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Targeting carnitine palmitoyl transferase 1A(CPT1A)induces ferroptosis and synergizes with immunotherapy in lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1675-1689页

作者： Lei Ma Chong Chen Chunxing Zhao Tong Li Lingyu Ma Jiayu Jiang Zhaojun Duan Qin Si Tsung-Hsien Chuang Rong Xiang Yunping Luo department of immunology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China Collaborative Innovation Center for Biotherapy Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China department of Lung Cancer Surgery Tianjin Medical University General HospitalTianjin 300052China immunology Research Center National Health Research InstitutesZhunanMiaoliTaiwanROC department of immunology Nankai UniversityTianjin 300071China

Despite the successful application of immune checkpoint therapy,no response or recurrence is typical in lung *** stem cells(CSCs)have been identified as a crucial player in immunotherapy-related ***,a form of cell death driven by iron-dependent lipid peroxidation,is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with *** adaption of CsCs drives tumor resistance,yet the mechanisms of their ferroptosis defense in tumor immune evasion remain ***,through metabolomics,transcriptomics,a lung epithelialspecific Cptla-knockout mouse model,and clinical analysis,we demonstrate that CPT1A,a key rate-limiting enzyme of fatty acid oxidation,acts with L-carnitine,derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8^(+)T cells inactivation in lung ***,CPT1A restrains ubiquitination and degradation of c-Myc,while c-Myc transcriptionally activates CPT1A *** CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating,thereby suppressing ferroptosis in ***,targeting CPT1A enhances immune checkpoint blockadeinduced anti-tumor immunity and tumoral ferroptosis in tumor-bearing *** results illustrate the potential of a mechanismguided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CsCs to improve the efficacy of lung cancer immunotherapy.

关键词： immunotherapy metabolism peroxidation

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Dual activities of a silencing information regulator complex in yeast transcriptional regulation and DNA-damage response

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mLife 2024年第2期3卷 207-218页

作者： Josephine Rybchuk Wei Xiao department of Biochemistry Microbiology and ImmunologyUniversity of SaskatchewanSaskatoonSaskatchewanCanada Toxicology Program University of SaskatchewanSaskatoonSaskatchewanCanada

The Saccharomyces cerevisiae silencing information regulator(SIR)complex contains up to four proteins,namely Sir1,Sir2,Sir3,and *** Sir2 encodes a NAD-dependent histone deacetylase,other SIR proteins mainly function as structural and scaffold components through physical interaction with various *** SIR complex displays different conformation and composition,including Sir2 homotrimer,Sir1-4 heterotetramer,Sir2-4 heterotrimer,and their derivatives,which recycle and relocate to different chromosomal *** activities of the SIR complex are transcriptional silencing through chromosomal remodeling and modulation of DNA double-strand-break repair *** activities allow the SIR complex to be involved in mating-type maintenance and switching,telomere and subtelomere gene silencing,promotion of nonhomologous end joining,and inhibition of homologous recombination,as well as control of cell *** review explores the potential link between epigenetic regulation and DNA damage response conferred by the SIR complex under various conditions aiming at understanding its roles in balancing cell survival and genomic stability in response to internal and environmental *** core activities of the SIR complex are highly conserved in eukaryotes from yeast to humans,knowledge obtained in the yeast may apply to mammalian Sirtuin homologs and related diseases.

关键词： chromatin remodeling DNA-damage response SiR complex transcriptional silencing yeast

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao department of immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands department of Tumor Biology and immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Resurgence of measles virus infection in an eliminated country, Sri Lanka

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 208-213页

作者： Merennage Anusha Yasanthi Fernando Gankandage Prabhath Chathuranga Kaanthaka Gunaradha Abeygunasekara Dedunu Dias Weligamage Janaki Indira Abeynayake department of Medical microbiology and immunology Faculty of MedicineUniversity of ColomboSri Lanka department of Virology Medical Research InstituteColombo 08Sri Lanka department of Medical Administration Medical Research InstituteColombo 08Sri Lanka

Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the ***:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri *** to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,*** RNA positive samples were sequenced at reference laboratory,*** of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella *** was analyzed using descriptive ***:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or ***(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive *** provinces reported measles positive *** samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing *** ***:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating ***,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.

关键词： Measles elimination Resurgence of measles Sri Lanka Genotype D8 National Measles Rubella Laboratory

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LPA_(1) antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities

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Nano Research 2024年第10期17卷 9095-9102页

作者： Jingyue Yan Diana D.Kang Chang Wang Xucheng Hou Shi Du Siyu Wang Yonger Xue Zhengwei Liu Haoyuan Li Yichen Zhong Binbin Deng David W.McComb Yizhou Dong Division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics Institute Precision Immunology InstituteDepartment of Immunology and ImmunotherapyDepartment of Oncological SciencesTisch Cancer InstituteBiomedical Engineering and Imaging InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Center for Electron Microscopy and Analysis The Ohio State UniversityColumbusOH 43212USA department of Materials Science and Engineering The Ohio State UniversityColumbusOH 43210USA

Activated fibroblasts are major mediators of pulmonary *** are generally found in the connective tissue but upon activation can generate excess extracellular matrix(ECM)in the lung interstitial ***,fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis(IPF).Here,we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1(LPA_(1))and the inflammatory pathway through tumor necrosis factorα-induced protein 3(TNFAIP3,also known as A20)in ***,we synthesized a series of LPA_(1) antagonists,AM095 and AM966,derived amino lipids(LA lipids)which were formulated into LA-lipid nanoparticles(LA-LNPs)encapsulating ***,LA5-LNPs,with AM966 head group and biodegradable acetal lipid tails,showed efficient A20 mRNA delivery to lung fibroblasts in vitro(80.2%±1.5%)and ex vivo(17.2%±0.4%).When treated to primary mouse lung fibroblasts(MLF),this formulation inhibited fibroblast migration and collagen production,thereby slowing the progression of ***,LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.

关键词： lysophosphatidic acid receptor 1(LPA_(1))antagonist tumor necrosis factorα-induced protein 3(A20) lung fibrosis lipid nanoparticles mRNA

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Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

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Neural Regeneration Research 2024年第4期19卷 833-845页

作者： Xiaoyan Liu Yi Liu Junlin Liu Hantao Zhang Chaofan Shan Yinglu Guo Xun Gong Mengmeng Cui Xiubin Li Min Tang School of Life Sciences Jiangsu University Institute of Animal Husbandry Jiangsu Academy of Agricultural Sciences department of Rheumatology&immunology Affiliated Hospital of Jiangsu University department of Neurology The Second Affiliated Hospital of Shandong First Medical University

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain *** a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral ***-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine ***,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut *** pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also ***,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

关键词： biomarker diet pattern gut microbiota gut-brain axis metagenomics mitochondrial dysfunction multi-omics neurodegenerative disease neuroinflammation probiotic

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Standardization is needed in reporting risk and outcomes of machine perfusion in liver transplantation

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 709-714页

作者： Chase J.Wehrle Charles Miller Koji Hashimoto Andrea Schlegel Transplantation Center Department of SurgeryDigestive Disease InstituteCleveland ClinicClevelandOHUSA department of immunology Lerner Research InstituteCleveland ClinicClevelandOHUSA

We congratulate Yamamoto et *** their study“Impact of Portable Normothermic Machine Perfusion for Liver Transplantation from Adult Deceased Donors”(1).The surge of interest in normothermic machine perfusion(NMP)in the United States(US)has generated considerable *** authors present generally exciting results from their single-center analysis of 541 liver *** these,469 were from donors after brain dead(DBD);58(12.4%)received NMP and 411 static cold storage(SCS,87.6%).Seventy-two transplants were from donors after circulatory death(DCD);52(72.2%)received NMP(device-to-donor)vs.20 SCS(27.8%).

关键词： Liver transplantation machine perfusion normothermic machine perfusion(NMP) transplantation viability assessment

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Ovarian function in patients with systemic lupus erythematosus:Pathogenesis,drug application and prospective therapies

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World Journal of Experimental Medicine 2024年第2期14卷 29-34页

作者： Min Xu Li-Li Tian Xiao-Liu Li Cheng Bao Hai-Wei Zhang Hong-Wei Chen department of Rheumatology and immunology Nanjing Drum Tower HospitalClinical College of Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina School of Life Science Nanjing Normal UniversityNanjing 210023Jiangsu ProvinceChina department of Rheumatology and immunology Nanjing Drum Tower HospitalNanjing 210008Jiangsu ProvinceChina department of Rheumatology and immunology Nanjing Pukou People’s HospitalNanjing 211800Jiangsu ProvinceChina department of Rheumatology and immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of School of MedicineNanjing UniversityNanjing 210008Jiangsu ProvinceChina

Systemic lupus erythematosus(SLE)is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile ***,glucocorticoids and immunosuppressants are widely used to treat SLE ***,ovarian dysfunction occurs following the use of these drugs in women with ***,we summarize recent progress in terms of understanding ovarian injury,the effects of drug application and strategies to improve ovarian function in women with *** review could be helpful to precisely cure SLE in women desiring to have offspring.

关键词： Systemic lupus erythematosus Ovarian reserve Ovarian insufficiency Mesenchymal stem cells Fertility Autoimmune disease

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Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe Keith J Roberts department of HPB and Liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

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Coming of age:the formation and function of age-associated B cells

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Cellular & Molecular immunology 2024年第4期21卷 311-312页

作者： Ke Rui Nan Che Kongyang Ma Hejian Zou Fan Xiao Liwei Lu department of Laboratory Medicine Institute of Medical Immunology of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina department of Rheumatology and immunology Nanjing First HospitalNanjing Medical UniversityJiangsuChina Centre for Infection and Immunity Studies School of MedicineThe Sun Yat-sen UniversityShenzhen518107GuangdongChina department of Rheumatology Huashan HospitalFudan UniversityShanghaiChina department of Pathology and Shenzhen Institute of Research and Innovation HKU Shenzhen HospitalThe University of Hong KongHong KongChina Centre for Oncology and immunology Hong Kong Science ParkHong KongChina

B cells are generated in the bone marrow during ontogeny and migrate to peripheral lymphoid organs,where they encounter antigens to elicit humoral *** the past decade,many novel B-cell subsets with distinct phenotypes and functions have been identified,and among these subsets,age-associated B cells(ABCs)were first characterized as a B-cell subset that accumulates with age[1].

关键词： organs lymphoid migrate

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