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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical college of Nanchang university Department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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CuInS_(2)quantum-dot-modified g-C_(3)N_(4)S-scheme heterojunction photocatalyst for hydrogen production and tetracycline degradation

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Journal of Materials Science & Technology 2024年第5期172卷 145-155页

作者： Jingjing Zhang Yue Zhao Kezhen Qi Shu-yuan Liu college of Pharmacy Dali UniversityDali 671000China Department of Pharmacology Shenyang Medical CollegeShenyang 110034China

CuInS_(2)quantum-dot(CIS QD)-modified g-C_(3)N_(4)(CN)catalysts(CIS/CN)were prepared with the aid of an in-situ growth *** as-obtained photocatalysts were explored by measuring their crystallinity,surface morphology,binding energy and light absorption *** photocatalytic efficiency of the pho-tocatalysts was evaluated through photocatalytic water splitting for hydrogen production and tetracycline(TC)antibiotic degradation under the simulated solar light and visible light *** optimized sample(10CIS/CN)showed the best photocatalytic activity:producing 102.4μmol g^(-1)h^(-1)of hydrogen in 1 h,or degrading 52.16%of TC in 120 min,which were respectively 48 or 3.4 times higher than the photocatalytic activity of CN *** enhancement in the efficiency of the composite system was prin-cipally accredited to the enlargement of light absorption,the more effective in charge transfer and the dropping of the charge carrier pair recombination through a formed S-scheme heterojunctional *** work is an effort to adjust CN-based polysulfide QD for speedy *** enriched photo-catalytic activity grants a new sense for adjusting the optical properties of CN.

关键词： CuInS_(2)QDs g-C_(3)N_(4) Photocatalysis Hydrogen production S-scheme heterojunction

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Differential expression of miRNAs and mRNAs in the livers of largemouth bass Micropterus salmoides under heat stress

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Journal of Oceanology and Limnology 2024年第2期42卷 594-608页

作者： Xuqian ZHAO Zijie LIN Caijuan LI Hao ZHU Lingling LI Wenjia MAO Qufei LING School of Biology and Basic medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Global warming threatens freshwater ecosystems and compromises fish *** elucidate the role of miRNAs in the livers of heat stressed largemouth bass,juvenile fish was subject to heat stress under 37°*** mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress *** gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles.A total of 406 differentially expressed genes(DEGs)were discovered,of which 212 were up-regulated and 194 were *** of the DEGs were significantly implicated in the regulation of“protein processing in endoplasmic reticulum”,“proteasome”,“steroid biosynthesis”,and“ornithine decarboxylase inhibitor activity”*** addition,47 differentially expressed miRNAs(DEMs)were identified in largemouth bass livers under heat stress,including 21 up-regulated and 25 down-regulated miRNAs.A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in“protein degradation”,“calcium ion regulation”,“cell apoptosis”,and“lipid metabolism”.Moreover,this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat *** study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress.

关键词： heat stress largemouth bass miRNA-mRNA interaction

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Heat stress induced hepatocyte apoptosis in largemouth bass Micropterus salmoides via IRE1α/TRAF2/ASK1/JNK pathway

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Journal of Oceanology and Limnology 2024年第3期42卷 988-1000页

作者： Xuqian ZHAO Wenjia MAO Zijie LIN Qufei LING School of Biology and Basic medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Heat stress(HS)has been shown to adversely affect fish livers and can lead to extensive *** investigate the relationship between endoplasmic reticulum(ER)stress and HS-induced apoptosis in fish livers,we isolated and cultured primary hepatocytes of largemouth bass,Micropterus salmoides by trypsin method,then established an in-vitro model of liver cells under HS(35℃).The contents of lactic dehydrogenase(LDH)and hydrogen peroxide(H2O2)were determined to evaluate the effects of HS on hepatocyte injury and oxidative ***-qPCR was performed to discover the key genes in unfolded protein response(UPR)pathways involved at different HS *** inhibitor 4-PBA and IRE1αinhibitor 4μ8C were used to further investigate the effects of HS on IRE1αapoptosis pathway in *** show that HS led to significant increases in the release of LDH,the content of H2O2,and the expressions of oxidative protein folding genes(ero1αand pdi)under HS,suggesting severe hepatocyte injury and oxidative stress happened in heat-stressed largemouth bass *** continuous activation of IRE1αpathway genes(grp78,grp94,atf6,perk,eif2a,atf4,chop,ire1α,traf2,ask1,jnk1,and jnk2)indicated that HS led significantly to ER *** particular,the mRNA expression levels of ER stress-related genes(grp78,grp94,atf6,perk,ire1α,chop,jnk1,and jnk2)in the high temperature(HT)+4-PBA group and the HT+4μ8C group were significantly down-regulated under *** 4μ8C treatment,the expression levels of apoptosis-related genes(caspase-2,caspase-3,caspase-6,caspase-7,caspase-8,caspase-9,and caspase-10)and LDH content were significantly decreased,whereas the cell survival rate was significantly increased when given 4-PBA or 4μ8C *** findings demonstrate that HS could induce liver apoptosis of largemouth bass through the IRE1αpathway,which may act as a key switch mediating liver apoptosis of largemouth bass under HS.

关键词： heat stress Micropterus salmoides endoplasmic reticulum stress apoptosis oxidative stress

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Comparative analysis of the microbiome of sympatric wintering Bean Geese,Domestic Ducks,humans,and soil at Shengjin Lake of China reveals potential public risk to human health

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Avian Research 2024年第2期15卷 279-286页

作者： Gang Liu Na Xu Chongyang Yu college of Life Sciences Anhui Medical UniversityHefei 230032China

The gut microbiota of migratory waterbirds is affected by various complex factors,including cross-species transmission,which increases the risk of pathogen spreading among sympatric animals and poses a potential public health risk to *** this study,we investigated the microbial communities of wintering Bean Geese(Anser fabalis),Domestic Ducks(*** domesticus),humans,and soil using high-throughput sequencing of the 16S rRNA gene region in Shengjin Lake,*** total,6,046,677 clean reads were obtained,representing 41,119 operational taxonomic units(OTUs)across the four *** dominant microbial phyla were the Proteobacteria,Firmicutes,Bacteroidota,and *** Sorensen similarity index and alpha and beta diversity results showed that the gut microbial communities of Bean Geese and Domestic Ducks were more similar to those of the other *** analysis revealed that Faecalibacterium prausnitzii,Pseudomonas fragi,and Bradyrhizobium elkanii were hubs of the three major *** common microbiomes were iden-tified in Bean Geese,Domestic Ducks,humans,and soil in Shengjin Lake.A total of 96 potential pathogens were identified among the four groups,with 20 specific potentially pathogenic microbiomes found in the gut of Bean *** of these pathogens are responsible for significant financial losses in the poultry industry and pose risks to human *** pneumoniae,Morganella morganii,Escherichia coli,and Ralstonia insidiosa are potential core pathogens found in the four groups at Shengjin Lake that can cause diseases in humans and an-imals and facilitate cross-species transmission through various ***,humans are at risk of con-tracting these pathogens from migratory birds because of their frequent contact with domestic ***,further studies are required to explore the potential pathogenic species and transmission pathways among sympatric wintering Bean Geese,Domestic Ducks,humans,and soil.

关键词： Microbiome Migratory waterbird Pathogens Poultry Sympatric species

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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim Department of Biochemistry and Convergence medical Sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence medical Sciences and Institute of medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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The role of lipid metabolism in osteoporosis:Clinical implication and cellular mechanism

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Genes & Diseases 2024年第4期11卷 220-233页

作者： Jing Zhang Wenhui Hu Zhi Zou Yuheng Li Fei Kang Jianmei Li Shiwu Dong college of Bioengineering Chongqing UniversityChongqing 400044China Department of Biomedical Materials Science College of Biomedical EngineeringArmy Medical University(Third Military Medical University)Chongqing 400038China State Key Laboratory of Trauma and Chemical Poisoning Army Medical University(Third Military Medical University)Chongqing 400038China

In recent years,researchers have become focused on the relationship between lipids and bone metabolism ***,many diseases related to lipid metabolism dis-orders,such as nonalcoholic fatty liver disease,atherosclerosis,obesity,and menopause,are associated with osteoporotic *** has been clinically observed in humans that these lipid metabolism disorders promote changes in osteoporosis-related indicators bone mineral density and bone ***,similar osteoporotic phenotype changes were observed in high-fat and high-cholesterol-induced animal *** lipid metabolism(such as increased oxidized lipids and elevated plasma cholesterol)affects bone microenvironment ho-meostasis via cross-organ communication,promoting differentiation of mesenchymal stem cells to adipocytes,and inhibiting commitment towards ***,disturbances in lipid metabolism affect the bone metabolism balance by promoting the secretion of cyto-kines such as receptor activator of nuclear factor-kappa B ligand by osteoblasts and stimulating the differentiation of ***,this review addresses the possible link be-tween lipid metabolism disorders and osteoporosis and elucidates the potential modulatory mechanisms and signaling pathways by which lipid metabolism affects bone metabolism *** also summarize the possible approaches and prospects of intervening lipid meta-bolismforosteoporosistreatment.

关键词： Bone homeostasis Cross-organ communication Lipid metabolism Osteoclast Osteoporosis

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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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Integrated analysis of single-cell and bulk RNA sequencing data reveals immune-related lncRNA-mRNA prognostic signature in triple-negative breast cancer

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Genes & Diseases 2024年第2期11卷 571-574页

作者： Hongying Zhao Lei Yu Lixia Wang Xiangzhe Yin Kailai Liu Wangyang Liu Shihua Lin Li Wang college of Bioinformatics Science and Technology Harbin Medical UniversityHarbinHeilongjiang 150081China college of Biomedical Information and Engineering Hainan Medical UniversityHaikouHainan 571199China

Triple-negative breast cancer(TNBC)is an aggressive subtype characterized by extensive tumor heterogeneity,with limited treatment options and a poor prognosis.1 We used cell type annotation and trajectory analysis to identify two distinct differentiation states of epithelial cells,while tumor cells predominantly resided on one of these *** the malignant state of epithelial cells based on copy number variation,280 tumor cells were eventually identified from epithelial *** genes between tumor cells and non-tumor cells were mainly enriched in immune-related functions and pathways.

关键词： breast cancer signature

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Cancer cachexia:Focus on cachexia factors and inter-organ communication

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Chinese medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai Dong Ziyi An Weilin Jin The First Clinical medical college of Lanzhou university LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia *** cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer *** cachexia factors are also a potential target for the diagnosis and *** pathogenesis of cachexia is unclear and no clear effective treatment is ***,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently *** the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and *** review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia *** summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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