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Miriplatin-loaded liposome,as a novel mitophagy inducer,suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4477-4501页

作者： Xiaowei Wang Mengyan Wang Meilian Cai Rongguang Shao Guimin Xia wuli zhao State Key Laboratory of Respiratory Health and Multimorbidity Key Laboratory of Antibiotic BioengineeringMinistry of HealthLaboratory of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Pharmaceutics Department Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pancreatic cancer is a more aggressive and refractory *** and toxicity limit drug ***,we report a lower toxic and higher effective miriplatin(MPt)-loaded liposome,LMPt,exhibiting totally different anti-cancer mechanism from previously reported platinum *** in gemcitabine(GEM)-resistant/sensitive(GEM-R/S)pancreatic cancer cells,LMPt exhibits prominent anti-cancer activity,led by faster cellular entry-induced larger accumulation of *** level of caveolin-1(Cav-1)determines entry rate and switch of entry pathways of LMPt,indicating a novel role of Cav-1 in nanoparticle *** endosome-lysosome processing,in unchanged metabolite,MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM,to degrade POLG and ***,via PINK1-Parkin axis,mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA(mtDNA)replication ***,POLG and TFAM are identified as novel prognostic markers of pancreatic cancer,and mtDNA replication-induced mitophagy blocking mediates their pro-cancer *** findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA(target of most platinum agents),and totally distinct mechanism of MPt and other formulations of ***-assembly offers LMPt special efficacy and *** action and characteristic mechanism make LMPt a promising cancer candidate.

关键词： Miriplatin-loaded liposome Pancreatic cancer Caveolae-mediated endocytosis Caveolin-1 Mitophagy Mitochondria DNA POLG TFAM

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Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents

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Acta Pharmaceutica Sinica B 2016年第3期6卷 222-228页

作者： Chongwen Bi Cheng Ye Yinghong Li wuli zhao Rongguang Shao Danqing Song Institute of Medicinal Biotechnology Chinese Academy of Medical Science & Peking Union Medical College Tianjin Medical University General Hospital

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 30-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine(1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin(AMD)-susceptible and resistant MCF-7 breast carcinoma cells,indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

关键词： Sophoridinic derivatives Synthesis Structure–activity relationship Anticancer Drug resistance

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Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

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Chinese Science Bulletin 2013年第24期58卷 3007-3014页

作者： zhao wuli HE HongWei REN KaiHuan ZHANG Hao CHEN Yi SHAO RongGuang Ministry of Health Key Laboratory of Antibiotic Bioengineering Department of Oncology Institute of Medicinal Biotechnology Peking Union Medical College Chinese Academy of Medical Sciences

Myofibrillogenesis regulator-1 (MR-1) is a gene overexpressed usually in many human cancers. However, the effects of MR-1 on cell proliferation, adhesion, migration and genome-wide gene regulation are still unclear. In this study, a human hepatoma cell line that highly overexpresses MR-1, BEL-7402/MR-1 cells was established. While the high expression of MR-1 did not promote cell proliferation, it significantly increased cell spreading, adhesion and migration compared with control cells. A total of 147 genes were regulated by MR-1 expression, 46 genes were down-regulated and 101 genes were up-regulated by MR-1 overexpression. Many of these genes were related to cell adhesion, cytoskeletal regulation, MAPK signaling, and cell cycle related pathways. Western blot analysis further confirmed the regulation of pathways associated with migration by MR-1. These results suggest that MR-1 is involved in the regulation of cancer cell adhesion, migration and related gene expression.

关键词：人肝癌细胞株迁移黏附人类基因表达调控调节器细胞粘附 blot分析

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The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells

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Acta Pharmaceutica Sinica B 2022年第1期12卷 210-227页

作者： Junxia Wang Minghua Chen Mengyan Wang Wenxia zhao Conghui Zhang Xiujun Liu Meilian Cai Yuhan Qiu Tianshu Zhang Huimin Zhou wuli zhao Shuyi Si Rongguang Shao Key Laboratory of Antibiotic Bioengineering Ministry of HealthLaboratory of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Pancreatic adenocarcinoma(PAAD) is one of the most lethal malignancies. Although gemcitabine(GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C(Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect(80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-L-cysteine(NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum(ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation(ERAD) ubiquitinates anddownregulates YAP to enhance ER stress via destruction complex(YAP-Axin-GSK-βTr CP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.

关键词： Pancreatic cancer Secoemestrin C YAP degradation ER stress inducer Resistance Fast shrinkage YAP destruction complex Lipid droplet formation

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Salmonella typhimurium strain SL7207 induces apoptosis and inhibits the growth of HepG2 hepatoma cells in vitro and in vivo

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Acta Pharmaceutica Sinica B 2012年第6期2卷 562-568页

作者： Baowei Li Hongwei He Shenghua Zhang wuli zhao Naren Li Rongguang Shao MOH Key Laboratory of Antibiotic Bioengineering Department of OncologyInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Salmonella typhimurium is probably most extensively studied tumor-targeting bacteria and SL7207 is one of its attenuated ***7207 was first made for bacterial vaccine development and its therapeutic efficacy and safety for hepatoellular carcinoma has not been *** this study,the inhibitory ability of SL 7207-lux on human hepatoma HepG2 cells was tested in vitro and in vivo.A bacterial luminescent gene cluster(lux CDA BE)was transfected into SL7207 to better monitor the invasion of the *** results show that SL7207-lux can rapidly enter HepG2 cells and localize in the *** invasion represses ell proliferation and induces *** vivo real-time invasion studies showed that the bacteria gradually accumulate in the *** enrichment was confirmed by anatomic observation at 5 days after *** 40%of tumor growth was inhibited by SL7207-lxx at 34 days post-treatment without significant loss of body *** area of necrosis of tumor tissue was clearly increased in the treated *** quantification showed that the number of colony-forming units per gram of bacteria within tumor tissue was approximately 1000-fold higher than that of liver and *** data suggest that attenuated *** strain SL7207 has potential for the treatment of cancers.

关键词： Salmonella typhimurium Hepatocellular carci-noma Apoptosis Cancer therapy

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Impact of Startup Strategy and Buffer Tank Volume on the Compressor Inlet State for a 3-MW sCO2 Brayton Cycle

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Journal of Thermal Science 2025年第1期34卷 159-175页

作者： zhao Decai WANG Bo Key Laboratory of Advanced Energy and Power Institute of Engineering Thermophysics(IET)Chinese Academy of Sciences (CAS) University of Chinese Academy of Sciences

The supercritical carbon dioxide（sCO2） Brayton cycle system has become an emerging and highly promising method of thermal power conversion due to its efficiency advantage,system compactness,and excellent adaptability of the heat *** the low carbon sCO2Brayton cycle testbed with cycle output power approaching 3 MW,a relatively detailed dynamic simulation model of the entire system is constructed to explore the dynamic response characteristics of the system with different startup strategies and different buffer tank volumes during the startup *** simulation results indicate that the smaller the volume of the buffer tank,the more rapid and obvious the parameter fluctuation in the buffer tank during the *** the allowable relative deviation limit of density is 5%,then the ratio of the buffer tank volume to the volume of the entire closed loop should not be lower than 36.80%.The strategy of simultaneous temperature and speed increase during turbine bypass start can effectively reduce the fluctuation of compressor inlet parameters and reach the steady-state more *** paper provides the recommended matching table for the opening of the turbine bypass valve（TBV） and the main regulating valve（MGV） to reduce the parameter fluctuation during the bypass *** effectiveness of the proposed turbine bypass and bypass switching startup strategy is verified by simulation,which may be used as a reference for test bench's future debugging and operation.

关键词： buffer tank dynamic characteristic dynamic model sCO2 Brayton cycle startup strategy

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LiDAR-Visual SLAM with Integrated Semantic and Texture Information for Enhanced Ecological Monitoring Vehicle Localization

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Computers, Materials & Continua 2025年第1期82卷 1401-1416页

作者： Yiqing Lu Liutao zhao Qiankun zhao Foreign Environmental Cooperation Center Ministry of Ecology and Environment of PRCBeijing100035China Beijing Computing Center Co. Ltd.Beijing Academy of Science and TechnologyBeijing100083China Beijing Guyu Interactive Artificial Intelligence Application Co. Ltd.Beijing100024China

Ecological monitoring vehicles are equipped with a range of sensors and monitoring devices designed to gather data on ecological and environmental *** vehicles are crucial in various fields,including environmental science research,ecological and environmental monitoring projects,disaster response,and emergency management.A key method employed in these vehicles for achieving high-precision positioning is LiDAR(lightlaser detection and ranging)-Visual Simultaneous Localization and Mapping(SLAM).However,maintaining highprecision localization in complex scenarios,such as degraded environments or when dynamic objects are present,remains a significant *** address this issue,we integrate both semantic and texture information from LiDAR and cameras to enhance the robustness and efficiency of data ***,semantic information simplifies the modeling of scene elements,reducing the reliance on dense point clouds,which can be less ***,visual texture information complements LiDAR-Visual localization by providing additional contextual *** incorporating semantic and texture details frompaired images and point clouds,we significantly improve the quality of data association,thereby increasing the success rate of *** approach not only enhances the operational capabilities of ecological monitoring vehicles in complex environments but also contributes to improving the overall efficiency and effectiveness of ecological monitoring and environmental protection efforts.

关键词： LiDAR-Visual simultaneous localization and mapping integrated semantic texture information

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Understanding the local structure and thermophysical behavior of Mg-La liquid alloys via machine learning potential

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 439-449页

作者： Jia zhao Taixi Feng Guimin Lu National Engineering Research Center for Integrated Utilization of Salt Lake Resource East China University of Science and TechnologyShanghai 200237China Joint International Laboratory for Potassium and Lithium Strategic Resources East China University of Science and TechnologyShanghai 200237China

The local structure and thermophysical behavior of Mg-La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg-La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results;the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg-La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg-La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg-La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg-La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

关键词： magnesium-lanthanum liquid alloys local structure macroscopic properties thermodynamic behavior deep potential mo-lecular dynamic simulation

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电感耦合等离子体发射光谱测定钼铝合金中硅含量的方法研究

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分析科学学报 2021年第5期37卷 711-715页

作者：罗策李剑颜燕刘婷康琼赵武丽卢凡宝钛集团有限公司陕西宝鸡721014 陕西省宝鸡教育学院陕西宝鸡721000

采用王水、氢氟酸在180℃加热条件下溶解试样,全面分析了硅元素的212.412、221.667、251.611、252.851、288.158 nm五条分析谱线的受干扰情况,最终选择了灵敏度和信噪比较高、受钼基体干扰程度较小的Si 288.158 nm为分析谱线。使用多谱... 详细信息

采用王水、氢氟酸在180℃加热条件下溶解试样,全面分析了硅元素的212.412、221.667、251.611、252.851、288.158 nm五条分析谱线的受干扰情况,最终选择了灵敏度和信噪比较高、受钼基体干扰程度较小的Si 288.158 nm为分析谱线。使用多谱线拟合(MSF)技术建立了Si 288.158 nm的光谱校正模型,通过校正模型对样品检测信号峰进行了校正,消除了基体钼(Mo 288.137 nm)的光谱干扰,建立了电感耦合等离子体发射光谱法(ICP-OES)测定钼铝合金中硅含量的方法。该方法在0.10~5.00 mg/L范围内(对应固体样品中硅的质量分数范围为0.010%~0.50%),硅的工作曲线线性关系良好,相关系数为0.9995;方法检出限和定量限分别为23μg/g和76μg/g;对3个不同含量的钼铝样品中的硅含量进行了测定,测定结果的相对标准偏差(RSD)在0.76%~1.36%之间,加标回收率在98.0%~106%范围,与标准(YS/T 1075.3-2015)中钼蓝分光光度法的测定结果一致。

关键词：电感耦合等离子体发射光谱法光谱干扰多谱线拟合钼铝合金硅

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Decision making module based on stochastic magnetic tunnel junctions

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 202-209页

作者： Yifan Miao Li zhao Yajun Zhang Zhe Yuan Center for Advanced Quantum Studies and Department of Physics Beijing Normal University Institute for Nanoelectric Devices and Quantum Computing Fudan University Interdisciplinary Center for Theoretical Physics and Information Sciences Fudan University

In biological neural systems, noise is ubiquitous but does not affect the correct decisions made in the complex cognitive ***-making in biological neural system is typically achieved by accumulating input information over a period of *** by recent developments in neurosciences, we design a decision-making module based on spintronic devices, utilizing superparamagnetic tunnel junctions as artificial neurons. The feasibility of this decision-making module is verified through circuit simulations. Taking a multi-layer perceptron as an example, the module significantly improves the accuracy of the perceptron in the handwritten digit recognition task. Furthermore, the spintronic decision-making module offers advantages over the conventional pooling methods, such as adaptive decision time, high performance and the absence of analog-to-digital conversion. The decision-making module is flexible to be integrated into artificial neural networks and provides a general yet effective solution to enhance performance against device noise.

关键词： neuromorphic computing spintronics magnetic tunnel junction neural networks

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