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Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(liver kinase B1)activity

Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei liu Chenxi Zhao Fujing Ge Yuekang li Meijia Qian Jiamin Du Weihua Wang yonghao li Yue liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China Center for Drug Safety Evaluation and Research of Zhejiang University Hangzhou 310058China Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China Department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer Center of Zhejiang University HangzhouChina Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths *** the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC ***,the need for novel strategies addressing NSCLC remains ***(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic ***,the mechanisms by which DUBs promote NSCLC remain poorly *** a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of *** of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in ***,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 ***,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in *** findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

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基于多粒度阅读器和图注意力网络的文档级事件抽取

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计算机应用研究 2024年第8期41卷 2329-2335页

作者：薛颂东李永豪赵红燕太原科技大学计算机科学与技术学院太原030024

文档级事件抽取面临论元分散和多事件两大挑战,已有工作大多采用逐句抽取候选论元的方式,难以建模跨句的上下文信息。为此,提出了一种基于多粒度阅读器和图注意网络的文档级事件抽取模型,采用多粒度阅读器实现多层次语义编码,通过图注... 详细信息

文档级事件抽取面临论元分散和多事件两大挑战,已有工作大多采用逐句抽取候选论元的方式,难以建模跨句的上下文信息。为此,提出了一种基于多粒度阅读器和图注意网络的文档级事件抽取模型,采用多粒度阅读器实现多层次语义编码,通过图注意力网络捕获实体对之间的局部和全局关系,构建基于实体对相似度的剪枝完全图作为伪触发器,全面捕捉文档中的事件和论元。在公共数据集ChFinAnn和DuEE-Fin上进行了实验,结果表明提出的方法改善了论元分散问题,提升了模型事件抽取性能。

关键词：多粒度阅读器图注意力网络文档级事件抽取

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螺杆式空压机故障检测控制系统设计

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自动化应用 2024年第13期65卷 176-178页

作者：李永浩焦玉金山东玻纤集团股份有限公司山东临沂276400

分析了螺杆式空压机的工作原理及常见故障,设计了一种用于螺杆式空气压缩机故障监测和管理的系统。通过设计该系统的硬件组件及软件部分,实现了螺杆式空压机故障检测与处理的功能,提高了机组的运行效率和可靠性。

关键词：螺杆式空压机故障检测

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锰基普鲁士蓝作为钠离子电池正极材料的研究进展

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化工新型材料 2024年第2期52卷 59-64页

作者：王培远朱登贵李永浩孙淑敏方少明郑州轻工业大学材料与化学工程学院郑州450001 郑州轻工业大学河南省表界面科学重点实验室郑州450001

近年来,由于锂资源的短缺和快速消耗,锂离子电池的成本急剧增加,因此寻找新型储能系统显得日益重要。钠离子电池具有和锂离子电池相似的工作原理,可以作为锂离子电池的一种经济高效的替代品。锰基普鲁士蓝材料因其原材料分布广泛、成本... 详细信息

近年来,由于锂资源的短缺和快速消耗,锂离子电池的成本急剧增加,因此寻找新型储能系统显得日益重要。钠离子电池具有和锂离子电池相似的工作原理,可以作为锂离子电池的一种经济高效的替代品。锰基普鲁士蓝材料因其原材料分布广泛、成本低、结构稳定、环境友好且制备工艺简单等优点,是一种极具潜力的钠离子电池正极材料。综述了有关锰基普鲁士蓝材料的储钠机理、合成方法、修饰路线及材料应用的最新进展,从迁移离子、过渡金属、结合水与空位分析了普鲁士蓝材料对钠离子电池电化学性能的影响,并对可能的发展方向进行了展望。

关键词：锰基普鲁士蓝正极材料钠离子电池合成工艺研究进展

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Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy

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Science China(life Sciences) 2015年第6期58卷 550-555页

作者： ZHU TiePei MA Jin li yonghao ZHANG Zheng Eye Hospital of Wenzhou Medical University State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University Eye Center Second Affiliated Hospital of Medical College Zhejiang University

The changes in retinal thickness and visual function in type 2 diabetic patients without clinical evidence of diabetic retinopathy were evaluated. A total of 141 diabetic subjects without retinopathy and 158 healthy subjects were enrolled in this study. Superior macular ganglion cell complex thicknesses were significantly decreased in diabetic cases, and no significant peripapillary retinal nerve fiber layer thickness changes were observed. The contrast sensitivities at all space frequencies were significantly different between diabetic patients and controls. The mean P50 amplitude from pattern electroretinogram results was reduced significantly in the diabetic group. In the diabetic group, average superior ganglion cell complex thicknesses positively correlated with both contrast sensitivities at high spatial frequencies and P50 amplitudes. The results indicated that ganglion cell complex thickness and visual function changes could be observed in diabetic subjects before the onset of any significant diabetic retinopathy. Macular ganglion cell complex reduction occurred much earlier than peripapillary retinal nerve fiber layer thinning in diabetic patients without retinopathy.

关键词： diabetes mellitus diabetic retinopathy retinal nerve fiber layer retinal ganglion cell contrast sensitivity electro-retinogram

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Glycogen synthase kinase-3： a key kinase in retinal neuron apoptosis in early diabetic retinopathy

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Chinese Medical Journal 2014年第19期127卷 3464-3470页

作者： li Zhaohui Ma ling Chen Xiaodong li yonghao li Shiyi Zhang Jinglin Lu lin State Key Laboratory of Ophthalmology Zhongshan OphthalmicCenter Sun Yat-sen University Guangzhou Guangdong 510060China Zhongnan Hospital of Wuhan University Wuhan Hubei 430071 China

Background Diabetes-related pathogenic factors can cause retinal ganglion cell （RGC） apoptosis, but the specific mechanism is not very clear. The aim of this study is to investigate the correlation between glycogen synthase kinase-3 （GSK-3） activation and retinal neuron apoptosis. Methods In an in vitro experiment, the number of apoptotic RGC-5 cells differentiated by staurosporine was evaluated via flow cytometry and nuclei staining using Hoechst 33258. GSK-3 phosphorylation and caspase-3 activation in RGC-5 cells after serum deprivation were determined using Western blotting. Mitochondrial membrane potential was detected using the dye 5,5＇,6,6＇-tetrachloro-l,l＇,3,3＇-tetrethyl benzimidalyl carbocyanine iodide, and reactive oxygen species （ROS） levels were measured with dihydroethidium. In an in vivo experiment, the number of apoptotic retinal neurons was evaluated via terminal transferase dUTP nick-end labeling （TUNEL）, and GSK-3 phosphorylation was determined using Western blotting, in the retinal nerve epithelial tissue of rats in which diabetes was induced by intravenous tail-vein injection of streptozotocin for 4 weeks. Results The levels of phosphorylated Ser21/9 in GSK-3α/13 and p-T308/S473-AKT were lower and the cleaved caspase-3 levels were higher in the serum-deprived model （P 〈0.05）. lithium chloride treatment was associated with a slower rate of apoptosis, increased mitochondrial membrane potential, and decreased ROS levels in differentiated RGC-5 cells （P 〈0.05）. The level of blood glucose and the number of TUNEL-positive cells in the whole-mounted retinas were higher （P 〈0.01）, and the levels of phosphorylated Ser21/9 in GSK-3α/13 and body weight were lower （P 〈0.05）. However, the thickness of the retinal nerve epithelial layer was not significantly less in diabetic rats compared with control group. lithium chloride intravitreal injection increased the levels of phosphorylated Ser21/9 in GSK-3α/13 and decreased TUNEL-positive cells in the whole-mounted

关键词： retinal neuron apoptosis lithium chloride glycogen synthase kinase-3 diabetic retinopathy mitochondrial dysfunction

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Occurrence and conceptual sedimentary model of Cambrian gypsum-bearing evaporites in the Sichuan Basin, SW China

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Geoscience Frontiers 2018年第4期9卷 1179-1191页

作者： Hong liu Xiucheng Tan yonghao li Jian Cao Bin Luo State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Southwest Petroleum University Division of Sedimentology and Hydrocarbon Accumulation Petro China Key Laboratory of Carbonate ReservoirSouthwest Petroleum University School of Earth Science and Technology Southwest Petroleum University School of Earth Sciences and Engineering Nanjing University Research Institute of Exploration and Development PetroChina Southwest Oil and Gas Field Company

During the Cambrian, gypsum-bearing evaporites formed in the Sichuan Basin, SW China. These rocks are important for oil and gas sealing, but details of their distribution and origin are not well established. This study examines the regional distribution and origin of the gypsum-bearing evaporites using a comprehensive analysis of drilling data from 34 wells, 5 measured cross-sections in the basin and surrounding area, and 96 maps of area-survey data. Results show that in the stratigraphic succession, the gypsum-bearing evaporites occur mainly in the Lower Cambrian Longwangmiao Formation, the Middle Cambrian Douposi Formation, and the Middle-Upper Cambrian Xixiangchi Group. Geographically, the rocks are found mainly in the southeastern part of the basin, and the distribution of deposits shows an overall SW-NE trend. The sedimentary environments for evaporite formation were evaporative lagoon and inter-platform basin in a platform setting. Gypsum was generated by the underwater concentration of sea water in a strongly evaporative environment. Both an evaporative restricted platform and a mixeddeposition restricted platform model appear to be applicable to the development of gypsum in the Sichuan Basin. The gypsum-bearing evaporites with the best sealing capacity are located mostly in the southeastern part of the basin. These constraints can be applied directly to regional exploration, and have implications for the regional paleogeography and paleoclimate.

关键词： Sichuan Basin Cambrian Gypsum-bearing evaporite Evaporative lagoon Inter-platform basin Platform

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大肠杆菌焦磷酸酶的表达及其酶学性质研究

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中国酿造 2024年第9期43卷 65-71页

作者：王赞丞王璐樊俊萍陈雨点陈婷婷刘露露李勇昊重庆科技大学化学化工学院重庆401331

该研究通过聚合酶链式反应(PCR)扩增克隆大肠杆菌(Escherichia coli)Rosetta(DE3)的焦磷酸酶(PPase)基因,采用无缝克隆技术构建焦磷酸酶表达载体pET-28a-ppa,并转化至感受态***(DE3),构建重组菌株*** PPa.采用单因素试验对其诱导表达条... 详细信息

该研究通过聚合酶链式反应(PCR)扩增克隆大肠杆菌(Escherichia coli)Rosetta(DE3)的焦磷酸酶(PPase)基因,采用无缝克隆技术构建焦磷酸酶表达载体pET-28a-ppa,并转化至感受态***(DE3),构建重组菌株*** PPa.采用单因素试验对其诱导表达条件进行优化,并进一步采用镍离子磁珠纯化重组PPas,研究其酶学性质。结果表明,成功构建重组菌株***,当异丙基-β-D硫代半乳糖苷(IPTG)诱导浓度、诱导温度和诱导时间分别为0.4 mmolL、20℃和8h时,重组PPase活性达到最高,为129.05 IU/mL,是优化前的3.14倍。重组PPase的理论分子质量为19.7kDa;最适反应温度和pH分别为55℃和9,在温度10~30℃及pH 7.0~9.0范围内稳定;金属离子K^(+)、Mg^(2+)和Na^(+)可极显著性提高该酶活性(P<0.01),而Mn^(2+)和Zn^(2+)对该酶有极显著抑制作用(P<0.01);重组PPase的动力学参数米氏常数(K_(m)值)为3.58 μmol/mL、最大反应速率(V_(max)值)为314.66μmol/(mL·min),催化常数(K_(cat)值)为87300.56S^(-1),半失活时间为10 min。该研究为后续工业化生产PPase及对该酶的理性设计提供依据。

关键词：焦磷酸酶大肠杆菌诱导表达酶学性质

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纤维二糖磷酸化酶表达条件的优化及其酶学性质研究

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食品与发酵工业 2024年第16期50卷 125-131页

作者：彭念陈婷婷王璐樊俊萍高玉杉冉小琴刘露露李勇昊重庆科技学院化学化工学院重庆401331

纤维二糖磷酸化酶(cellobiose phosphorylase,CBP)磷酸化裂解纤维二糖为葡萄糖-1-磷酸,它是木质纤维素转化淀粉的关键酶。该研究将来源于Clostridium thermocellum YM4的cbp基因通过表达载体pET-28a(+)构建重组菌Rosetta(DE3)/pET-28a-CBP用于表达CBP。对其诱导表达条件进行优化,结果显示当诱导温度、异丙基硫代-β-D-半乳糖苷(isopropylthio-β-D-galactoside,IPTG)浓度和诱导时间分别为15℃、0.2 mmol/L和12 h时CBP酶活力最高,为0.47 IU/mL。进一步利用Ni柱分离纯化出带有His标签的CBP,结果表明该重组酶分子质量为95 kDa,比酶活1.03 IU/mg;最适反应温度60℃,最适反应pH 6,半失活时间为60 min;金属离子Cu^(2+)显示出对该酶有强烈的抑制作用,然后依次是Zn^(2+)、Fe^(3+)、Ca^(2+)、Mn^(4+)(P0.05);最后对重组CBP的动力学参数进行了表征,K_(m)值为19.61μmol/mL,V_(max)值为1.19μmol/(mL·min)且K_(cat)值为21.38 s^(-1)。

关键词：纤维二糖磷酸化酶重组表达大肠杆菌酶学性质生物催化

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Cu_(2)Sb decorated Cu nanowire arrays for selective electrocatalytic CO_(2)to CO conversion

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Nano Research 2021年第8期14卷 2831-2836页

作者： Shiyong Mou yonghao li Luchao Yue Jie liang Yonglan Luo Qian liu Tingshuai li Siyu Lu Abdullah M.Asiri Xiaoli Xiong Dongwei Ma Xuping Sun College of Chemistry and Materials Science Sichuan Normal UniversityChengdu 610068China Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province School of Chemistry and Chemical engineeringChina West Normal UniversityNanchong 637002China Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of ChinaChengdu 610054China Green Catalysis Center and College of ChemistryZhengzhou UniversityZhengzhou 450001China Chemistry Department Faculty of Science&Center of Excellence for Advanced Materials ResearchKing Abdulaziz UniversityP.O.Box 80203Jeddah 21589Saudi Arabia Key Laboratory for Special Functional Materials of Ministry of Education and School of Materials Science and Engineering Henan UniversityKaifeng 475004China

The advancement of cost-effective and selective electrocatalyst towards CO_(2) to CO conversion is crucial for renewable energy conversion and storage,thus to achieve carbon-neutral cycle in a sustainable *** this communication,we report that CujSb decorated Cu nanowire arrays on Cu foil act as a highly active and selective electrocatalyst for CO_(2) to CO *** CO_(2)-saturated 0.1 M KHCO_(3),it achieves a high Faraday efficiency(FE)of 86.5%for CO,at-0.90 V *** hydrogen electrode(RHE).The H_(2)/CO ratio is tunable from 0.08:1 to 5.9:1 by adjusting the *** is worth noting that HCOO-product was totally suppressed on such catalyst,compared with Sb *** improving selectivity for CO could be attributed to the bimetallic effect and nanowire arrays structure.

关键词： Cu_(2)Sb nanowire arrays electrochemical CO_(2)reduction CO_(2)to CO conversion

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