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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell jun Okabe Ishant Khurana Thomas Karagiannis julia j.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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journal of Sport and Health Science 2024年第3期13卷 409-418页

作者： jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes Mikael Croyal bertrand Perret Sophie Guyonnet bruno Vellas Laurent O.Martinez Philipe de Souto barreto For the MAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France Centre d'Epidémiologie et de Recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France Service de biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France bioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy ***1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains ***,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP *** examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these ***:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were ***1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year *** linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 *** analyses were conducted to examine whether apoA-I mediated these *** linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in ***:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(b=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(b_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:b=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly med

关键词： Aging Apolipoprotein bioenergetics Exerkine Mitochondria

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： benjamin T.Schumacher Michael j.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada jr. john bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA Translational Gerontology branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

background:There exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:The baltimore Longitudinal Study of Aging(bLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall bLSA,(b)by sex,(c)using all bLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:The age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

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由超拍电子伏特加速器产生的超高能伽马射线气泡

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Science bulletin 2024年第4期69卷 449-457页

作者： LHAASO Collaboration Zhen Cao Chuandong Gao Cong Li Ruo-Yu Liu Ruizhi Yang 不详 Key Laboratory of Particle Astrophyics&Experimental Physics Division&Computing Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China TIANFU Cosmic Ray Research Center ChengduChina Institute of Frontier and Interdisciplinary Science Shandong UniversityQingdao 266237China School of Astronomy and Space Science Nanjing UniversityNanjing 210023China University of Science and Technology of China Hefei 230026China

We report the detection of aγ-ray bubble spanning at least 100deg2 in ultra-high energy(UHE)up to a few PeV in the direction of the star-forming region Cygnus X,implying the presence super PeVatron(s)accelerating protons to at least 10 PeV.A log-parabola form with the photon indexΓ(E)=(2.71±0.02)+(0.11±0.02)×log10(E/10 TeV)is found fitting the gamma-ray energy spectrum of the bubble *** sources,“hot spots”correlated with very massive molecular clouds,and a quasi-spherical amorphousγ-ray emitter with a sharp central brightening are observed in the *** the core of~0.5°,spatially associating with a region containing massive Ob association(Cygnus Ob2)and a microquasar(Cygnus X-3),as well as previously reported multi-TeV sources,an enhanced concentration of UHEγ-rays is observed with 2 photons at energies above 1 *** general feature of the bubble,the morphology,and the energy spectrum,are reasonably reproduced by the assumption of a particle accelerator in the core,continuously injecting protons into the ambient medium.

关键词： Cosmic rays γ-rays Interstellar medium Star cluster

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三轴形变核^(131)ba中的奇异集体激发模式

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物理学报 2024年第11期73卷 89-100页

作者：韦锐周厚兵王思成丁兵强赟华贾晨旭陈红星郭松 C.M.Petrache D.Mengoni A.Astier E.Dupont 吕冰锋 D.bazzacco A.boso A.Goasduff F.Recchia D.Testov F.Galtarossa G.jaworski D.R.Napoli S.Riccetto M.Siciliano j.j.Valiente-Dobon C.Andreoiu F.H.Garcia K.Ortner K.Whitmore A.Ataç-Nyberg T.bäck b.Cederwall E.A.Lawrie I.Kuti D.Sohler T.Marchlewski j.Srebrny A.Tucholski 广西师范大学物理科学与技术学院桂林541004 广西核物理与核技术重点实验室桂林541004 中国科学院近代物理研究所兰州730000 中国科学院大学北京100049 巴黎萨克雷大学 CNRS/IN2P3IJCLab奥赛91405 帕多瓦大学物理和天文学系帕多瓦I-35131 意大利国家核物理研究所帕多瓦分部帕多瓦I-35131 意大利国家核物理研究所莱尼亚罗国家实验室莱尼亚罗(帕多瓦)I-35020 费拉拉大学理学与自然科学院费拉拉西蒙菲莎大学化学系本拿比BC V5A 1S6 皇家理工学院物理系斯德哥摩尔S-10691 国家研究基金会iThemba加速器科学实验室西萨默塞特7123 西开普大学物理与天文系贝尔维尔ZA-7535 HUN-REN原子核研究所德布勒森4001 华沙巴斯德拉大学重离子实验室华沙02-093

利用意大利Legnaro实验室串列静电加速器提供的65 MeV^(13)C束流与122Sn靶的熔合蒸发反应布居了^(131)ba的高自旋态,并搭建了新的能级纲图.新的能级纲图由15条转动带组成,包括三对手征双重带,其中两对正宇称手征带为赝自旋-手征四重带.... 详细信息

利用意大利Legnaro实验室串列静电加速器提供的65 MeV^(13)C束流与122Sn靶的熔合蒸发反应布居了^(131)ba的高自旋态,并搭建了新的能级纲图.新的能级纲图由15条转动带组成,包括三对手征双重带,其中两对正宇称手征带为赝自旋-手征四重带.正负宇称手征带通过一系列增强的E1跃迁连接,表明它们之间存在八极关联.在低自旋区域搭建了一条新的转动带,通过一系列γ跃迁向νh1_(1/2)晕带退激.这种能级结构与摇摆带相似,但基于现有的实验证据还难以将它确认为摇摆带,不能排除其他集体激发机制,如γ振动的影响.

关键词：高自旋态手征带赝自旋八极关联摇摆运动

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地球演化历史中氧逸度变化对壳幔循环启动、风化和超大陆循环的指示

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Science bulletin 2024年第1期69卷 97-102页

作者：王瑞邬绍宸 Roberto F.Weinberg William j.Collins Peter A.Cawood State Key Laboratory of Geological Processes and Mineral Resources Institute of Earth SciencesChina University of GeosciencesBeijing 100083China Frontiers Science Center for Deep-time Digital Earth China University of Geosciences(Beijing)Beijing 100083China School of Earth Atmosphere and EnvironmentMonash UniversityClayton VIC 3800Australia The Institute for Geoscience Research Curtin UniversityPerth WA 6102Australia

We apply a zircon redox index to a global compilation of detrital zircons to track the variation of oxidation state,expressed asΔFMQ,through Earth's *** from I-type rocks,which comprise mantle and crustal igneous protoliths,including tonalite–trondhjemite–granodiorites(TTGs),generally have a high oxidation state(ΔFMQ>0).In contrast,zircons from igneous rocks derived from supracrustal source rocks(S-type)are commonly reduced(ΔFMQbability density function derived from the Gaussian-Kernel-Density-Estimation,we use the maximum likelihood estimation(MLE)to distinguish Stype from I-type zircons through Earth's history using zircon *** S-type magma production shows a ca.600 Ma cyclicity that is closely related to the supercontinent *** link a cyclic drop in redox values after 2.6 Ga to periodic S-type magma generation associated with burial and melting of metasedimentary rocks during supercontinent assembly and ***ΔFMQ of the detrital zircons rise at~3.5 Ga followed by a consistent averageΔFMQ>0 over the last 3 *** that the redox state of magmas is independent of crustal thickness and silica variation,and elevated values are likely more closely related to tectonic setting,we suggest that the consistent averageΔFMQ>0 from ca.3.5 Ga onwards relates to recycling of oceanic lithosphere back into the mantle in what eventually became established as subduction *** more reduced magmas associated with sedimentary sources,became established at 2.6 Ga,presumably in response to continental rocks rising above sealevel,and follow peaks of productivity associated with the supercontinent cycle.

关键词： Oxidation state Supercontinent Weathering Subduction Zircon Granite

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一种用于多核磁共振成像及波谱的鸟笼线圈与可更换单环线圈的一体化设计（英文）

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journal of Zhejiang University-Science b(biomedicine & biotechnology) 2024年第2期 168-181页

作者：张怡全枝艳楼飞洋方玉娇 Garth j.THOMPSON 陈高张孝通浙江大学医学院附属第二医院神经外科浙江省神经外科疾病精准诊治及临床转化重点实验室浙江大学教育部脑与脑机融合前沿科学中心浙江大学系统神经与认知科学研究所浙江大学医学院上海科技大学iHuman研究所浙江大学电气工程学院

能量代谢对生命活动至关重要，主要包括对碳水化合物、脂肪和蛋白质的利用过程，异常的能量代谢与诸多疾病密切相关。本研究提出了一种用于多核磁共振成像(MRI)与波谱(MRS)的射频线圈设计：通过3D打印线圈外壳和支架，将一个鸟笼1H线圈... 详细信息

能量代谢对生命活动至关重要，主要包括对碳水化合物、脂肪和蛋白质的利用过程，异常的能量代谢与诸多疾病密切相关。本研究提出了一种用于多核磁共振成像(MRI)与波谱(MRS)的射频线圈设计：通过3D打印线圈外壳和支架，将一个鸟笼1H线圈和可更换的单环X核(2H、13C、23Na和31P)线圈一体化集成，其中单环线圈通过一个弧形支架安装于鸟笼线圈内壁，使其可沿内壁轴向无阻碍地移动，方便实现成像实验中多核线圈的更换以及线圈相对于不同成像体的摆放。与商用鸟笼1H核线圈相比，本设计具有更好的1H信号激发均匀性和成像信噪比；小鼠的活体实验验证了线圈设计在成像与波谱研究方面的可行性与有效性，可同时满足结构成像和能量代谢检测的要求。综上所述，该多核线圈通过新型机械与电路设计可以简化多核磁共振成像能量代谢检测的实施过程。

关键词：能量代谢核磁共振成像磁共振波谱多核射频线圈 3D打印

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Robust hybrid bismuth perovskites as potential photocatalysts for overall water splitting

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Nano Research 2024年第5期17卷 4593-4601页

作者： Antonio j.Chacón-García Herme G.baldovi Artem A.babaryk Antonio Rodríguez-Diéguez Sergio Navalón Yolanda Pérez Hermenegildo García Patricia Horcajada Advanced Porous Materials Unit IMDEA Energy InstituteAvda.Ramón y Cajal 328935 MóstolesMadridSpain Departamento de Química Universitat Politècnica de València46022 ValènciaSpain Departamento Química Inorgánica Universidad de Granada1807GranadaSpain Departamento de biología y Geología Física y Química Inorgánica.ESCET.Universidad Rey Juan Carlos28933 MóstolesMadridSpain Instituto de tecnología química CSIC-UPV Universitat Politècnica de València(UPV)46022Spain

Organic-inorganic hybrid perovskites have gained great attention as promising photocatalysts for hydrogen ***,due to their poor stability in water,the use of aqueous hydrohalic acid solutions is specifically required for an efficient hydrogen ***,three novel photoactive lead-free hybrid perovskites based on bismuth and triazolium cations(denoted as IEF-15,IEF-16,and IEF-17(IEF stands for IMDEA energy frameworks))were synthesized and fully characterized(structural,compositional,optical,etc.).Further,these solids were proposed as photocatalysts for the challenging gas phase overall water splitting(OWS)***,IEF-16 thin films exhibited a remarkable photocatalytic activity in both H_(2) and O_(2) evolution,as a consequence of its appropriate bandgap and energy-band alignment,achieving hydrogen evolution rates ofμmol·g_(H_(2))^(-)1846 and 360 after 24 h under ultraviolet-visible(UV-vis)irradiation or simulated solar irradiation,*** study additionally highlights the remarkable structural and photochemical stability of IEF-16 under different operational conditions(*** volume,irradiation and temperature),paving the way for green hydrogen production from OWS using perovskite-based photocatalysts.

关键词： bismuth-based hybrid perovskites thin films photocatalysis overall water splitting green hydrogen

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Universal basis underlying temperature, pressure and size induced dynamical evolution in metallic glass-forming liquids

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Chinese Physics b 2024年第1期33卷 134-142页

作者：张华平范蓓蓓吴佳琦李茂枝 Department of Physics Beijing Key Laboratory of Opto-electronic Functional Materials&Micro-nano DevicesRenmin University of ChinaBeijing 100872China Songshan Lake Materials Laboratory Dongguan 523808China Key Laboratory of Quantum State Construction and Manipulation Renmin University of ChinaBeijing 100872China

The dramatic temperature-dependence of liquids dynamics has attracted considerable scientific interests and efforts in the past decades, but the physics of which remains elusive. In addition to temperature, some other parameters, such as pressure, loading and size, can also tune the liquid dynamics and induce glass transition, which makes the situation more complicated. Here, we performed molecular dynamics simulations for Ni_(50)Zr_(50) bulk liquid and nanodroplet to study the dynamics evolution in the complex multivariate phase space, especially along the isotherm with the change of pressure or droplet size. It is found that the short-time Debye–Waller factor universally determines the long-time relaxation dynamics no matter how the temperature, pressure or size changes. The basic correlation even holds at the local atomic scale. This finding provides general understanding of the microscopic mechanism of dynamic arrest and dynamic heterogeneity.

关键词： metallic glass-forming liquids structure relaxation dynamical heterogeneity Debye–Waller factor

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Skeletal stem cells in bone development,homeostasis,and disease

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Protein & Cell 2024年第8期15卷 559-574页

作者： Guixin Yuan Xixi Lin Ying Liu Matthew b.Greenblatt Ren Xu The First Affliated Hospital of Xiamen University-ICMRS Collaborating Center for Skeletal Stem Cell State Key Laboratory of Cellular Stress BiologySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361005China Xiamen Key Laboratory of Regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue RegenerationOrgan Transplantation InstituteSchool of MedicineXiamen UniversityXiamen 361102China Department of Pathology and Laboratory Medicine Weill Cormell Medical CollegeNew YorkNY 10065USA Research Division Hospital for Special SurgeryNew YorkNY10065USA

Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem *** studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and *** investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time ***,recent studies have shed light on the characteristics of ssCs in both physiological and pathological *** review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

关键词： skeletal stem cells bone development endochondral ossification intramembranous ossification lineage tracing

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