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Two hits are better than one:rational dual strategy efficiently fights neuroblastoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1802-1804页

作者： Jacques Zimmer Camille Rolin Markus Ollert Department of infection and immunity Luxembourg Institute of HealthEsch-sur-AlzetteLuxembourg university of Luxembourg Esch-sur-AlzetteLuxembourg Department of Dermatology and Allergy Center Odense Research Center for Anaphylaxis(ORCA)University of Southern DenmarkOdenseDenmark

The recently published landmark paper by Bergaggio et *** Roberto Chiarle’s group in Cancer Cell1 investigates an elegant double-hit strategy to improve anti-cancer *** important approach demonstrates in a preclinical model that chimeric antigen receptor(CAR)-T cell treatment can be rendered more efficient by increasing the cell surface expression of the CAR target structure via a small molecule.

关键词： neuroblastoma Cancer

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

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur research Pole School of Public HealthThe University of Hong KongHong KongChina research institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 immunity Intradermal Vaccine

The Triple Combination of Meropenem,Avibactam,and a Metallo-b-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different b-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford institute for Antimicrobial research University of OxfordOxford OX13REUK Chemistry research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

Psychological Impact of the 2022 Round COVID-19 Pandemic on China's College Students

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Journal of Shanghai Jiaotong university(Science) 2024年第1期29卷 141-149页

作者：洪冬羊王金霞张虹洋曹紫阳晏紫君邹琳 School of Pediatrics Shanghai Jiao Tong University School of MedicineShanghai 200001China institute of Pediatric infection Immunityand Critical Care MedicineShanghai Children's HospitalShanghai Jiao Tong University School of MedicineShanghai 200062China Clinical research Unit Shanghai Children's HospitalShanghai Jiao Tong University School of MedicineShanghai 200062China

In response to the new round of COVID-19 outbreaks since March 2022,universities with high outbreak rates around the country have taken quarantine measures to contain the *** from previous coronavirus outbreaks has shown that people under quarantine are at risk for mental health *** better understand the impacts of this round of COVID-19 quarantine on domestic college students and their responses,we conducted a systematic survey to assess the stress and anxiety,and to evaluate effective measurements in this *** searched relevant documents and literature,and designed a questionnaire from six aspects,including psychological status,epidemic situation,study,daily life,sports,and interpersonal communication,with 51 items in *** sent the questionnaire on the Wenjuanxing Web platform,from April 2 to 8,*** evaluated the mental status according to parts of the Generalized Anxiety Disorder-7(GAD-7)and Depression Anxiety Stress Scales-21(DASS-21),and investigated the influencing risk factors and *** analysis was performed by using the Chi-square test and multi-variable logistic *** total,508 college respondents were recruited in our survey,and the pooled prevalence of mild anxiety(GAD score≥5,or DASS-21 anxiety score≥8)or stress(DASS-21 pressure score≥14)caused by the new round of COVID-19 pandemic quarantine was 19.69%(100/508).The prevalence of the anxiety or stress in college students with COVID-19 quarantine between different genders,regions,and majors was not significantly *** risk factors for the mild anxiety or stress of undergraduates by COVID-19 quarantine included learning efficiency or duration[OR=1.36,95%CI(1.14—1.62),P=0.001],based on the combined analysis of Chi-square test analysis with multi-variable logistic regression ***,the mental well-beings before COVID-19 epidemic quarantine[OR=0.22,95%CI(0.130.36),P<0.0001],more low-intensity exercise[OR=0.36

关键词： COVID-19 psychological investigation college students anxiety stress

Clinical Trials of Respiratory Virus infections: How to Address Challenges and Prepare for the Future

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Infectious Diseases & immunity 2024年第3期4卷 101-102页

作者： Jingwen Ai Wenhong Zhang Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Shanghai Sci-Tech InnoCenter for infection and immunity Shanghai 20052China institute of infection and Health Fudan UniversityShanghai 200040China.

*** Prior to the coronavirus disease 2019(COVID-19)outbreak,the only antiviral treatment widely used in clinical settings was for ***,following the global pandemic,there has been renewed research interest in medications for respiratory viral *** trials of antiviral medications often need to consider multiple dimensions because of the significant differences in disease severity among *** example,during respiratory viral epidemic seasons,the clinical spectrum of diseases is usually complex,including asymptomatic infections,symptomatic infections(mild to moderate without hospitalization),severe cases(requiring hospitalization),and fatalities.

关键词： Clinical respiratory clinical

Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen Jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc J.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

Targeting a disintegrin and metalloprotease(ADAM)17-CD122 axis enhances CD8^(+)T cell effector differentiation and anti-tumor immunity

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3097-3111页

作者： Lina Sun Anjun Jiao Haiyan Liu Renyi Ding Ning Yuan Biao Yang Cangang Zhang Xiaoxuan Jia Gang Wang Yanhong Su Dan Zhang Lin Shi Chenming Sun Aijun Zhang Lianjun Zhang Baojun Zhang Department of Pathogenic Microbiology and Immunology School of Basic Medical SciencesXi’an Jiaotong UniversityXi’anShaanxi 710061China institute of infection and immunity Translational Medicine InstituteXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China Key Laboratory of Environment and Genes Related to Diseases Ministry of EducationXi’anShaanxi 710061China Xi’an Key Laboratory of Immune Related Diseases Xi’anShannxi 710061China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina Department of Pediatrics Qilu Hospital of Shandong UniversityJinanChina National Key Laboratory of immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina Key Laboratory of Synthetic Biology Regulatory Elements Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina

CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely *** ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane ***,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T *** and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and ***,ADAM17 regulated CD8^(+)T cells through cleavage of membrane ***17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T ***,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid *** findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

关键词： immunity stimulation involvement

Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

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International Journal of Oral Science 2024年第2期16卷 280-292页

作者： Ziming Wang Hao Zeng Can Wang Jiaolong Wang Jing Zhang Shuyuan Qu Yue Han Liu Yang Yueqi Ni Wenan Peng Huan Liu Hua Tang Qin Zhao Yufeng Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhanChina School of Stomatology Nanchang UniversityNanchangChina institute of infection and immunity Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanChina Medical research institute School of MedicineWuhan UniversityWuhanChina

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth *** the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone ***301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone ***,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain *** this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)*** first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b−macrophages via high-throughput RNA ***,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)*** single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in *** following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis ***,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in ***,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages *** a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

关键词： period upstream eventually