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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of pKm supports antitumor immunity

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Cellular & molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand p.Sharda mackenzie m.Lieberman Caitlin m.James Shivana m.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew m.Intlekofer Richard m.Higashi Teresa W.m.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin p.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and pathogenesis program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:massachusetts Institute of Technology BostonMA 02139USA present address:melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the m1 isoform of pyruvate kinase in favor of pKm2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,pKm alternative splicing occurred independently of CD28-driven pI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 pKm2

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Impact of COVID-19-related lifestyle changes on diabetic macular edema

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 97-106页

作者： Bryce p.Johnson Yu-Guang He Zachary m.Robertson Angeline Wang Rafael L.Ufret-Vincenty Department of Ophthalmology UT Southwestern Medical CenterDallasTexas 75390-9057USA

AIm:To assess diabetic macular edema(DmE)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office ***:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DmE seen on 3 separate visits between January 2019 and July *** 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was march 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).main outcome measures included visual acuity,body mass index(BmI),blood pressure(Bp),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DmE treatment(s)received at each *** facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT ***:There was no change of BmI,systolic Bp,and diastolic Bp between any of the time ***1c showed a very small increase from period 1(7.6%)to period 2(7.8%,p=0.015)and decreased back to 7.6%at period 3(p=0.12).macular thickness decreased for 100%of macular *** central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(p=0.0045).After analysis of multiple variables including HbA1c,BmI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in ***:DmE doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant *** identifying a mechanism behind our findings is beyond the scope of this study,potential explanat

关键词： COVID-19 diabetic macular edema diabetic retinopathy optical coherence tomography

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In vivo and in vitro study of resorbable magnesium wires for medical implants:mg purity,surface quality,Zn alloying and polymer coating

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Journal of magnesium and Alloys 2024年第6期12卷 2472-2488页

作者： K.Tesar J.Luňácková m.Jex m.Žaloudková R.Vrbová m.Bartoš p.Klein L.Vištejnová J.Dušková E.Filová Z.Sucharda m.Steinerová S.Habr K.Balík A.Singh Department of materials Faculty of Nuclear Sciences and Physical EngineeringCzech Technical University in PragueTrojanova 13Prague 12000Czech Republic Institute of physics Czech Academy of SciencesNa Slovance 2Prague 18221Czech Republic Institute of Dental medicine First Faculty of MedicineCharles University and General University Hospital in PragueKaterinská32Prague 12801Czech Republic Department of physics Faculty of Nuclear Sciences and Physical EngineeringCzech Technical University in PragueBrehová7Prague 11519Czech Republic Department of Composites and Carbon materials Institute of Rock Structure and MechanicsCzech Academy of SciencesV Holešovickách 41Prague 18209Czech Republic Institute of Anatomy First Faculty of MedicineCharles UniversityU Nemocnice 3Prague 12800Czech Republic Biomedical Center Faculty of Medicine in PilsenCharles UniversityAlej Svobody 76Pilsen 32300Czech Republic Department of pathological physiology Faculty of Medicine in PilsenCharles UniversityAlej Svobody 7632300 PilsenCzech Republic Department of Histology and Embryology Faculty of Medicine in PilsenCharles UniversityAlej Svobody 7632300 PilsenCzech Republic Institute of pathology First Faculty of MedicineCharles University and General University Hospital in PragueStudnickova 2Prague 12800Czech Republic Department of Biomaterials and Tissue Engineering Institute of PhysiologyCzech Academy of SciencesVidenska 1083Prague 14200Czech Republic Research Center for Structural materials National Institute for Materials Science1-2-1 SengenTsukuba 305-0047Japan

magnesium is an excellent material in terms of biocompatibility and its corrosion products can serve as an active source for new bone ***,localized corrosion and H_(2)generation limit the potential of mg-based *** low-alloyed mg-Zn wires can strongly reduce problems with large H_(2)bubbles and improve the mechanical properties considerably while maintaining excellent long-term *** pickling and a polymer coating can be effectively used to lower the rate of in vivo *** this work,microstructural,mechanical,and in vitro characterization of 250μm and 300μm extruded wires made from ultra-pure mg,commercially pure mg,mg-0.15Zn,mg-0.4Zn and mg-1Zn was ***,mg-0.4Zn wires together with a variant coated with a copolymer of L-lactide andε-caprolactone were tested in vivo on artificially damaged Wistar rat *** on the observed mg-induced osteogenesis,polymer-coated mg wires with a small addition of Zn are a perspective material for bone-support applications,such as cerclage and fixation wires.

关键词： magnesium Resorbable mg wire mg-Zn implant degradation Biocompatibility study Zn grain boundary segregation

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Organic-inorganic hybrid materials and architectures in optoelectronic devices: Recent advancements

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Chemphysmater 2024年第3期3卷 252-272页

作者： m.Arya S.Heera p.meenu K.G.Deepa Department of physics University of KeralaThiruvananthapuram 695581India Department of Nanoscience and Nanotechnology University of KeralaThiruvananthapuram 695581India

Organic-inorganic hybrids are next-generation materials for use in high-performance optoelectronic devices owing to their adaptabilities in terms of design and *** article reviews the application of hybrid materials and layers in several widely used optoelectronic devices,i.e.,light amplification by stimulated emission of radiation(LASER),solar cells,and light-emitting diodes(LEDs).The effects of the incorporation of inorganic particles on photostability and optical gain are analyzed in the first section with reference to dye and perovskite ***,the strategies used in blending inorganic nanostructures into organic solar cells and bulk heterojunctions are *** use of various organic layers as electron-and hole-transport materials in Si heterojunction solar cells is reviewed in ***,the benefits of the presence of organic components in quantum-dot-and perovskite-based LEDs are derived from the *** integration of organic and inorganic components with optimal interfaces and morphologies is a challenge in developing hybrid materials with improved efficiencies.

关键词： Optoelectronics Hybrid material Device performance photostability Advantages

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RBC aggregation,deformation and adhesion to endothelium:Role of nitric oxide derived from L-Arginine and sodium nitroprusside

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Journal of Innovative Optical Health Sciences 2024年第5期17卷 53-65页

作者： m.K.maksimov p.B.Ermolinskiy O.N.Scheglovitova N.N.Sklyankina A.V.muravyov A.E.Lugovtsov A.V.priezzhev Faculty of physics M.V.Lomonosov Moscow State University bld.1subbuilding.2Leninskie goryMoscow 11991Russia N.F.Gamaleya National Research Center for Epidemiology and microbiology 18 Gamaleya StreetMoscow 123098Russia K.D.Ushinsky Yaroslavl State pedagogical University 108/1 Respublikanskaya StreetYaroslavl 150000Russia

Red blood cells(RBCs)are the most abundant human blood *** aggregation and deformation strongly determine blood viscosity which impacts hemorheology and *** turn,RBC properties depend on di®erent endogenous and exogenous *** such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory *** the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The e®ect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the *** RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the°ow chamber method and myrenne *** con¯rmed that NO increases deformability and decreases aggregation of *** showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway *** the samples with the endothelium,the\bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by ***,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under *** our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not con¯rmed in another set of *** our knowledge,this is the¯rst attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.

关键词： Red blood cells aggregation L-arginine endothelium optical tweezers myrenne flow chamber

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Selenga River human dispersal path in Initial Upper paleolithic

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人类学学报 2024年第5期43卷 780-796页

作者： Evgeny p RYBIN Arina m KHATSENOVICH Institute of Archaeology and Ethnography Siberian Branch of Russian Academy of ScienceNovosibirsk 630090Russian Federation

Here,we consider earlier Upper paleolithic sites in the Selenga River Basin,the main fluvial input of Lake Baikal that flows through northern mongolia and the southwestern Transbaikal region of *** industries from these sites can be attributed to the laminar Initial Upper paleolithic(IUp)technocomplex,widespread in southern Siberia and Central *** industries appear in the Selenga Basin about 45 kaBp *** of regional typological variability and the transport of exotic raw materials over long distances indicate that these populations participated in developed exchange networks and employed high mobility targeting the acquisition of necessary raw *** site types are present:quarry-workshops in northern mongolia and generalized activity settlements in the southwestern *** faunal data are limited,we interpret available information as indicating a specialization on hunting,focusing on migrating steppe game *** distribution of sites in the mid-altitudes and landscapes of the Selenga-Orkhon geographical region and the geomorphological homogeneity of this territory also supported interregional human moves during the IUp.

关键词： Central Asia Initial Upper paleolithic migration raw material hunting

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CL2ES-KDBC:A Novel Covariance Embedded Selection Based on Kernel Distributed Bayes Classifier for Detection of Cyber-Attacks in IoT Systems

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Computers, materials & Continua 2024年第3期78卷 3511-3528页

作者： Talal Albalawi p.Ganeshkumar Computer Science Department College of Computer and Information SciencesImam Mohammad Ibn Saud Islamic University(IMSIU)Riyadh11432Saudi Arabia

The Internet of Things(IoT)is a growing technology that allows the sharing of data with other devices across wireless ***,IoT systems are vulnerable to cyberattacks due to its opennes The proposed work intends to implement a new security framework for detecting the most specific and harmful intrusions in IoT *** this framework,a Covariance Linear Learning Embedding Selection(CL2ES)methodology is used at first to extract the features highly associated with the IoT ***,the Kernel Distributed Bayes Classifier(KDBC)is created to forecast attacks based on the probability distribution value *** addition,a unique mongolian Gazellas Optimization(mGO)algorithm is used to optimize the weight value for the learning of the *** effectiveness of the proposed CL2ES-KDBC framework has been assessed using several IoT cyber-attack datasets,The obtained results are then compared with current classification methods regarding accuracy(97%),precision(96.5%),and other *** analysis of the CL2ES-KDBC system on IoT intrusion datasets is performed,which provides valuable insight into its performance,efficiency,and suitability for securing IoT networks.

关键词： IoT security attack detection covariance linear learning embedding selection kernel distributed bayes classifier mongolian gazellas optimization

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presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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Neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan Josépérez-moreno Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSp)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower *** ients can also experience peripheral neuropathy,cognitive impairment,and other neurological *** date,more than 80 genes have been implicated in HSp,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSp.

关键词： reticulum endoplasmic

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modelling dynamic pantograph loads with combined numerical analysis

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Railway Engineering Science 2024年第1期32卷 81-94页

作者： F.F.Jackson R.mishra J.m.Rebelo J.Santos p.Antunes J.pombo H.magalhaes L.Wills m.Askill School of Computing and Engineering University of HuddersfieldHuddersfieldUK School of Computing and Engineering Institute of Railway ResearchUniversity of HuddersfieldHuddersfieldUK IDmEC Instituto Superior TecnicoUniversidade de LisboaLisbonPortugal ISEL Instituto Politecnico de LisboaLisbonPortugal Hitachi Rail Newton AycliffeUK Wabtec/Brecknell Willis ChardUK

Appropriate interaction between pantograph and catenary is imperative for smooth operation of electric *** heights of overhead lines to accommodate level crossings,overbridges,and tunnels pose significant challenges in maintaining consistent current collection performance as the pantograph aerodynamic profile,and thus aerodynamic load changes significantly with operational *** research aims to analyse the global flow characteristics and aerodynamic forces acting on individual components of an HSX pantograph operating in different configurations and orientations,such that the results can be combined with multibody simulations to obtain accurate dynamic insight into contact ***,computational fluid dynamics simulations are used to investigate the pantograph component loads in a representative setting,such as that of the recessed cavity on a Class 800 *** an aerodynamic perspective,this study indicates that the total drag force acting on non-fixed components of the pantograph is larger for the knuckle-leading orientation rather than the knuckle-trailing,although the difference between the two is found to reduce with increasing pantograph *** the aerodynamic loads acting on individual components with multibody tools allows for realistic dynamic insight into the pantograph *** results obtained show how considering aerodynamic forces enhance the realism of the models,leading to behaviour of the pantograph-catenary contact forces closely matching that seen in experimental tests.

关键词： pantograph-catenary interaction pantograph aerodynamics Computational fluid dynamics pantograph loads Current collection performance

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Direct-to-indirect mapping for optimal low-thrust trajectories

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Astrodynamics 2024年第1期8卷 27-46页

作者： David Ottesen Ryan p.Russell Department of Aerospace Engineering and Engineering mechanics The University of Texas at AustinAustinTexas78712USA

Optimal,many-revolution spacecraft trajectories are challenging to solve.A connection is made for a class of models between optimal direct and indirect *** transfers that minimize thrust-acceleration-squared,primer vector theory maps direct,many-impulsive-maneuver trajectories to the indirect,continuous-thrust-acceleration *** mapping algorithm is independent of how the direct solution is obtained and requires only a solver for a boundary value problem and its partial derivatives.A Lambert solver is used for the two-body problem in this *** mapping is simple because the impulsive maneuvers and co-states share the same linear space around an optimal *** numerical results,the direct coast-impulse solutions are demonstrated to converge to the indirect continuous solutions as the number of impulses and segments *** two-body design space is explored with a set of three many-revolution,many-segment examples changing semimajor axis,eccentricity,and *** first two examples involve a small change to either semimajor axis or eccentricity,and the third example is a transfer to geosynchronous *** a single processor,the optimization runtime is seconds to minutes for revolution counts of 10 to 100,and on the order of one hour for examples with up to 500 *** of these thrust-acceleration-squared solutions are good candidates to start a homotopy to a higher-fidelity minimization problem with practical constraints.

关键词： direct optimization indirect optimization impulsive maneuvers Lambert's problem two-body dynamics primer vectortheory

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