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Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity

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Signal Transduction and Targeted Therapy 2021年第3期6卷 975-987页

作者： Ke-Wu Zeng Jing-Kang wang Li-Chao wang Qiang Guo Ting-Ting Liu fu-jiang wang Na Feng Xiao-Wen Zhang Li-Xi Liao Mei-Mei Zhao Dan Liu Yong jiang Pengfei Tu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Proteomics Laboratory Medical and Healthy Analytical CenterPeking University Health Science CenterBeijing 100191China

Mitochondrial fusion/hission dynamics plays a fundamental role in neuroprotection;however,there is till a severe lack oftherapeutic targets for this biological ***,we found that the naturally derived small molecule echinacoside(ECH)signifhcantly promotes mitochondrial fusion *** selectively binds to the previously uncharacterized casein kinase 2(CK2)α'subunit(CK2a)as a direct cellular target,and genetic knockdown of CK2α'abolishes ECH-mediated mitochondrial ***,ECH allosterically regulates CK2α'conformation to recruit basic transcription factor 3(BTF 3)to form a binary ***,the CK2α'/BTF3 complex facilitatesβ-catenin nuclear translocation to activate TCF/AEF transcription factors andstimulate transcription of the mitochondrial fusion gene ***,in a mouse middle cerebral artery occlusion(MCAO)model,ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2expression in wild-type but not CK2α'^(+/-)*** together,our findings reveal,for the first time,that CK2 is essential forpromoting mitochondrial fusion in a Wnt/B-catenin-dependent manner and suggest that pharmacologically targeting CK2 is apromising therapeutic strategy for ischemic stroke.

关键词： injuries cerebral Small

Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion

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Neural Regeneration Research 2019年第5期14卷 783-793页

作者： Zuo-Yan Sun fu-jiang wang Hong Guo Lu Chen Li-Juan Chai Rui-Lin Li Li-Min Hu Hong wang Shao-Xia wang Tianjin State Key Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese Medicine Department of Pharmacy Linyi Central Hospital School of Integrative Medicine Tianjin University of Traditional Chinese Medicine Key Laboratory of Pharmacology of Traditional Chinese Medical Formula Ministry of Education Tianjin University of Traditional Chinese Medicine

Shuxuetong injection composed of leech(Hirudo nipponica Whitman) and earthworm(Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells(bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N_2/5% CO_2 for 6 hours, followed by high-glucose medium containing 95% O_2 and 5% CO_2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations(diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1β, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viab

关键词： nerve regeneration Shuxuetong injection brain microvascular endothelial cells oxygen-glucose deprivation/reperfusion tight junction proteins mitochondrial function inflammatory factors blood-brain barrier neuroprotection neural regeneration

Correction: Small molecule induces mitochondrial fusion for neuroprotection via targeting CK2 without affecting its conventional kinase activity

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1388-1389页

作者： Ke-Wu Zeng Jing-Kang wang Li-Chao wang Qiang Guo Ting-Ting Liu fu-jiang wang Na Feng Xiao-Wen Zhang Li-Xi Liao Mei-Mei Zhao Dan Liu Yong jiang Pengfei Tu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China Proteomics Laboratory Medical and Healthy Analytical Center Peking University Health Science Center Beijing 100191 China

In the process of collating the published data,the editors noticed one inadvertent mistake occurred during the production process in Fig.6 that needs to be corrected.1 The correct data are provided as *** key findings... 详细信息

关键词： correction Small finding

Protection of Salvianolate Lyophilized Injection combined with Xueshuantong Injection (Lyophilized) against focal cerebral ischemia/reperfusion injury in rats through suppression of inflammatory response

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Chinese Herbal Medicines 2018年第1期10卷 46-53页

作者： fu-jiang wang zuo-yan sun rui-lin li li-min hu li-juan chai shao-xia wang hong guo yue zhang tianjin state key laboratory of modern chinese medicine tianjin university of traditional chinese medicinetianjin 300193China key laboratory of formula of traditional chinese medicine ministry of educationtianjin university of traditional chinese medicinetianjin 300193China

Objective： Inflammatory reactions induced by microglia in the brain play an important part in the pathogenesis of focal cerebral ischemia/reperfusion （I/R） injury, resulting in neuronal death. Salvianolate Lyophilized Injection （SLI） and Xueshuantong Injection （Lyophilized）（XST）, which have been widely used in the treatment of acutely cerebral infarction clinically in China, exhibit various biological activities. In this study, the neuroprotective properties of SLI combined with XST in a rat model of middle cerebral artery occlusion- reperfusion （MCAO/R） were investigated. Methods： In this study, male Wistar rats were subjected to 1.5h of middle cerebral artery occlusion followed by reperfusion for 24 h. The rats were randomly divided into the following six groups： normal group （NOR）, model group （MOD）, SLI group （21 mg/kg, SLI）, ）（ST group （100 mg/kg, ）（ST）, SLI combined with XST （XST 100 mg/kg ＋ SLI 21 mg/kg, 1X1S）, and Edaravone （as a positive control drug, 6 mL/kg, EDI）, once a day for 3 d. The neuronal injury, the expression of glial fibrillary acidic protein （GFAP） and ionized calcium binding adaptor molecule 1 （IBA-1）, and the changes of pro-inflammatory mediators interleukin- 6 （IL-6）, tumor necrosis factor alpha （TNF-α） and anti-inflammatory mediator interleukin-10 （IL-10） were observed. Results： 1X1S treatment significantly increased the number of neuron, compared with the MOD group, SH group and XST group. Gliosis （GFAP and IBA-1） and expression of pro-inflammatory mediators IL-6 and TNF-a were significantly reduced. Meanwhile, 1XIS significantly increased the expression of anti- inflammatory mediator IL-10 in the brains of MCAO/R rats, compared with the MOD group, SLI and XST groups. SLI and XST also remarkably down-regulated the expression of IL-6 and TNF-α compared with the MOD group. Conclusions： This study shows that SLI combined with XST （1X1S） can protect cerebral ischemia- reperfusion injury due to its anti-inflammatory property, and may provide

关键词： cerebral ischemia-reperfusion injury inflammatory reaction Salvianolate Lyophilized Injection Xueshuantong Injection (Lyophilized)

Staged dendrite suppression for high safe and stable lithium-sulfur batteries

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Journal of Energy Chemistry 2025年第1期100卷 674-683页

作者： Jun jiang Zhenjie Lu Yanwen Ding Shujun Liu Zhijie Qi Tian Tang Yunfan Zhang Zhiyuan Ma Jingwen Sun Liang Xue Wenyao Zhang Pan Xiong Xin wang Junwu Zhu Yongsheng fu Key Laboratory for Soft Chemistry and functional Materials of Ministry of Education Nanjing University of Science and Technology jiangsu Pylon Battery Co.Ltd

The unavoidable dendrite growth and shuttle effect have long been stranglehold challenges limiting the safety and practicality of lithium-sulfur ***,we propose a dual-action strategy to address the lithium dendrite issue in stages by constructing a multifunctional surface-negatively-charged nanodiamond layer with high ductility and robust puncture resistance on polypropylene （PP） *** uniformly loaded compact negative layer can not only significantly enhance electron transmission efficiency and promote uniform lithium deposition,but also reduce the formation of dendrite during early deposition *** importantly,under the strong puncture stress encountered during the deterioration of lithium dendrite growth under limiting current,the high ductility and robust puncture resistance（145.88 MPa） of as-obtained nanodiamond layer can effectively prevent short circuits caused by unavoidable lithium *** Li||Li symmetrical cells assembled with nanodiamond layer modified PP demonstrated a stable cycle of over 1000 h at 2 mA cm-2with a polarization voltage of only 29.3 ***,the negative charged layer serves as a physical barrier blocking lithium polysulfide ions,effectively mitigating capacity *** improved cells achieved a capacity decay of only 0.042%per cycle after 700 cycles at 3 C,demonstrating effective suppression of dendrite growth and capacity attenuation,showing promising prospect.

关键词： Lithium-sulfur batteries Staged dendrite suppression Shuttle effect Surface-negatively-charged nanodiamond

Pole Assignment Method with State Constraints for Missile Three-loop Autopilot Design

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Pole Assignment Method with State Constraints for Missile Th...

考虑损伤及非饱和效应的炭质泥岩路堤稳定性分析

2009中国控制与决策会议

作者： CHANG Chao,LIN De-fu,wang jiang School of Aerospace Science and Engineering,Beijing Institute of Technology,Beijing 100081

＜正＞The three-loop autopilot is transformed into states space model,and the feasibility of presupposition of some nuisance parameter is proved.A new pole assignment method is *** the actuator state feedback constraints,search methods are used to find the additional poles introduced by *** design results show that, with the new method,all the poles of the system can be assigned to the desired place.

关键词： three-loop autopilot pole assignment state feedback constraints

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中南大学学报（自然科学版） 2016年第10期47卷 3546-3554页

作者：曾铃邱祥付宏渊蒋中明王桂尧何忠明长沙理工大学道路结构与材料交通行业重点实验室湖南长沙410076 长沙理工大学土木与建筑学院湖南长沙410076 长沙理工大学交通运输工程学院湖南长沙410076 现代公路交通基础设施先进建养技术湖南省协同创新中心湖南长沙410004

为了分析降雨条件下炭质泥岩路堤的稳定性,基于考虑岩土体损伤的Hoek-Brown准则,结合非饱和抗剪强度理论,提出一种考虑损伤及非饱和效应的路堤稳定性分析方法,并利用该方法对算例炭质泥岩路堤的降雨入渗过程及稳定性进行研究。研究结果... 详细信息

为了分析降雨条件下炭质泥岩路堤的稳定性,基于考虑岩土体损伤的Hoek-Brown准则,结合非饱和抗剪强度理论,提出一种考虑损伤及非饱和效应的路堤稳定性分析方法,并利用该方法对算例炭质泥岩路堤的降雨入渗过程及稳定性进行研究。研究结果表明:提出的路堤稳定性分析方法具有较强的针对性和实用性,能够同时考虑损伤及非饱和效应对路堤稳定性的影响;在降雨条件下,边坡表层孔隙水压力变化幅度、暂态饱和区形成范围均与降雨强度、降雨时间呈正比;在降雨过程中,边坡表层孔隙水压力逐渐增大,暂态饱和区自坡面向路堤内部不断延伸,路堤表层及内部塑性区沿坡面及路堤内部不断向坡顶延伸,路堤安全系数逐渐降低;降雨停止后,边坡表层孔隙水压力持续降低,暂态饱和区自上往下逐渐消散,路堤表层及内部塑性区均先增加后减小,路堤安全系数先小幅度降低,后持续增大。

关键词：损伤变量非饱和效应暂态饱和区塑性区安全系数

反式-PtHL2X配合物中Pt—H核自旋偶合常数的量子化学计算

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化学学报 1986年第12期44卷 1185-1190页

作者：张良辅丁涪江王树梅李广年中国科学院成都有机化学研究所中国科学院成都有机化学研究所成都

在计算两个核之间的自旋偶合常数时,一般只考虑两个核与各自的s价电子的Fermi接触相互作用.这种近似处理不能解释反式-PtHL2X配合物的Pt—H偶合常数.本文考虑到铂原子的6s价轨道在氢核处有较大的数值,除考虑核与各自的s价电子的Fermi接... 详细信息

在计算两个核之间的自旋偶合常数时,一般只考虑两个核与各自的s价电子的Fermi接触相互作用.这种近似处理不能解释反式-PtHL2X配合物的Pt—H偶合常数.本文考虑到铂原子的6s价轨道在氢核处有较大的数值,除考虑核与各自的s价电子的Fermi接触相互作用之外,引入铂的6s价电子与氢核的Fermi接触相互作用,称为Fermi交换接触相互作用.在有限微扰理论和EHMO近似下,计算了上述配合物的铂氢偶合常数,得到与实验值一致的结果.

关键词：配合物 PtHL2X 核自旋偶合常数铂原子极化度微扰理论反式几何构型

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基于轮式小车的焊缝视觉信息的获取与跟踪

上海交通大学学报 2010年第S1期44卷 8-10页

作者：马国红秦佳姜芙蓉汪鎏南昌大学机电工程学院南昌330031

针对铝合金自动焊接,采用基于视觉的方式,探讨了适合双目视觉传感器的焊缝图像处理与跟踪方法;搭建了基于轮式行走小车的焊缝跟踪与控制平台,开发出一套切合系统的软件跟踪控制策略与软件平台;提出机器指令生成方法,开展基于铝合金对接... 详细信息

针对铝合金自动焊接,采用基于视觉的方式,探讨了适合双目视觉传感器的焊缝图像处理与跟踪方法;搭建了基于轮式行走小车的焊缝跟踪与控制平台,开发出一套切合系统的软件跟踪控制策略与软件平台;提出机器指令生成方法,开展基于铝合金对接焊缝非起弧跟踪实验.实验结果表明:跟踪效果良好,能够达到焊枪预期的位置和姿态,为后期小车系统起弧焊接与控制奠定了基础.

关键词：图像处理焊缝跟踪双目视觉