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Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng Huize Han Zhipu Fan Wenbing Dai Hua Zhang xueqing wang Qiang Zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

Homogenization Function of Microchannel on Heat Absorber with Compound Parabolic Concentrator

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Journal of Thermal Science 2022年第6期31卷 2022-2031页

作者： wang xueqing WU Haifeng MA Yusen wang Suilin XU Rongji Beijing Engineering Research Center of Sustainable Energy and Buildings Beijing University of Civil Engineering and ArchitectureBeijing 100044China

Microchannels offer unique advantages on heat transfer performance. In this paper, microchannels are applied to the compound parabolic concentrator(CPC) system. A multi-physical field coupling model based on Finite Element Method is proposed to investigate the homogenization effect of the microchannel heat absorber on the CPC non-uniform concentration. The energy conversion process from optics to heat is simulated using TracePro software, and the heat transfer processes in the microchannel are computed by Fluent using user defined functions(UDF). It is found that the microchannels behave well on weakening the influence of the nonuniformity solar heat flux on the performance of the CPC. The temperature nonuniformity of the outlet section is less than 10^(-3) in the direction of fluid flow caused by the microchannel, although the maximum surface heat flux inhomogeneity of the microchannel reaches 2.3. The peak value of the heat flux on the surface of the absorber changes from double peak to single peak, and moves to the edge, resulting in more uneven heat flux distribution with the increase of the incident angle within the acceptance semi-angle of the CPC. The result of TracePro clearly shows that when the concentration ratio is less than 5, the heat flux nonuniformity on the surface of the absorber decreases with the increase in concentration ratio. It was interestingly found that the temperature distribution of the heat transfer fluid has weak sensitivity to the changes of truncation ratio. This work provides a way to design a CPC solar collector.

关键词： solar energy microchannel compound parabolic concentrator multi-physical field

Boosting synergism of chemo- and immunotherapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

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Acta Pharmaceutica Sinica B 2024年第2期14卷 836-853页

作者： Ge Song Minghui Li Shumin Fan Mengmeng Qin Bin Shao Wenbing Dai Hua Zhang xueqing wang Bing He Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Medical Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijing 100142China

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

关键词： Bisphosphonate coordinationlipid nanogranules Ferroptosis Mevalonatemetabolism Mitochondrial metabolism Nano-systematic biology

Electrophilic Halogen Reagents-mediated Halogenation: Synthesis of Halogenated Dihydro-1,3-oxazine Derivatives

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Chemical Research in Chinese Universities 2023年第6期39卷 933-947页

作者： QI Liang QIN Yuji wang xueqing CHAI Hongli ZHU Weiwei ZHOU Yifeng Department of Pharmacy College of Life SciencesChina Jiliang UniversityHangzhou 310018P.R.China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006P.R.China School of Basic Medical Science Lanzhou UniversityLanzhou 730000P.R.China

Halogenation of N-cinnamylbenzamides and N-[(2H-chromen-3-yl)methyl]benzamides using electrophilic halogen source was reported.Various halogenated dihydro-1,3-oxazine derivatives(45 examples)were synthesized in high to excellent yields(up to 98%yields),as well as halogenated dihydrochromeno-1,3-oxazine derivatives(56 examples,up to 96%yields).The properties of mild conditions,metal-free and high efficiency of the reaction made it a promising strategy in future applications for the construction of carbon-halogen(fluorine,F;chlorine,Cl;bromine,Br;iodine,I)bond and 1,3-oxazine derivatives.

关键词： Carbon halogen bond 1 3-Oxazine Heterocyclization

Responses of ephemeral plant germination and growth to water and heat conditions in the southern part of Gurbantunggut Desert

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Chinese Science Bulletin 2006年第A1期51卷 110-116页

作者： wang xueqing JIANG Jin wang Yuanchao LUO Weilin SONG Chunwu CHEN Junjie Xinjiang Institute of Ecology and Geography Chinese Academy of Sciences Urumqi 830011 China Xinjiang Administration of Engineering Construction in Erqis River Basin Urumqi 830000 China Graduate School of Chinese Academy of Sciences Beijing 100039 China

在 Gurbantunggut 沙漠的南部的部分的短暂植物系统地从 2002 ～ 2004 被监视，气象学的数据和土壤潮湿在一样的时期期间被分析。结果证明短暂植物萌芽和生长对水和热状况的变化敏感。超过 0 的每日的温度的时间 ?????????

关键词：短生植物水热环境 Gurbantunggut沙漠积极响应

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低围压双向压缩条件下竖直裂纹扩展机制研究

矿业研究与开发 2024年第1期44卷 104-111页

作者：王家豪汪学清高阳胡明明中国矿业大学(北京)力学与建筑工程学院北京100083 中国科学院武汉岩土力学研究所湖北武汉430071

为研究地下洞室开挖等岩石工程中双向压缩应力状态下的岩体裂纹扩展机制,以低围压三向受压或单轴压缩条件下含竖直裂纹的岩体试样为研究对象,通过数值模拟的方式分析不同泊松比μ和裂纹迹长a条件下远场轴向压应力和裂纹尖端应力的分布... 详细信息

为研究地下洞室开挖等岩石工程中双向压缩应力状态下的岩体裂纹扩展机制,以低围压三向受压或单轴压缩条件下含竖直裂纹的岩体试样为研究对象,通过数值模拟的方式分析不同泊松比μ和裂纹迹长a条件下远场轴向压应力和裂纹尖端应力的分布规律。基于叠加原理得到双向压缩条件下竖直裂纹/翼裂纹尖端近场应力的表达式,并推导出该应力状态下裂纹岩体试样的应力强度因子及裂纹扩展方向。结果表明:存在远场轴向压应力时,泊松比μ和裂纹迹长a对裂纹尖端应力分布规律有明显影响。裂纹尖端应力σxx与平行于裂纹面的轴向压应力σn的比值与泊松比μ成一次函数关系,与裂纹迹长a成三次函数关系。

关键词：双向压缩应力远场轴向压应力近场应力泊松比裂纹迹长

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弱化矿岩破碎动力系统的能量转化和时效特性

矿冶工程 2024年第1期44卷 25-30页

作者：汪学清唐红平王建华邹煜中国矿业大学(北京)力学与建筑工程学院北京100083 深海矿产资源开发利用技术国家重点实验室湖南长沙410012

基于弱化性质矿岩典型的非线性负指数本构关系和灾变特性,分析了灾变和非灾变两种破碎动力学模式下能量转化和时效特性随机构刚度的变化情况。结果表明,低机构刚度诱发的灾变破碎模式会急剧降低破碎动力系统的能量传递效率和破岩时效。... 详细信息

基于弱化性质矿岩典型的非线性负指数本构关系和灾变特性,分析了灾变和非灾变两种破碎动力学模式下能量转化和时效特性随机构刚度的变化情况。结果表明,低机构刚度诱发的灾变破碎模式会急剧降低破碎动力系统的能量传递效率和破岩时效。从能量利用和破岩功效角度考虑,破碎动力系统不宜采用低机构刚度;给出了机构刚度设计适宜的选用范围。

关键词：矿岩弱化特性破碎动力系统能量传递破岩时效

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环境工程建设与生态环境的关系研讨

皮革制作与环保科技 2024年第6期5卷 125-127页

作者：王雪晴安徽省公路工程检测中心安徽合肥230051

随着社会经济的快速发展,人类对环境资源的需求日益增加。环境工程建设不仅对提高人类的生活质量和健康水平起到关键作用,同时也对生态环境产生了深远影响。环境工程建设包括水资源管理、废水治理、固体废弃物管理、土壤修复与大气污染... 详细信息

随着社会经济的快速发展,人类对环境资源的需求日益增加。环境工程建设不仅对提高人类的生活质量和健康水平起到关键作用,同时也对生态环境产生了深远影响。环境工程建设包括水资源管理、废水治理、固体废弃物管理、土壤修复与大气污染治理等多个方面,其目标是通过改善环境质量来促进人类与自然生态系统的和谐共存。然而在实际操作中,环境工程建设的一些过程可能会使生态环境受到不同程度的影响。因此,如何在保障环境工程建设质量的基础上,减少其对生态环境的负面影响,成为环境工程与生态环境研究领域的焦点。本文旨在深入探讨环境工程建设与生态环境的关系,为推动环境工程建设的可持续发展提供指导和建议。

关键词：环境工程生态环境关系研讨

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中国食用菌出口贸易现状、风险及对策

北方园艺 2024年第12期 142-149页

作者：马驰宇王雪晴米志鹃哈尔滨商业大学经济学院黑龙江哈尔滨150028 东北财经大学金融学院辽宁大连116012 黑龙江农业工程职业学院农学院黑龙江哈尔滨150025

基于中国海关数据库HS编码,筛选和分类汇总蘑菇菌丝、鲜或冷藏类食用菌、冷冻类食用菌、盐水(暂时保藏)类食用菌、干制类食用菌、食用菌罐头共6类产品2015—2022年的出口贸易总额和出口量,分析食用菌出口产品结构和主要出口贸易伙伴及... 详细信息

基于中国海关数据库HS编码,筛选和分类汇总蘑菇菌丝、鲜或冷藏类食用菌、冷冻类食用菌、盐水(暂时保藏)类食用菌、干制类食用菌、食用菌罐头共6类产品2015—2022年的出口贸易总额和出口量,分析食用菌出口产品结构和主要出口贸易伙伴及其产品结构,并对出口贸易方式加以总结,以期促进中国食用菌贸易发展,增强食用菌贸易出口核心竞争优势,提升应对贸易保护主义的能力,为实现贸易经济高质量发展添砖加瓦。结果表明:干品类、罐头类食用菌仍占据主要出口地位,但鲜或冷藏类食用菌产品或可借助“一带一路”贸易便利化措施斩获新的增长机遇。通过梳理2015—2023年食用菌出口贸易受阻情况发现,要充分保障食用菌食品安全,进一步提升中国食用菌产业的国际竞争力,一是在国家立法层面上,完善规则标准,推进绿色生产转型;二是在地方政府层面上,打造地域品牌,细分市场精准营销;三是在政企合作层面上,应用先进技术,构建循环生态生产模式。

关键词：食用菌出口贸易贸易壁垒