,in B16 tumor-bearing mice,combination therapy showed superior antitumor effects than *** occurred whether the OV was administered intratumorally or *** therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8^(+)T cells to the TME to trigger antitumor immune *** with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment,downregulating the expression of PD-1,and restoring effector T-cell *** offer a combination therapy with greater translational value,mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T *** combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged *** study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens,in terms of synergistic efficacy and mechanism.

关键词： transferred rational boosting

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MODELS: a six-step framework for developing an infectious disease model

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贫困所致传染病(英文) 2024年第2期13卷 66-76页

作者： Rui Jia Li Kangguo Wei Hongjie Guo Xiaohao Zhao Zeyu Wang Yao Song Wentao Abudunaibi Buasiyamu Chen Tianmu State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University Xiamen city China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine Research Xiamen University Xiamen City China

Since the COVID-19 pandemic began, a plethora of modeling studies relatedto COVID-19 have been released. While some models stand out due to their innovative approaches, others are flawed in their methodology. To assist novices, frontline healthcare workers, and public health policymakers in navigating the complex landscape of these models, we introduced a structured framework named MODELS. This framework is designed to detail the essential steps and considerations for creating a dependable epidemic model, offering direction to researchers engaged in epidemic modeling endeavors.

关键词： Epidemic models Model construction MODELS framework

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Immune landscape and response to oncolytic virus-based immunotherapy

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Frontiers of Medicine 2024年第3期18卷 411-429页

作者： Chaolong Lin Wenzhong Teng Yang Tian Shaopeng Li Ningshao Xia Chenghao Huang State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryDepartment of Laboratory MedicineSchool of Public HealthXiamen UniversityXiamen361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsXiamen UniversityXiamen361102China

Oncolytic virus(OV)-based immunotherapy has emerged as a promising strategy for cancer treatment,offering a unique potential to selectively target malignant cells while sparing normal ***,the immunosuppressive nature of tumor microenvironment(TME)poses a substantial hurdle to the development of OVs as effective immunotherapeutic agents,as it restricts the activation and recruitment of immune *** review elucidates the potential of OV-based immunotherapy in modulating the immune landscape within the TME to overcome immune resistance and enhance antitumor immune *** examine the role of OVs in targeting specific immune cell populations,including dendritic cells,T cells,natural killer cells,and macrophages,and their ability to alter the TME by inhibiting angiogenesis and reducing tumor ***,we explore strategies to optimize OV-based drug delivery and improve the efficiency of OV-mediated *** conclusion,this review offers a concise and comprehensive synopsis of the current status and future prospects of OV-based immunotherapy,underscoring its remarkable potential as an effective immunotherapeutic agent for cancer treatment.

关键词： oncolytic virus immunotherapy immunotherapeutic agents immune landscape

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Basic Research Advances in China on Embryo Implantation,Placentation,and Parturition

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Maternal-Fetal Medicine 2024年第1期6卷 37-49页

作者： Haili Bao Haibin Wang Fujian Provincial Key Laboratory of Reproductive Health Research Department of Obstetrics and GynecologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of MedicineXiamen UniversityXiamen 361102China

This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent *** was systematically searched from January 2020 to November *** that reported the progress in embryo implantation,placentation,and parturition made by Chinese scientists in the last 3 years were *** milestone events during gestation,embryo implantation,endometrial decidualization,placentation,and parturition are pivotal to a successful *** implantation requires intricate interactions between implantation-competent blastocysts and receptive *** adapt to pregnancy,endometrial stromal cells transform into specialized decidual cells,which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in *** embryonic development,the placenta forms to support fetal growth until *** maternal-fetal interface is composed of diverse cell types,including endometrial decidual cells,placental trophoblast cells,endothelial cells,and various immune cells,a sophisticated interplay among which contributes to the maintenance of *** term,the uterus transitions from quiescence to contractility,in preparation for *** to these events lead to pregnancy-related disorders such as repeated implantation failure,recurrent pregnancy loss,preeclampsia,fetal growth restriction,preterm birth,and *** recent years,Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy *** scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years,highlighting future research directions in this field.

关键词： Embryo implantation Decidualization Placentation Maternal-fetal interface Parturition

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Stepping forward:T-cell redirecting bispecific antibodies in cancer therapy

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2361-2377页

作者： Xiaojing Qin Wenjing Ning Han Liu Xue Liu Wenxin Luo Ningshao Xia State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for IndustryeEducation Integration in Vaccine Researchthe Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamen UniversityXiamen 361102China

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell *** linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor *** antibodies have emerged as one of the most promising avenues within tumor ***,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be *** this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.

关键词： Bispecific antibody(BsAbs) T-cell redirecting BsAbs Tumor-associated antigens Toxicity Cytokine release syndrome Tumor microenvironment Cancer immunotherapy Combination therapy strategies

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Tuberculosis Prevalence Trends from a Predictive Modelling Study-10 High-Burden Countries,1980-2035

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China CDC weekly 2024年第12期6卷 225-229,I0001,I0002页

作者： Qiuping Chen Qiao Liu Kangguo Li Laurent Gavotte Roger Frutos Tianmu Chen CIRAD IntertrypMontpellierFrance Universitéde Montpellier MontpellierFrance State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen CityFujian ProvinceChina State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina Espace-Dev Universitéde MontpellierMontpellierFrance

What is already known about this topic?Given the challenges presented by drug-resistant strains of tuberculosis(TB)and the rising mobility of the population,achieving the objective of eradicating TB appears *** is added by this report?The examination of TB incidence trends in 10 highburden countries(HBCs)indicated a steady rise in cases,with India and China jointly accounting for nearly 70%of the *** for the future show diverse trajectories in these countries,with potential difficulties in reaching the TB elimination target,especially in Nigeria,Congo,and South *** are the implications for public health practice?The number of TB cases is on the *** is crucial to learn from successful strategies to improve TB prevention and control worldwide through collaborative efforts.

关键词： tuberculosis uncertain Tuberculosis

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Trends in Respiratory Infectious Pathogens in Children Under the Age of 14—Xiamen City,Fujian Province,China,2017-2023

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China CDC weekly 2024年第8期6卷 143-147页

作者： Jiali Cao Jie Pan Xiaoqing Yang Jumei Liu Min Zhu Zeyu Zhao Ling Chen Tianmu Chen Huiming Ye Department of Laboratory Medicine Fujian Key Clinical Specialty of Laboratory MedicineWomen and Children’s HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen CityFujian ProvinceChina Department of Pediatrics Women and Children's HospitalSchool of MedicineXiamen UniversityXiamen CityFujian ProvinceChina

Summary What is already known about this topic?Respiratory infections pose a significant burden on public *** recent outbreaks occurring in various locations,there is limited information available on the prevalence tr... 详细信息

关键词： Xiamen spite Fujian

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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

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Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key Laboratory of vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Innovation Platform for Industry-Education Integration in Vaccine Research Xiamen University Department of Nutrition Zhongshan Hospital (Xiamen) Fudan University Xiamen Clinical Research Center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

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Zoological Research 2024年第3期45卷 551-566页

作者： Chen Ling Su-Su Liu Yu-Ya Wang Gui-Tao Huo Yan-Wei Yang Nan Xu Hong Wang Yong Wu Yu-Fa Miao Rui Fu Yu-Wei Zhao Chang-Fa Fan College of Life Sciences Northwest UniversityProvincial Key Laboratory of Biotechnology of Shaanxi ProvinceXi’anShaanxi 710069China Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control(NIFDC)Beijing 100176China Division of HIV/AIDS and Sexually Transmitted Virus vaccines Institute for Biological Products ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China Division of Laboratory Animal Monitoring Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic *** etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and ***,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic ***,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle *** symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in ***-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene *** murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the *** on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to ***,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

关键词： HRAS THBS1 HCC driver factor NASH Fibrosis Cirrhosis HCC Treatment evaluation

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mRNA cancer vaccines:Advances,trends and challenges

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Acta Pharmaceutica Sinica B 2022年第7期12卷 2969-2989页

作者： Qing He Hua Gao Dejiang Tan Heng Zhang Jun-zhi Wang National Institutes for Food and Drug Control State Key Laboratory for Evaluation and Standardization of Innovative Vaccines and Biotechnology ProductsBeijing 102629China

Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and *** vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex(MHC)restriction,are relatively easy to control and can be rapidly mass *** 2021,the *** and Drug Administration(FDA)approved the first m RNA-based coronavirus disease 2019(COVID-19)vaccine produced by Pfizer and Bio NTech,which has generated enthusiasm for m RNA vaccine research and *** on the above characteristics and the development of m RNA vaccines,m RNA cancer vaccines have become a research hotspot and have undergone rapid development,especially in the last five *** review analyzes the advances in m RNA cancer vaccines from various perspectives,including the selection and expression of antigens/targets,the application of vectors and adjuvants,different administration routes,and preclinical evaluation,to reflect the trends and challenges associated with these vaccines.

关键词： mRNA Cancer vaccine Tumor-associated antigens Neoantigens mRNA delivery vectors Adjuvants Administration routes

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