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Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis

International Journal of Ophthalmology(English edition) 2024年第7期17卷 1344-1362页

作者： Zi-Ling Hu Yu-Xuan Wang Zi-Yue Lin Wen-Shuo Ren Bo Liu Hui Zhao Qiong Qin Five year program of Ophthalmology and Optometry 2019 Beijing Tong Ren HospitalCapital Medical UniversityBeijing 100054China Four year program of Traditional Chinese Pharmacy 2020 School of Traditional Chinese MedicineCapital Medical UniversityBeijing 100069China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Beijing Key Laboratory of TCM Collateral Disease Theory Research Beijing 100069China Five year program of Ophthalmology and Optometry 2021 School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Biochemistry&Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Age-related macular degeneration(AMD)is a complicated disease that causes irreversible visual *** evidences pointed retinal pigment epithelia(RPE)cells as the decisive cell involved in the progress of AMD,and the function of anti-oxidant capacity of PRE plays a fundamental physiological *** factor erythroid 2 related factor 2(Nrf2)is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative *** functions of protecting RPE cells against oxidative stress(OS)and ensuing physiological changes,including inflammation,mitochondrial damage and autophagy dysregulation,have already been *** the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD *** the first time,this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis,including proteins and miRNAs,and their underlying molecular mechanisms,which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.

关键词： Nrf2 upstream regulators retinal pigment epithelia age-related macular degeneration oxidative stress

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Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1711-1728页

作者： Crystal Ngofi Zumbi Chun-Hsu Pan Hui-Yu Huang Chieh-Hsi Wu program in Clinical Drug Development from Herbal Medicine College of PharmacyTaipei Medical UniversityTaipei 11031China program in Drug Discovery and Development Industry College of PharmacyTaipei Medical UniversityTaipei 11031China School of Pharmacy Taipei Medical UniversityTaipei 11031China Graduate Institute of Metabolism and Obesity Sciences Taipei Medical UniversityTaipei 11031China

Restenosis is a common complication following coronary *** traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut *** aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured *** indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of *** was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in ***,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured *** conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

关键词： Ascophyllum nodosum Fucus vesiculosus PTEN/PI3K/AKT Restenosis Macrophage Vascular smooth muscle cells Gut microbiota

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HCCDB v2.0:Decompose Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 131-142页

作者： Ziming Jiang Yanhong Wu Yuxin Miao Kaige Deng Fan Yang Shuhuan Xu Yupeng Wang Renke You Lei Zhang Yuhan Fan Wenbo Guo Qiuyu Lian Lei Chen Xuegong Zhang Yongchang Zheng Jin Gu Eight-year program of Clinical Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100006China MOE Key Laboratory of Bioinformatics BNRIST Bioinformatics DivisionInstitute for Precision Medicine&Department of AutomationTsinghua UniversityBeijing 100084China Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Fuzhou Institute for Data Technology Fuzhou 350207China university of Michigan-Shanghai Jiao Tong university Joint Institute Shanghai Jiao Tong UniversityShanghai 200240China Department of Automation Shanghai Jiao Tong UniversityShanghai 200240China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 201805China

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma(HCC).Integrated 15 transcriptomic datasets of HCC clinical samples,the first version of HCC database(HCCDB v1.0)was released in *** the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets,it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and *** four years having passed,the database now needs integration of recently published ***,the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial ***,we present HCCDB v2.0,an updated version that combines bulk,single-cell,and spatial transcriptomic data of HCC clinical *** dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples,thereby enhancing the reliability of transcriptomic meta-analysis.A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections,respectively.A novel single-cell level and 2-dimension(sc-2D)metric is proposed as well to summarize cell type-specific and dysregulated gene expression *** are all graphically visualized in our online portal,allowing users to easily retrieve data through a user-friendly interface and navigate between different *** extensive clinical phenotypes and transcriptomic data in the database,we show two applications for identifying prognosis-associated cells and tumor *** v2.0 is available at http://***/database/hccdb2.

关键词： Hepatocellular carcinoma Database Integrative analysis Single-cell RNA sequencing Spatial transcriptomics

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Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome:A Systematic Review and Meta-Analysis

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Chinese medical Sciences Journal 2024年第2期39卷 122-130页

作者： Xia-Xiao Yan Yue-Lun Zhang Yu-Pei Zhang Ying-Yun Yang Dong Wu Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Eight-year medical Doctor program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and *** We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September ***-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were *** estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the *** Four studies were *** pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for ***,limited high-quality data make the results'validity and applicability *** is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

关键词： irritable bowel syndrome bowel sound analysis diagnostic accuracy systematic review meta-analysis

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The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

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Nanoparticle targeting cGAS-STING signaling in disease therapy

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Nano Research 2024年第8期17卷 7315-7336页

作者： Lan Zhou Yu Huang Yuzhang Wu Shupei Tang Frontier medical Training Brigade Third Military Medical UniversityHutubi 831200China Department of Gastroenterology Xinqiao HospitalThird Military Medical UniversityChongqing 400037China Institute of Immunology Third Military Medical UniversityChongqing 400038China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse 857000China

The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon(IFN)genes(cGAS-STING)signaling pathway is crucial for sensing abnormal DNA accumulation in the *** binds to abnormal DNA,cGAS catalyzes the production of second messenger cyclic dinucleotides,followed by the activation of downstream *** activation induces the expression of type I interferon and other inflammatory cytokines,ultimately initiating an immune *** to the involvement of the cGAS-STING pathway in various diseases,including infection,tumor,autoimmune disease and kidney disease,ongoing research is focused on developing drugs and treatment methods to target and regulate this *** the development of nanotechnology,nanomedicines targeting cGAS-STING signaling are of great significance in clinical applications due to their targeted delivery,controlled drug release,improved solubility,multifunctionality,and enhanced *** comprehensive review focuses on the most recent progress of nanoplatforms targeting cGAS-STING in disease therapy,aiming to provide references and guidelines for further design and optimization of nanomedicines.

关键词： nanomedicine cGAS-STING pathway and related disease anti-tumor nanotherapy anti-viral nanotherapy

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Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

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Oncology Research 2024年第2期32卷 393-407页

作者： HONGYUAN LIANG YANQIU LI YONGGANG QU LINGYUN ZHANG Department of Radiology Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology The First Affiliated Hospital of China Medical UniversityShenyangChina Department of Clinical Medicine China Medical UniversityShenyangChina Department of medical Oncology The First Hospital of China Medical UniversityShenyangChina

Advanced LUAD shows limited response to treatment including immune *** the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response *** GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R *** constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression *** calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier *** also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model *** addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment *** also used the TIDE algorithm to predict immunotherapy responses in the CDI ***,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture *** study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with *** KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological *** study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk *** comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS *** addition,the study used unsupervised cluster analysis to d

关键词： Lung adenocarcinoma programmed cell death Iron-death Drug sensitivity Cancer therapy

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Aluminum exposure impairs oocyte quality via subcellular structure disruption and DNA damage-related apoptosis in mice

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Journal of Environmental Sciences 2024年第5期139卷 308-319页

作者： Hongge Li Jingcai Liu Weihua Nong Mengying Shen Sheng Dou Shaochen Sun Junli Wang The Affiliated Hospital of Youjiang medical university for Nationalities Guangxi 533000China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China School of medical Laboratory Youjiang Medical University for NationalitiesGuangxi 533000China Industrial College of Biomedicine and Health Industry Youjiang Medical University for NationalitiesGuangxi 533000China Reproductive Medicine Guangxi Medical and Health Key Discipline Construction ProjectThe Affiliated Hospital of Youjiang Medical University for NationalitiesGuangxi 533000China

Aluminum(Al)can lead to an exposure of creature in varieties ways for its universality,and it could disturb normal physiological metabolism,with the damage to multisystem including *** the oocyte quality is critical for female reproduction,we inspected the toxicity of Al on mouse oocyte *** constructed in vitro exposure mouse model,and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and *** spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation,as well as abnormal distribution of actin dynamics could hinder normal meiosis of *** dysfunction indicated that Al affected proteins synthesis,transport and digestion,which would further damage oocyte *** order to explore the mechanism of Al toxicity,our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis,resulting in limited energy ***,high level of reactive oxygen species,DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on *** conclusion,our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization,actin dynamics,organelle function and the induction of DNA damage-related apoptosis with mouse model.

关键词： Aluminum Oocyte Cytoskeleton Organelle DNA damage

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Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Science china Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong Xu Qiaochu Jiang Hai-Dong Xu Fuqiang Wang Gaolin Liang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis Center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

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Search for an exotic vectorlike X-quark in same-sign dilepton final states at the future 3 TeV CLIC

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Chinese Physics C 2024年第7期48卷 67-74页

作者：张艳菊常金龙刘太刚 School of medical Engineering Xinxiang Medical UniversityXinxiang 453003China

Vectorlike quarks(VLQs)with masses at the TeV-scale have been predicted in many new physics scenarios beyond the Standard Model(SM).Based on a simplified(X,T)doublet model including the exotic vectorlike X quark(VLQ-X)with an electric charge 5/3,we study the production of the VLQ-X decaying into tW at the future Compact Linear Collider(CLIC)with √s=3 TeV including the initial state radiation and beamstrahlung *** focus on the final signals,including same-sign dileptons(electrons or muons),at least one b-tagged jet,and large missing transverse *** performing detailed signal-to-background analyses and detector simulations,we obtain the 2σexclusion capabilities and discovery reaches,respectively,on the mass of the VLQ-Xmx as well as the relevant parameters(Br(X→_(t)W))for mx≥1500GeV and the coupling strength g^(*) for mx≥1500 GeV)for some typical luminosities at the 3 TeV CLIC.

关键词： Vectorlike quarks CLIC same-sign dilepton

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