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Polyaspers A and B,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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Chinese Journal of Chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China institute of organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei Key Laboratory of Wudang Local Chinese Medicine Research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

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Chinese expert consensus on the application of immune checkpoint inhibitors in liver transplantation for hepatocellular carcinoma

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中华医学杂志(英文版) 2024年第18期137卷 2024 Aug 15页

作者： Wang Zhengxin Yang Jiayin Li Guangming Liver transplantation Center General Surgery Department Huashan Hospital Affiliated to Fudan University Organ Transplantation Institute of Fudan University Shanghai China organ transplantation Center West China Hospital Sichuan University Chengdu Sichuan China Liver transplantation Center General Surgery Department of Beijing Youan Hospital Capital Medical University Beijing China

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Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China institute of organ Donation and transplantation of Qingdao University Qingdao 266000China Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Innovative Research Group for Hepatobiliary&Pancreatic Surgery and Digestive organ transplantation Zhengzhou 450052China Henan organ transplantation Quality Control Centre Zhengzhou 450052China Henan Engineering Technology Research Center for organ transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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Development of a diagnostic nomogram for alpha-fetoproteinnegative hepatocellular carcinoma based on serological biomarkers

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2463-2475页

作者： Li He Cui Zhang Lan-Lan Liu Li-Ping Huang Wen-Jing Lu Yuan-Yuan Zhang De-Yong Zou Yu-Fei Wang Qing Zhang Xiao-Li Yang School of Clinical Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of organ transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Department of Laboratory Medicine Jingyu County People’s HospitalBaishan 135200Jilin ProvinceChina School of Laboratory Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer-related death *** biomarkers play an important role in the early diagnosis and prognosis of *** a certain percentage of HCC patients are negative for alpha-fetoprotein(AFP),the diagnosis of AFP-negative HCC is essential to improve the detection rate of *** To establish an effective model for diagnosing AFP-negative HCC based on serum tumour *** A total of 180 HCC patients were enrolled in this *** expression levels of GP73,des-γ-carboxyprothrombin(DCP),CK18-M65,and CK18-M30 were detected by a fully automated chemiluminescence *** variables were selected by logistic regression *** models were constructed using stepwise backward logistic *** performance of the models was compared using the C statistic,integrated discrimination improvement,net reclassification improvement,and calibration *** clinical utility of the nomogram was assessed using decision curve analysis(DCA).RESULTS The results showed that the expression levels of GP73,DCP,CK18-M65,and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls(P<0.001).Multivariate logistic regression analysis revealed that GP73,DCP,and CK18-M65 were independent factors for diagnosing AFP-negative *** comparing the diagnostic performance of multiple models,we included GP73 and CK18-M65 as the model variables,and the model had good discrimination ability(area under the curve=0.946)and good goodness of *** DCA curves indicated the good clinical utility of the *** Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative *** diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

关键词： Hepatocellular carcinoma Alpha-fetoprotein-negative Diagnostic Nomogram Biomarker

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Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第21期30卷 2763-2776页

作者： Li He Wan-Sheng Ji Hai-Long Jin Wen-Jing Lu Yuan-Yuan Zhang Hua-Guang Wang Yu-Yu Liu Shuang Qiu Meng Xu Zi-Peng Lei Qian Zheng Xiao-Li Yang Qing Zhang Department of organ transplantation The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China School of Clinical Medicine Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina Clinical Research Center The Affiliated Hospital of Shandong Second Medical UniversityWeifang 261053Shandong ProvinceChina Department of Laboratory Medicine The Third Medical Centre of Chinese PLA General HospitalBeijing 100039China Physiatry Department Naval Aviation UniversityYantai 100071Shandong ProvinceChina

BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver *** To develop a model for predicting prognosis after LT in patients with *** Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and *** expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence *** best cutoff value of biomarkers was determined using the Youden *** regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest *** evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the *** The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after *** nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou *** calibration curve analyses indicated a good *** survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical *** The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after *** can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.

关键词： Hepatocellular carcinoma Liver transplantation Liver cancer Nomogram Prognosis

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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & Medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu Zhejiang University School of Medicine Hangzhou 310030China institute of organ transplantation Zhejiang UniversityHangzhou 310030China Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital of HangzhouHangzhou 310006China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Liver transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China Department of organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Liver Surgery and Liver transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Pplant pattern was associated with the poorest post-LT *** from male donors may provide the most benefit to female *** results indicate that sex should be considered as a critical factor in organ allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The institute for organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China institute of organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

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Animal Models and Experimental Medicine 2024年第4期7卷 584-590页

作者： Jing Xu Jilong Ren Kai Xu Minghui Fang Meina Ka Fei Xu Xin Wang Jing Wang Zhiqiang Han Guihai Feng Ying Zhang Tang Hai Wei Li Zheng Hu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Key Laboratory of organ Regeneration and Reconstruction Chinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Beijing institute for Stem Cell and Regenerative Medicine BeijingChina Key Laboratory of organ Regeneration and transplantation of the Ministry of Education The First HospitalJilin UniversityChangchunChina Beijing Farm Animal Research Center Institute of ZoologyChinese Academy of SciencesBeijingChina

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and *** knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC II molecule plays critical ***:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions ***:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue ***,the safety of our animals after gene editing was verified by using whole-genome sequencing and *** have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional ***:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC I and II deletion.

关键词： CD4 T cell genetically edited pig immune rejection major histocompatibility complex II xenotransplantation

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Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

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The Innovation 2024年第3期5卷 55-68页

作者： Rui Wang Xiao Peng Yixin Yuan Baojie Shi Yuan Liu Hengxiao Ni Wenzhi Guo Qiwei Yang Pingguo Liu Jie Wang Zhaojie Su Shengnan Yu Dehua Liu Jinyan Zhang Junjie Xia Xueni Liu Hao Li Zhengfeng Yang Zhihai Peng organ transplantation Clinical Medical Center of Xiamen University Department of General SurgeryXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China organ transplantation institute of Xiamen University Xiamen Human Organ Transplantation Quality Control CenterXiamen Key Laboratory of Regeneration MedicineFujian Provincial Key Laboratory of Organ and Tissue RegenerationSchool of MedicineXiamen UniversityXiamen 361102China Department of General Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Hepatobiliary&Pancreatic Surgery The National Key Clinical SpecialtyZhongshan Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Precision Research Center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management ***,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time *** was performed in two independent cohorts with additional LT patients and healthy *** study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this *** intensity of the immune response differs between the ACR and non-ACR ***,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of *** study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.

关键词： process analysis precise

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