检索结果-南通市图书馆

Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

引用

Acta Pharmaceutica Sinica B 2024年第4期14卷 1742-1758页

作者： Renming Fan Ruizhuo Lin Shuo Zhang Aohua Deng Yongrui Hai Junyan Zhuang Yang Liu Maosheng Cheng Gaofei Wei Institute of Medical Research Northwestern Polytechnical UniversityXi'an 710072China Research&development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Key Laboratory of structure-Based Drug design and Discovery Ministry of EducationSchool of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

关键词： Anti-tumor drug Prodrug Platinum Chemo-immunotherapy Mitochondrial membrane modeling STING Pyroptosis mtDNA

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Study on theoretical model for electrical explosion resistivity of Al/Ni reactive multilayer foil

引用

Defence Technology（防务技术） 2024年第2期32卷 348-356页

作者： Zehao Wang Tao Wang Pengfei Xue Mingyu Li Qingxuan Zeng State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081China China Ship development and design Center Wuhan 430064China

Al/Ni reactive multilayer foil(RMF)possesses excellent comprehensive properties as a promising substitute for traditional Cu bridge.A theoretical resistivity model of Al/Ni RMF was developed to guide the optimization of ***/Ni RMF with different bilayer thicknesses and bridge dimensions were prepared by MEMS technology and electrical explosion tests were carried *** to physical and chemical reactions in bridge,the electrical explosion process was divided into 5 stages:heating of condensed bridge,vaporization and diffusion of Al layers,intermetallic combination reaction,intrinsic explosion,ionization of metal gases,which are obviously shown in measured voltage *** of interface and grain boundary scattering on the resistivity of film metal were *** on variations of substance and state,the resistivity was developed as a function of temperature at each *** explosion curves were calculated by this model at different bilayer thicknesses,bridge dimensions and capacitor voltages,which showed an excellent agreement with experimental ones.

关键词： Al/Ni reactive multilayer foil Electrical explosion Resistivity model Phase transition Calculation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Directly targeting BAX for drug discovery:Therapeutic opportunities and challenges

引用

Acta Pharmaceutica Sinica B 2024年第6期14卷 2378-2401页

作者： Zhenwei Zhang Linghui Hou Dan Liu Shenglin Luan Min Huang Linxiang Zhao Key Laboratory of structure-Based Drugs design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China China Resources Sanjiu Medical&Pharmaceutical Co. Ltd.Shenzhen 518000China

For over two decades,the development of B-cell lymphoma-2(Bcl-2)family therapeutics has primarily focused on anti-apoptotic proteins,resulting in the first-in-class drugs called BH3 mimetics,especially for Bcl-2 inhibitor *** pro-apoptotic protein Bcl-2-associated X protein(BAX)plays a crucial role as the executioner protein of the mitochondrial regulated cell death,contributing to organismal development,tissue homeostasis,and *** dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death,such as cancer,neurodegeneration,and heart *** addition to conducting thorough investigations into the physiological modulation of BAX,research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX,as well as diverse all-molecule BAX *** review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on ***,it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX,offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.

关键词： Apoptosis Pro-apoptotic protein BAX Dynamic conformational activation Small-molecule apoptosis modulators

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer

引用

Acta Pharmaceutica Sinica B 2024年第8期14卷 3605-3623页

作者： Zehui Tan Ning Guo Zhi Cao Shuyu Liu Jiayu Zhang Deyi Ma Jiahao Zhang Wencai Lv Nan Jiang Linghe Zang Lihui Wang Xin Zhai Key Laboratory of structure-Based Drug design and Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacology Shenyang Pharmaceutical UniversityShenyang 110016China

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung ***,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q *** most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar *** cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS *** the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in *** study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling ***,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.

关键词： DOT1L R231Q mutation Lung cancer Adenosine-containing inhibitors Epigenetics

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Comparative Analysis of Reaction to Fire and Flammability of Hemp Shives Insulation Boards with Incorporated Microencapsulated Phase Change Materials

引用

Journal of Renewable Materials 2024年第3期12卷 603-613页

作者： Inga Zotova Edgars Kirilovs Laura Ziemele Institute of Architecture and design Riga Technical UniversityRigaLV-1048Latvia Forest and Wood Products Research and development Institute JelgavaLV-3001Latvia

Nowadays buildings contain innovative materials,materials from local resources,production surpluses and rapidly renewable natural *** Change Materials(PCM)are one such group of novel materials which reduce building energy *** the wider availability of microencapsulated PCM,there is an opportunity to develop a new type of insulating materials,combinate PCM with traditional insulation materials for latent heat energy *** materials are typically flammable and are located on the interior wall finishing yet there has been no detailed assessment of their fire *** this research work prototypes of low-density insulating boards for indoor spaces from hemp shives using carbamide resin binder and cold pressing were ***-scale cone calorimeter tests were conducted to evaluate fire risk,with a focus on assessing material flammability properties and the influence of PCM on the *** this research,the amount of smoke,heat release rate,effective heat of combustion,specific extinction coefficient,mass loss,carbon dioxide yield,specific loss factor,ignition time of hemp straws samples and samples of hemp straws with 10%and without PCM admixture were *** is a risk of flammability for PCM and their fire reaction has not been evaluated when incorporating PCM into interior wall finishing *** obtained results can be used by designers to balance the potential energy savings of using PCM with a more complete understanding and predictability of the associated fire risk when using the proposed *** also allows for appropriate risk mitigation strategies.

关键词： Encapsuled phase change material renewable resources reaction to fire flammability

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Wind Turbine Gearbox Fault Diagnosis Based on Multi-sensor Signals Fusion

引用

Protection and Control of Modern Power Systems 2024年第4期9卷 96-109页

作者： Yao Zhao Ziyu Song Dongdong Li Rongrong Qian Shunfu Lin the College of Electrical Engineering Shanghai University of Electric PowerShanghai 200090China IEEE the design Research and development Center AECC Commercial Aircraft Engine Co. Ltd.Shanghai 200241China

This paper proposes a novel fault diagnosis method by fusing the information from multi-sensor signals to improve the reliability of the conventional vibration-based wind turbine drivetrain gearbox fault diagnosis *** method fully extracts fault features for variable speed,insufficient samples,and strong noise scenarios that may occur in the actual operation of a wind turbine planetary ***,multiple sensor signals are added to the diagnostic model,and multiple stacked denoising auto-encoders are designed and improved to extract the fault ***,a cycle reservoir with regular jumps is introduced to fuse multidimensional fault information and output diagnostic results in response to the insufficient ability to process fused information by the conventional Softmax *** addition,the competitive swarm optimizer algorithm is introduced to address the challenge of obtaining the optimal combination of parameters in the ***,the validation results show that the proposed method can increase fault diagnostic accuracy and improve robustness.

关键词： Wind turbine gearbox fault diagnosis multiple scenarios deep learning stacked denoising au-to-encoder cycle reservoir with regular jumps feature fusion network

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Identifying Brand Consistency by Product Differentiation Using CNN

引用

Computer Modeling in Engineering & Sciences 2024年第7期140卷 685-709页

作者： Hung-Hsiang Wang Chih-Ping Chen Department of Industrial design National Taipei University of TechnologyTaipeiTaiwan Department of Product design Ming Chuan UniversityTaoyuanTaiwan

This paper presents a new method of using a convolutional neural network(CNN)in machine learning to identify brand consistency by product appearance *** Experiment 1,we collected fifty mouse devices from the past thirty-five years from a renowned company to build a dataset consisting of product pictures with pre-defined design features of their appearance and *** show that it is a challenge to distinguish periods for the subtle evolution of themouse devices with such traditionalmethods as time series analysis and principal component analysis(PCA).In Experiment 2,we applied deep learning to predict the extent to which the product appearance variation ofmouse devices of various *** investigation collected 6,042 images ofmouse devices and divided theminto the Early Stage and the Late *** show the highest accuracy of 81.4%with the CNNmodel,and the evaluation score of brand style consistency is 0.36,implying that the brand consistency score converted by the CNN accuracy rate is not always perfect in the real *** relationship between product appearance variation,brand style consistency,and evaluation score is beneficial for predicting new product styles and future product style *** addition,the CNN heat maps highlight the critical areas of design features of different styles,providing alternative clues related to the blurred *** study provides insights into practical problems for designers,manufacturers,and marketers in product *** not only contributes to the scientific understanding of design development,but also provides industry professionals with practical tools and methods to improve the design process and maintain brand *** can use these techniques to find features that influence brand ***,capture these features as innovative design elements and maintain core brand values.

关键词： Machine learning product differentiation brand consistency principal component analysis convolutional neural network computer mouse

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Exploring the combination of biochar‐amended soil and automated irrigation technology for water regulation and preservation in green infrastructure

引用

Deep Underground Science and Engineering 2024年第1期3卷 39-52页

作者： Honghu Zhu Yuanxu Huang Haihong Song Jian Chen Songlei Han Tanwee Mazumder Ankit Garg School of Earth Sciences and Engineering Nanjing UniversityNanjingChina Department of Civil and Smart Engineering Construction Guangdong Engineering Center for Structure Safety and Health MonitoringShantou UniversityShantouChina Shanghai Municipal Engineering design Co. LtdShanghaiChina Indian Institute of Technology Madras ChennaiIndia

Biochar is a carbon sink material with the potential to improve water retention in various ***,for the long‐term maintenance of green infrastructure,there is an additional need to regulate the water contents in the covers to maintain vegetation growth in semiarid *** this study,biochar‐amended soil was combined with subsurface drip irrigation,and the water preservation characteristics of this treatment were investigated through a series of one‐dimensional soil column *** ascertain the best treatment method specific to semiarid climatic conditions,the test soil was amended with 0%,1%,3%,and 5%*** irrigation devices equipped with soil moisture sensors were used to control the subsurface water content with the aim of enhancing vegetation *** soil column test lasted 150 h,during which the volumetric water contents and soil suction data were *** experimental results reveal that the soil specimen amended with 3%biochar is the most water‐saving regardless of the time *** with a higher biochar content(e.g.,5%)consumes a more significant amount of water due to the enhancement of the water‐holding *** on the experimental results,it can be concluded that the appropriate ratio can be determined within 1%–3%,which can reduce not only the amount of irrigated/used water but also the time *** technology can be explored for water content regulation in green infrastructure and the development of barriers for protecting the environment around deep underground waste containment.

关键词： biochar drip irrigation underground water preservation water regulation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Problem identification and revitalization strategies for the recovery and reconstruction of traditional villages in the Ms 6.8 Luding Earthquake

引用

Journal of Mountain Science 2024年第2期21卷 361-379页

作者： HUANG Chao QIU Jian LIU Chun JIANG Rui ZHAO Chuanrong ZHANG Yi School of Architecture and Research Center of Space Planning and Engineering design Southwest Jiaotong UniversityChengdu 611756China Sichuan Provincial Rural Construction and development Center Chengdu 610041China Sichuan Institute of Urban and Rural Construction Chengdu 610043China China Association for Promoting Democracy(CAPD)Sichuan Provincial Committee Chengdu 610016China Sichuan Provincial Architectural design and Research Institute(SADI) Chengdu 610095China

Post-disaster reconstruction is a topic of global concern,and traditional villages have special heritage attributes and need to face more requirements and obstacles in post-disaster *** paper summarizes four concepts based on the research on post-disaster reconstruction both domestically and internationally,as well as the recovery and reconstruction of cultural *** a field survey of traditional villages in the Ms 6.8 Luding earthquake-stricken area,it is found that there are problems such as insufficient awareness of heritage value,misalignment of scientific reconstruction technology,and insufficient protection of reconstruction elements during the reconstruction *** villages face the risk of declining or even loss of heritage *** order to effectively protect traditional villages and inherit the carrier of regional culture,four targeted reconstruction response strategies are proposed,i.e.,to"establish special planning for traditional village preservation","emphasize recovery of the authenticity of village heritage","ensure elements for village heritage recovery"and"promote the activation and utilization of village heritage",based on the problems discovered during the survey and the four concepts summarized in the research on post-disaster reconstruction of traditional *** research results hope to provide useful reference for ancient cultural areas affected by earthquakes on how to protect cultural heritage during the post-disaster reconstruction process.

关键词： Seismic hazard Decision making Traditional village Cultural heritage protection Post-earthquake recovery and reconstruction Revitalization strategy

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Resonance mechanism of flapping wing based on fluid structure interaction simulation

引用

Chinese Journal of Aeronautics 2024年第5期37卷 243-262页

作者： Yueyang GUO Wenqing YANG Yuanbo DONG Dong XUE National Key Laboratory of Science and Technology on Aerodynamic design and Research School of AeronauticsNorthwestern Polytechnical UniversityXi'an 710072China Research&development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518063China Yangtze River Delta Research Institute of Northwestern Polytechnical University Taicang 215400China

Certain insect species have been observed to exploit the resonance mechanism of their *** order to achieve resonance and optimize aerodynamic performance,the conventional approach is to set the flapping frequency of flexible wings based on the Traditional Structural Modal(TSM)***,there exists controversy among researchers regarding the relationship between frequency and aerodynamic *** that the structural response of wings can be influenced by the surrounding air vibrations,an analysis known as Acoustic structure Interaction Modal(ASIM)is introduced to calculate the resonant *** this study,Fluid structure Interaction(FSI)simulations are employed to investigate the aerodynamic performance of flapping wings at modal frequencies derived from both TSM and ASIM *** performance is evaluated for various mass ratios and frequency ratios,and the findings indicate that the deformation and changes in vortex structure exhibit similarities at mass ratios that yield the highest aerodynamic ***,the flapping frequency associated with the maximum time-averaged vertical force coefficient at each mass ratio closely aligns with the ASIM frequency,as does the frequency corresponding to maximum ***,the ASIM analysis can provide an effective means for predicting the optimal flapping frequency for flexible ***,it enables the prediction that flexible wings with varying mass ratios will exhibit similar deformation and vortex structure *** paper offers a fresh perspective on the ongoing debate concerning the resonance mechanism of Flexible Flapping Wings(FFWs)and proposes an effective methodology for predicting their aerodynamic performance.

关键词： Flexible Flapping Wing(FFW) Acoustic structure Interaction Modal(ASIM) Fluid structure Interaction(FSI) Resonance mechanism Aerodynamic performance

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：