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Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

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neural Regeneration Research 2024年第7期19卷 1407-1408页

作者： naomi Hartopp Andrea Markovinovic christopher CJ Miller Patricia Gomez-Suaga Sheffield Institute for Translational neuroscience University of SheffieldSheffieldUK Department of Basic and Clinical neuroscience Institute of PsychiatryPsychology and NeuroscienceLondonUK Universidad de Extremadura.Departamento de Bioquímica y Biología Molecular y Genética Facultad de Enfermería y Terapia OcupacionalCáceresSpain Centro de Investigación Biomédica en Red en Enfermedades neurodegenerativas-Instituto de Salud Carlos Ⅲ(CIBER-CIBERnED-ISCⅢ) MadridSpain Instituto Universitario de Investigación Biosanitaria de Extremadura(InUBE) CáceresSpain

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron *** is currently no cure and approximately 90% of cases are *** shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile *** and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

关键词： senile sclerosis

Dynamics of self-hybridized exciton–polaritons in 2D halide perovskites

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Light(Science & Applications) 2024年第1期13卷 13-22页

作者： Surendra B.Anantharaman Jason Lynch christopher E.Stevens christopher Munley Chentao Li Jin Hou Hao Zhang Andrew Torma Thomas Darlington Francis Coen Kevin Li Arka Majumdar PJames Schuck Aditya Mohite Hayk Harutyunyan Joshua R.Hendrickson Deep Jariwala Department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPA19104USA KBR Inc. BeavercreekOH45431USA Air Force Research Laboratory Sensors DirectorateWright-Patterson Air Force BaseOH45433USA Department of Physics University of WashingtonSeattleWA98195USA Department of Physics Emory UniversityAtlantaGA30322USA Department of Chemical and Biomolecular Engineering Rice UniversityHoustonTX77005USA Department of Materials Science and nanoengineering Rice UniversityHoustonTX77005USA Applied Physics Program Smalley‐Curl InstituteRice UniversityHoustonTX77005USA Department of Mechanical Engineering Columbia UniversityNew YorkNY10027USA Department of Electrical and Computer Engineering University of WashingtonSeattleWA98195USA

Excitons,bound electron–hole pairs,in two-dimensional hybrid organic inorganic perovskites(2D HOIPs)are capable of forming hybrid light-matter states known as exciton-polaritons(E–Ps)when the excitonic medium is confined in an optical *** the case of 2D HOIPs,they can self-hybridize into E–Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the ***,the fundamental properties of these self-hybridized E–Ps in 2D HOIPs,including their role in ultrafast energy and/or charge transfer at interfaces,remain ***,we demonstrate that>0.5µm thick 2D HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E–P *** E–Ps have high Q factors(>100)and modulate the optical dispersion for the crystal to enhance sub-gap absorption and *** varying excitation energy and ultrafast measurements,we also confirm energy transfer from higher energy E–Ps to lower energy E–***,we also demonstrate that E–Ps are capable of charge transport and transfer at *** findings provide new insights into charge and energy transfer in E–Ps opening new opportunities towards their manipulation for polaritonic devices.

关键词： charge polar excitation

Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

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World Journal of Diabetes 2024年第4期15卷 758-768页

作者： Enriqueta Muñoz-Islas Edgar David Santiago-SanMartin Eduardo Mendoza-Sánchez Héctor Fabián Torres-Rodríguez Laura Yanneth Ramírez-Quintanilla christopher Michael Peters Juan Miguel Jiménez-Andrade Unidad Académica Multidisciplinaria Reynosa-Aztlán Universidad Autónoma de TamaulipasReynosa 88740TamaulipasMexico Department of Anesthesiology Wake Forest University School of MedicineWinston SalemNC 27101United States

BACKGROUnD Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain *** To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with *** GDM was induced by *** of streptozotocin(STZ)in ICR mouse *** 12 wk old,fasting blood glucose levels were determined in *** 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for *** quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal *** Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated ***,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control ***,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control *** GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

关键词： Gestational diabetes mellitus Immunohistochemistry Confocal microscopy Pancreas Offspring

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja nolte Theresa Dombrowski Franz Cemic natascha Sommer Robert Ringseis Klaus Eder Karsten Krüger christopher Weyh Department of Exercise Physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal nutrition and nutrition Physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

Landscape of global urban environmental resistome and its association with local socioeconomic and medical status

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Science China(Life Sciences) 2024年第6期67卷 1292-1301页

作者： Jun Wu Yige Hu Michael H Perlin David Danko Jun Lu Manuela Oliveira Johannes Werner Maria M Zambrano Maria A Sierra Olayinka O Osuolale Paweł Łabaj nicolás Rascovan nur Hazlin Hazrin-Chong Soojin Jang Haruo Suzuki Marina nieto-Caballero Bharath Prithiviraj Patrick K H Lee Agnieszka Chmielarczyk Anna Różańska Yongxiang Zhao Lan Wang christopher E Mason Tieliu Shi Center for Bioinformatics and Computational Biology and the Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Biology Program on Disease EvolutionUniversity of LouisvilleLouisville 40292USA Weill Cornell Medicine New York 10065USA The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine New York 10065USA Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200025China i3S-Instituto de Investiga玢o e Inova玢o em Saúde Universidade do PortoPorto 4050-290Portugal Ipatimup-Instituto de Patologia e Imunologia Molecular da Universidade do Porto Porto 4200-465Portugal Departamento de Biologia Faculdade de CiênciasUniversidade do PortoPorto 4050-290Portugal High Performance and Cloud Computing Group Zentrum für Datenverarbeitung(ZDV)Eberhard Karls University of TübingenW鋍hterstra遝7672074TübingenGermany Corporación Corpogen Research Center Bogotá110311Colombia Applied Environmental Metagenomics and Infectious Diseases Research(AEMIDR) Department of Biological SciencesElizade UniversityIlara-Mokin 340271Nigeria Maopolska Centre of Biotechnology Jagiellonian UniversityKraków 30-005Poland Aix-Marseille Université Mediterranean Institute of OceanologyUniversitéde ToulonCNRSIRDUM 110Marseille 83041France Department of Biological Sciences and Biotechnology Faculty of Science and TechnologyUniversiti Kebangsaan Malaysia43600 UKM BangiSelangor Institut Pasteur Korea Seoul 13488Republic of Korea Faculty of Environment and Information Studies Keio UniversityFujisawaKanagawa 252-0882Japan University of Colorado at Boulder CivilEnvironmental and Architectural DepartmentBoulder 80303USA Brooklyn College of the City University of new York Brooklyn 11210USA School of Energy and Environment City University of Hong KongHong Kong 999077China Department of Microbiology Faculty of MedicineJagiellonian UniversityKraków 30-005Poland Biological Targeting Diagnosis and The

Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban *** address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based *** findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical *** also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel *** study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

关键词： urban environment metagenome antibiotic resistance resistance diversity biosynthetic gene clusters

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius niroshan Siriwardena Joanna M Wardlaw nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service nHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of neuroscience Newcastle UniversityNewcastle upon TyneUK Department of neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and nIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTn,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTn in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTn did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTn may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTn in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KnOWn On THIS TOPIC⇒Transdermal glyceryl trinitrate(GTn)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

Characterization of the tribologically relevant cover layers formed on copper in oxygen and oxygen-free conditions

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Friction 2023年第8期11卷 1505-1521页

作者： Selina RAUMEL Khemais BARIEnTI Hoang-Thien LUU nina MERKERT Folke DEnCKER Florian nÜRnBERGER Hans Jürgen MAIER Marc christopher WURZ Institute of Micro Production Technology Leibniz Universität HannoverGarbsen 30823Germany Institut für Werkstoffkunde(Materials Science) Leibniz Universität HannoverGarbsen 30823Germany Institute of Applied Mechanics Clausthal University of TechnologyClausthal-Zellerfeld 38678Germany

Engineering in vacuum or under a protective atmosphere permits the production of materials, wherever the absence of oxygen is an essential demand for a successful processing. However, very few studies have provided quantitative evidence of the effect of oxidized surfaces to tribological properties. In the current study on 99.99% pure copper, it is revealed that tribo-oxidation and the resulting increased abrasive wear can be suppressed by processing in an extreme high vacuum (XHV) adequate environment. The XHV adequate atmosphere was realized by using a silane-doped shielding gas (1.5 vol% SiH4 in argon). To analyse the influence of the ambient atmosphere on the tribological and mechanical properties, a ball–disk tribometer and a nanoindenter were used in air, argon, and silane-doped argon atmosphere for temperatures up to 800 ℃. Resistance measurements of the resulting coatings were carried out. To characterize the microstructures and the chemical compositions of the samples, the scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) were used. The investigations have revealed a formation of η-Cu3Si in silane-doped atmosphere at 300 ℃, as well as various intermediate stages of copper silicides. At temperatures above 300 ℃, the formation of γ-Cu5Si were detected. The formation was linked to an increase in hardness from 1.95 to 5.44 GPa, while the Young’s modulus increased by 46% to 178 GPa, with the significant reduction of the wear volume by a factor of 4.5 and the suppression of further oxidation and susceptibility of chemical wear. In addition, the relevant diffusion processes were identified using molecular dynamics (MD) simulations.

关键词： wear behavior tribochemical reaction oxidation behavior surface analysis molecular dynamics(MD)simulation

An aqueous 2.1 V pseudocapacitor with MXene and V-MnO_(2) electrodes

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nano Research 2022年第1期15卷 535-541页

作者： Jiabin Wu Qun Li christopher E.Shuck Kathleen Maleski Husam n.Alshareef Jun Zhou Yury Gogotsi Liang Huang Wuhan national Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China Department of Materials Science and Engineering and A./.Drexel nanomaterials Institute Drexel UniversityPhiladelphiaPennsylvania 19104USA Materials Science and Engineering Physical Science and Engineering DivisionKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia

MXenes have shown record-breaking redox capacitance in aqueous electrolytes,but in a limited voltage window due to oxidation under anodic potential and hydrogen evolution under high cathodic *** Ti3C2Tx Xene negative electrode with RuO_(2) or carbon-based positive electrodes expanded the voltage window in sulfuric acid electrolyte to about 1.5 ***,we present an asymmetric pseudocapacitor using abundant and eco-friendly vanadium doped MnO_(2) as the positive and Ti_(3)C_(2)Tx MXene as the negative electrode in a neutral 1M Li2SO4 *** all-pseudocapacitive asymmetric device not only uses a safer electrolyte and is a much less expensive counter-electrode than RuO_(2),but also can operate within a 2.1 V voltage window,leading to a maximum energy density of 46 Wh/*** study also demonstrates the possibility of using MXene electrodes to expand the working voltage window of traditional redox-capable materials.

关键词： MXene pseudocapacitors metal oxides supercapacitors manganese oxide

Genome and clonal hematopoiesis stability contrasts with immune,cfDnA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox christopher Chin Deena najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DnA *** length was measured by quantitative PCR,while whole genome and cfDnA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DnA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight