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Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei jianqiang yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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Computer-aided molecular design and optimization of potent inhibitors disrupting APC-Asef interaction

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2631-2645页

作者： Xuefei Wang Zeqian Du yuegui Guo Jie Zhong Kun Song Junyuan Wang jianqiang yu Xiuyan Yang Chen-Ying Liu Ting Shi Jian Zhang Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Basic Science Research Center Base(Pharmaceutical Science) Yantai UniversityYantai 264005China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Colorectal cancer(CRC)is the second leading cause of cancer mortality *** initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging *** this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported *** model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental *** addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound ***,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef *** results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.

关键词： APC-Asef Peptidomimetic Computer-aided molecular design ONIOM model π-πstacking Metastatic colorectal cancer

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Traditional Chinese medicines derived natural inhibitors of ferroptosis on ischemic stroke

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Chinese Journal of Natural Medicines 2024年第8期22卷 746-755页

作者： WANG Yongliang LAN Xiaobing LIU Ning MA Lin DU Juan WEI Wei HAI Dongmei WU Jing yu jianqiang LIU yue School of Pharmacy Ningxia Medical UniversityYinchuan 750000China Ningxia Key Laboratory of Drug Development and Generic Drug Research Ningxia Medical UniversityYinchuan 750000China Ningxia Characteristic Traditional Chinese Medicine Modern Engineering Research Center Ningxia Medical UniversityYinchuan 750000China College of Basic Medical Sciences Ningxia Medical UniversityYinchuan 750000China

Ischemic stroke(IS)is a globally prevalent cerebrovascular disorder resulting from cerebral vessel occlusion,leading to significant morbidity and *** intricate pathological mechanisms underlying IS complicate the development of effective therapeutic ***,a form of programmed cell death(PCD)characterized by iron overload and accumulation of lipid peroxidation products,has been increasingly recognized as a key contributor to IS *** Chinese medicines(TCMs)have long been utilized in the management of IS,prompting extensive research into their potential as sources of natural ferroptosis *** review investigates the critical role of ferroptosis in IS and provides a comprehensive analysis of current research on natural ferroptosis inhibitors identified in TCMs,aiming to lay a theoretical groundwork for the development of innovative anti-IS therapies.

关键词： Ischemic stroke Traditional Chinese medicines Natural inhibitors Ferroptosis

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磁流变惯容器设计与性能分析

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重庆大学学报 2024年第8期47卷 39-46页

作者：于建强尹佳威张赓苏喜吴晅陈世嵬中国电子科技南湖研究院机器人实验室浙江嘉兴314000 重庆科技大学土木与水利工程学院重庆401331 嘉兴南湖学院新材料工程学院浙江嘉兴314001

为了提高传统磁流变阻尼器在低频域的减振性能,提出了一种新型磁流变惯容器,包括变阻尼单元和惯容单元两部分,由磁流变阀、液压马达与飞轮等组成。利用活塞杆与缸筒的相对运动,实现变阻尼单元内的磁流变液在磁流变阀内往复流动,通过调... 详细信息

为了提高传统磁流变阻尼器在低频域的减振性能,提出了一种新型磁流变惯容器,包括变阻尼单元和惯容单元两部分,由磁流变阀、液压马达与飞轮等组成。利用活塞杆与缸筒的相对运动,实现变阻尼单元内的磁流变液在磁流变阀内往复流动,通过调控线圈上电流大小改变输出阻尼的大小;同时,实现油液推动液压马达输出轴及飞轮转动,输出器件的惯容特性。为提高磁流变阀内置通道的磁场利用率,提出了磁路设计优化方法,采用有限元方法对磁流变阀内部磁场强度进行仿真。结合磁场仿真与理论分析,设计并试制了样机,搭建了器件性能平台进行测试。结果表明,所设计器件能够表现出惯容特性,具有良好的阻尼可控性。

关键词：磁流变变阻尼器件惯容磁场

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园艺专业复合种养实践教学改革调查

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安徽农学通报 2024年第15期30卷 122-125页

作者：于建强生利霞扬州大学园艺园林学院江苏扬州225009

在乡村振兴建设背景下,对园艺专业毕业生进行问卷调查。调查结果显示,毕业生对该专业实践教学条件和各实践教学模块的满意度总体上比较高,也有不同比例的受访者认为一般,还有部分受访者不满意。说明目前园艺专业的实践教学条件和各模块... 详细信息

在乡村振兴建设背景下,对园艺专业毕业生进行问卷调查。调查结果显示,毕业生对该专业实践教学条件和各实践教学模块的满意度总体上比较高,也有不同比例的受访者认为一般,还有部分受访者不满意。说明目前园艺专业的实践教学条件和各模块还有较大的提升空间。参与调查的大部分受访者对农业面源污染以及种养结合实现农业物质循环的综合经营模式比较了解,有96.67%的受访者认为应该在实践实习教学中增加种养结合、生态农业相关内容。根据调研结果,提出了优化园艺专业果—禽复合种养实践教学改革的具体建议,包括增加园艺植物种养结合模块,打通院级壁垒,加强师资队伍建设,加强实践教学基地建设,以及加强创新创业能力实践训练。目的在于为园艺应用型人才实践教学培养方案改革提供数据支撑,为新农科背景下农业人才实践教学体系优化与改革提供参考。

关键词：园艺复合种养农业物质循环生态农业

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Basic helix-loop-helix(bHLH)transcription factor MdbHLH3 negatively affects the storage performance of postharvest apple fruit

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Horticultural Plant Journal 2022年第6期8卷 700-712页

作者： Wenyan Wang jianqiang yu Mengchi Du Jiahui Wang Dagang Hu National Key Laboratory of Crop Biology MOA Key Laboratory of Horticultural Crop Biology and Germplasm InnovationShandong Collaborative Innovation Center for Fruit and Vegetable Production with High Quality and EfficiencyCollege of Horticulture Science and EngineeringShandong Agricultural UniversityTai'anShandong 271018China College of Horticulture and Plant Protection Yangzhou UniversityYangzhou225009China

The storage period of fleshy fruits greatly affects their quality and selection,and is largely controlled by genetic ***,it is imperative to elucidate how genetic factors affect fruit ripening and its ***,we evaluated the postharvest storage properties of the basic helix-loop-helix(bHLH)transcription factor MdbHLH3-overexpressing transgenic Royal gala apple *** storage,the contents of starch,malic acid,fructose,glucose,and sucrose in fruits of three MdbHLH3 transgenic lines were always higher than those of the wild-type(WT)***,the sugar-acid ratio also showed the same trend during fruit ***,the fruit firmness decreased with increasing storage time,and the contents of cell wall components such as water-soluble pectin and cellulose in transgenic fruits were higher than those in control fruits,while the firmness of transgenic fruits was lower than that in WT control *** the ethylene release rate in both showed the same trend(firstly increasing,then decreasing,and finally peaking)in 90-day stored fruits,transgenic apples had higher ethylene levels than the WT control throughout ***,the activities of membrane peroxidase,antioxidant enzymes,and fruit ripening enzymes in all transgenic fruits were significantly higher than those in the WT ***,our findings show how MdbHLH3 negatively regulates and reduces apple storage *** may prove useful for not only developing biotechnological strategies,but also support traditional breeding programs,to help improve the storage time of fleshy fruits.

关键词： Apple MdbHLH3 Postharvest storage Firmness Ethylene Enzyme activity

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Spontaneous polarization enhanced bismuth ferrate photoelectrode:fabrication and boosted photoelectrochemical water splitting property

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Frontiers in Energy 2021年第3期15卷 781-790页

作者： Yan ZHANG yukun ZHU Yanhua PENG Xiaolong YANG Jian LIU Wei JIAO jianqiang yu School of Chemistry and Chemical Engineering Qingdao UniversityQingdao 266071China State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Laboratory of Clean Energy Chemistry and Materials Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China

In this paper,the fabrication of a highly orientated Bi_(2)Fe_(4)O_(9)(BFO)photoelectrode in the presence of two-dimensional(2D)graphene oxide(GO)was *** was found that the GO can be used as a template for controlling the growth of BFO,and the nanoplate composites of BFO/reduced graphene oxide(RGO)with a high orientation can be *** thickness of the nanoplates became thinner as the ratio of GO *** a result,the ferroelectric spontaneous polarization unit arranges itself in the space in a periodic manner,leading to the formation of a polarization field along a special ***,the created built-in electric field of the nanoplate composites of BFO/RGO is improved upon the increase of the amount of *** expected,carrier separation is enhanced by the built-in electric field,therefore substantially enhancing the photoelectrochemical(PEC)activity of water splitting compared to pure BFO under the irradiation of visible-light.

关键词： bismuth ferrate ferroelectric polarisation photoelectrochemical(PEC)water splitting graphene oxide(GO) high orientation

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Fusion of clathrin and caveolae endocytic vesicles revealed by line-switching dual-color STED microscopy

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Journal of Innovative Optical Health Sciences 2021年第6期4卷 71-80页

作者： Hefei Ruan jianqiang yu Yayun Wu Xiaojun Tang Jinghe yuan Xiaohong Fang Beijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of Chemistry Chinese Academy of SciencesBeijing 100190P.R.China University of Chinese Academy of Sciences Beijing 100049P.R.China

Clathrin-and caveolae-mediated endocytosis are the most commonly used pathways for the internalization of cell membrane ***,due to their dimensions are within the diffraction limit,traditional fluorescence microscopy cannot distinguish them and little is known about their interactions underneath cell *** this study,we proposed the line-switching scanning imaging mode for dual-color triplet-state relaxation(T-Rex)stimulated emission depletion(STED)super-resolution *** this line-switching mode,the cross-talk between the two channels,the side effects from pulse picker and image drift in frame scanning mode can be effectively *** dual-color super-resolution imaging results in mixed fluorescent beads validated the excellent *** this super-resolution microscope,not only the ring-shaped structure of clathrin and caveolae endocytic vesicles,but also their semi-fused structures underneath the cell membrane were distinguished *** resultant infor-mation will greatly facilitate the study of clathrin-and caveolae-mediated receptor endocytosis and signaling process and also our home-built dual-color T-Rex STED microscope with this line-switching imaging mode provides a precise and convenient way to study subcellular-scale protein interactions.

关键词： Super-resolution microscopy STED dual-color endocytosis line-switching

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Nanoscale imaging with an integrated system combining stimulated emission depletion microscope and atomic force microscope

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Chinese Science Bulletin 2013年第33期58卷 4045-4050页

作者： yu jianqiang yuAN JingHe ZHANG XueJie LIU JianLi FANG XiaoHong Beijing National Laboratory for Molecular Sciences Key Laboratory of Molecular Nanostructure and NanotechnologyInstitute of ChemistryChinese Academy of Sciences

We have built an integrated imaging system by combining stimulated emission depletion(STED)microscope and atomic force microscope(AFM).The STED microscope was constructed based on the supercontinuum fiber laser and a super lateral resolution of42 nm was *** this integrated imaging system,morphological features,mechanical parameters and fluorescence super resolution imaging were obtained simultaneously for both nanobeads and fixed cell *** new integrated imaging system is expected to obtain comprehensive information at the nanoscale for studies in nanobiology and nanomedicine.

关键词：原子力显微镜成像系统集成系统受激发射纳米级损耗光纤激光器横向分辨率

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Highly Efficient Photocatalytic Remediation of Simulated Polycyclic Aromatic Hydrocarbons （PAHs） Contaminated Wastewater under Visible Light Irradiation by Graphene Oxide Enwrapped Ag3PO4 Composite

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Chinese Journal of Chemistry 2017年第10期35卷 1549-1558页

作者： Xiaolong Yang Haoyuan Cai Mutai Bao jianqiang yu Jinren Lu Yiming Li Key Laboratory of Marine Chemistry Theory and Technology Ministry of Education Ocean University of China Qingdao Shandong 266100 China School of Chemistry and Chemical Engineering Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles of Shandong Province Qingdao University Qingdao Shandong 266071 China

Effective removal of polycyclic aromatic hydrocarbons （PAHs） from wastewater before their discharge into the environment is an ever pressing requirement. In this study, for the first time, simulated PAHs contaminated wastewater was photocatalytically remediated with graphene oxide （GO） enwrapped silver phosphate as visible light-driven photocatalysts. The GO/Ag3PO4 photocatalysts exhibited superior photocatalytic activity and stability compared with pure Ag3PO4, g-C3N4 and TiO2 （P25）. The degradation efficiency of naphthalene, phenanthrene and pyrene could reach 49.7%, 100.0% and 77.9%, rspectively within 5 min irradiation. The apparent rate constants of photocatalytic degradation of 3 wt% GO/Ag3PO4 composRe photocatalyst were 0.14, 1.21 and 2.46 rain^-1 for naphthalene, phenanthrene and pyrene, respectively. They were about 1.8, 1.5 and 2.0 times higher than that of pure Ag3PO4, and much higher than that of g-C3N4 and TiO2. Meanwhile, the efficiencies of 44.6%, 95.2% and 83.8% were achieved for naphthalene, phenanthrene and pyrene degradation even after 5 times of recycling in the GO/Ag3POa-PAHs photocatalysis system. Reactive species of O2^- and h^＋ were considered as the main partici- pants for oxidizing naphthalene, phenanthrene and pyrene.

关键词： polycyclic aromatic hydrocarbons (PAHs) photocatalysis silver phosphate graphene oxide degradation

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