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Chinese Chemical Letters 2024年第8期35卷 187-200页

作者： Si Ha Jiacheng Zhu Hua Xiang guoshun luo State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China

Small molecule inhibitors have dominated the pharmaceutical landscape for a long time as the primary therapeutic paradigm targeting pathogenic ***,their efficacy heavily relies on the amino acid composition and spatial constitution of proteins,rendering them susceptible to drug resistance and failing to target undruggable *** recent years,the advent of targeted protein degradation(TPD)technology has captured substantial attention from both industry and *** an event-driven mode,TPD offers a novel approach to eliminate pathogenic proteins by promoting their degrada-tion,thus circumventing the limitations associated with traditional small molecule ***-bic tag tethering degrader(HyTTD)technology represents one such TPD approach that is currently in the burgeoning *** employ endogenous protein degradation systems to induce the degrada-tion of target proteins through the proteasome pathway,which displays significant potential for medical *** this review,we provide a comprehensive overview of the development history and the reported mechanism of action of ***,we delve into the physiological roles,structure-activity re-lationships,and medical implications of HyTTDs targeting various disease-associated ***,we propose insights into the challenges that necessitate resolution for the successful development of HyTTDs,with the ultimate goal of initiating a new age of clinical treatment leveraging the immense po-tential of HyTTDs.

关键词： Targeted protein degradation(TPD) Hydrophobic tag Degrader Hydrophobic tag tethering degrader(HyTTD) Targeted therapy

Structural and mechanical properties of nano-crystal TiN coatings

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Science China(Physics,Mechanics & Astronomy) 2004年第Z1期47卷 1-7页

作者： ZHANG Chenhui PAN guoshun luo Jianbin LI Wenzhi CHEN Darong State Key Laboratory of Tribology Tsinghua University Beijing 100084 China State Key Laboratory of Tribology Tsinghua University Beijing 100084 China State Key Laboratory of Tribology Tsinghua University Beijing 100084 China State Key Laboratory of Tribology Tsinghua University Beijing 100084 China State Key Laboratory of Tribology Tsinghua University Beijing 100084 China

The structural and mechanical properties of TiN coatings prepared by ion beam assisted deposition (IBAD) were studied. The coatings have a polycrystal structure with grain size of ～10 nm or less. The hardness of the coatings increases with increasing grain size of TiN crystallites. The coating with grain size of 10.3 nm even has a superhardness of 44.7GPa. The relationship between the hardness and the grain size in the nano-crystalline coatings was discussed on the basis of grain-boundary triple junctions.

关键词： TiN, nano-crystal, microstructure, hardness, grain-boundary triple junctions.

Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo

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Acta Pharmaceutica Sinica B 2021年第5期11卷 1300-1314页

作者： guoshun luo Zhenbang Li Xin Lin Xinyu Li Yu Chen Kun Xi Maoxu Xiao Hanlin Wei Lizhe Zhu Hua Xiang State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China School of Life and Health Sciences and Warshel Institute for Computational Biology the Chinese University of Hong KongShenzhen 518172China Key Laboratory of Smart Drug Delivery Ministry of Education School of PharmacyFudan UniversityShanghai 201203China

HMG-CoA reductase(HMGCR) protein is usually upregulated after statin(HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera(PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC(21 c) comprising a VHL ligand conjugated to lovastatin acid that potently degrades HMGCR in Insig-silenced HepG2 cells(DC50 Z 120 nmol/L) and forms a stable ternary complex, as predicated by a holistic modeling protocol. Most importantly, oral administration of the corresponding lactone 21 b reveled favorable plasma exposures referring to both the parent 21 b and the conversed acid 21 c. Further in vivo studies of 21 b demonstrated robust HMGCR degradation and potent cholesterol reduction in mice with diet-induced hypercholesterolemia, highlighting a promising strategy for treating hyperlipidemia and associated diseases.

关键词： HMGCR PROTACs Oral bioavailability Cholesterol reduction

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某车型排气系统隔振性能及优化研究

现代制造工程 2024年第3期 62-69页

作者：张国顺罗建国张建傅爱军杨晋博广西科技大学机械与汽车工程学院柳州545006 广西科技大学柳州市汽车排气控制技术重点实验室柳州545006

为提高某车型排气系统隔振性能,用HyperMesh软件构建排气系统有限元模型并对其进行隔振性能分析,经测试分析发现其传递力过大,通过重新设定将各个吊耳传递力之和及其标准差作为优化目标一;将各个吊耳静态位移之和与预载力标准差作为优... 详细信息

为提高某车型排气系统隔振性能,用HyperMesh软件构建排气系统有限元模型并对其进行隔振性能分析,经测试分析发现其传递力过大,通过重新设定将各个吊耳传递力之和及其标准差作为优化目标一;将各个吊耳静态位移之和与预载力标准差作为优化目标二。在HyperStudy软件中通过拉丁超立方采样并进行试验设计(Design of Experiments,DOE),以进行变量筛选,最终确定以6个吊耳的Z向动刚度作为设计变量,并构建响应面模型,用多目标遗传算法(Multi-Objective Genetic Algorithm,MOGA)得出最优的吊耳动刚度值。将最优的吊耳动刚度值代入排气系统有限元模型进行分析,结果表明优化目标均有所提升。最后,将实际生产的吊耳装载后在实际道路上进行测试,试验结果表明,隔振率均大于20 dB,与有限元结果相同,符合生产设计要求。

关键词：排气系统拉丁超立方多目标遗传算法隔振率

A comparative study between graphene oxide and diamond nanoparticles as water-based lubricating additives

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Science China(Technological Sciences) 2013年第1期56卷 152-157页

作者： LIU YuHong WANG XiaoKang PAN guoshun luo JianBin State Key Laboratory of Tribology Tsinghua University

The tribological properties of graphene oxide(GO) nanosheets and modified diamond(MD) nanoparticles with excellent water-solubility were *** nanosheets were synthesized using carbon fibers with a regular and uniform size,the lateral size being around 30 nm and the thickness being 2 or 3 nm,while MD nanoparticles were about 30 nm in the three *** friction properties of ceramics were improved by GO nanosheets or MD nanoparticles used as additives in water-based lubrication,though the effects of two nanoparticles were quite *** GO nanosheets,the friction coefficient at the beginning decreased sharply from 0.6 to 0.1,as compared with the dionized water *** the same time,the running-in period was shortened from 2000 s to 250 s.A steady state characterized by ultralow friction(friction coefficient=0.01) was obtained after the running-in *** the case of MD nanoparticles,the friction coefficient stayed at 0.1 without further decrease during the whole *** on the observation of wear scar and characterization of remains on the wear track,the positive effect of GO nanosheets was attributed to their lamellar structure and geometric *** nanoparticles reduced friction by forming the regularly grained surface on the mating surfaces,and prevented further reduction in steady-state friction coefficient owing to their larger size and *** conclusion,GO nanosheets exhibited favorable potential as an effective additive for water-based lubrication.

关键词： graphene oxide diamond lubrication nanoparticles additive

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汽车排气系统尾管噪声声品质研究与优化

应用声学 2024年第4期43卷 865-873页

作者：张建罗建国张国顺傅爱军尧潇雪广西科技大学机械与汽车工程学院柳州市汽车排气控制技术重点实验室柳州545616 佛吉亚(柳州)排气控制技术有限公司柳州545616

针对某型汽车排气系统尾管噪声声品质问题,提出一种以径向基函数神经网络建立排气系统结构—尾管噪声声品质预测模型,并通过自适应模拟退火算法对排气系统噪声声品质进行优化的方法,来提高排气系统的声品质。以某型汽车排气系统为研究对... 详细信息

针对某型汽车排气系统尾管噪声声品质问题,提出一种以径向基函数神经网络建立排气系统结构—尾管噪声声品质预测模型,并通过自适应模拟退火算法对排气系统噪声声品质进行优化的方法,来提高排气系统的声品质。以某型汽车排气系统为研究对象,建立包含结构参数的样本数据库,并用GT-POWER进行仿真计算得到得到样本数据的噪声数据,对仿真得到的声音数据进行声品质的主观评价打分,通过径向基函数神经网络建立排气系统结构—尾管噪声声品质预测模型,对作为模型自变量的排气系统结构参数对尾管噪声声品质的贡献量和灵敏度进行了分析,最后采用自适应模拟退火算法对排气系统结构参数进行了优化,并对优化结果进行实验验证,结果表明排气系统声品质显著提升。

关键词：尾管噪声声品质径向基函数神经网络主观评价自适应模拟退火算法

Progress in material removal mechanisms of surface polishing with ultra precision

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Chinese Science Bulletin 2004年第16期49卷 1687-1693页

作者： XU Jin luo Jianbin LU Xinchun ZHANG Chaohui PAN guoshun State Key Laboratory of Tribology Tsinghua UniversityBeijing 100084China

Chemical mechanical polishing (CMP) process is commonly regarded as the best method for achieving global planarization in the field of surface finishing with ultra-precision. The development of investigation on material removal mechanisms for different materials used in com-puter hard disk and ultra-large scale integration fabrication are reviewed here. The mechanisms underlying the interac-tion between the abrasive particles and polished surfaces during CMP are addressed, and some ways to investigate the polishing mechanisms are presented.

关键词：化学机械抛光 CMP 物质迁移机理磨损 ULSL 计算机硬盘

Modification on the tribological properties of ceramics lubricated by water using fullerenol as a lubricating additive

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Science China(Technological Sciences) 2012年第9期55卷 2656-2661页

作者： LIU YuHong WANG XiaoKang LIU PengXiao ZHENG JunPeng SHU ChunYing PAN guoshun luo JianBin State Key Laboratory ofTribology Tsinghua UniversityBeijing 100084China Key Laboratory of Molecular Nanostructure and Nanotechnology Institute of ChemistryCASBeijing 100190China

It is necessary to modify the running-in process for the application of ceramics using water as a lubricant in real conditions because ceramics sliding in water are characterized by a running-in period with severe friction and ***,a kind of highly water-soluble nanoparticle,was synthesized and then used to ameliorate the tribological properties of Si 3 N 4 sliding against Al 2 O 3 in pure *** the addition of fullerenol,the running-in period was shortened from 30 min to 100 s at a speed of 250 mm/*** speed threshold above which ultralow friction can be obtained in a short time was expanded from 450 mm/s to 80 mm/***,the load-carrying ability of water film was *** role of fullerenol was discussed based on observation of the wear scar by an optical interferometer and XPS characterization of the tribo-film on the wear track.

关键词： water-based lubrication running.in ceramics water-soluble nanoparticle

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刺葡萄新品种湘刺3号的选育

果树学报 2024年第4期41卷 781-785页

作者：黎炎夏罗飞雄许延帅李双江陈文婷谭君王美军徐丰杨国顺白描湖南农业大学园艺学院·湖南省葡萄工程技术研究中心长沙410128

湘刺3号是从怀化市中方县桐木镇通过实生选种得到的一个极晚熟刺葡萄新品种。果穗多呈圆柱形,少部分有副穗,松紧适中,成熟时果皮呈蓝黑色,果粉薄,果皮厚,平均穗质量163 g,平均单粒质量3.4 g,果形指数1.1(纵径/横径),每颗果实中含种子2~3... 详细信息

湘刺3号是从怀化市中方县桐木镇通过实生选种得到的一个极晚熟刺葡萄新品种。果穗多呈圆柱形,少部分有副穗,松紧适中,成熟时果皮呈蓝黑色,果粉薄,果皮厚,平均穗质量163 g,平均单粒质量3.4 g,果形指数1.1(纵径/横径),每颗果实中含种子2~3粒,多为3粒,种子颜色黑褐色。可溶性固形物含量(w,后同)15.2%,可滴定酸含量0.28%。果实发育期130 d左右,3月下旬至4月初萌芽,4月底至5月上旬开花,9月下旬果实成熟。该品种抗旱性强,极抗多湿土壤;抗黑痘病、白粉病、炭疽病、灰霉病能力强,但不抗霜霉病;抗虫性强,但不抗根瘤蚜。适宜在湖南、贵州、四川、江西、福建、湖北、云南、广东、广西、重庆等省份的葡萄产区春、秋两季种植。

关键词：刺葡萄新品种湘刺3号抗性

维普期刊数据库博看期刊

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沅江芦笋可溶性膳食纤维提取工艺的优化

食品研究与开发 2024年第13期45卷 106-111页

作者：冯昭仪张博宁杨国舜罗扬肖茜刘成国周辉湖南农业大学食品科学技术学院湖南长沙410128 沅江市芦小妹食品有限公司湖南沅江413100 湖南博大天能实业股份有限公司湖南沅江413100 长沙市农产品质量监测中心湖南长沙410003

以沅江芦笋为原料,通过超声辅助酶法提取可溶性膳食纤维,探讨α-淀粉酶与糖化酶质量比、浸提时间、超声功率、超声温度以及料液比对可溶性膳食纤维提取得率的影响,并采用正交试验优化可溶性膳食纤维最佳提取工艺。结果表明,最佳提取工... 详细信息

以沅江芦笋为原料,通过超声辅助酶法提取可溶性膳食纤维,探讨α-淀粉酶与糖化酶质量比、浸提时间、超声功率、超声温度以及料液比对可溶性膳食纤维提取得率的影响,并采用正交试验优化可溶性膳食纤维最佳提取工艺。结果表明,最佳提取工艺条件为料液比1∶200(g/mL),α-淀粉酶与糖化酶质量比5∶5,浸提时间4 h。在该工艺条件下沅江芦笋可溶性膳食纤维提取得率为16.77%。

关键词：沅江芦笋可溶性膳食纤维提取优化超声辅助正交试验