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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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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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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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Combining thermal scanning probe lithography and dry etching for grayscale nanopattern amplification

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Microsystems & Nanoengineering 2024年第1期10卷 335-344页

作者： Berke Erbas Ana Conde-Rubio Xia Liu Joffrey Pernollet Zhenyu Wang Arnaud Bertsch Marcos Penedo Georg Fantner Mitali Banerjee Andras Kis Giovanni Boero Juergen Brugger Microsystems Laboratory École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Center of MicroNanoTechnology(CMi) EPFLLausanne 1015Switzerland Laboratory of Nanoscale Electronics and Structures École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory for Bio-and Nano-Instrumentation École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory of Quantum Physics Topology and CorrelationsÉcole Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland present address:Institute of Materials Science of Barcelona ICMAB-CSIC Campus UABBellaterra 08193Spain present address:School of Integrated Circuits and Electronics MIIT Key Laboratory for Low-Dimensional Quantum Structure and DevicesBeijing Institute of TechnologyBeijing 100081China

Grayscale structured surfaces with nanometer-scale features are used in a growing number of applications in optics and *** scanning probe lithography achieves a lateral resolution below 10 nm and a vertical resolution below 1 nm,but its maximum depth in polymers is ***,we present an innovative combination of nanowriting in thermal resist and plasma dry etching with substrate cooling,which achieves up to 10-fold amplification of polymer nanopatterns into SiO_(2) without proportionally increasing surface *** nanopatterns in SiO_(2) with 400 nm pitch and 150 nm depth are fabricated free of shape distortion after dry *** exemplify the possible applications of the proposed method,grayscale dielectric nanostructures are used for scalable manufacturing through nanoimprint lithography and for strain nanoengineering of 2D *** a method for aspect ratio amplification and smooth grayscale nanopatterning has the potential to find application in the fabrication of photonic and nanoelectronic devices.

关键词： lithography thermal pattern

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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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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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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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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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