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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

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

Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of Pediatrics 2024年第5期20卷 444-450页

作者： Hong-Qiang Du Xiao-Dong Zhao Department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited *** such,our current knowledge of this new disease remains *** review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel *** sources A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 *** search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript *** The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric *** some cases,immunodeficiency and autoimmunity can also be *** Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 *** blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the *** fully confirm the pathogenicity of the variant,further functional test is strongly *** and biologics are the mainstream management of ELF4 deficiency *** Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of *** atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 *** of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

Single-cell RNA sequencing in juvenile idiopathic arthritis

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Genes & Diseases 2024年第2期11卷 633-644页

作者： Xiwen Luo Xuemei Tang Department of Rheumatology and Immunology Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of Child infection and immunity Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children,with onset before age 16 and lasting for more than 6 *** is a highly heterogeneous condition with various consequences for health and quality of *** some JIA patients,early detection and intervention remain *** a result,further investigation of the complex and unknown mechanisms underlying JIA is *** in technology now allow us to describe the biological heterogeneity and function of individual cell populations in *** this review,we hope to provide novel ideas and potential targets for the diagnosis and treatment of JIA by summarizing the current findings of single-cell RNA sequencing studies and understanding how the major cell subsets drive JIA pathogenesis.

关键词： Juvenile idiopathic arthritis Macrophage Macrophage activation syndrome Monocyte Single-cell RNA sequencing Synoviocyte T cell

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

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

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

Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou Clinical research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for Clinical Molecular Laboratory Medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014China Clinical research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

Complementary and alternative medicine on cognitive defects and neuroinflammation after sepsis

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Journal of Traditional Chinese Medicine 2024年第2期44卷 408-416页

作者： LI Zhenxuan WANG Xuerui Luis Ulloa Ayman Youssef BAI Yunjing XU Xiaolong LIU Qingquan Department of Infectious Diseases Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China Beijing Key Laboratory of Basic research with Traditional Chinese Medicine on Infectious Diseases Beijing 100010China infection immunity laboratory Beijing Institute of Traditional Chinese MedicineBeijing 100010China Clinical College of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Center for Perioperative Organ Protection Department of AnesthesiologyDuke University Medical CenterDurhamNorth Carolina 27710USA

Sepsis-associated encephalopathy(SAE)is a common manifestation of sepsis,ranging from mild confusion and delirium to severe cognitive impairment and deep *** is associated with higher mortality and long-term outcomes,particularly substantial declines in cognitive *** mechanisms of SAE probably include neuroinflammation that is mediated by systemic inflammation and ischemic lesions in the brain,a disrupted blood–brain barrier,oxidative stress,neurotransmitter dysfunction,and severe microglial *** evidence suggests that complementary and alternative medicine,especially Traditional Chinese Medicine(TCM),is favorable in alleviating cognitive decline after ***,we summarized the studies of traditional herbal remedies,TCM formulas and acupuncture therapy in animal models of neurological dysfunctions after sepsis in recent decades and reviewed their potential mechanisms.

关键词： sepsis-associated encephalopathy cognitive dysfunction complementary therapies neuroinflammatory diseases medicine Chinese traditional review