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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

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Scorpiones,Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1αSignaling Pathway

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Chinese Journal of Integrative Medicine 2024年第9期30卷 799-808页

作者： MAO Qi-yuan WANG Xue-qian LIN Fei YU Ming-wei FAN Hui-ting ZHENG Qi LIU Lan-chun ZHANG Chu-chu LI Dao-rui LIN Hong-sheng Department of Oncology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China Department of Oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Cardiology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China Institute of Traditional Chinese Medicine Information China Academy of Chinese Medical SciencesBeijing100700China

Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans ***(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α(PI3K/AKT/mTOR/HIF-1α)signaling ***:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models,with rapamycin and cyclophosphamide as positive *** methyl cellulose solutions of Scorpiones,Scolopendra and Gekko were administered intragastrically as 0.33,0.33,and 0.83 g/kg,respectively once daily for 21 *** expression were detected every 7 days after inoculation,and tumor growth curves were *** was performed to determine CD31 and HIF-1αexpressions in tumor tissue and microvessel density(MVD)was *** blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling pathway-related ***-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in ***:Scorpiones,Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α(all P<0.01).Moreover,Scorpiones,Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase(p70S6K)(P<0.05 or P<0.01).In addition,they also decreased the expression of CD31,MVD,bFGF,TGF-β1 and VEGF compared with the model group(P<0.05 or P<0.01).Conclusion:Scorpiones,Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway.

关键词： Scorpiones Scolopendra Gekko dredging collaterals and activating blood Chinese medicine of worms lung cancer hypoxic tumor microenvironment phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling pathway

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MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

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BIOCELL 2024年第5期48卷 771-792页

作者： CHENG-GONG LUO jiao ZHANG YUN-ZHAO AN XUAN LIU SHUAI-JIE LI WEI ZHANG KAI LI XU ZHAO DONG-BO yuan LING-YUE AN WEI CHEN YE TIAN BIN XU Department of Urology Guizhou Provincial People’s HospitalGuiyangChina Department of Urology First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient ***:A risk model incorporating four ferroptosis-related genes was developed and *** risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological *** corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in ***,we conducted further experiments involving ferroptosis-related analysis to validate its association with ***:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa ***-activated protein kinase 9(MAPK9)emerged as a crucial gene within the *** vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and ***:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

关键词： Ferroptosis Biochemical recurrence Prostate cancer TCGA GEO MAPK9

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Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury

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Biomedical and Environmental Sciences 2024年第5期37卷 494-502页

作者： CAO Wei Hua JIANG Ting Ting SHEN Ge DENG Wen WANG Shi Yu ZHANG Zi Yu LI Xin Xin LU Yao ZHANG Lu LIU Ru Yu CHANG Min WU Shu Ling GAO yuan jiao HAO Hong Xiao CHEN Xiao Xue HU Lei Ping XU Meng jiao YI Wei XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China Department of Gynecology and Obstetrics Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical *** The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with *** on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five *** were measured by Luminex *** characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were *** 73 patients were *** among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine ***-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs *** was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs *** Older age may be more prone to *** with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

关键词： Drug-induced liver injury Cytokines Non-steroidal anti-inflammatory drugs Inflammation

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民族传统体育参与中女性角色的变化——基于“撒尔嗬”的个案分析

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成都体育学院学报 2024年第4期50卷 147-154页

作者：袁娇熊欢中央民族大学民族学与社会学学院北京100081 上海体育大学新闻与传媒学院上海200438

文章以“撒尔嗬”的女性参与实践为个案,考察女性在民族传统体育参与中的角色变化。研究发现,女性在“撒尔嗬”参与中经历了从“缺场”到“在场”的角色变化,这种角色变化呈现在参与人数、参与行为、多元角色扮演3方面。但女性角色转变... 详细信息

文章以“撒尔嗬”的女性参与实践为个案,考察女性在民族传统体育参与中的角色变化。研究发现,女性在“撒尔嗬”参与中经历了从“缺场”到“在场”的角色变化,这种角色变化呈现在参与人数、参与行为、多元角色扮演3方面。但女性角色转变的过程并不是一蹴而就,而是经历了来自社会、文化制度和观念等方面带来的阻碍,为获得“在场”角色,女性在性别关系下进行了性别权利、性别分工与性别文化的博弈与协商,动力与阻力同时存在。

关键词：民族传统体育参与 “撒尔嗬” 女性角色变化障碍性别博弈

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Property evolution and service life prediction of novel metallic materials for future lunar bases

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Rare Metals 2024年第10期43卷 5318-5331页

作者： Sen-Kuan Meng rui-Song Zhu Hong-Liang Zheng Tong Gao Shi-Hao Jiang Wen-Hao Wang Shu-Hao Zhang Zi-yuan Zhao Xuan Ge Wei-Min Wang Li-Na Hu Zheng Wang Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education) School of Materials Science and EngineeringShandong University Department of Chemistry and Bioscience Aalborg University

While lunar bases have been a focus of development in recent years, the complex and extreme environment of the lunar surface remains a considerable challenge for lunar exploration. Unlike those on Earth,lunar day and night temperature variations cause the properties of materials, especially metallic materials, to evolve in completely different manners. In this study, we investigated the property evolution of nine typical highperformance metallic materials using laboratory simulations of the extremely long-period lunar temperature environment. While lunation treatment improves the properties of all metallic materials, the microscopic mechanisms vary for amorphous and crystalline alloys with different structures. The treatment reduces both the loosely packed regions and heterogeneity in amorphous alloys while causing significant phase changes in crystalline alloys. Furthermore, a conservative prediction of the service life of metallic materials on lunar bases is provided based on analyzing microplastic events, followed by the practical material selection recommendations in various lunar application scenarios.

关键词： Lunar exploration Metallic glass Metallic material Property evolution

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税收制度与数字经济的适配性:适配逻辑、适配向度及改革前瞻

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税务研究 2024年第10期 17-23页

作者：袁娇王敏云南财经大学财政与公共管理学院云南财经大学

数字经济时代,如何对现行税制进行适配性改革以有效应对新业态带来的税收挑战,助力税收治理效能的提升,已成为当下函待破解的重大问题。鉴于此,本文立足我国国情及数字经济时代背景,在深入分析税制适配逻辑的基础上,搭建“价值+结构+职... 详细信息

数字经济时代,如何对现行税制进行适配性改革以有效应对新业态带来的税收挑战,助力税收治理效能的提升,已成为当下函待破解的重大问题。鉴于此,本文立足我国国情及数字经济时代背景,在深入分析税制适配逻辑的基础上,搭建“价值+结构+职能”三维税制适配向度分析框架,并从税制适配要求、适配原则、适配思路和适配重点四个方面,对未来税制改革进行整体谋划,以期更好地推动我国数字经济高质量发展,助力实现中国式现代化。

关键词：数字经济数据要素新业态税收制度适配性

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Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy:Network pharmacology analysis and experimental validation

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World Journal of Diabetes 2024年第9期15卷 1942-1961页

作者： Yi-Fan Yang Ling yuan Xiang-Yang Li Qian Liu Wen-Jie Jiang Tai-Qiang jiao Jia-Qing Li Meng-Yi Ye Yang Niu Yi Nan Key Laboratory of Ningxia Minority Medicine Modernization Ministry of Education Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina College of Pharmacy Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Traditional Chinese Medicine College Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Diabetic retinopathy(DR)is a common microvascular complication of diabetes *** blindness rate is high;therefore,finding a reasonable and safe treatment plan to prevent and control DR is ***,there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic *** To investigate the effects of Buqing granule(BQKL)on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo *** This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions(PPI),identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,and preliminarily validated the screened core targets by molecular ***,we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection,and administered the appropriate drugs for 12 weeks after the model was successfully *** mass and fasting blood glucose and lipid levels were measured,and pathological changes in retinal tissue were detected by hematoxylin and eosin *** was used to detect the oxidative stress index expression in serum and retinal tissue,and immunohistochemistry,real-time quantitative reverse transcription PCR,and western blotting were used to verify the changes in the expression of core *** Six potential therapeutic targets of BQKL for DR treatment,including Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3,were screened using *** analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR *** docking prediction indica

关键词： Diabetic retinopathy Network pharmacology Animal models Oxidative stress Inflammatory

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Hydrogen-rich surface of MoC catalysts for efficient CO_(2) hydrogenation induced by a coupled hydrogen donator

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Nano Research 2024年第8期17卷 7762-7767页

作者： Dong Xu Si-yuan Xia Qi-yuan Li Jie-Sheng Chen Xin-Hao Li School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesShanghai Jiao Tong UniversityShanghai 200240China

Direct CO_(2) hydrogenation offers an important strategy for promoting the global carbon balance,but high thermodynamic and kinetic stability of CO_(2) has restricted its applicability to only a handful of industrial ***,we introduce a proof-of-concept application of the electron-rich Pt surface to promote hydrogen donation for electron-rich MoC particles acting as hydrogen acceptors,thereby constructing hydrogen-rich surface of MoC active ***,the formed hydrogen-rich and electronrich surface could greatly decrease reaction activation energy to boost the efficient CO_(2) hydrogenation into formic acid over the MoC *** optimized MoC@NC/Pt-0.1(NC:nitrogen-doped carbon)catalyst exhibits a high turnover frequency(TOF)value of 1.2 h^(−1) at a lower temperature of 60℃and a TOF of 24.2 h^(−1) under standard reaction conditions widely used in the literature,exceeding 7 times of MoC@NC catalyst and surpassing the benchmark classical non-noble metal active center-based heterogeneous catalyst.

关键词： electron-rich Pt nanoparticles hydrogen donation hydrogen-rich MoC nanoparticles CO_(2) hydrogenation formic acid

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Gamma/Hadron Separation Method for the HADAR Experiment

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Research in Astronomy and Astrophysics 2024年第3期24卷 70-74页

作者： Yang-Zhao Ren Tian-Lu Chen You-Liang Feng Dan-Zeng Luo-Bu Yi-Qing Guo Cheng Liu Qi Gao Mao-yuan Liu Xiang-Li Qian Ya-Ping Wang Zi-Hao Zhang Xin-Long Li Qing-yuan Hou Heng-jiao Liu Qing-Qian Zhou Shan-Jie Shu The Key Laboratory of Cosmic Rays(Tibet University) Ministry of EducationLhasa 850000China Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of Sciences University of Chinese Academy of Sciences School of Intelligent Engineering Shandong Management University

Ground-based arrays of imaging atmospheric Cherenkov telescopes(IACTs)are the most sensitiveγ-ray detectors for energies of approximately 100 Ge V and *** such IACT is the High Altitude Detection of Astronomical Radiation(HADAR)experiment,which uses a large aperture refractive water lens system to capture atmospheric Cherenkov photons(i.e.,the imaging atmospheric Cherenkov technique).The telescope array has a low threshold energy and large field of view,and can continuously scan the area of the sky being observed,which is conducive to monitoring and promptly responding to transient *** process ofγ-hadron separation is essential in very-high-energy(>30 Ge V)γ-ray astronomy and is a key factor for the successful utilization of *** this study,Monte Carlo simulations were carried out to model the response of cosmic rays within the HADAR *** analyzing the Hillas parameters and the distance between the event core and the telescope,the distinction between air showers initiated byγ-rays and those initiated by cosmic rays was ***,a Quality Factor was introduced to assess the telescope’s ability to suppress the background and to provide a more effective characterization of its performance.

关键词： astroparticle physics-telescopes-methods data analysis

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