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Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

Protein & Cell 2024年第8期15卷 594-611页

作者： Jian Wu Chaoye Wang Shuhui Sun Tianmin Ren Lijie Pan Hongyi Liu Simeng Hou Shen Wu Xuejing Yan Jingxue Zhang Xiaofang Zhao Weihai Liu Sirui Zhu Shuwen Wei Chi Zhang Xu Jia Qi Zhang Ziyu Yu Yehong Zhuo Qi Zhao Chenlong Yang Ningli Wang Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Key Laboratory of Ophthalmology and Visual SciencesBeijing 100730China State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China State key laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China State key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Department of Neurosurgery Peking University Third HospitalCenter for Precision Neurosurgery and Oncology of Peking University Health Science CenterBeijing 100191China Spencer Center for Vision Research Byers Eye InstituteSchool of MedicineStanford UniversityPalo AltoCA 94304USA

The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle ***,the molecular basis and biological significance of the aging process in TM have not been fully ***,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM ***,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two ***,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM *** work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal *** work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

关键词： single-cell transcriptomic atlas macaque trabecular meshwork ocular outflow tissue aging

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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of Nuclear medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing key laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively ***: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low ***: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(Pprecision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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The key mediator of diabetic kidney disease:Potassium channel dysfunction

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Genes & diseases 2024年第4期11卷 188-200页

作者： Jia Guo Chaojie Zhang Hui Zhao Yufan Yan Zhangsuo Liu Nephrology Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China key laboratory of precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province ZhengzhouHenan 450052China Research Center for Kidney Disease ZhengzhouHenan 450052China

Diabetic kidney disease is a leading cause of end-stage renal disease,making it a global public health *** molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex ***,exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney *** channels are important proteins that maintain the physiological functions of cells and *** ion channels,potassium channels stand out,because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell *** potassium channel abnormalities have been found to be closely related to diabetic kid-ney disease progression and genetic susceptibility,such as K_(ATP),K_(ca),K_(ir),and K_(v).In this review,we summarized the roles of different types of potassium channels in the occurrence and devel-opment of diabetic kidney disease to discuss whether the development of DKD is due to potas-sium channel dysfunction and present new ideas for the treatment of DKD.

关键词： Channel dysfunction Diabetic kidney disease End-stage renal disease lon channel Potassium

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Fluorogenic sensing of amorphous aggregates,amyloid fibers,and chaperone activity via a near-infrared aggregation-induced emission-active probe

Aggregate

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Aggregate 2024年第1期5卷 309-320页

作者： Wei He Yuanyuan Yang Yuhui Qian Zhuoyi Chen Yongxin Zheng Wenping Zhao Chenxu Yan Zhiqian Guo Shu Quan State key laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing(SCICB)East China University of Science and TechnologyShanghaiChina key laboratory for Advanced Materials and Joint International Research laboratory of precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials ChemistryFrontiers Science Center for Materiobiology and Dynamic ChemistryInstitute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism East China University of Science and TechnologyShanghaiChina

The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these *** the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates,there is still a lack of tools capable of simultaneously detecting both types of ***,we demonstrate the quantitative discernment of amorphous aggregates by QM-FN-SO3,an aggregationinduced emission(AIE)probe initially designed for detecting amyloid *** probe easily penetrates the membranes of the widely-used prokaryotic model organism Escherichia coli,enabling the visualization of both amorphous aggregates and amyloid fibers through near-infrared ***,the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins,regardless of whether they form amorphous aggregates or amyloid fibers in *** properties contribute to the successful application of the QM-FN-SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein(OMP)chaperones,both in vitro and in their physiological ***,our work introduces a near-infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in ***,it demonstrates the applicability of the probe in chaperone biology and its potential as a high-throughput screening tool for protein aggregation inhibitors and folding factors.

关键词： aggregation-induced emission fluorescence molecular chaperone protein aggregation

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Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients

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Virologica Sinica 2024年第2期39卷 319-330页

作者： Guixin Li Danli Yang Xin Liu Ting Zhang Hui Liu Jun Zou Zimeng Xu Xiangmei Chen Lizhong Dai Hongsong Chen Fengmin Lu Peking University People's Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijing100044China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijing100191China Baruch S.Blumberg Institute DoylestownPA18901USA Shenzhen Sanyuansheng Biotechnology Co. LtdShenzhen518000China precision medicine Center of Zhengzhou University Academy of Medical SciencesZhengzhou UniversityZhengzhou450001China Peking University-Sansure Biotech Joint laboratory of Molecular medicine Sansure Biotech Co.LtdChangsha410205China

Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative ***,the replicative capacity of HBV with PC/BCP mutations remains ***,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the *** PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse *** human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein ***,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative ***,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric *** study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

关键词： Hepatitis B virus Precore mutation Basal core promoter mutations Endoplasmic reticulum stress

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Epidemiological Characteristics of Human Parainfluenza Viruses Infections-China,2019-2023

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China CDC weekly 2024年第12期6卷 235-241,I0003,I0004页

作者： Yixuan Gao Yingwei Ma Daxing Feng Feng Zhang Biao Wang Xiaoqing Liu Bing Zhu Hui Xie Linqing Zhao Xiaoru Long Ying Chen Bing Wang Jie Jiang Zhen Zhu Yan Zhang Aili Cui Baicheng Xia Naiying Mao National key laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina precision medicine Research Center Children’s Hospital of ChangchunChangchun CityJilin ProvinceChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina laboratory of Viral diseases Qingdao Municipal Centre for Disease Control and PreventionQingdao CityShandong ProvinceChina Virus laboratory Gansu Provincial Center for Disease Control and PreventionLanzhou CityGansu ProvinceChina Jiangxi Provincial Center for Disease Control and Prevention Nanchang CityGansu ProvinceChina Virus laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Institute for Immunization and Prevention Beijing Center for Disease Prevention and ControlAcademy for Preventive MedicineInstitute of Tuberculosis Control Research and PreventionBeijingChina laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijingChina Department of Infection Children’s Hospital of Chongqing Medical UniversityChongqingChina Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention Hohhot CityInner Mongolia Autonomous RegionChina Shenyang Prefecture Center for Disease Control and Prevention Shenyang CityLiaoning ProvinceChina

Introduction:A retrospective study based on sentinel surveillance was conducted in 10 provinciallevel administrative divisions(PLADs)in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses(HPIVs).Methods:From January 2019 to June 2023,respiratory specimens were collected from individuals with acute respiratory infections(ARIs)and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction(PCR).This study analyzed the association of HPIVs infections with seasonal patterns,geographical distribution,demographic profiles,clinical features,and co-infection ***:During the study period,a total of 12,866 ARIs were *** overall detection rate of HPIVs was 6.15%,varying from 5.04%in 2022 to 9.70%in *** median age of HPIVs-infected patients was 3 ***2 was more prevalent among individuals aged 5–17 years(42.57%),while HPIV4 was more common in those over 65 years(12.24%).HPIV3(54.16%)and HPIV1(27.18%)were the predominant serotypes,and their prevalence exhibited significant seasonal fluctuations postcoronavirus disease 2019(COVID-19)*** peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak *** peaks of HPIV1 were observed in 2021 following the peak of ***,coinfections were frequent in HPIVs cases(overall rate:22.12%),with human rhinovirus being the most common co-infecting ***:The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1,and their seasonal patterns were altered by pandemic ***,continuous surveillance of HPIVs is essential.

关键词： prevalence seasonal Human

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Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Nano Research 2024年第2期17卷 858-865页

作者： Xiaowan Fan Tao Zhang Xin Ding Yushuo Gu Qing Li Wei Jiang Kelong Fan Nanozyme Medical Center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Department Central-China Branch of National Center for Cardiovascular DiseasesHean Cardiovascular Disease CenterFuwai Central-China HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou 450046China Application Center for precision medicine the Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Engineering laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 101408China Department of General Surgery Strategic Support Force Medical CenterBeijing 100101China Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory ***-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing ***,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and ***,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic *** nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of *** the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve ***,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion ***,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

关键词： bioinspired nanozyme thermosensitive hydrogel Parkinson’s disease oxidative stress neuroinflammatory

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A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

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Neuroscience Bulletin 2024年第3期40卷 310-324页

作者： Man Yuan Sen Jin Gao Tan Siyuan Song Yizong Liu Huadong Wang Yin Shen Eye Center Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan430060China The Brain Cognition and Brain Disease Institute Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNational Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen518055China Jan and Dan Duncan Neurological Research Institute Baylor College of MedicineHouston77030USA State key laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyCASWuhan430071China Frontier Science Center of Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan430071China

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various ***,their role in transmitting visual information remains ***,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual *** applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole ***,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual ***,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic ***,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual *** results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

关键词： Parvalbumin-positive retinal ganglion cell Innate fear Superior colliculus Excitatory-excitatory neuronal connection Looming-evoked defensive response Subcortical pathway

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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

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Science China(Life Sciences) 2024年第8期67卷 1635-1647页

作者： Feng-Qi Liu Qing-Yuan Qu Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China Beijing key laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044China National Clinical Research Center for Hematologic Disease Beijing 100044China Collaborative Innovation Centre of Hematology Peking UniversityBeijing 100044China CAS key laboratory of Genomic and precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100074China State key laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the *** soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP *** the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T *** contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell *** a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune ***-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of *** conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of *** may offer novel targets to develop personalized immunotherapies.

关键词： immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow

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Exploring the Pathogenesis of autoimmune Liver diseases from the Heterogeneity of Target Cells

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 659-666页

作者： Zi-Xuan Qiu Lin-Xiang Huang Xiao-Xiao Wang Zi-Long Wang Xiao-He Li Bo Feng Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina

The incidence of autoimmune liver diseases(ALDs)and research on their pathogenesis are increasing ***,except for autoimmune hepatitis,which responds well to immunosuppression,primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive *** the known effects of the environment,genetics,and immunity on ALDs,the heterogeneity of target cells provides new insights into their *** review started by exploring the heterogeneity in the development,structures,and functions of hepatocytes and epithelial cells of the small and large bile *** example,cytokeratin(CK)8 and CK18 are primarily expressed in hepatocytes,while CK7 and CK19 are primarily expressed in intrahepatic ***,emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study *** review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.

关键词： autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis Disease heterogeneity Single-cell RNA sequencing Pathogenesis

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