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Targeting a disintegrin and metalloprotease(ADAM)17-CD122 axis enhances CD8^(+)T cell effector differentiation and anti-tumor immunity

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3097-3111页

作者： lina Sun Anjun Jiao Haiyan Liu Renyi Ding Ning Yuan Biao yang Cangang zhang Xiaoxuan Jia Gang Wang Yanhong Su Dan zhang lin Shi Chenming Sun Aijun zhang Lianjun zhang Baojun zhang Department of Pathogenic Microbiology and Immunology School of Basic Medical SciencesXi’an Jiaotong UniversityXi’anShaanxi 710061China Institute of Infection and Immunity Translational Medicine InstituteXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China Key Laboratory of Environment and Genes Related to Diseases Ministry of EducationXi’anShaanxi 710061China Xi’an Key Laboratory of Immune Related Diseases Xi’anShannxi 710061China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina Department of Pediatrics Qilu Hospital of Shandong UniversityJinanChina National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina Key Laboratory of Synthetic Biology Regulatory Elements Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina

CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely *** ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane ***,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T *** and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and ***,ADAM17 regulated CD8^(+)T cells through cleavage of membrane ***17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T ***,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid *** findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

关键词： immunity stimulation involvement

Efficient and Fast X-Ray Luminescence in Organic Phosphors Through High-Level Triplet-Singlet Reverse Intersystem Crossing

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CCS Chemistry 2024年第2期6卷 334-341页

作者： yang zhang Minghong Chen Xiaoze Wang Miao lin Hongyu Wang Weihong Li Fuhai Chen Qing Liao Hongming Chen Qiushui Chen Meijin lin Huanghao yang Key Laboratory of Molecule Synthesis and Function Discovery College of ChemistryFuzhou UniversityFuzhouFujian 350116 New Cornerstone Science Laboratory MOE Key Laboratory for Analytical Science of Food Safety and BiologyCollege of ChemistryFuzhou UniversityFuzhouFujian 350108 College of Materials Science and Engineering Fuzhou UniversityFuzhouFujian 350116

Organic scintillators that efficiently generate bright triplet excitons are of critical importance for highperformance X-ray-excited luminescence in radiation ***,the nature of triplet-singlet spinforbidden transitions in these materials often result in long-lived phosphorescence,which is undesirable for ultrafast X-ray detection and *** we demonstrate that the effect of hybridized local and charge-transfer(HLCT)excited states enables organic scintillators to exhibit highly efficient and fast radioluminescence(RL)in response to X-ray *** experimental and theoretical investigation shows that the oxidized 1,8-naphthalimide-phenothiazine dyad(OMNI-PTZ 2)with HLCT-excited states has an enhanced overlap integral of the highest occupied molecular orbital(HOMO)and lowest unoccupied molecular orbital(LUMO)on MNIπ-orbitals,and moderate donor–acceptor electron *** a result,the RL of these crystals exhibits a 61-fold increase and its monoexponential decay lifetime is three orders of magnitude faster compared to its corresponding thermally activated delayed fluorescence(TADF)molecule MNI-PTZ *** further demonstrate the practical utility of the OMNI-PTZ 2(G)in high-performance X-ray detection and imaging,achieving an X-ray dose sensitivity of 97 nGy s−1 and an exceptional spatial resolution of 20 lp/*** study provides a promising molecular design principle for utilizing triplet excitons to develop high-efficiency and fast X-ray scintillators for the development of next-generation flexible and stretchable X-ray imaging detectors.

关键词： organic scintillators X-ray imaging hybridized local and charge transfer excited state triplet-singlet reverse intersystem crossing high exciton utilization

Robust reinforcement learning with UUB guarantee for safe motion control of autonomous robots

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Science China(Technological Sciences) 2024年第1期67卷 172-182页

作者： zhang RuiXian HAN YiNing SU Man lin ZeFeng LI HaoWei zhang LiXian School of Astronautics Harbin Institute of TechnologyHarbin 150001China School of Management Harbin Institute of TechnologyHarbin 150001China Beijing Institute of Tracking and Telecommunication Technology Beijing 100094China

This paper addresses the issue of safety in reinforcement learning(RL)with disturbances and its application in the safety-constrained motion control of autonomous *** tackle this problem,a robust Lyapunov value function(rLVF)is *** rLVF is obtained by introducing a data-based LVF under the worst-case disturbance of the observed *** the rLVF,a uniformly ultimate boundedness criterion is *** criterion is desired to ensure that the cost function,which serves as a safety criterion,ultimately converges to a range via the policy to be ***,to mitigate the drastic variation of the rLVF caused by differences in states,a smoothing regularization of the rLVF is *** train policies with safety guarantees under the worst disturbances of the observed states,an off-policy robust RL algorithm is *** proposed algorithm is applied to motion control tasks of an autonomous vehicle and a cartpole,which involve external disturbances and variations of the model parameters,*** experimental results demonstrate the effectiveness of the theoretical findings and the advantages of the proposed algorithm in terms of robustness and safety.

关键词： motion control reinforcement learning robustness stability

Benchmark experiment on slab^(238)U with D-T neutrons for validation of evaluated nuclear data

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Nuclear Science and Techniques 2024年第2期35卷 145-159页

作者： Yan-Yan Ding yang-Bo Nie Yue zhang Zhi-Jie Hu Qi Zhao Huan-Yu zhang Kuo-Zhi Xu Shi-Yu zhang Xin-Yi Pan Chang-lin Lan Jie Ren Xi-Chao Ruan Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China School of Nuclear Science and Technology Lanzhou UniversityLanzhou 730000China Institute of Fluid Physics China Academy of Engineering PhysicsMianyang 62100China

A benchmark experiment on^(238)U slab samples was conducted using a deuterium-tritium neutron source at the China Institute of Atomic *** leakage neutron spectra within energy levels of 0.8-16 MeV at 60°and 120°were measured using the time-of-flight *** samples were prepared as rectangular slabs with a 30 cm square base and thicknesses of 3,6,and 9 *** leakage neutron spectra were also calculated using the MCNP-4C program based on the latest evaluated files of^(238)U evaluated neutron data from CENDL-3.2,ENDF/B-Ⅷ.0,JENDL-5.0,and *** on the comparison,the deficiencies and improvements in^(238)U evaluated nuclear data were *** results showed the following.(1)The calculated results for CENDL-3.2 significantly overestimated the measurements in the energy interval of elastic scattering at 60°and 120°.(2)The calculated results of CENDL-3.2 overestimated the measurements in the energy interval of inelastic scattering at 120°.(3)The calculated results for CENDL-3.2 significantly overestimated the measurements in the 3-8.5 MeV energy interval at 60°and 120°.(4)The calculated results with JENDL-5.0 were generally consistent with the measurement results.

关键词： Leakage neutron spectra Uranium D-T neutron source Evaluated nuclear data

Ammonia volatilization losses and ^(15)N balance from urea applied to rice on a paddy soil

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Journal of Environmental Sciences 2006年第2期18卷 299-303页

作者： FAN Xiao-hui SONG Yong-sheng lin De-xi yang lin-zhang LUO Jia-fa Institute of Soil Science Chinese Academy of Sciences Nanjing 210008 China Land and Environmental Management Group AgRsearch Ruakura Research Centre East Street Private Bag 3123 Hamilton New Zealand

Ammonia volatilization loss and ^15N balance were studied in a rice field at three different stages after urea application in Taihu Lake area with a micrometeorological technique. Factors such as climate and the NH4^＋-N concentration in the field floodwater affecting ammonia loss were also investigated. Results show that the ammonia loss by volatilization accounted for 18.6%-38.7% of urea applied at different stages, the greatest loss took place when urea was applied at the tillering stage, the smallest at the ear bearing stage, and the intermediate loss at the basal stage. The greatest loss took place within 7 d following the fertilizer application. Ammonia volatilization losses at three fertilization stages were significantly correlated with the ammonium concentration in the field floodwater after the fertilizer was applied. ^15N balance experiment indicated that the use efficiency of urea by rice plants ranged between 24.4% and 28.1%. At the early stage of rice growth, the fertilizer nitrogen use efficiency was rather low, only about 12%. The total amount of nitrogen lost from different fertilization stages in the rice field was 44.1%-54.4%, and the ammonia volatilization loss was 25.4%-33.3%. Reducing ammonia loss is an important treatment for improving N use efficiency.

关键词： ammonia volatilization urea ^15N balance rice influence factors, Taihu region

Advanced cellulose-based materials toward stabilizing zinc anodes

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Science China Chemistry 2024年第5期67卷 1465-1484页

作者： Zhijiang Li Xiang Chen Rui zhang Taoyi Shen Jianchao Sun Zhongce Hu lin Li Lanlan yang Hou-Yong Yu College of Textile Science and Engineering(International Institute of Silk) Zhejiang Sci-Tech UniversityHangzhou 310018China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Donghua UniversityShanghai 201620China School of Environment and Material Engineering Yantai UniversityYantai 264005China Institute for Carbon Neutralization College of Chemistry and Materials EngineeringWenzhou UniversityWenzhou 325035China

Rechargeable aqueous zinc metal batteries(RAZMBs) have received extensive attention for large-scale energy storage systems due to the merits of Zn anodes, including moderate volumetric and gravimetric energy density, low redox potential, abundant reserve, low cost and impressive intrinsic safety. However, Zn anodes suffer from a series of adverse reactions(dendrite growth,hydrogen evolution, and surface passivation) resulting in low Coulombic efficiency, large polarization, and unsatisfied cycling performance, which inevitably hinder the wide application of RAZMBs. To address the above issues, cellulose-based materials are widely used for Zn anode protection because of their unique physical and chemical properties and other advantages such as biocompatibility, non-toxicity, degradability and easy extraction. In order to better understand the current progress in cellulosebased materials for the Zn anode protection, we have classified and summarized the relevant literatures. In this review, we summarize and elaborate the causes of poor reversibility for Zn anodes, including dendrite formation, hydrogen evolution, and surface passivation. Subsequently, the effective strategies(anode interfacial engineering, gel electrolyte optimization, and separator modification) of cellulose-based materials toward stabilizing Zn anodes are overviewed. In the end, the existing challenges and prospects of cellulose-based materials in Zn anode protection are summarized to shed light on future work.

关键词： Zn anode cellulose anode interfacial engineering gel electrolyte optimization separator modification

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TRPM2 Mediates Hepatic Ischemia–Reperfusion Injury via Ca^(2+) -Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression

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Research 2024年第1期2023卷 351-368页

作者： Cheng Zhong Jing yang Yiyin zhang Xiaoxiao Fan yang Fan Ning Hua Duguang Li Shengxi Jin Yirun Li Peng Chen Yongle Chen Xiaobo Cai Yi zhang linhua Jiang Wei yang Peilin Yu Hui lin Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouP.R.China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhou 310000P.R.China Department of Physiology and Pathophysiology and Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province Xinxiang Medical University453003 XinxiangHenanP.R.China School of Biomedical Sciences Faculty of Biological SciencesUniversity of LeedsLS29JT LeedsUK Department of Toxicology and Department of Medical Oncology of Second Affiliated Hospital Zhejiang University School of MedicineHangzhouP.R.China Zhejiang Engineering Research Center of Cognitive Healthcare Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310020P.R.China College of Biomedical Engineering and Instrument Science Zhejiang UniversityHangzhou 310058P.R.China

Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and *** recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still ***,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR *** data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in ***,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related ***,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed ***,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR ***,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in ***,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.

关键词： TRPM2 Lipid Hepatic

Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury

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World Journal of Clinical Cases 2024年第4期12卷 688-699页

作者： Ya-Kuan Wang Huang lin Shu-Rui Wang Ru-Tao Bian yang Tong Wen-Tao zhang Ying-lin Cui Department of Encephalopathy The Second Clinical College of Henan University of Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Integrated Chinese and Western MedicineZhengzhou 450000Henan ProvinceChina Department of Traditional Chinese Medicine Classics Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Department of Central Laboratory Zhengzhou Traditional Chinese Medicine HospitalZhengzhou 450000Henan ProvinceChina Department of Encephalopathy Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina Famous Doctor Hall Henan Provincial Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Chinese Medicine)Zhengzhou 450000Henan ProvinceChina

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently ***,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical *** a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular *** main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate *** the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral *** the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic *** addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western ***,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable *** this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua *** hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.

关键词： Sanhua Decoction Cerebral ischemia-reperfusion Mechanism of action Application progress Traditional Chinese medical science Review

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis

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Biomedical and Environmental Sciences 2024年第6期37卷 607-616页

作者： Mengqing zhang Chu lin Xiaoling Cai Ruoyang Jiao Shuzhen Bai Zonglin Li Suiyuan Hu Fang Lyu Wenjia yang linong Ji Department of Endocrinology and Metabolism Peking University People’s HospitalBeijing 100044China

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and ***,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or *** PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and *** were systematically searched from inception to July *** controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were *** were computed as risk ratios(RR)using a fixedeffects *** Overall,39 RCTs with a total of 85,755 participants were *** to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug ***,no significant associations were *** Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist *** investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

关键词： Glucagon-like peptide-1 receptor agonists Twincretins Asthma Type 2 diabetes mellitus Obesity