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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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Grain refinement of mg-Ca alloys by native mgO particles

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Journal of magnesium and Alloys 2024年第3期12卷 980-996页

作者： Shihao wang Yun wang Quentin m.Ramasse Zhongyun fan Super STEm Laboratory SciTech Daresbury CampusDaresbury WA44ADUK School of Chemical and Process Engineering University of LeedsLeeds LS29JTUK BCAST Brunel University LondonUxbridgeMiddlesex UB83PHUK

In mg-Ca alloys the grain refining mechanism,in particular regarding the role of nucleant substrates,remains the object of debates.Although native mgO is being recognised as a nucleating substrate accounting for grain refinement of mg alloys,the possible interactions of mgO with alloying elements that may alter the nucleation potency have not been elucidated yet.Herein,we design casting experiments of mg-xCa alloys varied qualitatively in number density of native mgO,which are then comprehensively studied by advanced electron microscopy.The results show that grain refinement is enhanced as the particle number density of mgO increases.The native mgO particles are modified by interfacial layers due to the co-segregation of Ca and N solute atoms at the mgO/mg interface.Using aberration-corrected scanning transmission electron microscopy and electron energy loss spectroscopy,we reveal the nature of these Ca/N interfacial layers at the atomic scale.Irrespective of the crystallographic termination of mgO,Ca and N co-segregate at the mgO/mg interface and occupy mg and O sites,respectively,forming an interfacial structure of a few atomic layers.The interfacial structure is slightly expanded,less ordered and defective compared to the mgO matrix due to compositional deviations,whereby the mgO substrate is altered as a poorer template to nucleate mg solid.Upon solidification in a TP-1 mould,the impotent mgO particles account for the grain refining mechanism,where they are suggested to participate into nucleation and grain initiation processes in an explosive manner.This work not only reveals the atomic engineering of a substrate through interfacial segregation but also demonstrates the effectiveness of a strategy whereby native mgO particles can be harnessed for grain refinement in mg-Ca alloys.

关键词： mg-Ca alloy Grain refinement mgO Interfacial segregation STEm/EELS Solidification.

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metabolic reprogramming in tumors:Contributions of the tumor microenvironment

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Genes & Diseases 2020年第2期7卷 185-198页

作者： Andrew N.Lane Richard m.Higashi teresa w.m.fan Center for Environmental and Systems Biochemistry Markey Cancer CenterDepartment of Toxicology and Cancer BiologyUniversity of KentuckyUSA

The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment,and prepare for metastasis.Qualitatively,the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells,but the cancer cells produce a local environment,the TmE,that is hostile to the stromal cells,and compete for nutrients.In order to proliferate,cells need sufficient nutrients,either those that cannot be made by the cells themselves,or must be made from simpler precursors.However,in solid tumors,the nutrient supply is often limiting given the potential for rapid proliferation,and the poor quality of the vasculature.Thus,cancer cells may employ a variety of strategies to obtain nutrients for survival,growth and metastasis.Although much has been learned using established cell lines in standard culture conditions,it is becoming clear from in vivo metabolic studies that this can also be misleading,and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor,and even within the same tumor.Here we review the operation of metabolic networks,and how recent understanding of nutrient supply in the TmE and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.

关键词： Cancer metabolism Nutrient supply Stable isotope resolved metabolomics Tumor microenvironment metabolic flux

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Processing,microstructure,and properties of porous ceramic composites with directional channels

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Journal of materials Science & Technology 2024年第1期168卷 1-15页

作者： Bo Zhang Yang Yang Xueling fan Key Laboratory of Service Performance and Protection Technology in Extreme Environments Xi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Strength and Vibration of mechanical Structures School of Aerospace EngineeringXi’an Jiaotong UniversityXi’an 710049China

Porous ceramic composites with directional microchannels from micrometer to dozens of micrometer levels have attracted more and more attention in various fields including aerospace,biomedicines,and thermal insulation due to their excellent fluid permeability,mechanical properties,etc.In this article,we summarize the recent directional porous ceramics developments including their main processing routes and respective properties.meanwhile,the properties get from different processing routes have been com-pared and analyzed in terms of microstructures,mechanical properties,and permeability.Emphasis has been given to the deeper understanding which can allow one to control the microstructural features of these porous ceramic composites to obtain the desired characteristics.This work can provide a useful reference for the development and application of porous ceramic composites with directional microchan-nels.

关键词： Porous ceramic composites Directional microchannels Processing routes Permeability

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Observation of an upward lightning flash with 21 upward positive leaders initiated from different wind turbines in wind farm

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High Voltage 2024年第1期9卷 163-171页

作者： Li Cai Yifeng Ke wenchao fan Ruisheng Yan mi Zhou Jianguo wang Yadong fan Engineering Research Center of ministry of Education for Lightning Protection and Grounding Technology School of Electrical Engineering and AutomationWuhan UniversityWuhanChina

As the wind turbine height increases,the probability of multiple upward leaders flashes within the wind farm increases.In this study,an upward lightning flash containing 21 upward positive leaders(UPLs)initiated from different wind turbines in Zhangbei wind Farm was analysed.The average speed of the UPLs was 1.2×10^(5) m/s,which mostly decreased to zero before reaching the cloud height.Only four UPLs developed to cloud height,with prolonged periods of bright light on three of them and with a minimum duration of 126 ms.A total of nine return strokes occurred on the other two dissipated leader channels,and the numbers of strokes on the two channels was six and three,respectively.The average interstroke interval for the return strokes was 10.5 ms.most of these nine return strokes had peak currents smaller than 10 kA.The high-speed video frames confirmed that competition does exist between the UPLs,and the range of shielding effects increases as the height of the ULs increases.The effect of fan rotation on the initiation of upward leaders and the shielding effect between the wind turbines and upward leaders are discussed.

关键词： flash return initiated

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Grow rice under sunshine of Xizang/Tibet:promise and challenges

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Journal of Genetics and Genomics 2024年第3期51卷 265-267页

作者： Chunkun fan Xiaoming Zheng Qingbo Yuan Tao wang Qian Qian Qingyun Bu fan Chen Agricultural Institute Xizang Academy of Agricultural and Animal Husbandry ScienceLasaXizang 850032China National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop SciencesChinese Academy of AgriculturalSciencesBeijing 100081China Sanya National Research Institute of Breeding in Hainan Chinese Academy of Agricultural SciencesBeijing 572000China Yazhouwan National Laboratory SanyaHainan 572704China Chengdu Institute of Biology Chinese Academy of SciencesChengduSichuan 610041China Northeast Institute of Geography and Agroecology Chinese Academy of SciencesHarbinHeilongjiang 150081China

Xizang,previously known as Tibet,is located in the southwest region of China and is the highest region of the Qinghai-Tibet Plateau(QzP),with an average altitude of over 4000 m.with the development of modern agriculture,the grain productivity in Xizang has been effectively improved.The total annual grain production has increased from 558,700 tons in 1988 to 1044,000 tons in 2018(Xizang Statistical Year Book).

关键词： sunshine Tibet southwest

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Ternary layered boride moAlB:A novel thermo-regulation microwave absorbing ceramic material

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Journal of Advanced Ceramics 2024年第5期13卷 699-710页

作者： Zhangjue wang fan Zhang Nannan wang wei Li Yongqiang Chen Hailong wang Rui Zhang Yanqiu Zhu Bingbing fan School of material Science and Engineering Zhengzhou UniversityZhengzhou 450001China Henan Academy of Sciences Zhengzhou 450046China State Key Laboratory of Featured metal materials and Life Cycle Safety for Composite Structures MOE Key Laboratory of New Processing Technology for Nonferrous Metals MaterialsSchool of ResourcesEnvironment and MaterialsGuangxi UniversityNanning 530004China Department of materials and Earth Sciences Technical University of DarmstadtDarmstadt 64287Germany School of material Science and Engineering Luoyang Institute of Science and TechnologyLuoyang 471023China Department of Engineering Faculty of EnvironmentScience and EconomyUniversity of ExeterExeter EX44QFUK

In the context of the fifth-generation(5G)smart era,the demand for electromagnetic wave(Emw)-absorbing materials has become increasingly prominent,so it is necessary to explore promising candidate materials.This work focuses on the exploration of the material absorbing properties of a moAlB mAB(mAB represents a promising group of alternatives,where m stands for a transition metal,A typically denotes Al,and B is boron)phase system.First,the first-principles calculations were performed to reveal the unique crystal and layered structure of the moAlB ceramics and to predict their potential for use as an Emw absorption material.Subsequently,a series of moAlB ceramics were synthesized at temperatures ranging from 800 to 1300°C,and the influence of temperature on the phase compositions and microstructures of the obtained moAlB ceramics was characterized and analyzed.Finally,the practical Emw absorption performance of the prepared moAlB ceramics was evaluated via a combination of experiments and radar cross-sectional calculations.The moAlB sample synthesized at 900°C exhibits superior Emw absorption performance,achieving an impressive minimum reflection loss(RL)of−50.33 dB.The unique layered structure and good electrical conductivity of the moAlB samples are the main reasons for their enhanced wave absorption performance,which provides interfacial polarization and multiple dielectric loss mechanisms.Therefore,this study not only contributes to the understanding of the preparation of moAlB materials but also provides potential guidance for their utilization in the realm of electromagnetic wave absorption.

关键词： moAlB electronic band structure electromagnetic wave(Emw)absorption layered ternary boride density of states

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Grain yield and N uptake of maize in response to increased plant density under reduced water and nitrogen supply conditions

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Journal of Integrative Agriculture 2024年第1期23卷 122-140页

作者： Jingui wei Qiang Chai wen Yin Hong fan Yao Guo Falong Hu Zhilong fan Qimingwang State Key Laboratory of Aridland Crop Science Lanzhou 730070China College of Agronomy Gansu Agricultural UniversityLanzhou 730070China College of Life Sciences Northwest Normal UniversityLanzhou 730070China

The development of modern agriculture requires the reduction of water and chemical N fertilizer inputs.Increasing the planting density can maintain higher yields,but also consumes more of these restrictive resources.However,whether an increased maize density can compensate for the negative effects of reduced water and N supply on grain yield and N uptake in the arid irrigated areas remains unknown.This study is part of a long-term positioning trial that started in 2016.A split-split plot field experiment of maize was implemented in the arid irrigated area of northwestern China in 2020 to 2021.The treatments included two irrigation levels:local conventional irrigation reduced by 20%(w1,3,240 m^(3)ha^(-1))and local conventional irrigation(w2,4,050 m^(3)ha^(-1));two N application rates:local conventional N reduced by 25%(N1,270 kg ha^(-1))and local conventional N(360 kg ha^(-1));and three planting densities:local conventional density(D1,75,000 plants ha^(-1)),density increased by 30%(D2,97,500 plants ha-1),and density increased by 60%(D3,120,000 plants ha^(-1)).Our results showed that the grain yield and aboveground N accumulation of maize were lower under the reduced water and N inputs,but increasing the maize density by 30% can compensate for the reductions of grain yield and aboveground N accumulation caused by the reduced water and N supply.when water was reduced while the N application rate remained unchanged,increasing the planting density by 30% enhanced grain yield by 13.9% and aboveground N accumulation by 15.3%.Under reduced water and N inputs,increasing the maize density by 30% enhanced N uptake efficiency and N partial factor productivity,and it also compensated for the N harvest index and N metabolic related enzyme activities.Compared with w2N2D1,the N uptake efficiency and N partial factor productivity increased by 28.6 and 17.6%under w1N1D2.w1N2D2 had 8.4% higher N uptake efficiency and 13.9% higher N partial factor productivity than w2N2D1.w1N2D2 improved urease activity and nitrate reductase activit

关键词： water and N reduction plant density maize grain yield N uptake compensation effect

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Kinetically and thermodynamically expediting elementary steps via high-valence Cr-incorporated of nickel selenide for water electrolysis

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Nano Research 2024年第3期17卷 1199-1208页

作者： Huafeng fan Dongxu Jiao Jinchang fan Dewen wang Bilal Zaman wei Zhang Lei Zhang weitao Zheng Xiaoqiang Cui State Key Laboratory of Automotive Simulation and Control School of Materials Science and EngineeringKey Laboratory of Automobile Materials of MOEJilin Provincial International Cooperation Key Laboratory of High-Efficiency Clean Energy MaterialsElectron Microscopy CenterJilin UniversityChangchun 130012China College of Chemistry Jilin UniversityChangchun 130012China

Designing high-performance electrocatalysts toward hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)is essential to reduce the activation barrier and optimize free adsorption energy of reactive intermediates.Herein,we report that incorporating high-valence Cr into NiSe_(2)(Cr_(x)Ni_(1-x)Se_(2))kinetically and thermodynamically expedites elementary steps of both HER and OER.The as-prepared Cr_(0.05)Ni_(0.95)Se_(2) catalyst displays excellent HER and OER activities,with low overpotentials of 89 and 272 mV at the current density of 10 mA·cm^(-2)(j10),respectively,and remains stable during operation for 30 h.A low cell voltage of only 1.59 V is required to drive j10 in alkaline media.In situ Raman spectroscopy reveals that Cr incorporation facilitates the formation of NiOOH active species during the OER process.meanwhile,theoretical explorations demonstrate that high-valence Cr incorporation efficiently accelerates water dissociation kinetics and improves H*adsorption during HER process,lowering the activation barrier of OER and optimizing the adsorption energy of oxygen-based intermediate,thus kinetically and thermodynamically enhancing the intrinsic performance of NiSe_(2) for over water splitting.This strategy provides a new horizon to design transition metal based electrocatalysts in the clean energy field.

关键词： nickel selenide electrocatalytic water splitting high-valence Cr density functional theory(DFT)calculation

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Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 4-13页

作者： Ji-Yao Sheng Zi-fan meng Qiao Li Yong-Sheng Yang Department of Hepatobiliary and Pancreatic Surgery the Second Hospital of Jilin UniversityChangchun 130041China Jilin Engineering Laboratory for Translational medicine of Hepatobiliary and Pancreatic Diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.with recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in Pubmed,mEDLINE and web of Science for relevant articles published up to may 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

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