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Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： Ke-Gang Linghu Tian Zhang guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang hua Yu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target Keap1/Nrf2 Alkylation Ubiquitination

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Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics

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Journal of Integrative Medicine 2024年第5期22卷 588-599页

作者： Wei-wei Jia hua-wei Lin Min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao Sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of Rehabilitation Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina The Institute of Rehabilitation Industry Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina

Objective Studies have shown that electroacupuncture(EA)can alleviate cognitive impairments from Alzheimer’s disease(AD)by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK),but the specific mechanism involved remains to be ***,this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial *** The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKα1-subunit conditional knockout(AMPKα1-cKO)were used for *** evaluate the effects of EA treatment on cognitive function,the T-maze and Morris water maze were *** addition,chemical exchange saturation transfer,thioflavin staining,transmission electron microscopy,mitochondrial membrane potential,and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 *** Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory *** of the AMPK/peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)pathway increased pathological amyloid-β(Aβ)deposition and aggravated the dysfunction in mitochondrial *** addition,EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1αpathway,specifically by reducing pathological Aβdeposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission ***,the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 *** The regulation of hippocampal mitochondrial dynamics and reduction in Aβdeposition via the AMPK/PGC-1αpathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

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网球训练机器人发球动作轨迹线形控制方法

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机械设计与制造 2024年第10期 309-314页

作者：郅光华桂林电子科技大学(北海分校)基础教学部广西北海536000

为了准确控制网球训练机器人的击球轨迹和移动路线,帮助运动员培养对不同球的应对能力和适应性,提出网球训练机器人发球动作轨迹线形控制方法。采用计算机三维视觉采集方法对网球训练机器人发球动作轨迹图像展开采集,利用对比度自适应... 详细信息

为了准确控制网球训练机器人的击球轨迹和移动路线,帮助运动员培养对不同球的应对能力和适应性,提出网球训练机器人发球动作轨迹线形控制方法。采用计算机三维视觉采集方法对网球训练机器人发球动作轨迹图像展开采集,利用对比度自适应直方图均衡化(Contrast Limited Adaptive Hisogram Equalization,CLAHE)算法对采集到的网球训练机器人发球动作轨迹的图像展开增强处理,以提高图像质量和轨迹的准确性。采用模板树结构管理储存多个网球训练机器人发球动作轨迹,通过使用卷积神经网络(Convolutional Neural Networks,CNN)获得关于轨迹线形的估计值。为了提高精度和稳定性,采用所有CNN估计值的加权平均值来优化更新输出,以获得最终的控制结果。实验结果表明:所提方法具有良好的图像增强效果,且动作轨迹控制精度和效率高,适用于网球训练机器人发球动作轨迹线形控制。

关键词：网球训练机器人发球动作轨迹轨迹线形控制 CLAHE算法模板树计算机三维视觉

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Numerical modeling and simulation of PEM fuel cells: Progress and perspective

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Acta Mechanica Sinica 2013年第3期29卷 318-334页

作者： guang-hua Song hua meng School of Aeronautics and Astronautics Zhejiang University

This paper provides a comprehensive review on the research and development in multi-scale numerical modeling and simulation of PEM fuel cells. An overview of recent progress in PEM fuel cell modeling has been provided. Fundamental transport phenomena in PEM fuel cells and the corresponding mathematical formulation of macroscale models are analyzed. Various important issues in PEM fuel cell modeling and simulation are examined in detail, including fluid flow and species transport, electron and proton transport, heat transfer and thermal management, liquid water transport and water management, transient response behaviors, and cold-start processes. Key areas for further improvements have also been discussed.

关键词： PEM fuel cell · Numerical modeling · Multiscale simulation · Two-phase transport · Water management · Thermal management

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Regeneration of photovoltaic industry silicon waste toward high-performance lithium-ion battery anode

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Rare Metals 2024年第10期43卷 4948-4960页

作者： Kai Wang Xiao-Bin Zhong Yue-Xian Song Yao-Hui Zhang Yan-Gang Zhang Xiao-Gang You Pu-guang Ji Kurbanov Mirtemir Shodievich Umedjon Khalilov Gong-Kai Wang Xin Zhang Xing-Liang Yao Feng Li Jun-Fei Liang hua Wang School of Energy and Power Engineering North University of China Zhongyuan Critical Metals Laboratory Zhengzhou University Tianjin Key Laboratory of Materials Laminating Fabrication and Interface Control Technology School of Material Science and EngineeringHebei University of Technology Arifov Institute of Ion-Plasma and Laser Technologies Academy of Sciences of the Republic of Uzbekistan New Uzbekistan University Arifov Institute of Ion-Plasma and Laser Technologies Academy of Sciences of Uzbekistan University of Antwerp School of Chemistry Beihang University

The diamond-wire sawing silicon waste（DWSSW） from the photovoltaic industry has been widely considered as a low-cost raw material for lithium-ion battery silicon-based electrode,but the effect mechanism of impurities presents in DWSSW on lithium storage performance is still not well understood;meanwhile,it is urgent to develop a strategy for changing DWSSW particles into high-performance electrode *** this work,the occurrence state of impurities presents in DWSSW was carefully analyzed using in situ Ar ion etching technology Then,the novel Si@C@SiOx@PAl-NDC composite was designed through in situ encapsulation *** obtained Si@C@SiOx@PAl-NDC electrode shows a high first capacity of 2343.4 mAh·g-1with an initial Coulombic efficiency （ICE） of 84.4%under current density of 1.0 A·g-1,and can deliver an impressive capacity of 984.9 mAh·g-1after 200 *** numerical simulation modeling calculations,the increase in proportion of Si4+/Si0and Si3+/Si0valence states in SiOxlayer leads to a decrease in von Mises stress,which ultimately improves the cycling structural ***,the porous 2D-3D aluminum/nitrogen （Al/N） co-doped carbon layer and nanowires on SiOxlayer can provide abundant active sites for lithium storage due to its developed hierarchical pores structure,which facilitates ion transport What is more,the performance of Si@C@SiOx@PAl-NDC//LiFePO4full cell shows its great potential in practical application.

关键词： Aluminum/nitrogen co-doped In situ encapsulation Lithium-ion batteries Porous carbon nanowires Sawing silicon waste

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Progress and prospect of mid-deep geothermal reinjection technology

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Journal of Groundwater Science and Engineering 2024年第3期12卷 321-338页

作者： Jing Hu Yan-guang Liu Xin Wang Ying-nan Zhang Mei-hua Wei Jiangsu Universiy of Science and Technology Zhenjiang 212100JiangsuChina Institule of Hydrogeology and Environmental Geology Chinese Academy of Geological SciencesXiamen 3651021Fujian ProvinceChina School of Earth science and Engineering Hebei University of EngineeringHandan 056009Hebei ProvinceChina Technology Innovation Center for Geothermal&Hot Dry Rock Exploration and Development Ministry of Natural ResourcesShijiazhuang 050061China Shanxit Key Laboratory for Exploration and Exploitation of Geothermal Resources Taiyuan 030024China.

Mid-deep geothermal reinjection technology is crucial for the sustainable development of geothermal resources,which has garnered significant attention and rapid growth in recent ***,various geothermal reinjection technologies lag behind,lacking effective integration to address issues like low reinjection rates and thermal *** paper reviews the basic principles and development history of mid-deep geothermal reinjection technology,focusing on various technical methods used in the process and analyzing their applicability,advantages,and disadvantages under different geological *** highlights the unique challenges posed by deep geothermal resources,including high temperature,high pressure,high stress,chemical corrosion,and complex geological ***,it addresses challenges in equipment selection and durability,system stability and operation safety,environmental impact,and sustainable ***,the paper explores future directions for mid-deep geothermal reinjection technology,highlighting key areas for further research and potential pathways for technological *** comprehensive analysis aims to accelerate the advancement of geothermal reinjection technology,offering essential guidance for the efficient reinjection and sustainable development of geothermal resources.

关键词： Middle and deep geothermal Geothermal reinjection Sustainable development Technological progress Research path

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The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

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Military Medical Research 2024年第3期11卷 323-344页

作者： Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-guang Wang Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research the Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000ZhejiangChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan UniversityWuhan 430071China National Engineering Research Center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina School and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325035ZhejiangChina

Background:Most bone-related injuries to grassroots troops are caused by training or accidental *** establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone ***:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)*** physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were *** and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in ***:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated *** to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 *** in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury *** underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 ***:The piezoelectric Cs/Gel/PHA/PBT hy

关键词： Piezoelectric hydrogel Tissue engineering scafold Immunomodulation Angiogenesis Osteogenic differentiation

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粗糙和光滑椭球胶体的受限扩散

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物理学报 2024年第14期73卷 268-274页

作者：梁建王华光张泽新苏州大学材料与化学化工学部苏州215123 苏州大学物理科学与技术学院软凝聚态物理及交叉研究中心苏州215006 苏州大学高等研究院苏州215006

复杂受限环境中的扩散研究在凝聚态物理领域中备受关注.胶体体系的出现,为定量研究微观粒子的受限扩散提供了卓越的实验模型系统.当胶体粒子的形状由球形变为椭球形时,体系展现出各向异性的扩散动力学特性.近年来,研究者们发现粗糙表面... 详细信息

复杂受限环境中的扩散研究在凝聚态物理领域中备受关注.胶体体系的出现,为定量研究微观粒子的受限扩散提供了卓越的实验模型系统.当胶体粒子的形状由球形变为椭球形时,体系展现出各向异性的扩散动力学特性.近年来,研究者们发现粗糙表面能够诱发球形胶体体系异常的旋转动力学.然而,由于实验体系的局限性,粗糙表面对椭球形胶体粒子的受限扩散的影响依然知之甚少.本文建立了胶体受限扩散的模型体系,由粗糙圆球胶体构成受限环境,研究了粗糙和光滑椭球在其中的受限扩散.当圆球的堆积分数较低时,粗糙表面未发挥作用,因此光滑和粗糙椭球的平动和转动扩散相近.随着圆球堆积分数的增高,粗糙表面之间发生互锁,导致粗糙椭球的平动扩散明显慢于光滑椭球;随着堆积分数的进一步增高,由于粗糙表面产生的空间位阻效应,粗糙椭球的转动扩散也显著慢于光滑椭球.该工作表明粗糙表面会改变椭球的受限扩散,为揭示复杂环境中具有粗糙表面物质的扩散规律提供了实验依据.

关键词：胶体椭球粗糙粒子受限扩散动力学

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Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： Li-Wen Tan Jun-Li Wan Chun-hua Zhu Hong Xu Zheng-Kun Xia Li-Zhi Chen Xiao-Chuan Wu Fang Wang Xiao-Rong Liu Cheng-guang Zhao Xiao-Zhong Li Jian-hua Mao Xiao-Wen Wang Wen-Yan huang Yu-Hong Li Jian-Jiang Zhang Shi-Pin Feng Jun Yang Jiao-Jiao Liu Chun-Lin Gao Li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia Zhang Qiu Li Ai-hua Zhang Mo Wang Department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China Department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina Department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina Department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina Department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina Department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina Department of Pediatrics Peking University First HospitalBeijingChina Department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina Department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina Department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina Department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina Department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal ***,there are few studies on the risk factors and predictive models for renal outcomes of AAV in *** Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected *** risk factors and predictive model of end-stage renal disease(ESRD)in AAV were *** Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 *** eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal *** on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive *** Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external *** Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into *** predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis

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Tough Hydrogen Bonding Crosslinked Poly (3-fluorothiophene) Network via Electrosynthesis for High-performance Electrochromic Supercapacitors

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Chinese Journal of Polymer Science 2024年第11期 1749-1757页

作者： Chun-Hui Du Yu-hua Xu Hui Li Zhi-Xin Wu Han-Jun Yang Xi-Mei Liu Bao-Yang Lu guang-Ming Nie Ge Zhang Jiangxi Key Lab of Flexible Electronics Flexible Electronics Innovation InstituteJiangxi Science & Technology Normal University Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science MOEState Key Laboratory Base of Eco-chemical EngineeringCollege of Chemistry and Molecular EngineeringQingdao University of Science and Technology

As a type of bi-functional device,electrochromic supercapacitors （EC-SCs） have attracted extensive attention in diverse applications such as flexible ***,despite recent encouraging progress,rational design and development of high-performance EC-SC materials with desirable stability remain challenging for practical ***,we propose a fluorination strategy to develop high-performance EC-SC materials with tough hydrogen bonding cross-linked intermolecular polymer network by one-step electrosynthesis of *** electrosynthesized free-standing poly（3-fluorothiophene）(PFT) films simultaneously achieve high electrochromic performance （optical contrast 42%at 560 nm with reversible color changes between purple and blue）,and good capacitance property (290 F·g-1,1 A·g-1),as well as outstanding cyclic stability （<2%reduction after 20000 cycles）.We further demonstrate the fabrication of PFT-based flexible electrochromic supercapacitor devices （FESDs）,and the resultant devices can be used to visually monitor the energy storage state in real-time and maintain outstanding stability under mechanical distortion like *** a tough fluorination hydrogen bonding cross-linking strategy may provide a new design concept for high-performance EC-SC materials and reliable FESDs toward practical applications.

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