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Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats

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Acta Pharmaceutica Sinica B 2021年第7期11卷 1835-1852页

作者： Chenchen Han Yifan Li Yuwen Zhang Yang Wang Dongqian Cui Tingting luo Yu Zhang Qian Liu hao Li Chun Wang Dexiang Xu Yang Ma wei wei Institute of Clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune Medicine(Anhui Medical University)Ministry of EducationAnhui Collaborative Innovation Center of Antiinflammatory and Immune MedicineHefei 230032China Public Health and Preventive Medicine Postdoctoral Research Station of Anhui Medical University Hefei 230032China

Rheumatoid arthritis(RA)is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes(FLS).The up-regulated cellular membrane expression of G protein coupled receptor kinase 2(GRK2)of FLS plays a critical role in RA progression,the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor(EP4)signaling and FLS abnormal ***,although our group found that paeoniflorin-6’-O-benzene sulfonate(CP-25),a novel compound,could reverse FLS dysfunction via GRK2,little is known as to how GRK2 translocation activity is *** findings revealed that GRK2 expression up-regulated and EP4 expression down-regulated in synovial tissues of RA patients and collagen-induced arthritis(CIA)rats,and prostaglandin E2(PGE2)level increased in ***-25 could down-regulate GRK2 expression,up-regulate EP4 expression,and improve synovitis of CIA ***-25 and GRK2 inhibitors(paroxetine or GSK180736 A)inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 *** results of microscale thermophoresis(MST),cellular thermal shift assay,and inhibition of kinase activity assay indicated that CP-25 could directly target GRK2,increase the protein stability of GRK2 in cells,and inhibit GRK2 kinase *** docking of CP-25 and GRK2 suggested that the kinase domain of GRK2 might be an important active pocket for CP-25.G201,K220,K230,A321,and D335 in kinase domain of GRK2 might form hydrogen bonds with ***-directed mutagenesis and co-immunoprecipitation assay further revealed that CP-25 down-regulated the interaction of GRK2 and EP4 via controlling the key amino acid residue of Ala321 of *** data demonstrate that FLS proliferation is regulated by GRK2 translocation to *** inhibition of GRK2 kinase domain by CP-25 improves FLS function and represents an innovative drug for the treatment of RA by targeting G

关键词： CP-25 Rheumatoid arthritis Fibroblast-like synoviocyte MH7A G protein coupled receptor kinase 2 Prostaglandin E4 receptor

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In situ atomic-scale observation of dislocation behaviors in twin-structured Pt nanocrystals

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Science China(Technological Sciences) 2021年第3期64卷 599-604页

作者： GUO YiZhong SUN Tao FU LiBo hao LongHu HUANG Ming wei RuJian luo JunFeng HE Xin WANG XingQuan XIONG XiaoDong WANG LiHua HAN XiaoDong Beijing Key Lab of Microstructure and Property of Advanced Materials Institute of Microstructure and Properties of Advanced MaterialsBeijing University of TechnologyBeijing 100124China Grikin Advanced Materials CO. LTD.Beijing 102200China

The deformation mechanisms of twin-structured metallic materials have attracted great *** previous theoretical predictions have suggested that the repulsive force of the twin boundary(TB)can significantly affect the deformation of twinstructured metals,it remains unclear whether this prediction applies to experimental *** this paper,the atomic-scaled deformation process of twin-structured Pt nanocrystals was in situ observed using our home-made device in a high-resolution transmission electron *** have shown that the plastic deformation of the twin-structured Pt nanocrystals was governed by full dislocation generation as well as Lomer dislocation(LD)lock formation and *** LD locks were destructed,these full dislocations tended to move towards the surface of the *** findings revealed that due to the ultra-high repulsive force of TB on dislocation,there was no dislocation-TB reaction during the *** findings can enrich our understanding of the dislocation behaviors of twin-structured nanocrystals.

关键词： deformation mechanism repulsive force twin boundary dislocations in situ

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Insight into microstructure evolution on anti-corrosion property of Al_(x)CoCrFeNiC_(0.01) high-entropy alloys using scanning vibration electrode technique

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Rare Metals 2023年第10期42卷 3455-3467页

作者： Bo-Kai Liao Zhan-Xiang Liang Zhi-Gang luo Yue Liu hao-wei Deng Tao Zhang Xing-Peng Guo Qi-Sen Ren Hong-En Ge School of Chemistry and Chemical Engineering Guangzhou UniversityGuangzhou510006China School of Physics and Materials Science Center of Advanced Functional MaterialsGuangzhou UniversityGuangzhou510006China Joint Institute of Guangzhou University and Institute of Corrosion Science and Technology Guangzhou UniversityGuangzhou510006China Science and Technology Digitization Department China General Nuclear Power CorporationShenzhen518038China Institute of Nuclear Fuel and Materials China Nuclear Power Technology Research InstituteShenzhen518031China Hubei Key Laboratory of Material Chemistry and Service Failure School of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan430074China

The effect of micro structure on the corrosion resistance of Al_(x)CoCrFeNiC_(0.01)(x=0.2,0.7,and 1.2)high-entropy alloys(HEAs) was systematically studied in this *** microstructure evolution by regulating the Al content was analyzed in *** behavior was in situ monitored using the scanning vibration electrode technique,as well as some traditional electrochemical *** is interesting to find that the compositions of body-centered cubic(bcc) and face-centered cubic(fcc)phases changed with the rising Al content,while the corresponding electrochemical responses for both phases were discriminated using the scanning Kelvin probe force microscopy *** element was mainly distributed in the bcc phase for Al0.2(x=0.2) alloy,while its distribution changed to the fcc phase for the A10.7 and *** micro-galvanic corrosion cells formed between Cr-depleted and Cr-rich phases,resulting in the localized corrosion behaviors for the Al_(x)CoCrFeNiC_(0.01) HEAs,and the order for anti-corrosion property was Al0.2>Al1.2> Al0.7 HEAs.

关键词： High-entropy alloy Corrosion Mechanical property Scanning vibration electrode technique

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A 3D Geological Model Constrained by Gravity and Magnetic Inversion and its Exploration Implications for the World-class Zhuxi Tungsten Deposit, South China

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Acta Geologica Sinica(English Edition) 2020年第6期94卷 1940-1959页

作者： YAN Jiayong LÜ Qingtian QI Guang FU Guangming ZHANG Kun LAN Xueyi GUO Xin wei Jin luo Fan WANG hao WANG Xu Chinese Academy of Geological Sciences Beijing 100037China China Deep Exploration Center China Geological Survey&Chinese Academy of Geological SciencesBeijing 100037China School of Geophysics and Measurement-control Technology East China University of TechnologyNanchang 330013China Geological Exploration Technology Institute of Anhui Province Hefei 230031China No.912 Geological Surveying Team of Jiangxi Bureau of Geology and Mineral Exploration and Development YingtanJiangxi 335001China

The Zhuxi tungsten deposit in Jiangxi Province,South China,contains a total W reserve of about 2.86 Mt at an average grade of 0.54 wt%WO3,representing the largest W deposit in the *** studies on the metallogeny of the deposit have included its timing,the ore-controlling structures and sedimentary host rocks and their implications for mineral ***,the deep nappe structural style of Taqian-Fuchun metallogenic belt that hosts the W deposit,and the spatial shape and scale of deeply concealed intrusions and their sedimentary host rocks are still poorly defined,which seriously restricts the discovery of new deposits at depth and in surrounding areas of the W *** 3 D geological modeling is an important tool for the exploration of concealed orebodies,especially in brownfield *** are obvious density contrast and weak magnetic contrast in the ore-controlling strata and granite at the periphery of the deposit,which lays a physical foundation for solving the 3 D spatial problems of the ore-controlling geological body in the deep part of the study area through gravity and magnetic *** data(1:50000)and aeromagnetic data(1:50000)from the latest geophysical surveys of 2016-2018 have been used,firstly,to carry out a potential field separation to obtain residual anomalies for gravity and magnetic interactive ***,on the basis of the analysis of the relationship between physical properties and lithology,under the constraints of surface geology and borehole data,human-computer interactive gravity and magnetic inversion for 18 cross-sections were ***,the 3 D geological model of the Zhuxi tungsten deposit and its periphery have been established through these 18 sections,and the spatial shape of the intrusions and strata with a depth of 5 km underground were obtained,initially realizing―transparency‖for ore-controlling *** the analysis of the geophysical,geochemical,and geological charact

关键词： 3D geological modelling gravity and magnetic data interactive inversion tungsten exploration of concealed W mineralization Taqian-Fuchun metallogenic belt Jiangxi province

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Rational design ternary platinum based electrocatalysts for effective methanol oxidation reaction

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Journal of Energy Chemistry 2022年第7期31卷 230-235,I0007页

作者： hao Tian Daoxiong Wu Jing Li Junming luo Chunman Jia Zhongxin Liu wei Huang Qi Chen Chong Michael Shim Peilin Deng Yijun Shen Xinlong Tian State Key Laboratory of Marine Resource Utilization in South China Sea Hainan Provincial Key Lab of Fine ChemistrySchool of Chemical Engineering and TechnologyHainan UniversityHaikou 570228HainanChina

Exploring effective, durable, and affordable electrocatalysts of methanol oxidation reaction(MOR) is of vital significance for the industrial application of direct methanol fuel cells. Herein, an efficient, general,and expandable method is developed to synthesis two-dimensional(2D) ternary Pt Bi M nanoplates(NPLs), in which various M(Co, Ni, Cu, Zn, Sn) is severed as the third component to the binary Pt Bi system. The MOR performance of Pt Bi M NPLs is entirely investigated, demonstrating that both the MOR activity and durability is enhanced with the introduction of the additional composition. Pt3Bi3Zn NPLs shows much higher MOR activity and stability than that of the Pt Bi counterparts, not to mention the current advanced Pt Ru/C and Pt/C catalysts. The prominent performances are attributed to the modulated electronic structure of the surface Pt in Pt Bi NPLs by the addition of Zn, resulting in a weakened affination between Pt and the adsorbed poisoning species(mainly CO) compared with Pt Bi NPLs, verified by density functional theory(DFT) calculations. In addition, the absorbed OH can be generated on the surface of Zn atom due to its favorable water activation properties, thus the CO removal on the adjacent Pt atoms is accelerated, further leading to a high activity and anti-poisoning performance of the resulting Pt_(3)Bi_(3)Zn catalyst. This work provides new insights and robust strategy for highly efficient MOR electrocatalyst with extraordinary anti-poisoning performance and stability.

关键词： Fuel cells Ternary nanoplates Durability Methanol oxidation reaction Anti-poisoning

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Antagonism of Protease-Activated Receptor 4 Protects Against Traumatic Brain Injury by Suppressing Neuroinflammation via Inhibition of Tab2/NF-κB Signaling

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Neuroscience Bulletin 2021年第2期37卷 242-254页

作者： Jianing luo Xun Wu Haixiao Liu Wenxing Cui wei Guo Kang Guo hao Guo Kai Tao Fei Li Yingwu Shi Dayun Feng hao Yan Guodong Gao Yan Qu Department of Neurosurgery Tangdu HospitalThe Fourth Military Medical UniversityXi’an 710038China Department of Operative Dentistry and Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’an 710038China

Traumatic brain injury(TBI)triggers the activation of the endogenous coagulation mechanism,and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors,also known as protease-activated receptors(PARs).However,thrombin is one of the most critical factors in secondary brain ***,the PARs may be effective targets against hemorrhagic brain *** the PAR1 antagonist has an increased bleeding risk in clinical practice,PAR4 blockade has been suggested as a more promising ***,we explored the expression pattern of PAR4 in the brain of mice after TBI,and explored the effect and possible mechanism of BMS-986120(BMS),a novel selective and reversible PAR4 antagonist on secondary brain *** with BMS protected against TBI in ***-seq analysis,Western blot,and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes,and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this *** findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI,and suggest that BMS has a potential clinical application in the management of TBI.

关键词： Protease-activated receptors BMS Traumatic brain injury Inflammation Astrocyte Tab2

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Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells

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Protein & Cell 2016年第5期7卷 351-361页

作者： Jie Gao Yue Ma Hua-Lin Fu Qian luo ZhenWang Yu-Huan Xiao hao Yang Da-Xiang Cui wei-Lin Jin School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China institute of Nano Biomedicine and Engineering Department of Instrument Science and Engineering School of Electronic Information and Electronic Engineering Shanghai Jiao Tong University Shanghai 200240 China National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China Department of Experimental Surgery Tangdu Hospital Fourth Military Medical University Xi'an 710038 China Clinical Stem Cell Research Center Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China

The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.

关键词： methylcytosine dioxygenase TET1,srGAP3 neuronal differentiation neuroblastoma cells

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Regulating the radical intermediates by conjugated units in covalent organic frameworks for optimized lithium ion storage

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Journal of Energy Chemistry 2022年第6期31卷 428-433,I0012页

作者： Shuai Gu Xiaoxia Ma Jingjing Chen Rui hao Zhiqiang Wang Ning Qin wei Zheng Qingmeng Gan Wen luo Muqing Li Zhiqiang Li Kemeng Liao hao Guo Guiyu Liu Kaili Zhang Zhouguang Lu Department of Materials Science and Engineering Shenzhen Key Laboratory of Interfacial Science and Engineering of MaterialsGuangdong-Hong Kong-Macao Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and DevicesSouthern University of Science and TechnologyShenzhen 518055GuangdongChina Department of Mechanical Engineering City University of Hong KongKowloonHong Kong 999077China

Organic active units often transform into radical intermediates during the redox processes but exhibit poor cycling stability due to the uncontrollable redox of the radicals. Herein, we report a facile and efficient strategy to modulate the molecular orbital energies, charge transport capacities, and spin electron densities of the active units in covalent organic frameworks(COFs) via regulating the conjugated unit size to optimize the redox activity and stability of the organic radicals. COFs based on different imide conjugated units exhibit tunable discharge voltages, rate performance and cycling stabilities. Detailed characterizations and theoretical calculation reveal that imide radicals are the important active intermediates during the redox processes of these COFs. Specifically, increasing the size of the imide conjugated units could effectively delocalize the radical electrons and improve the stability of the COFs electrodes. This study offers a very effective strategy to modulate the redox chemistry of organic materials for electrochemical energy storage.

关键词： Organic electrodes Radical intermediates Covalent organic frameworks

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考虑电力-信息-交通网络耦合的配电网韧性提升策略分析

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电网技术 2024年第1期48卷 361-372页

作者：张巍罗浩上海理工大学机械工程学院上海市杨浦区200093

韧性是评估系统在极端灾害下吸收抵御扰动并恢复至正常状态的能力指标。基于电力-信息-交通网络之间紧密耦合的特性,提出考虑多网络耦合特性的多阶段配电网韧性提升策略。首先,在灾前预防阶段提出考虑网络抗毁性与电力信息风险价值的最... 详细信息

韧性是评估系统在极端灾害下吸收抵御扰动并恢复至正常状态的能力指标。基于电力-信息-交通网络之间紧密耦合的特性,提出考虑多网络耦合特性的多阶段配电网韧性提升策略。首先,在灾前预防阶段提出考虑网络抗毁性与电力信息风险价值的最优线路加固策略,并对应急中心进行优化布点。其次,基于网络损毁导致的拓扑变化对分布式电源与联络开关进行动态联合调控,最小化灾害抵御阶段的负荷损失价值。然后,结合耦合网络间的关联制约属性,提出灾后阶段多网协同恢复策略。最后,建立组合式评估框架对系统韧性进行多时段精细化分析。基于IEEE33节点系统搭建三网耦合系统算例进行仿真,所得结果表明所提策略可有效提高灾害下系统的抵御力并提升恢复效率。

关键词：韧性多网络耦合线路加固联合调控协同恢复组合式评估

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Tailoring the microstructural characteristics and enhancing creep properties of as-cast Mg-5Bi-5Sn alloy through Mn addition

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Journal of Magnesium and Alloys 2023年第9期11卷 3350-3361页

作者： Yi-hao luo wei-li Cheng Hui Yu Hong-xia Wang Xiao-feng Niu Li-fei Wang Hang Li Zhi-yong You Hua Hou School of Materials Science and Engineering Taiyuan University of TechnologyTaiyuan 030024China Key Laboratory of Interface Science and Engineering in Advanced Materials Ministry of Education Taiyuan University of TechnologyTaiyuan 030024China School of Materials Science and Engineering Hebei University of TechnologyTianjin 300132China School of Materials Science and Engineering North University of ChinaTaiyuan 030051China

The creep properties, microstructural characteristics and creep mechanisms of as-cast Mg-5Bi-5Sn(BT55) alloy without and with Mn(BTM550) addition were investigated via creep at 423, 448, and 473 K as well as stresses of 30, 50 and 75 MPa. The results indicate that adding Mn can result in the formation of primary and the dynamic precipitated α-Mn phases. In addition, the morphology of the precipitated Mg_(3)Bi_(2) phase and the orientation relationship between Mg_(2)Sn precipitates and α-Mg can be effectively modified. Tailoring the microstructural characteristics is responsible for the improved creep performance of BTM550 alloy. The dominant creep mechanisms in BT55 and BTM550 alloys are dislocation cross-slip and climb, respectively. Furthermore, twinning and pyramidal slip play an assisting part in both alloys during creep process.

关键词： Mg alloy Microstructural characteristics Creep properties Precipitates Dislocation

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