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Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： xintian Ding chun Chen Heng zhao Bin Dai Lei Ye Tao Song Shuai Huang Jia Wang Tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2

The cGAS-STIng-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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Neural Regeneration Research 2025年第8期20卷 2361-2372页

作者： Shengyang Zhou Ting Li Wei Zhang Jian Wu Hui Hong Wei Quan xinyu Qiao chun Cui Chenmeng Qiao Weijiang zhao Yanqin Shen Laboratory of Neurodegenerative and Neuroinjury Diseases Wuxi Medicine SchoolJiangnan UniversityWuxiJiangsu ProvinceChina

Interferon regulatory factor 7 plays a crucial role in the innate immune ***,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains *** we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial *** the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 *** addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and *** together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关键词： cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease neuroinflammation Parkinson’s disease RU521 STIng type I interferon

Shear Fracture of Advanced High Strength Steels

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Journal of Iron and Steel Research International 2014年第10期21卷 938-944页

作者： Sheng HUAng Yi-xi zhao chun-feng HE State Key Laboratory of Mechanical System and Vibration Shanghai Jiao Tong University Shanghai Key Laboratory of Digital Manufacture for Thin-walled Structures Shanghai Jiao Tong University

Failure experiments were carried out through a stretch-bending test system for advanced high strength steels, i.e. dual-phase （DP） steels and martensitic steels （MS）. The die radius in this system was designed from 1 to 15 mm to investigate the failure mode under different geometries. Two failure modes were observed during the ex- periments. As a result, critical relative radii （the ratio of inner bending radius R to sheet thickness t） for DP590 and DP780 steels were obtained. The stretch-bending tests of DP980 display some trends unlike DP590 and DP780 steels, and curve of DP980 in different thicknesses does not coincide well. High blank holder force exhibits more possibility of shear fracture tendency than low blank holder force. The unique character of high strength martensitic steel （1500MS） is that no shear fracture is found especially over small bending radius （R =2 mm） under the same experi- mental conditions. Microstructure analysis indicates that there are obviously elongated grains on shear fracture sur- face. It shows smaller diameter and shallower depth of the dimples than the necking failure.

关键词： advanced high strength steel shear fracture critical R/t blank holder force microstructure

Analysis and optimization of thermal management system for cylindrical power battery based on distributed liquid cooling plates

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Science China Technological Sciences 2024年第12期67卷 3695-3706页

作者： zhao Yang ZHAng Tao WAng chun TAng YinBo xi Huan National Innovation Platform (Center) for Industry-Education Integration of Energy Storage Technology Xi'an Jiaotong University Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education School of Energy and Power Engineering Xi'an Jiaotong University School of Future Technology Xi'an Jiaotong University Ningbo Deye Energy Storage Technology Co. Ltd.

To ensure the battery works in a suitable temperature range, a new design for distributed liquid cooling plate is proposed, and a battery thermal management system(BTMS) for cylindrical power battery pack based on the proposed cooling plate is also investigated. To verify the accuracy of the battery model and battery pack numerical calculation model used for simulation, an experiment is conducted for the liquid cooling BTMS. The influence of key working parameters, including the cooling water inlet flow, ambient temperature and working conditions, are investigated. The results show that at the discharge rate of 3 C, the best cooling performance can be achieved when the total inlet mass flow rate is 3.2 g/s and the flow distribution is 3:1:1:3. The obtained maximum temperature is 29.6°C and the maximum temperature difference is 2.1°C. When the ambient temperature is in the range of 20°C to 50°C, the proposed BTMS can keep the temperature of battery pack in the proper range. Finally, different inlet flow rates are recommended according to different battery working states.

关键词： lithium battery battery model battery thermal management liquid cooling plate distributed cooling

Stage identification and process optimization for fast drilling EDM of film cooling holes using KBSI method

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Advances in Manufacturing 2023年第3期11卷 477-491页

作者： Jian Wang Xue-Cheng xi Ya-Ou Zhang Fu-chun zhao Wan-Sheng zhao State Key Laboratory of Mechanical System and Vibration Shanghai 200240People's Republic of China School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai 200240People's Republic of China

Fast drilling electrical discharge machining(EDM)is widely used in the manufacture of film cooling holes of turbine ***,due to the various hole orientations and severe electrode wear,it is relatively intricate to accurately and timely identify the critical moments such as breakout,hole completion in the drilling process,and adjust the machining strategy *** breakout detection and hole completion determination methods are not suitable for the high-efficiency and fully automatic production of film cooling holes,for they almost all depend on preset thresholds or training data and become less appropriate when machining condition *** the breakout and hole completion detection problems can be abstracted to an online stage identification problem,in this paper,a kurtosis-based stage identification(KBSI)method,which uses a novel normalized kurtosis to denote the recent changing trends of gap voltage signals,is developed for online stage *** identification accuracy and generalization ability of the KBSI method have been verified in various machining *** improve the overall machining efficiency,the influence of servo control parameters on machining efficiency of each machining stage was analyzed experimentally,and a new stage-wise adaptive control strategy was then proposed to dynamically adjust the servo control parameters according to the online identification *** performance of the new strategy is evaluated by drilling film cooling holes at different hole *** results show that with the new control strategy,machining efficiency and the machining quality can be significantly improved.

关键词： Fast drilling electrical discharge machining(EDM) Film cooling holes Breakout detection Hole completion determination Stage identification Process optimization

Stability of passive film and antibacterial durability of Cu-bearing L605 alloy in simulated physiological solutions

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Rare Metals 2021年第5期40卷 1126-1133页

作者： Peng-Fei Geng Jin-Long zhao Tong xi chun-Guang Yang Ke Yang School of Nano Science and Technology Institute University of Science and Technology of ChinaSuzhou 215300China Institute of Metal Research Chinese Academy of SciencesShenyang 110016China

In this work,the stability of passive film for long-time immersed Cu-bearing L605(L605-Cu) alloy in the phosphate buffer solution(PBS) was studied by potentiodynamic polarization and electrochemical impedance *** results showed that the impedance of passive film for L605-Cu alloy experienced an initial increase and subsequent stabilization with the increase in the immersion *** addition,the plate count method was employed to assess the antibacterial durability of L605-Cu alloy against Escherichia coli after long-time *** results indicated that the antibacterial rate of L605-Cu alloy presented a declining tendency with the immersion time prolonging.X-ray photoelectron spectroscopy(XPS) was used to analyze the change of the chemical composition in the passive film on L605-Cu alloy immersed in the PBS for different *** results showed that Cu content and its compounds in the passive film gradually increased with the immersion time prolonging,hinting declined activity of Cu ions penetrating into the passive film,which resulted in a decrease in the antibacterial performance.

关键词： L605-Cu alloy Passive film Antibacterial rate Implant

Scheduling piece requests blindly and randomly for peer-to-peer live streaming

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The Journal of China Universities of Posts and Telecommunications 2010年第2期17卷 76-84页

作者： CHEN Yi-shuai CHEN Chang-jia zhao Yong-xiang LI chun-xi School of Electrical and Information Engineering Beijing Jiaotong University Beijing 100044 China

The design of piece scheduling algorithm is fundamental in mesh-based peer-to-peer （P2P） live streaming systems. This article regards the piece propagation process in P2P live streaming system as a conflict process, where peers compete to get the piece as soon as possible to meet the tight timing requirement of the live system. In this vision, the authors reduce the piece scheduling problem as a conflict resolution problem, and propose a blind random scheduling method to resolve it. The algorithm can be described as： 1） pieces are scheduled independently; 2） conflicts are resolved by the random back off algorithm. The theoretical analysis and simulation results prove that the algorithm scales well with the network size, and can obtain near-optimal in-time delivery of pieces. The algorithm is also easy to implement in the real-world system.

关键词： peer-to-peer live streaming conflict resolution exponential back off piece scheduling

Syntheses, Crystal Structures and Catalytic Activities of Two Novel Mn_2Dy_2O_2 Complexes

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Chinese Journal of Structural Chemistry 2019年第1期38卷 109-116,4页

作者： zhao Guo-Qing LI Yan-xi CHEN Chang-Hui ZHAng chun-xi Laboratory of Photochemistry Institute of ChemistryChinese Academy of Sciences University of Chinese Academy of Sciences

Two novel heteronuclear manganese-dysprosium complexes have been synthesized and characterized, both of which contain a [Mn_2Dy_2O_2] core ligated by eight But CO_2-anions and four neutral ligands. In complex 1, [Mn_2Dy_2O_2(Bu^tCO_2)_8(Bu^tCO_2H)_4], all the four neutral ligands coordinated to Dy^(3+) are pivalic acids; Instead, two of these four pivalic acids have been replaced by ethanol in complex 2 [Mn2 Dy2 O2(Bu^tCO_2)_8(Bu^tCO_2H)_2(CH_3CH_2OH)_2]. The crystal of complex 1(C_(60)H_(112)Dy_2Mn_2O_(26), Mr = 1684.36) belongs to the orthorhombic system, space group Pbca with a =19.853(3), b = 18.565(3), c = 20.952(3) ?, V = 7723(2) ?3, Z = 4, Dc = 1.449 g/cm^3, S = 1.210, μ =2.302 mm^(-1), F(000) = 3448, the final R = 0.0802 and w R = 0.1570 for 8736 independent *** crystal of complex 2(C_(54)H_(104)Dy_2Mn_2O_(24), Mr = 1572.25) belongs to the monoclinic system,space group C2/c with a = 27.814(6), b = 13.194(3), c = 22.912(5) ?, β = 124.89(3)o, V = 6897(3) ?3,Z = 4, Dc = 1.514 g/cm^3, S = 1.086, μ = 2.570 mm^(-1), F(000) = 3208, the final R = 0.0256 and wR =0.0592 for 7763 independent reflections. The cyclic voltammogram and catalytic activity measurements of complex 1 suggest that this type of complex can serve as a catalyst for oxygen-evolving reaction.

关键词： manganese-dysprosium cluster crystal structure catalytic activity

π-conjugated chromophore functionalized high-nuclearity titanium-oxo clusters containing structural unit of anatase for photocatalytic selective oxidation of sulfides

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Rare Metals 2024年第4期43卷 1736-1746页

作者： Ling-Rong Liao Dong-chun Zheng Pin-xi Ou Qi-xin zhao Wei-Min Xuan Qi Zheng State Key Laboratory for Modification of Chemical Fibers and Polymer Materials&College of Materials Science and Engineering Donghua UniversityShanghai201620China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials and College of Chemistry and Chemical Engineering Donghua UniversityShanghai 201620China

N-doping has significant influence in manipulating the properties of TiO_(2),and this has stimulated the development of N-donor-functionalized titanium-oxo clusters(TOCs)as molecular models to study the structure-property ***,the structural type and photoresponsive application are still limited for such TOCs,especially regarding the high-nuclearity TOCs that contain structure unit of TiO_(2)for ***,we showed the synthesis of a series of high-nuclearity TOCs 1-3 compounds usingπ-conjugated 1,10-phenanthroline(phen)as chromophore and N-donor functional *** 1 features cocrystal structure composed of one[Ti_(26)]~(2+)and half[Ti_(22)]~(2+),which renders it as the first cocrystallized TOC containing two positively charged species and phen-functionalized TOC showing the highest nuclearity up to 37 Ti *** adjusting the synthetic conditions,the individual{Ti_(22)}and{Ti_(26)}clusters can also be isolated as Compounds 2 and 3,*** core structure of{Ti_(22)}is mainly constructed from four lacunary{Ti_(4)}derived from pentagonal{Ti(Ti)_5}unit,while{Ti_(26)}is built from four complete{Ti(Ti)_5}***,a{Ti_8O_(14)}structure unit of anatase TiO_(2)can be identified in{Ti_(26)}.Based on the unique structural features and proper photophysical and photochemical properties of Compounds 1-3,they are applied for photocatalytic *** to the presence of anatase structure unit in{Ti_(26)}and the synergistic effect from{Ti_(22)}and{Ti_(26)},the catalytic performance presents in the order of Compound 1>Compound 3>Compound *** work provides excellent models to understand the structureproperty relationship from the perspective of cocrystallization and Ti-O binding model and will further promote the application of TOCs as functional catalysts for organic transformation.

关键词： Titanium-oxo cluster Molecular model of anatase TiO_(2) High nuclearity π-conjugated chromophore Photocatalytic sulfoxidation