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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Neural Regeneration Research 2024年第12期19卷 2698-2707页

作者： Bhupender Sharma Melissa MTorres Sheryl Rodriguez Laxman Gangwani Subodh Kumar center of Emphasis in Neuroscience Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences CenterEl PasoTXUSA bond life sciences center and department of veterinary pathobiology University of MissouriColumbiaMOUSA L.Frederick Francis Graduate School of Biomedical sciences Texas Tech University Health Sciences CenterEl PasoTXUSA

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related *** previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease *** study investigated a new molecular relationship between miR-502-3p and GABAergic synapse *** vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and *** silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 *** assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase ***,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 ***,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be *** whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse ***,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p *** present study provides insight into the molecular mechanism of regulation of GABAergic synapses by *** propose that micro-RNA,in particular miR-502-3p,could be a potential the

关键词： Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization Patch-clamp

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Anti-oxidative stress treatment and current clinical trials

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World Journal of Hepatology 2024年第2期16卷 294-299页

作者： Chun-Ye Zhang Ming Yang bond life sciences center University of MissouriColumbiaMO 65211United States department of Surgery University of MissouriColumbiaMO 65212United States

Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological *** plays an important role in the development and progression of many chronic *** exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling *** processes are involved in many ***,oxidative stress has gained more attraction as a targeting process for disease ***,anti-oxidative stress agents have been widely explored in pre-clinical ***,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in *** this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different *** pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

关键词： Anti-oxidative stress treatment Clinical trials Drugs Dietary invention Reactive oxygen species

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How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer sciences Tsinghua University College of life sciences Nankai University Chinese Institute for Brain Research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

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Integrins and their potential roles in mammalian pregnancy

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Journal of Animal Science and Biotechnology 2024年第1期15卷 1-19页

作者： Gregory A.Johnson Robert C.Burghardt Fuller W.Bazer Heewon Seo Joe W.Cain department of veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843‑4459USA department of Animal Science College of Agriculture and Life SciencesTexas A&M UniversityCollege StationTX 77843‑2471USA

Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of integrin adhesion complexes(IACs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the sc

关键词： Humans Implantation Integrins Pigs Pregnancy Rodents Sheep

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Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica S.Brady Michael T.Craig department of Clinical and Biomedical sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA School of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday *** is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 *** 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

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Detection of a reassortant swine H1N2 influenza A virus from pigs in Hong Kong

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Virologica Sinica 2024年第2期39卷 343-346页

作者： Guoqian Gu Congnuan Liu Song Hao Lee Lewis Sze Chun Choi Michael T.Wilson Dirk U.Pfeiffer Yun Young Go department of Infectious Diseases and Public Health Jockey Club College of Veterinary Medicine and Life SciencesCity University of Hong KongHong Kong SARChina center for Applied One Health Research and Policy Advice Jockey Club College of Veterinary Medicine and Life SciencesCity University of Hong KongHong Kong SARChina College of veterinary Medicine Konkuk UniversitySeoul143-701Republic of Korea

Dear Editor,Influenza A viruses(IAVs)are responsible for significant respiratory illnesses in humans and a broad range of animal *** outbreaks and the rapid spread of genetically and antigenically distinct IAVs represent a considerable challenge for swine *** are susceptible to avian and human IAV infections and are considered“mixing vessels”where human,avian,and swine IAVs can recombine and generate novel reassortant influenza viruses with pandemic potential(Vincent et al.,2014).

关键词： swine influenza mixing

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Roles of fibroblast growth factors in the treatment of diabetes

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World Journal of Diabetes 2024年第3期15卷 392-402页

作者： Chun-Ye Zhang Ming Yang bond life sciences center University of MissouriColumbiaMO 65211United States department of Surgery University of MissouriColumbiaMO 65212United States NextGen Precision Health Institution University of MissouriColumbiaMO 65212United States

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each ***,the incidence of diabetes is increasing,including several types of *** 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the *** evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 *** consists of 23 family members(FGF-1-23)in ***,we review current findings of FGFs in the treatment of diabetes and management of diabetic *** FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical ***,the roles of FGFs in diabetes and diabetic complications are involved in numerous ***,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose ***,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and ***,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

关键词： Fibroblast growth factors Type 1 diabetes Type 2 diabetes Metabolic disorders Treatment Clinical trials

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Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of life sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

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Shallow sub-lakes are essential for sustaining the successful wintering of waterbirds in Poyang Lake,China

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Avian Research 2024年第2期15卷 219-228页

作者： Mengjie Lu Zhen Zhang Peng Chen Changxin Xu Bin Gao Luzhang Ruan School of life sciences Nanchang UniversityNanchang330031China Jiangxi Province Key Laboratory of Watershed Ecosystem Change and Biodiversity Center for Watershed EcologyInstitute of Life Science and School of Life SciencesNanchang UniversityNanchang330031China

For migratory waterbirds,the quality of wintering habitat is related to spring migration and successful breeding in the next *** availability of food resources in the habitat is critical and varies within water *** the water-level fluctuations in Poyang Lake have been extremely variable interannually in recent years,the wintering waterbird populations have remained relatively ***,the mechanism of maintaining the stability is worth *** study aimed to compare the distribution of vegetation and herbivorous wa-terbirds in 2015-2016 and 2016-2017,focusing on three shallow sub-lakes and one main lake *** results showed that the emergence of tubers and the growth of Carex *** a continuous food supply and habitat for wintering waterbirds with a gradual decline in the water *** sub-lakes supported almost all of the tuber-eating waterbirds(1.42-1.62×10^(5))and most geese(1.34-1.53×10^(6)).However,the main lake area,covered with Persicaria hydropiper,did not provide adequate and accessible *** resulted in almost no distribution of tuber-eating waterbirds,with only a few geese congregating in early *** results demonstrated that the shallow sub-lakes under human control provided a different environment from the main lake and are key to sustaining the successful wintering of hundreds of thousands of migratory waterbirds in Poyang ***,we recommend refining the anthropogenic management of the shallow sub-lakes to regulate the water level to ensure the carrying capacity of Poyang Lake.

关键词： Anthropogenic management Carrying capacity Seasonal lake Water level Wintering habitat

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