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In search of a pan-coronavirus vaccine:next-generation vaccine design and immune mechanisms

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Cellular & Molecular Immunology 2024年第2期21卷 103-118页

作者： S.Cankat M.U.Demael L.Swadling Division of Infection and immunity Institute of Immunity and TransplantationUniversity College LondonPears BuildingLondon NW32PPUK

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent *** this review,we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus *** will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2,MERS-CoV and the four seasonal coronaviruses(HCoV-OC43,NL63,HKU1 and 229E)in humans and the potential for future zoonotic *** will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine *** will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer ***,we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

关键词： Vaccine Coronavirus Cross-reactive immunity Cross-protection Universal

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

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World Journal of Gastroenterology 2024年第11期30卷 1488-1493页

作者： Alessandro Parente Keyue Sun Philipp Dutkowski AM James Shapiro Andrea Schlegel Department of Surgery Division of TransplantationUniversity of Alberta HospitalEdmonton T6G 2B7Canada immunity and Inflammation Lerner Research InstituteClevelandOH 44195United States Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryUniversity Hospital ZurichZurich 8091Switzerland immunity and Inflammation Digestive Disease and Surgery InstituteClevelandOH 44195United States

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver *** evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ *** editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

关键词： Liver transplantation Machine perfusion Viability assessment Hypothermic oxygenated perfusion Normothermic machine perfusion

Establishment of a humanized mouse model using steady-state peripheral blood-derived hematopoietic stem and progenitor cells facilitates screening of cancer-targeted T-cell repertoires

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Cancer Innovation 2024年第3期3卷 1-21页

作者： Yulin Xu Wei Shan Qian Luo Meng Zhang Dawei Huo Yijin Chen Honghu Li Yishan Ye Xiaohong Yu Yi Luo He Huang Bone Marrow transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu Laboratory Zhejiang UniversityHangzhouChina institute of Hematology Zhejiang UniversityHangzhouChina Zhejiang Province Engineering Research Center for Stem Cell and immunity Therapy HangzhouChina School of Medicine Zhejiang UniversityHangzhouChina

Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast ***,approaches to obtain cancer-reactive TCR-T cells have been ***:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune *** steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized *** human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and *** fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 ***,human T cells were processed for TCRβ-chain(TRB)sequencing *** the repertoires had been constructed,features such as the fraction,diversity,and immune signature were ***:The results demonstrated an increase in diversity and clonality of T cells after *** preferential usage and features of TRBV,TRBJ,and the V–J combination were also *** stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 *** burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized ***:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T *** platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.

关键词： cancer-targeted T-cell receptor T(TCR-T)cells circulating hematopoietic stem and progenitor cells(HSPCs) humanized mouse model steady-state peripheral blood T-cell receptorβ-chain(TRB) three-dimensional culture

The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone Division of Immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging Centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 111-116页

作者： Jan Lerut institute for Experimental and Clinical Research(IREC) Universitécatholique Louvain(UCL)Avenue Hippocrate 561200 Woluwe Saint PierreBrusselsBelgium

Although Starzl designed in the 1960’s liver transplantation(LT)to treat unresectable primary and also secondary liver tumors,transplantation still occupies a(too)small place in the respective therapeutic algorithms[1].Due to the lack of(any)selection criteria,the concept of transplantation became rapidly challenged because of the prohibitively high incidence of tumor recurrence[1–3].

关键词： liver tumors Liver

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng Xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng Chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Neuropsychiatric Disease and institute of Neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal *** dysfunction can precede the onset of motor symptoms by several *** microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain ***/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease *** this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota *** found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor ***,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with ***,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and *** of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier *** results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s ***,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that c

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

The capsid revolution

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Journal of Molecular Cell Biology 2023年第11期15卷 1-11页

作者： Ian A.Taylor Ariberto Fassati Macromolecular Structure Laboratory The Francis Crick InstituteLondon NW11ATUK Division of Infection and immunity University College LondonLondon WC1E 6JFUK institute of immunity and transplantation University College LondonLondon NW32PPUK

Lenacapavir,targeting the human immunodeficiency virus type-1(HIV-1)capsid,is the first-in-class antiretroviral drug recently approved for clinical *** development of Lenacapavir is attributed to the remarkable progress in our understanding of the capsid protein made during the last few *** little more than a component of the virus shell to be shed early during infection,the capsid has been found to be a key player in the HIV-1 life cycle by interacting with multiple host factors,entering the nucleus,and directing ***,we describe the key advances that led to this‘capsid revolution’.

关键词： HIV-1 capsid CPSF6 Lenacapavir integration IP6 nucleus reverse transcription

Activation of immune signals during organ transplantation

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1545-1570页

作者： Qingwen Li Peixiang Lan institute of Organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of Organ transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanChina

The activation of host’s innate and adaptive immune systems can lead to acute and chronic graft rejection,which seriously impacts graft ***,it is particularly significant to clarify the immune signals,which are critical to the initiation and maintenance of rejection generated after *** initiation of response to graft is dependent on sensing of danger and stranger *** ischemia and reperfusion of grafts lead to cell stress or death,followed by releasing a variety of damage-associated molecular patterns(DAMPs),which are recognized by pattern recognition receptors(PRRs)of host immune cells to activate intracellular immune signals and induce sterile *** addition to DAMPs,the graft exposed to‘non-self’antigens(stranger molecules)are recognized by the host immune system,stimulating a more intense immune response and further aggravating the graft *** polymorphism of MHC genes between different individuals is the key for host or donor immune cells to identify heterologous‘non-self’components in allogeneic and xenogeneic organ *** recognition of‘nonself’antigen by immune cells mediates the activation of immune signals between donor and host,resulting in adaptive memory immunity and innate trained immunity to the graft,which poses a challenge to the long-term survival of the *** review focuses on innate and adaptive immune cells receptor recognition of damage-associated molecular patterns,alloantigens and xenoantigens,which is described as danger model and stranger *** this review,we also discuss the innate trained immunity in organ transplantation.

关键词： immunity damage graft

Relapse after CAR-T cell therapy in B-cell malignancies: challenges and future approaches

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第10期23卷 793-811页

作者： Tianning GU Meng ZHU He HUANG Yongxian HU Bone Marrow transplantation Center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China institute of Hematology Zhejiang UniversityHangzhou 310058China Zhejiang Province Engineering Laboratory for Stem Cell and immunity Therapy Hangzhou 310058China

Chimeric antigen receptor-T(CAR-T)cell therapy,as a novel cellular immunotherapy,has dramatically reshaped the landscape of cancer treatment,especially in hematological ***,relapse is still one of the most troublesome obstacles to achieving broad clinical *** intrinsic factors and superior adaptability of tumor cells mark a fundamental aspect of *** unique biological function of CAR-T cells governed by their special CAR construction also affects treatment ***,complex cross-interactions among CAR-T cells,tumor cells,and the tumor microenvironment(TME)profoundly influence clinical outcomes concerning CAR-T cell function and ***,in this review,based on the most recent discoveries,we focus on the challenges of relapse after CAR-T cell therapy in B-cell malignancies from the perspective of tumor cells,CAR-T cells,and the *** also discuss the corresponding basic and clinical approaches that may overcome the problem in the *** aim to provide a comprehensive understanding for scientists and physicians that will help improve research and clinical practice.

关键词： Chimeric antigen receptor-T(CAR-T) B-cell malignancies Mechanisms of relapse Strategy