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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： yun Zhang Lijun Du Chenxi Wang Zhangsheng jiang Qingchi Duan yiping Li Zhijun Xie Zhixing He yi Sun Lin Huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of Zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to *** dysregulation of double-negative(DN)T cells is considered as a crucial commander during ***,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune ***,the function of neddylation in SLE is still ***,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus *** investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus *** double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus *** findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus ***,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was ***,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation ***,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE ***,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： yi-Nan Zhang Sarah Auclair jiang Zhu Department of Integrative Structural and Computational Biology The Scripps Research Institute Department of Immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

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World Journal of Emergency Medicine 2024年第3期15卷 197-205页

作者： Subi Abudurexiti Shihai Xu Zhangping Sun yi jiang Ping Gong Department of Emergency Medicine Ruijin Hospital Affi liated to Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Emergency Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affi liated HospitalSouthern University of Science and Technology)Shenzhen 518020China Department of Emergency Medicine the First Affi liated Hospital of Dalian Medical UniversityDalian 116011China Department of Emergency Medicine General Hospital of Tianjin Medical UniversityTianjin 300052China

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were *** to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as *** serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after *** Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were *** Cerebral Performance Category(CPC) score was recorded on day 28 after ***:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabo

关键词： Glucose metabolic reprogramming Lactate dehydrogenase Cardiac arrest Prognosis

2D multifunctional devices:from material preparation to device fabrication and neuromorphic applications

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International Journal of Extreme Manufacturing 2024年第3期6卷 91-118页

作者： Zhuohui Huang Yanran Li yi Zhang Jiewei Chen Jun He Jie jiang Hunan Key Laboratory of Nanophotonics and Devices School of PhysicsCentral South UniversityChangshaHunanPeople’s Republic of China Department of Applied Physics The Hong Kong Polytechnic UniversityHong Kong Special Administrative Region of ChinaPeople’s Republic of China

Neuromorphic computing systems,which mimic the operation of neurons and synapses in the human brain,are seen as an appealing next-generation computing method due to their strong and efficient computing ***-dimensional (2D) materials with dangling bond-free surfaces and atomic-level thicknesses have emerged as promising candidates for neuromorphic computing *** a result,2D neuromorphic devices may provide an ideal platform for developing multifunctional neuromorphic ***,we review the recent neuromorphic devices based on 2D material and their multifunctional *** synthesis and next micro–nano fabrication methods of 2D materials and their heterostructures are first *** recent advances of neuromorphic 2D devices are discussed in detail using different operating *** importantly,we present a review of emerging multifunctional neuromorphic applications,including neuromorphic visual,auditory,tactile,and nociceptive systems based on 2D *** the end,we discuss the problems and methods for 2D neuromorphic device developments in the *** paper will give insights into designing 2D neuromorphic devices and applying them to the future neuromorphic systems.

关键词： 2D material micro–nano fabrication multifunctional system neuromorphic electronics artificial intelligence

Wetting alternating with partial drying during grain filling increases lysine biosynthesis in inferior rice grain

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The Crop Journal 2024年第1期12卷 262-270页

作者： yi jiang Wenli Tao Weiyang Zhang Zhiqin Wang Jianchang Yang jiangsu Key Laboratory of Crop Genetics and Physiology/Co-Innovation Center for Modern Production Technology of Grain Crops Yangzhou UniversityYangzhou 225009JiangsuChina

Lysine content is a criterion of the nutritional quality of *** the process of lysine biosynthesis in early-flowering superior grain(SG)and late-flowering inferior grain(IG)of rice would advance breeding and cultivation to improve nutritional ***,little information is available on differences in lysine anabolism between SG and IG and the underlying mechanism,and whether and how irrigation regimes affect lysine anabolism in these grains.A japonica rice cultivar was grown in the field and two irrigation regimes,continuous flooding(CF)and wetting alternating with partial drying(WAPD),were imposed from heading to the mature *** content and activities of key enzymes of lysine biosynthesis,and levels of brassinosteroids(BRs)were lower in the IG than in the SG at the early grainfilling stage but higher at middle and late grain-filling *** increased activities of these key enzymes,BR levels,and contents of lysine and total amino acids in IG,but not SG relative to *** of 2,4-epibrassinolide to rice panicles in CF during early grain filling reproduced the effects of WAPD,but neither treatment altered the activities of enzymes responsible for lysine catabolism in either SG or *** and elevated BR levels during grain filling increased lysine biosynthesis in *** in lysine biosynthesis in rice should focus on IG.

关键词： Brassinosteroids Inferior grain Lysine biosynthesis Rice Wetting alternating with partial drying

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 577-582页

作者： Qiu-Yu jiang Ru-yi Xue Department of Gastroenterology and Hepatology Zhongshan HospitalShanghai Institute of Liver DiseaseFudan UniversityShanghai 200032China Department of Gastroenterology and Hepatology Shanghai Baoshan District Wusong Central Hospital(Zhongshan Hospital Wusong BranchFudan University)Shanghai 200940China

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting ***,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers *** and PLR are promising markers for clinical *** models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite ***,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

关键词： Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio Immunecheckpoint inhibitor Immune-related adverse event

Part-Whole Relational Few-Shot 3D Point Cloud Semantic Segmentation

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Computers, Materials & Continua 2024年第3期78卷 3021-3039页

作者： Shoukun Xu Lujun Zhang Guangqi jiang yining Hua yi Liu School of Computer Science and Artificial Intelligence Aliyun School of Big Data and School of SoftwareChangzhou UniversityChangzhou213164China Department of Computer Science University of AberdeenKing’s CollegeAberdeenAB243FXUK

This paper focuses on the task of few-shot 3D point cloud semantic *** some progress,this task still encounters many issues due to the insufficient samples given,e.g.,incomplete object segmentation and inaccurate semantic *** tackle these issues,we first leverage part-whole relationships into the task of 3D point cloud semantic segmentation to capture semantic integrity,which is empowered by the dynamic capsule routing with the module of 3D Capsule Networks(CapsNets)in the embedding ***,the dynamic routing amalgamates geometric information of the 3D point cloud data to construct higher-level feature representations,which capture the relationships between object parts and their ***,we designed a multi-prototype enhancement module to enhance the prototype ***,the single-prototype enhancement mechanism is expanded to the multi-prototype enhancement version for capturing rich ***,the shot-correlation within the category is calculated via the interaction of different samples to enhance the intra-category *** studies prove that the involved part-whole relations and proposed multi-prototype enhancement module help to achieve complete object segmentation and improve semantic ***,under the integration of these two modules,quantitative and qualitative experiments on two public benchmarks,including S3DIS and ScanNet,indicate the superior performance of the proposed framework on the task of 3D point cloud semantic segmentation,compared to some state-of-the-art methods.

关键词： Few-shot point cloud semantic segmentation CapsNets

Improvement of mechanical properties and investigation of strengthening mechanisms on the Ti_(3)AlC_(2) ceramic with nanosized WC addition

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Journal of Advanced Ceramics 2024年第6期13卷 861-876页

作者： yi Zhong ying Liu Qinkai jiang Na Jin Zifeng Lin Jinwen Ye School of Materials Science&Engineering Sichuan UniversityChengdu 610065China yibin R&D Park Yibin Industrial Technology Research InstituteSichuan UniversityYibin 644005China

Ti_(3)AlC_(2) (TAC) has great potential for use as an ablation material in aerospace applications due to its great oxidation/ablation resistance, but its high-temperature strength and thermal shock resistance still have much room for simultaneous improvement under fast temperature variation conditions. Herein, we used Ti_(3)AlC_(2) and WC powders as raw materials and successfully fabricated textured (Ti,W)_(3)AlC_(2) ceramic with small amounts of TiC and Al_(2)O_(3), and room temperature mechanical properties such as flexural strength (1146±46.9 MPa), fracture toughness (11.78±0.44 MPa·m^(1/2)), and hardness (5.81±0.11 GPa) at 5 wt% WC addition were achieved. The high-temperature strength of the ceramic was significantly improved, and better thermal shock resistance from 298 to 1173 K was simultaneously acquired together with the regulation of the elastic modulus, thermal conductivity, and thermal expansion coefficient, providing (Ti,W)_(3)AlC_(2) with more possibilities for fast-temperature variation applications. Strengthening and toughening mechanisms were proposed. Scanning transmission electron microscopy high-angle annular dark-field imaging (STEM-HADDF) showed that W randomly replaced the Ti1 and Ti2 sites of Ti_(3)AlC_(2), providing a good reference for establishing crystal models, and further density functional theory (DFT) calculations based on these models indicated a higher fracture energy of (Ti,W)_(3)AlC_(2) along different crystal planes, providing superior resistance to transgranular fracture;a lower mismatch degree of (Ti,W)_(3)AlC_(2)/Al_(2)O_(3) resulted in stronger interface bonding, resulting in greater resistance to intergranular fracture as well as more balanced stress distributions at different interfaces.

关键词： mechanical properties solid solution MAX phase transmission electron microscopy(TEM) ceramic atomic structure

High-precision nondestructive evaluation of a thermal barrier coating based on perovskite quantum dot anion exchange

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Nano Research 2024年第5期17卷 4582-4592页

作者： Tao Han Shufang Ding Zifan Wang Sirong jiang Pengjiang Jing Tianshang yi Yaqi Chen Chunzhi jiang Xiaofeng Zhang Microelectronics and Optoelectronics Technology Key Laboratory of Hunan Higher Education School of Physics and Electronic Electrical EngineeringXiangnan UniversityChenzhou 423000China National Engineering Laboratory for Modern Materials Surface Engineering Technology&The Key Lab of Guangdong for Modern Surface Engineering Technology Guangdong Institute of New MaterialsGuangdong Academy of SciencesGuangzhou 510650China

Thermal barrier coatings(TBCs)in gas turbine engines are used in expressly harsh environments;thus,assessing TBC integrity status is critical for safety and ***,traditional periodic maintenance involves visual inspections of the TBCs,requiring the gas turbine to be decommissioned and partially *** importantly,tiny defects or internal damages that easily cause coating failure cannot be *** this work,a new nondestructive evaluation(NDE)technique of TBCs based on quantum dot(QD)anion exchange is first explored *** exchanging anions between the Cl ions and the CsPbBr_(3) QDs,the degrees of salt corrosion of the TBCs are *** resultant NDE technique shows that the colour of the TBCs obviously changes from green to blue,accompanied by a large blueshift(~100 nm)of the photoluminescence(PL)peak *** addition,the relationship between the PL peak position and coating thermophysical properties indicates that the precision of this NDE technique may easily identify theμm-level of the thermal growth oxide(TGO)changes inside the TBCs.

关键词： thermal barrier coatings nondestructive evaluation CsPbBr_(3)quantum dot anion exchange thermal growth oxide