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Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration research 2024年第2期19卷 405-406页

作者： Fabio Coppedè Department of Translational research and of New Surgical and Medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

De Novo Dissecting the Three‑Dimensional Facial Morphology of 2379 Han Chinese Individuals

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Phenomics 2024年第1期4卷 1-12页

作者： Hui Qiao Jingze Tan Shaoqing Wen Menghan Zhang Shuhua Xu Li Jin State Key Laboratory of Genetic Engineering Center for Evolutionary BiologyCollaborative Innovation Center for Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 200438China Ministry of Education Key Laboratory of Contemporary Anthropology Human Phenome InstituteZhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Institute of Archaeological Science Fudan UniversityShanghai 200433China Institute of Modern Languages and Linguistics Fudan UniversityShanghai 200433China Department of liver Surgery and Transplantation liver Cancer Institute Zhongshan HospitalFudan UniversityShanghai 200032China

Phenotypic diversity,especially that of facial morphology,has not been fully investigated in the Han Chinese,which is the largest ethnic group in the *** this study,we systematically analyzed a total of 14,838 facial traits representing 15 categories with both a large-scale three-dimensional(3D)manual landmarking database and computer-aided facial segmented phenotyping in 2379 Han Chinese *** results illustrate that homogeneous and heterogeneous facial morphological traits exist among Han Chinese populations across the three geographical regions:Zhengzhou,Taizhou,and *** identifed 1560 shared features from extracted phenotypes,which characterized well the basic facial morphology of the Han *** particular,heterogeneous phenotypes showing population structures corresponded to geographical *** greatest facial variation among these geographical populations was the angle of glabella,left subalare,and right cheilion(p=3.4×10^(−161)).Interestingly,we found that Han Chinese populations could be classifed into northern Han,central Han,and southern Han at the phenotypic level,and the facial morphological variation pattern of central Han Chinese was between the typical diferentiation of northern and southern Han *** result was highly consistent with the results revealed by the genetic *** fndings provide new insights into the analysis of multidimensional phenotypes as well as a valuable resource for further facial phenotype-genotype association studies in Han Chinese and East Asian populations.

关键词： Phenotypes Three-dimensional facial imaging Facial morphology Han Chinese

Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein dietinduced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1292-1311页

作者： Daojie Li Hongying Cai Guohua Liu Yunsheng Han Kai Qiu Weiwei Liu Kun Meng Peilong Yang Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs Institute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China National Engineering research center of Biological Feed Beijing 100081China

Background Fatty liver hemorrhage syndrome(FLHS)becomes one of the most major factors resulting in the laying hen death for caged egg *** study aimed to investigate the therapeutic effects of Lactiplantibacillus plan-tarum(***)FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism,and gut *** The FLHS model of laying hens was established by feeding a high-energy low-protein(HELP)diet,and the treatment groups were fed a HELP diet supplemented with differential proportions of *** *** results indicated that *** FRT4 increased laying rate,and reduced the liver lipid accumulation by regulating lipid metabolism(lipid synthesis and transport)and improving the gut microbiota ***,***-tarum FRT4 regulated the liver glycerophospholipid ***,“gut-liver”axis analysis showed that there was a correlation between gut microbiota and lipid *** The results indicated that *** FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating“gut-liver”*** findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of *** FRT4 and for future use of *** FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

关键词： Fatty liver hemorrhage syndrome Gut microbiota Lactiplantibacillus plantarum FRT4 Laying hens Lipid metabolism

表位结构指导免疫优势转移的HPV交叉疫苗的理性设计

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Science Bulletin 2024年第4期69卷 512-525页

作者：王致萍王大宁陈洁高飞江雅楠杨澄宇钱兹英池鑫张姝玥许钰洁卢一涵沈璟佳张承宗李瑾瑾周立志李婷婷郑清炳俞海李少伟夏宁邵顾颖 State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China National Institute of diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCollaborative Innovation Center of Biologic ProductsNational Innovation Platform for Industry-Education Integration in Vaccine ResearchXiamen UniversityXiamen 361102China research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China Xiamen Innovax Biotech Co. Ltd.Xiamen 361022China

In vaccine development,broadly or cross-type neutralizing antibodies(bnAbs or cnAbs)are frequently targeted to enhance *** immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization ***,the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly *** this study,we discovered a cross-type neutralizing monoclonal antibody,13H5,against human papillomavirus 6(HPV6)and *** nAb exhibited a marked preference for HPV6,demonstrating superior binding activity to virus-like particles(VLPs)and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum(90%vs.31%).Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex,we delineated the epitope as spanning four segments of amino acids(Phe42-Ala47,Gly172-Asp173,Glu255-Val275,and Val337-Tyr351)on the L1 surface *** interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and *** Ser341 with alanine,which is the residue type present in HPV11 L1,almost completely abolished binding activity to *** swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1(Ser341,Thr338,and Thr339),we engineered chimeric HPV11-6HI ***,the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human *** approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

关键词： Human papillomavirus Cross-neutralization antibody Immunodominance shift Vaccine design

Parasites of the liver:A global problem?

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World Journal of Gastroenterology 2024年第30期30卷 3554-3559页

作者： Vladislav V Tsukanov Alexander V Vasyutin Julia L Tonkikh Clinical Department of the Digestive System Pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

Parasitic liver diseases can be caused by trematodes,cestodes,nematodes,and *** pathology is significant because millions of people in different parts of the world have liver parasites,which can manifest themselves in the development of inflammation,liver cysts,cholecystitis,cholelithiasis,pancreatitis and liver cirrhosis that are often threatening their *** International Agency for research on Cancer considers three species of trematodes,Schistosoma haematobium,Opisthorchis viverrini and Clonorchis sinensis,to be *** modern examination methods,in some cases including extensive screening of large populations,are required for diagnosing liver *** of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic *** is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

关键词： liver Parasites Epidemiology Diagnosis Clinics Treatment Echinococcosis Opisthorchiasis Fascioliasis Schistosomiasis

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal Cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

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World Journal of Gastroenterology 2024年第22期30卷 2839-2842页

作者： Chen-Xiao Huang Xiao-Dong Zhou Calvin Q Pan Ming-Hua Zheng Metabolic Dysfunction-Associated Fatty liver Disease research center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Cardiovascular Medicine The Key Laboratory of Cardiovascular Diseases of WenzhouThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Division of Gastroenterology and Hepatology Department of MedicineNew York University Langone HealthNew York University Grossman School of MedicineNew YorkNY 11355United States Institute of Hepatology Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang ProvinceWenzhou 325000Zhejiang ProvinceChina

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition *** liver enzyme-based screening methods have limitations that may missed diagnoses and treatment *** Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal ***,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early *** paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

关键词： Metabolic dysfunction-associated fatty liver disease Non-alcoholic fatty liver disease Alanine aminotransferase liver enzymes Screening Noninvasive liver fibrosis scores

Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

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Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon Yuekun Zhu Hailian Shi Yundong He Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina center for Clinical research Fudan University Pudong Medical CenterShanghaiChina Clinical research center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA center for Medical research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and Health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina Medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb Medical Radiological research center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,*** exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular *** also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient *** advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular *** therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular ***,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer *** review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer *** conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms acr

关键词： PCSK9 metabolism convert

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

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Oncology research 2024年第4期32卷 679-690页

作者： XINFENG ZHANG SHUANG LI MEIRU SONG YUE CHEN LIANGZHENG CHANG ZHERUI LIU HONGYUAN DAI YUTAO WANG GANGQI YANG YUN JIANG YINYING LU The PLA 307 Clinical College of Anhui Medical University The Fifth Clinical Medical College of Anhui Medical UniversityHefei230032China liver Tumor Diagnosis and research center 5th Medical Center of the PLA General HospitalBeijing100039China Department of Infection Diseases Guizhou Medical UniversityGuiyang550025China 4302 Clinical Medical School Peking UniversityBeijingChina Cell and Gene Therapy Innovation center Beijing Lotuslake BiomedicalScience and Technology ParkBeijing102206China State Key Laboratory of Chemical Oncogenomics and the Institute of Biopharmaceutical and Health Engineering(iBHE) Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

liver cancer is a prevalent malignant cancer,ranking third in terms of mortality *** and recurrence primarily contribute to the high mortality rate of liver *** carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and ***,the efficacy of FAK phosphorylation inhibitors is currently ***,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC *** study examined the correlation between FAK expression and the prognosis of ***,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor *** expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying *** results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in *** expression of E-cadherin and decreased expression of vimentin indicated that EMT was ***,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

关键词： Hepatocellular carcinoma(HCC) Focal adhesion kinase(FAK) Proteolytic targeting chimera technology(PROTAC) Epithelial-mesenchymal transformation(EMT) Metastasis