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MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB

Signal Transduction and Targeted Therapy 2024年第11期9卷 5267-5285页

作者： Xiujian Wang Xiao Tao Pengjie Chen Penglei Jiang Wenxiao Li Hefeng Chang Cong Wei Xinyi Lai Hao Zhang Yihan Pan Lijuan Ding zuyu liang Jiazhen Cui Mi Shao Xinyi Teng Tianning Gu Jieping Wei Delin Kong Xiaohui Si Yingli Han Huarui Fu Yu Lin Jian Yu Xia Li Dongrui Wang Yongxian Hu Pengxu Qian He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou 311121China Institute of Hematology Zhejiang UniversityHangzhou 310003China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Hangzhou 310003China Center of Stem Cell and Regenerative Medicine Zhejiang University School of MedicineHangzhou 310058China Department of Hematology The Third Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325200China

Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T(CAR-T)***1/2 inhibitors(MEKIs),widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling,have shown potential synergistic effects when combined with ***,the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and *** address this,we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T *** findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation,thereby improving CAR-T cell efficacy against hematological and solid ***,these effects were independent of the specific scFvs and costimulatory domains utilized in ***,analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and ***,the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK ***,our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion,differentiation,anergy,glycolysis,and *** summary,our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal *** mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.

关键词： JunB metabolism stimulation

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“Slope-adsorption&plateau-pore filling”mechanism unlocking the potential of hard carbon anodes for“fast-charging&large-sized”batteries

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Science China Materials 2025年第1期68卷 309-311页

作者： Tian liang Xiaoming Zhu Hubei Key Laboratory of Radiation Chemistry and Functional Materials School of Nuclear Technology and Chemistry&BiologyHubei University of Science and TechnologyXianning 437100China

To date,there has been no report on fast-charging and Ahlevel sodium-ion batteries(SIBs)by utilizing thick hard carbon anodes that demonstrate prolonged cycling life and high areal capacity at high ***,the relationship among the complex structure of hard carbon,storage mechanism,and fastcharging performance in alkali-metal ion batteries has been a subject of ongoing debate[1,2].

关键词： mechanism charging utilizing

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Disordered hyperuniformity and thermal transport in monolayer amorphous carbon

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Science China(Physics,Mechanics & Astronomy) 2025年第2期68卷 145-152页

作者： Nianjie liang Yuxi Wang Bai Song Department of Energy and Resources Engineering Peking UniversityBeijing 100871China Department of Advanced Manufacturing and Robotics Peking UniversityBeijing 100871China

Disordered hyperuniformity(DHU)is a recently discovered novel state of amorphous systems characterized by strongly suppressed density fluctuations at large length scales as in crystalline materials,which offers great potential for achieving unusual mechanical,electronic,and photonic ***,despite the fundamental and technological importance of thermal transport in amorphous solids,the effect of DHU remains largely ***,we theoretically study thermal transport in a class of two-dimensional DHU materials—monolayer amorphous carbon(MAC).Beginning with a perfect graphene lattice,we continuously apply Stone-Wales transformations to generate a series of MAC models with varied degrees of disorder and defects,which are quantified through comprehensive structural analysis including the so-called hyperuniformity index(H),where a smaller H indicates a higher degree of ***,we conduct molecular dynamics simulations to obtain the thermal conductivity(κ).A significant correlation between the thermal transport behavior and degree of hyperuniformity is observed,with the room-temperatureκdecreasing from 26.3 to 5.3 W m^(-1)K^(-1)while H is tuned from 0.0004 to ***,two distinct transport regimes are identified,including a nearly-DHU regime at small H(<0.005)whereκdrops sharply and a non-DHU region at larger H whereκbecomes relatively ***-resolved analysis reveals longer lifetime and higher participation ratio for the heat carriers in nearly-DHU MAC,implying that the hidden long-range correlations could support extended modes that enhance *** work highlights the impact of DHU on the thermal properties of amorphous materials and represents a conceptual advancement that is worthy of future exploration.

关键词： disordered hyperuniformity thermal transport amorphous material two-dimensional monolayer amorphous carbon

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The dopaminergic system and Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2495-2512页

作者： Yuhan Zhang Yuan liang Yixue Gu International Medical College Chongqing Medical UniversityChongqingChina College of Pharmacy Chongqing Medical UniversityChongqingChina Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqingChina

Alzheimer's disease is a common neurodegenerative disorder in older *** its prevalence,its pathogenesis remains unclea *** addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this *** is a crucial catecholaminergic neurotransmitter in the human ***-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical *** r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive *** review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related *** aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关键词： adverse drug reaction Alzheimer's disease catecholamine dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease neurotransmitter signaling pathways traditional Chinese medicine treatment

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Co-doped cryptomelane-type manganese oxide in situ grown on a nickel foam substrate for high humidity ozone decomposition

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Journal of Environmental Sciences 2025年第2期148卷 529-540页

作者： Haoyuan liang Xu Wang Hui Wang Zhenping Qu Key Laboratory of Industrial Ecology and Environmental Engineering School of Environmental Science and TechnologyDalian University of TechnologyDalian 116024China

Monolithic catalysts with excellent O_(3)catalytic decomposition performance were prepared by in situ loading of Co-doped KMn_(8)O_(16)on the surface of nickel *** triple-layer structure with Co-doped KMn_(8)O_(16)/Ni6MnO_(8)/Ni foam was grown spontaneously on the surface of nickel foam by tuning the molar ratio of KMnO_(4)to Co(NO_(3))_(2)·6H_(2)O ***,the formed Ni6MnO_(8)structure between KMn_(8)O_(16)and nickel foam during in situ synthesis process effectively protected nickel foam from further etching,which significantly enhanced the reaction stability of *** optimum amount of Co doping in KMn_(8)O_(16)was available when the molar ratio of Mn to Co species in the precursor solution was 2:*** the Mn2Co1 catalyst had abundant oxygen vacancies and excellent hydrophobicity,thus creating outstanding O_(3)decomposition *** O_(3)conversion under dry conditions and relative humidity of 65%,90%over a period of 5 hr was 100%,94%and 80%with the space velocity of 28,000 hr^(−1),*** in situ constructed Co-doped KMn_(8)O_(16)/Ni foam catalyst showed the advantages of low price and gradual applicability of the preparation process,which provided an opportunity for the design of monolithic catalyst for O_(3)catalytic decomposition.

关键词： Co-doped cryptomelane-type manganese O3 decomposition High humidity Nickel foam Monolithic catalyst

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Numerical Study of the Shallow-Water Effect on the Hydrodynamic Loads and Wake of a Ship in Oblique Flow

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Journal of Ocean University of China 2025年第1期24卷 63-74页

作者： FENG liang WANG Longsheng ZHANG Yuxin College of Engineering Ocean University of ChinaQingdao 266404China Shanghai Merchant Ship Design and Research Institute Shanghai 201203China

When a ship moves in an oblique flow,its hydrodynamic loads and wake characteristics vary substantially from those in straight-ahead *** dissimilarity can be even more complex when the ship operates in a seaway of shallow *** this paper,a numerical analysis of the shallow-water effect on the hydrodynamic forces and wake characteristics of an international ship model,KVLCC2,in oblique flows is *** simulations are performed based on the Reynolds Averaged NavierStokes equation in conjunction with the shear stress transport(SST)k-ωturbulence *** relative water depths(h=1.2T,1.5T,3.0T,and 24T;T is the ship draft)and five different drift angles(β=0°,5°,10°,15°,and 20°)are *** reveal the following:i)The shallow-water effect is strong and leads to nonlinear increases in the longitudinal force regardless of drift angles and on the transverse force and yaw moment whenever the drift angle ***)In shallow water,the mean wake fraction is sensitive to the drift angle,and the strength of the aft-body vortex on the leeward side increases.

关键词： oblique flow shallow-water effect hull wake computational fluid dynamics

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Understanding the iodine electrochemical behaviors in aqueous zinc batteries

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Journal of Energy Chemistry 2025年第2期101卷 402-415页

作者： Xuefang Xie Xiaoxin Xu Shuquan liang Guozhao Fang College of Physical Science and Technology Xinjiang University Xinjiang Key Laboratory of Solid State Physics and Devices Xinjiang University School of Materials Science & Engineering Key Laboratory of Electronic Packaging and Advanced Functional Materials of Hunan Province Central South University National Energy Metal Resources and New Materials Key Laboratory Central South University

Iodine is widely used in aqueous zinc batteries（ZBs） due to its abundant resources,low cost,and active redox *** addition to the active material in zinc-iodine batteries,iodine also plays an important role in other ZBs,such as regulating the electrochemical behavior of zinc ions,promoting the reaction kinetic and reversibility of other redox pairs,catalytic behaviors related to iodine reactions,coupling with other halogen ions,shuttle behaviors of polyiodides,***,there is currently a lack of comprehensive discussion on these ***,this review provides a comprehensive overview of the electrochemical behaviors of iodide in the aqueous *** effect of iodine ions on the Zn2+desolvation behaviors and the interfacial behaviors of Zn anode was *** redox pairs boosting other redox pairs,such as MnO2/Mn2+redox pair and vanadium redox pair to obtain high reversibility and capacity was also ***,the catalytic behaviors related to iodine reactions in aqueous ZBs,synergistic reaction with other halogen ions and suppression of shuttle behaviors for high performance zinc-iodine batteries were systematically ***,future prospects for designing effective iodine electrochemical behaviors with practicability are proposed,which will provide scientific guidance for the practical application of iodine-related aqueous ZBs.

关键词： Catalytic behavior Iodide ion Redox pairs Shuttle effect Zinc batteries

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Joint Probabilistic Scheduling and Resource Allocation for Wireless Networked Control Systems

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IEEE/CAA Journal of Automatica Sinica 2025年第1期12卷 258-260页

作者： Meng Zheng Lei Zhang Wei liang IEEE the State Key Laboratory of Robotics and the Key Laboratory of Networked Control Systems Shenyang Institute of Automation Chinese Academy of Sciences the University of Chinese Academy of Sciences

Dear Editor,This letter presents a joint probabilistic scheduling and resource allocation method(PSRA) for 5G-based wireless networked control systems(WNCSs). As a control-aware optimization method, PSRA minimizes the linear quadratic Gaussian(LQG) control cost of WNCSs by optimizing the activation probability of subsystems, the number of uplink repetitions, and the durations of uplink and downlink phases. Simulation results show that PSRA achieves smaller LQG control costs than existing works.

关键词： Networked control systems

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Distributed State and Fault Estimation for Cyber-Physical Systems Under DoS Attacks

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IEEE/CAA Journal of Automatica Sinica 2025年第1期12卷 261-263页

作者： Limei liang Rong Su Haotian Xu the School of Control Science and Engineering Shandong University IEEE the School of Electrical and Electronic Engineering Nanyang Technological University

Dear Editor,The letter deals with the distributed state and fault estimation of the whole physical layer for cyber-physical systems(CPSs) when the cyber layer suffers from DoS attacks. With the advancement of embedded computing, communication and related hardware technologies, CPSs have attracted extensive attention and have been widely used in power system, traffic network, refrigeration system and other fields.

关键词： Observers Estimation error Sensors Physical layer Sensor systems Security Power system stability

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Design strategies and insights of flexible infrared optoelectronic sensors

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Journal of Semiconductors 2025年第1期46卷 21-56页

作者： Yegang liang Wenhao Ran Dan Kuang Zhuoran Wang School of Integrated Circuits and Electronics Beijing Institute of TechnologyBeijing 100081China

Infrared optoelectronic sensing is the core of many critical applications such as night vision,health and medication,military,space exploration,*** including mechanical flexibility as a new dimension enables novel features of adaptability and conformability,promising for developing next-generation optoelectronic sensory applications toward reduced size,weight,price,power consumption,and enhanced performance(SWaP^(3)).However,in this emerging research frontier,challenges persist in simultaneously achieving high infrared response and good mechanical deformability in devices and integrated ***,we perform a comprehensive review of the design strategies and insights of flexible infrared optoelectronic sensors,including the fundamentals of infrared photodetectors,selection of materials and device architectures,fabrication techniques and design strategies,and the discussion of architectural and functional integration towards applications in wearable optoelectronics and advanced image ***,this article offers insights into future directions to practically realize the ultra-high performance and smart sensors enabled by infrared-sensitive materials,covering challenges in materials development and device micro-/*** for scaling these techniques across fabrication,performance,and integration are presented,alongside perspectives on potential applications in medication and health,biomimetic vision,and neuromorphic sensory systems,etc.

关键词： flexible infrared sensor infrared-sensitive materials device architectures fabrication techniques design strategies

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