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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 determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among 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 function.Importantly,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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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 fluidics.Thermal scanning probe lithography achieves a lateral resolution below 10 nm and a vertical resolution below 1 nm,but its maximum depth in polymers is limited.Here,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 roughness.Sinusoidal nanopatterns in SiO_(2) with 400 nm pitch and 150 nm depth are fabricated free of shape distortion after dry etching.To 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 materials.Such 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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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 synthesis.We report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available dichlorocyclobutanones.The substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic conditions.Further 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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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.Eukaryotic cells are defined as cells containing distinct nuclei and other membranous organelles.However,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： al. membranous maintain

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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 subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,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 irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(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 cells.Adoptive 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 cells.In 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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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 mechanisms.POLAR-2 is expected to utilize an on-board polarimeter that is sensitive to soft X-rays(2-10 keV),called low-energy polarization detector.We 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 operation.The 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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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 toxicity.The potential for environmental pollution and explosions resulting from battery damage or fracture is a critical concern.Water-based(aqueous)electrolytes have been receiving attention as an alternative to organic electrolytes.However,a narrow electrochemicalstability window,water decomposition,and the consequent low battery operating voltage and energy density hinder the practical use of aqueous electrolytes.Therefore,developing novel aqueous electrolytes for sustainable,safe,high-performance LIBs remains challenging.This 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 electrolytes.These 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 electrolytes.In 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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An anti-icing scaling method for wind tunnel tests of aircraft thermal ice protection system

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Chinese Journal of Aeronautics 2024年第6期37卷 1-6页

作者： Yu LIU Qiang WANG Xian YI Ningli CHEN Jinghao REN Weihao LI Key laboratory of Icing and Anti/de-icing China Aerodynamics Research and Development CenterMianyang 621000China State Key laboratory of Aerodynamics Mianyang 621000China

The efficiency of the aircraft Ice Protection Systems(IPSs)needs to be verified through icing wind tunnel tests.However,the scaling method for testing the IPSs has not been systematically established yet,and further research is needed.In the present study,a scaling method specifically designed for thermal IPSs was derived from the governing equation of thin water film.Five scaling parameters were adopted to address the heat and mass transfer involved in the thermal anti-icing process.For method validation,icing wind tunnel tests were conducted using a jet engine nacelle model equipped with a bleed air IPS.The non-dimensional surface temperature and runback ice closely matched for both the reference and scaled conditions.The validation confirms that the scaling method is capable of achieving the similarity of surface temperature and the runback ice coverage.The anti-icing scaling method can serve as an important supplement to the existing icing similarity theory.

关键词： Scaling method Ice protection system Water film Anti-icing test Icing wind tunnel

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NADPH oxidase family proteins:signaling dynamics to disease management

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Cellular & Molecular Immunology 2022年第6期19卷 660-686页

作者： Rizwana Begum Shilpa Thota Abubakar Abdulkadir Gagandeep Kaur Prathyusha Bagam Sanjay Batra present address:Department of Environmental Medicine University of RochesterSchool of Medicine and DentistryRochesterNY14642USA laboratory of Pulmonary Immunotoxicology Department of Environmental ToxicologySouthern University and A&M CollegeBaton RougeLA70813USA present address:Division of Systems biology National Center for Toxicological ResearchJeffersonAR72079USA

Reactive oxygen species(ROS)are pervasive signaling molecules in biological systems.In humans,a lack of ROS causes chronic and extreme bacterial infections,while uncontrolled release of these factors causes pathologies due to excessive inflammation.Professional phagocytes such as neutrophils(PMNs),eosinophils,monocytes,and macrophages use superoxide-generating NADPH oxidase(NOX)as part of their arsenal of antimicrobial mechanisms to produce high levels of ROS.NOX is a multisubunit enzyme complex composed of five essential subunits,two of which are localized in the membrane,while three are localized in the cytosol.In resting phagocytes,the oxidase complex is unassembled and inactive;however,it becomes activated after cytosolic components translocate to the membrane and are assembled into a functional oxidase.The NOX isoforms play a variety of roles in cellular differentiation,development,proliferation,apoptosis,cytoskeletal control,migration,and contraction.Recent studies have identified NOX as a major contributor to disease pathologies,resulting in a shift in focus on inhibiting the formation of potentially harmful free radicals.Therefore,a better understanding of the molecular mechanisms and the transduction pathways involved in NOX-mediated signaling is essential for the development of new therapeutic agents that minimize the hyperproduction of ROS.The current review provides a thorough overview of the various NOX enzymes and their roles in disease pathophysiology,highlights pharmacological strategies,and discusses the importance of computational modeling for future NOX-related studies.

关键词： NADPH oxidase Reactive oxygen species Inflammation Inhibitors In silico

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A high aspect ratio surface micromachined accelerometer based on a SiC-CNT composite material

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Microsystems & Nanoengineering 2024年第2期10卷 219-230页

作者： Jiarui Mo Shreyas Shankar Roberto Pezone Guoqi Zhang Sten Vollebregt laboratory of Electronic Components Technology and Materials(ECTM)Department of MicroelectronicsDelft University of TechnologyDelftThe Netherlands

Silicon carbide(SiC)is recognized as an excellent material for microelectromechanical systems(MEMS),especially those operating in challenging environments,such as high temperature,high radiation,and corrosive environments.However,SiC bulk micromachining is still a challenge,which hinders the development of complex SiC MEMS.To address this problem,we present the use of a carbon nanotube(CNT)array coated with amorphous SiC(a-SiC)as an alternative composite material to enable high aspect ratio(HAR)surface micromachining.By using a prepatterned catalyst layer,a HAR CNT array can be grown as a structural template and then densified by uniformly filling the CNT bundle with LPCVD a-SiC.The electrical properties of the resulting SiC-CNT composite were characterized,and the results indicated that the electrical resistivity was dominated by the CNTs.To demonstrate the use of this composite in MEMS applications,a capacitive accelerometer was designed,fabricated,and measured.The fabrication results showed that the composite is fully compatible with the manufacturing of surface micromachining devices.The Young’s modulus of the composite was extracted from the measured spring constant,and the results show a great improvement in the mechanical properties of the CNTs after coating with a-SiC.The accelerometer was electrically characterized,and its functionality was confirmed using a mechanical shaker.

关键词： composite surface electrical

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