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

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 *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(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 *** 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 ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** 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 *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery 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

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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 *** is critical to inspire new potential to remodel the value of this classical therapeutic ***,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic *** 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 *** synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic *** 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 ***,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

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Chemical, carbon and sulfur isotopic compositions constrain the origin of Upper Carboniferous-Lower Triassic gases in eastern Sichuan Basin, SW China

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Science China Earth Sciences 2024年第10期67卷 3169-3185页

作者： Chunfang CAI Ilya KUTUZOV Wenhua MEI Daowei WANG bing LUO Shipeng HUANG bing he Alon AMRANI China University of Petroleum National Key Lab Petroleum Resource & Engineering State Key Laboratory of Lithospheric and Environmental Coevolution Institute of Geology and Geophysics Chinese Academy of Sciences College of Earth and Planetary Sciences University of Chinese Academy of Sciences Institute of Earth Sciences The Hebrew University Yulin University Research Institute of Exploration and Development Southwest Oil & Gas Field Company Petro China Petro China Research Institute of Petroleum Exploration and Development

Methane dominated gas is one of the cleanest energy resources; however, there is no direct method to determine its source rock. Natural gases produced from the eastern Sichuan Basin together with seismic data were studied for their sources and secondary alteration by thermochemical sulfate reduction（TSR）. Our results demonstrate that Upper Permian to Lower Triassic（P3ch-T1f） gases in the surrounding of the Kaijiang-Liangping area show volatile organic sulfur compounds（VOSCs） δ34S values close to those of the associated H2S, and may have been altered by methane-dominated TSR, resulting in positive shift in methane δ13C1values with increasing TSR extents. Other（or group 2） gases produced from the P3ch-T1f reservoirs from the southern area and the Upper Carboniferous to Middle Permian（C2h-P2q） from the eastern Sichuan Basin are not significantly changed by TSR, show similar δ34S values between the kerogens and some VOSCs, and may have been derived from the Lower Silurian and Middle Permian source rocks. This study demonstrates a case for the first time showing the δ34S values of VOSCs can be used as a tool for direct correlation between non-TSR altered gas and source rocks. Methane-dominated gas pools can be found using gas and source rock geochemistry combined with seismic data.

关键词： Sulfur isotopes Volatile organic sulfur compounds Thermochemical sulfate reduction Sichuan Basin Gas-source rock correlation

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A signaling cascade mediating fruit trait development via phosphorylation-modulated nuclear accumulation of JAZ repressor

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Journal of Integrative Plant Biology 2024年第6期66卷 1106-1125页

作者： Wei Wang Jinyao Ouyang Yating Li Changsheng Zhai bing he Huahan Si Kunsong Chen Jocelyn K.C.Rose Wensuo Jia College of Horticulture China Agricultural UniversityBeijing 100193China College of Agriculture and Biotechnology Zhejiang UniversityZijingang CampusHangzhou 310058China Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthaca14853NYUSA Institute of Horticulture Crops Xinjiang Academy of Agricultural SciencesUrumqi 830000China

It is generally accepted that jasmonate-ZIM domain(JAZ)repressors act to mediate jasmonate(JA)signaling via CORONATINE-INSENSITIVE1(COI1)-mediated ***,we report a cryptic signaling cascade where a JAZ repressor,FvJAZ12,mediates multiple signaling inputs via phosphorylation-modulated subcellular translocation rather than the COI1-mediated degradation mechanism in strawberry(Fragaria vesca).FvJAZ12 acts to regulate flavor metabolism and defense response,and was found to be the target of Fv MPK6,a mitogen-activated protein kinase that is capable of responding to multiple signal ***6 phosphorylates FvJAZ12 at the amino acid residues S179 and T183 adjacent to the PY residues,thereby attenuating its nuclear accumulation and relieving its repression for FvMYC2,which acts to control the expression of lipoxygenase 3(FvLOX3),an important gene involved in JA biosynthesis and a diverse array of cellular *** data reveal a previously unreported mechanism for JA signaling and decipher a signaling cascade that links multiple signaling inputs with fruit trait development.

关键词： defense response JAZ repressor phosphorylation strawberry subcellular translocation

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Improved YOLOv7 Algorithm for Floating Waste Detection Based on GFPN and Long-Range Attention Mechanism

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Wuhan University Journal of Natural Sciences 2024年第4期29卷 338-348页

作者： PENG Cheng he bing XI Wenqiang LIN Guancheng School of Physics and Electrical Engineering Weinan Normal UniversityWeinan 714099ShaanxiChina Engineering Research Center for X-ray Imaging and Detection of Shaanxi Provincal Universities Weinan 714099ShaanxiChina

Floating wastes in rivers have specific characteristics such as small scale,low pixel density and complex *** characteristics make it prone to false and missed detection during image analysis,thus resulting in a degradation of detection *** order to tackle these challenges,a floating waste detection algorithm based on YOLOv7 is proposed,which combines the improved GFPN(Generalized Feature Pyramid Network)and a long-range attention ***,we import the improved GFPN to replace the Neck of YOLOv7,thus providing more effective information transmission that can scale into deeper ***,the convolution-based and hardware-friendly long-range attention mechanism is introduced,allowing the algorithm to rapidly generate an attention map with a global receptive ***,the algorithm adopts the WiseIoU optimization loss function to achieve adaptive gradient gain allocation and alleviate the negative impact of low-quality samples on the *** simulation results reveal that the proposed algorithm has achieved a favorable average accuracy of 86.3%in real-time scene detection *** marks a significant enhancement of approximately 6.3%compared with the baseline,indicating the algorithm's good performance in floating waste detection.

关键词： floating waste detection YOLOv7 GFPN(Generalized Feature Pyramid Network) long-range attention

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MnS–MnO heterogeneous nanocube@N,S-doped carbon as a highly efficient bifunctional water splitting electrocatalyst

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Rare Metals 2024年第5期43卷 1977-1988页

作者： Xue-Qian Wang Xiang-Ying Ma Wang-Zhi Wu Hui-bing he Nan-Nan Wang Ren-Ji Zheng Shao-Jian Ma Yan-Qiu Zhu Pei-Kang Shen Jin-Liang Zhu School of Resources Environment and MaterialsState Key Laboratory of Featured Metal Materials and Life-Cycle Safety for Composite StructuresCollege of Chemistry and Chemical EngineeringGuangxi UniversityNanning 530004China School of Chemistry and Chemical Engineering Guangxi MinzuUniversity Nanning 530006 China School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China

A stable,efficient,and economical bifunctional electrolytic catalyst would be incredibly beneficial for the development of hydrogen production by electrocatalytic water *** this study,we synthesized a novel MnS–MnO heterogeneous nanocube@N,S-doped carbon(MnS–MnO@NSC).MnS–MnO nanocubes possess rich heterogeneous interfaces and plentiful catalytic active sites to promote electrochemical reactions,while the N,S-doped carbon shell possesses excellent conductivity and catalytic properties and protects the ***–MnO@NSC exhibited excellent electrochemical properties as an effective bifunctional electrocatalyst for the hydrogen evolution reaction(heR)and oxygen evolution reaction(OER)in KOH *** the heR,the overpotential was as low as 124 mV at a current density of 10 mA·cm^(-2)while in the OER,it was only 340 mV at 100 mA·cm^(-2)under the same *** addition,a MnS–MnO@NSC||MnS–MnO@NSC electrolyzer exhibited almost comparable activity and higher steadiness than those exhibited by the state-of-the-art Pt/C||RuO_(2)/C system for full water splitting in KOH solution.

关键词： Manganese sulfide Manganese oxide Doped carbon heterogeneous nanocube Water splitting

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Production and test of sPheNIX W/SciFiber electromagnetic calorimeter blocks in China

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Nuclear Science and Techniques 2024年第8期35卷 167-176页

作者： Xiao‑Zhou Yu Xi‑Yang Wang Wei‑Hu Ma Shi‑Hong Fu Peng‑Fei Sun Jin‑Xing Song Wan‑bing he Yang Shen Long Ma Jin‑Hui Chen Huan‑Zhong Huang Si‑Guang Wang Jing Zhou Xiao‑Mei Li Institute of Modern Physics Fudan UniversityShanghai 200433China Key Laboratory of Nuclear Physics and Ion‑Beam Application(MOE) Fudan UniversityShanghai 200433China Science and Technology on Nuclear Data Laboratory China Institute of Atomic EnergyBeijing 102413China Department of Physics and Astronomy University of CaliforniaLos AngelesCA 90095USA State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China

The sPheNIX experiment is a new generation of large acceptance detectors at the relativistic heavy ion collider at Brookhaven National Laboratory,with scientific goals focusing on probing the strongly interacting Quark–Gluon plasma with hard probes of jets,open heavy flavor particles,andγ*** EMCal detector,which covers the pseudo-rapidity region of|η|≤1.1,is an essential subsystem of *** this study,we focused on producing and testing EMCal blocks covering a pseudo-rapidity of|η|∈[0.8,1.1].These,in conjunction with the central pseudo-rapidity EMCal blocks,significantly enhance the sPheNIX physics capability of the jet andγparticle *** this paper,the detector module production and testing of sPheNIX W-powder/scintillating fiber(W/ScFi)electromagnetic calorimeter blocks are *** selection of the tungsten powder,mold fabrication,QA procedures,and cosmic ray test results are discussed.

关键词： sPheNIX Tungsten/scintillating fiber electromagnetic calorimeter Cosmic ray test

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儿童暴发性心肌炎诊治进展

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中国实用儿科杂志 2024年第3期39卷 203-207页

作者：庹虎何兵武汉大学人民医院儿科湖北武汉430060

儿童暴发性心肌炎是儿童心肌炎中最严重的类型,进展迅速,可表现为心力衰竭、心源性休克以及严重心律失常,危及患儿生命。一旦怀疑本病,需要高度重视、迅速诊断、多专业合作、全力救治。在中华医学会儿科学分会心血管学组心肌炎协作组的... 详细信息

儿童暴发性心肌炎是儿童心肌炎中最严重的类型,进展迅速,可表现为心力衰竭、心源性休克以及严重心律失常,危及患儿生命。一旦怀疑本病,需要高度重视、迅速诊断、多专业合作、全力救治。在中华医学会儿科学分会心血管学组心肌炎协作组的推动下,2018年我国已经更新了儿童心肌炎诊断的专家建议,随后多次组织全国儿童心血管病专家对暴发性心肌炎诊疗开展研讨及宣讲。各医疗中心对儿童暴发性心肌炎的诊治认识不断提高,也积累了丰富的经验。文章就目前儿童暴发性心肌炎的诊治进展进行综述。

关键词：儿童暴发性心肌炎诊断治疗预后

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石墨烯基材料在电磁屏蔽领域的研究进展

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新型炭材料（中英文） 2024年第2期39卷 223-239页

作者：杨赏娟曹赟贺艳兵吕伟清华大学深圳国际研究生院广东深圳518055

通信技术在为人类的生活带来便利的同时,其产生的电磁辐射对社会安全、人体健康产生的危害也受到了社会各界的广泛关注,宽屏蔽范围、高吸收效率和高稳定性的电磁屏蔽材料逐渐成为研究热点。石墨烯是一种导电性高、比表面积大且可调控性... 详细信息

通信技术在为人类的生活带来便利的同时,其产生的电磁辐射对社会安全、人体健康产生的危害也受到了社会各界的广泛关注,宽屏蔽范围、高吸收效率和高稳定性的电磁屏蔽材料逐渐成为研究热点。石墨烯是一种导电性高、比表面积大且可调控性高的轻质材料,可有效实现电磁衰减,保护精密电子设备和人体健康,在电磁屏蔽领域具有广阔的应用前景。本综述从电磁屏蔽的基本原理与石墨烯基材料的结构特性角度,阐述了石墨烯及其衍生物的电磁屏蔽特点,总结了结构调控以及表面异质化、复合化策略在电磁屏蔽领域的应用。结构调控有利于提高石墨烯基材料对电磁波的吸收损耗和多重反射损耗;表面异质化和复合化策略有利于提高石墨烯基材料的界面极化和磁特性,从而加强对电磁波的吸收损耗和磁损耗。总结了石墨烯基电磁屏蔽材料的改性方法,旨在为开发新一代绿色、轻薄、高屏蔽带宽的电磁屏蔽材料提供启发,指明石墨烯基电磁屏蔽材料的未来发展方向。

关键词：石墨烯电磁屏蔽结构调控异质掺杂复合材料

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芍药苷对多囊卵巢综合征大鼠子宫内膜容受性的改善作用及对Wnt/β-catenin通路的影响

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中药药理与临床 2024年第2期40卷 90-95页

作者：李琳马本玲贺冰湖南中医药大学第二附属医院妇科长沙410005

目的:探讨芍药苷对多囊卵巢综合征(PCOS)大鼠子宫内膜容受性的改善作用及其可能作用机制。方法:40只雌性大鼠建立PCOS模型,随机分为模型对照组、芍药苷50、100 mg/kg组和阳性对照(达英-350 mg/kg)组,另设正常对照组。各组灌胃相应药物,... 详细信息

目的:探讨芍药苷对多囊卵巢综合征(PCOS)大鼠子宫内膜容受性的改善作用及其可能作用机制。方法:40只雌性大鼠建立PCOS模型,随机分为模型对照组、芍药苷50、100 mg/kg组和阳性对照(达英-350 mg/kg)组,另设正常对照组。各组灌胃相应药物,正常对照组及模型对照组给予等体积生理盐水,连续21 d。ELISA法测定血清中雌二醇(E2)、睾酮(T)、促卵泡生成素(FSH)和促黄体生成素(LH)含量以及子宫内膜组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-6含量;he染色观察子宫内膜组织病理变化,计算并分析子宫内膜腺体数量、子宫内膜厚度;RT-qPCR法检测子宫内膜组织中Wnt3a和β连环蛋白(Bcatenin)mRNA表达;Western blot法检测子宫内膜组织中Wnt3a、β-catenin、雌激素受体(ER)和孕激素受体(PR)蛋白表达。结果:与正常对照组比较,模型对照组血清E2、FSH、子宫内膜厚度、腺体数量明显降低、子宫内膜组织Wnt3a、Bcatenin mRNA和蛋白表达明显下调,血清T、LH、TNF-α、IL-1β、IL-6含量明显升高、ER和PR蛋白表达明显上调(P<0.05);与模型对照组比较,芍药苷50、100 mg/kg组及达英-350 mg/kg组大鼠血清E2、FSH含量、子宫内膜厚度、腺体数量明显升高,子宫内膜组织Wnt3a、Bcatenin mRNA和蛋白表达明显上调,血清T、LH、TNF-α、IL-1β、IL-6含量明显降低、ER和PR蛋白表达明显下调(P<0.05)。结论:芍药苷可调节PCOS大鼠性激素水平,减轻炎性反应,提高子宫内膜容受性,可能是通过影响Wnt/β-catenin通路发挥作用。

关键词：芍药苷多囊卵巢综合征子宫内膜容受性 β连环蛋白

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