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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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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology leiden university Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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TRP Channels in Stroke

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Neuroscience Bulletin 2024年第8期40卷 1141-1159页

作者： Pengyu Zong Cindy XLi Jianlin Feng Mara Cicchetti Lixia Yue Department of Cell Biology Calhoun Cardiology CenterSchool of Medicine(UConn Health)University of ConnecticutFarmingtonCT 06030USA Institute for the Brain and Cognitive Sciences University of Connecticut337 Mansfield RoadUnit 1272StorrsCT 06269USA present address:Department of Neuroscience University of Pittsburgh4200 Fifth AvePittsburghPA 15260USA

Ischemic stroke is a devastating disease that affects millions of patients ***,there are no effective medications for mitigating brain injury after ischemic *** channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular *** date,many members of the TRP superfamily have been reported to contribute to ischemic brain injury,including the TRPC subfamily(1,3,4,5,6,7),TRPV subfamily(1,2,3,4)and TRPM subfamily(2,4,7).These TRP channels share structural similarities but have distinct channel functions and *** activation during ischemic stroke can be beneficial,detrimental,or even *** this review,we focus on discussing the interesting features of stroke-related TRP channels and summarizing the underlying cellular and molecular mechanisms responsible for their involvement in ischemic brain injury.

关键词： Stroke TRP channels-Neuronal death Immune cell infiltration Blood-brain barrier Glial activation

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Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research Center for Molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China present address: Department of Cancer Biology Dana-Farber Cancer Institute Department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic *** report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available *** substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic *** transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

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Multitarget Thiol-Activated Tetrapyridyl Gold(Ⅲ)Complexes for Hypoxic Cancer Therapy

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CCS Chemistry 2024年第3期6卷 783-797页

作者： Xue-Quan Zhou Selda Abyar Imma Carbo-Bague Lan Wang Sebastian Türck Maxime ASiegler Uttara Basu Ingo Ott Rongfang Liu Adriaan PIJzerman Sylvestre Bonnet Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School(SIGS)Tsinghua UniversityShenzhen 518055 leiden Institute of Chemistry Leiden University2333 CC Leiden Department of Chemistry Simon Fraser UniversityBurnabyBritish Columbia V5A 1S6 Institute of Medicinal and Pharmaceutical Chemistry Technische Universität Braunschweig38106 Braunschweig Department of Chemistry Johns Hopkins UniversityBaltimoreMaryland 21218 Division of Drug Discovery&Safety Leiden Academic Centre for Drug ResearchLeiden University2333 CC Leiden

Gold complexes have emerged as promising anticancer metallodrugs due to their efficient thioredoxin reductase(TrxR)inhibition,which disturbs the redox balance of cancer ***,in this model,the role of the ligand(s)coordinated to gold is often *** this work,we present a series of tetrapyridyl Au(Ⅲ)complexes that exhibit thiol-induced release of a Au(Ⅰ)ion and a tetrapyridyl *** formation of a free Au(Ⅰ)center is responsible for the expected TrxR ***,the released ligand,which was visible in cells due to its intense blue fluorescence,showed excellent binding properties to the hERG potassium ***,these ligands ended up in the lysosomes,resulting in significant lysosome ***,the Au(Ⅲ)complexes presented in this work showed broad-spectrum anticancer properties,both in hypoxic 2D monolayers and 3D tumor *** suggest that the interaction of the released Au(Ⅰ)center and the tetrapyridyl ligand with two different protein targets may combine into prodrugs that overcome hypoxia-induced drug deactivation.

关键词： anticancer Au(Ⅲ)complexes enzyme inhibtion potassium channel affinity lysosome damage cell imaging prodrug

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Trend of Developing Aqueous Liquid and Gel Electrolytes for Sustainable,Safe,and High‑Performance Li‑Ion Batteries

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Nano-Micro Letters 2024年第1期16卷 17-34页

作者： Donghwan Ji Jaeyun Kim School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&Technology(SAIHST)Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Institute of Quantum Biophysics(IQB) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea present address:Department of NanoEngineering University of California San DiegoLa JollaSan DiegoCA 92093USA

Current lithium-ion batteries(LIBs)rely on organic liquid electrolytes that pose significant risks due to their flammability and *** potential for environmental pollution and explosions resulting from battery damage or fracture is a critical ***-based(aqueous)electrolytes have been receiving attention as an alternative to organic ***,a narrow electrochemicalstability window,water decomposition,and the consequent low battery operating voltage and energy density hinder the practical use of aqueous ***,developing novel aqueous electrolytes for sustainable,safe,high-performance LIBs remains *** Review first commences by summarizing the roles and requirements of electrolytes–separators and then delineates the progression of aqueous electrolytes for LIBs,encompassing aqueous liquid and gel electrolyte development trends along with detailed principles of the *** aqueous electrolytes are progressed based on strategies using superconcentrated salts,concentrated diluents,polymer additives,polymer networks,and artificial passivation layers,which are used for suppressing water decomposition and widening the electrochemical stability window of water of the *** addition,this Review discusses potential strategies for the implementation of aqueous Li-metal batteries with improved electrolyte–electrode interfaces.A comprehensive understanding of each strategy in the aqueous system will assist in the design of an aqueous electrolyte and the development of sustainable and safe high-performance batteries.

关键词： Lithium-ion battery(LIB) Aqueous electrolyte Gel electrolyte Electrochemical stability window Li dendrite

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Gas microchannel plate-pixel detector for X-ray polarimetry

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Nuclear Science and Techniques 2024年第5期35卷 60-73页

作者： Huan-Bo Feng Hong-Bang Liu Dong Wang Zi-Li Li Shu-Lin Liu Qian Liu Hang-Zhou Li Bin-Long Wang Yan-Jun Xie Zong-Wang Fan Hui Wang Ran Chen Di-Fan Yi Rui-Ting Ma Fei Xie Bo Peng Xiang-Ming Sun Jin Li En-Wei Liang present address:Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China PLAC Key Laboratory of Quark and Lepton Physics(MOE)Central China Normal UniversityWuhan 430079China School of Science Huzhou UniversityHuzhou 313000China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China School of Physical Science University of Chinese Academy of SciencesBeijing 100049China The 13th Research Institute of China Electronics Technology Group Corporation Shijiazhuang 050057China

POLAR-2 is a gamma-ray burst(GRB)polarimeter that is designed to study the polarization in GRB radiation emissions,aiming to improve our knowledge of related ***-2 is expected to utilize an on-board polarimeter that is sensitive to soft X-rays(2-10 keV),called low-energy polarization *** have developed a new soft X-ray polari-zation detector prototype based on gas microchannel plates(GMCPs)and pixel chips(Topmetal).The GMCPs have bulk resistance,which prevents charging-up effects and ensures gain stability during *** detector is composed of low outgassing materials and is gas-sealed using a laser welding technique,ensuring long-term stability.A modulation factor of 41.28%±0.64% is obtained for a 4.5 keV polarized X-ray beam.A residual modulation of 1.96%±0.58% at 5.9 keV is observed for the entire sensitive area.

关键词： X-ray polarimetry Gas microchannel plate-pixel detector Gamma-ray bursts

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo D’Alessandro Steven L.Spitalnik Vassilis L.Tzounakas Department of Biochemistry School of MedicineUniversity of Patras26504 PatrasGreece Department of Pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA Laboratory of Reliability and Quality Control in Laboratory Hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA present address:Institute for Fundamental Biomedical Research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood *** cells are defined as cells containing distinct nuclei and other membranous ***,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： membranous maintain

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Azimuthal rotation-controlled nanoinscribing for continuous patterning of period-and shapetunable asymmetric nanogratings

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Microsystems & Nanoengineering 2024年第3期10卷 207-218页

作者： Useung Lee Hyein Kim Dong Kyo Oh Nayeong Lee Jonggab Park Jaewon Park Hyunji Son Hyunchan Noh Junsuk Rho Jong G.Ok Department of Mechanical and Automotive Engineering Seoul National University of Science and TechnologySeoul 01811Republic of Korea Department of Mechanical Engineering Pohang University of Science and Technology(POSTECH)Pohang 37673Republic of Korea Department of Chemical Engineering Pohang University of Science and Technology(POSTECH)Pohang 37673Republic of Korea POSCO-POSTECH-RIST Convergence Research Center for Flat Optics and Metaphotonics Pohang 37673Republic of Korea National Institute of Nanomaterials Technology(NINT) Pohang 37673Republic of Korea present address:Department of Mechanical Engineering Korea University145 Anam-roSeongbuk-guSeoul 02841Republic of Korea Research Team Hyundai Motor Group150 Hyundaiyeonguso-roHwaseong-siGyeonggi 18280Republic of Korea

We present an azimuthal-rotation-controlled dynamic nanoinscribing(ARC-DNI)process for continuous and scalable fabrication of asymmetric nanograting structures with tunable periods and shape profiles.A sliced edge of a nanograting mold,which typically has a rectangular grating profile,slides over a polymeric substrate to induce its burrfree plastic deformation into a linear *** this continuous nanoinscribing process,the“azimuthal angle,”that is,the angle between the moving direction of the polymeric substrate and the mold’s grating line orientation,can be controlled to tailor the period,geometrical shape,and profile of the inscribed *** modulating the azimuthal angle,along with other important ARC-DNI parameters such as temperature,force,and inscribing speed,we demonstrate that the mold-opening profile and temperature-and time-dependent viscoelastic polymer reflow can be controlled to fabricate asymmetric,blazed,and slanted nanogratings that have diverse geometrical profiles such as trapezoidal,triangular,and ***,period-and profile-tunable ARC-DNI can be utilized for the practical fabrication of diverse optical devices,as is exemplified by asymmetric diffractive optical elements in this study.

关键词： tunable asymmetric rotation

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