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

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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

Chemoselective Dual Functionalization of Phenols via Relay Catalysis of Borane with Different Forms

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CCS Chemistry 2021年第8期3卷 2248-2261页

作者： Xiaowen Tang Xiang Luo Qiong Su gaofei wei Shan-Shui Meng Albert S.C.Chan School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006 School of Pharmacy Qingdao UniversityQingdao 266021 Institute of Medical Research Northwestern Polytechnical UniversityXi’an 710072

A highly efficient and chemoselective dual functionalization of unprotected phenols withα-orβ-hydroxyl acids is presented.A variety of valuable benzofuranones and dihydrocoumarins are delivered in moderate to high *** functional theory(DFT)calculations and control experiments indicate that an untypical Friedel–Crafts alkylation and the subsequent lactonization are catalyzed by the Lewis acid form and the Brønsted acid form of borane,***-scale experiments and late-stage functionalization of complex molecules have been performed to highlight the utility of this reaction.

关键词： relay catalysis Friedel–Crafts alkylation unprotected phenols borane ortho-selectivity

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基于局域均值分解的船舶轴系故障特征分析

上海船舶运输科学研究所学报 2019年第1期42卷 27-32页

作者：魏高飞张丹瑞上海船舶运输科学研究所航运技术与国家安全重点实验室上海200135

针对船舶轴系故障振动信号的非线性和非平稳性特点,结合轴系试验台,提出基于局域均值分解(Local Mean Decomposition,LMD)的轴系故障特征分析方法。基于LMD方法将船舶轴系的轴承座振动信号分解成若干个PF(Product Function)分量进行分析... 详细信息

针对船舶轴系故障振动信号的非线性和非平稳性特点,结合轴系试验台,提出基于局域均值分解(Local Mean Decomposition,LMD)的轴系故障特征分析方法。基于LMD方法将船舶轴系的轴承座振动信号分解成若干个PF(Product Function)分量进行分析,得到各PF分量的幅值和频率,实现对原始数据的解调。采用1.5维谱对LMD分解得到的具有故障特征的PF分量进行后处理,得到振动信号的故障特征,证明试验台的轴系存在不对中故障。

关键词：局域均值分解船舶轴系振动分析故障特征

建筑施工液压模架体系智能多点同步顶升技术应用

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施工技术 2017年第16期46卷 14-17页

作者：潘春龙王高飞魏小海张万实陈思明中建三局集团有限公司辽宁沈阳110000

沈阳宝能环球金融中心项目T1塔楼为在建东北第一高楼,其结构形式为巨型外框+伸臂桁架+劲性混凝土核心筒结构。本工程液压模架的同步顶升控制系统主要包括多功能阀组、位移及压力数据监测系统和控制系统,在主顶升油缸顶升/缩回过程中,行... 详细信息

沈阳宝能环球金融中心项目T1塔楼为在建东北第一高楼,其结构形式为巨型外框+伸臂桁架+劲性混凝土核心筒结构。本工程液压模架的同步顶升控制系统主要包括多功能阀组、位移及压力数据监测系统和控制系统,在主顶升油缸顶升/缩回过程中,行程监测装置全程连续监测14支油缸的位移及压力,并通过电控系统以电信号形式传递给控制台及对应电磁闸阀,自动调节输送的油量,实现对14支顶升油缸的同步控制。操作人员只需在中央控制室与计算机进行简单的人机交互便可实现液压模架各支承点的同步升降。操作人员不仅能够实时监控各液压缸的压力、位移大小,而且还能够检测压力、位移的变化趋势、历史纪录等,对于泵站各阀件的工作状态也能够实时监控,便于故障的排除。

关键词：高层建筑液压模架同步升降监测应用

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催化裂化新工艺发展现状

石油工程建设 2019年第5期45卷 1-4,11页

作者：葛营杨林邴生彬卫高飞中国石油天然气第一建设公司

随着环保要求的日益严格,对降低汽油烯烃含量和生产低碳烯烃提出了迫切需求。催化裂化装置作为炼厂改质重质馏分油和生产轻质清洁燃料的核心装置,在改善产品品种分布和满足不同工艺生产目的方面取得了各种进展。简要介绍了单提升管反应... 详细信息

随着环保要求的日益严格,对降低汽油烯烃含量和生产低碳烯烃提出了迫切需求。催化裂化装置作为炼厂改质重质馏分油和生产轻质清洁燃料的核心装置,在改善产品品种分布和满足不同工艺生产目的方面取得了各种进展。简要介绍了单提升管反应器、多段进料提升管反应器、双提升管反应器、下行式催化裂化反应器、提升管与下行床反应器组合装置等,重点阐述各类型催化裂化反应装置的结构形式、工作原理、性能设计特点及适用范围。最后指出当前催化裂化工艺存在的问题,并对发展趋势进行了展望。

关键词：催化裂化反应器发展现状结构形式工作原理性能设计适用范围

Daylight and thermal performance of a switchable ethylene tetra-fluoro-ethylene cushion with dynamic control in different climates

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Building Simulation 2022年第1期15卷 29-40页

作者： Wanfang Zhao wei He Zhongting Hu Xiaoyu Zheng Sheng Zhang gaofei Xu Hongbing Chen Yanping Yuan Department of Building Environment and Equipment Hefei University of TechnologyHefei 230009China Anhui KEEN New Energy Co. LtdHefei 230000China School of Environment and Energy Engineering Beijing University of Civil Engineering and ArchitectureBeijing 100044China School of Mechanical Engineering Southwest Jiaotong UniversityChengdu 610031China

Switchable multi-layer ethylene tetra-fluoro-ethylene(ETFE)cushion controls the natural light and heat flux passing through the cushion with varying outdoor conditions by dynamically modifying its *** this paper,the switchable ETFE cushions with ink printing of different optical and thermal properties were adopted as the window in a typical office model,and the indoor daylight and energy consumption were simulated by using Grasshopper *** model was built to validate the numerical *** locations representing five climate zones in China were selected to analyze the feasibility of the switchable ETFE cushion in different *** hourly indoor daylight and heat gain in a single day revealed the effects of the dynamic mechanism of ETFE cushion in improving indoor natural light and thermal *** addition,the annual daylight performance at the working area(1.5 m from the window)was *** cushion with printing of the lowest transmittance(ETFE1)was the optimal option for most cities and window-to-wall ratios,with the percentage of annual useful daylight hours up to 78.6%,except for the cases where the window-to-wall ratio(WWR)was 0.35 in Harbin,Beijing,and *** distribution of useful daylight hours revealed that ETFE cushions with low,medium,and high printing transmittance were suitable for offices where people work in the front,medium,and back region of the room,*** consumption calculation revealed that ETFE1 showed advantages over other windows in most cities except for cities highly dominated by ***1 delivered up to 33%of energy saving over a year in Kunming compared with the conventional double glazing but was not superior in cities with high heating and low cooling demands,such as Harbin.

关键词： ethylene tetra-fluoro-ethylene(ETFE) useful daylight illuminance(UDI) energy consumption office building double glazing

Geometric modeling of underground ferromagnetic pipelines for magnetic dipole reconstruction-based magnetic anomaly detection

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Petroleum 2020年第2期6卷 189-197页

作者： Dandan Zhao Zhiyong Guo Jian Du Zhongxiang Liu wei Xu gaofei Liu School of Mechatronic Engineering Southwest Petroleum UniversityChengdu610500China China Petroleum Pipeline Insptection Technologies Co. LtdLangfang065000China

To aid the magnetic anomaly detection(MAD)of underground ferromagnetic pipelines,this paper proposes a geometric modeling method based on the magnetic dipole reconstruction method(MDRM).First,the numerical modeling of basic pipe components such as straight sections,bends and elbows,and tee joints are discussed and the relevant mathematical formulations for these components are ***,after analyzing the function of MDRM and various element division strategies,the sectional division and blocked division methods are introduced and applied to the appropriate pipeline components to determine the volume and center coordinates of each element,establishing the general models for the three typical pipeline components *** resulting volume and center coordinates of each component are the fundamental parameters for determining the MAD forwarding of underground ferromagnetic pipelines using the ***,based on the combination and transformation of the basic pipeline components considered,the visualized geometric models of typical pipeline layouts including parallel pipelines,pipelines with elbows,and a pipeline with a tee joint are *** results demonstrate the feasibility of the proposed method of geometric modeling for the MDRM,which can be further applied to the finite element modeling of these and other components when analyzing MAD ***,the models with output parameters proposed in this paper establish a foundation for the inversion of MAD.

关键词： Magnetic anomaly detection Magnetic dipole reconstruction Segmentation method Pipeline detection Geometric modeling

Peak compression technique in high-performance liquid chromatography

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Chinese Science Bulletin 2009年第16期54卷 2805-2809页

作者： wei YuXia WANG Lin XIAO ShengYuan QING Hong ZHU Yong HU gaofei DENG YuLin School of Life Science and Technology Beijing Institute of Technology Beijing 100081 China

Peak compression technique based on the difference of the solute migration velocity in two different mobile phases was described theoretically and confirmed using benzaldehyde and 4-hydroxyquinoline (4-HQ) as model compounds. After peak compression, the peak compression factors (the ratio of peak width at half-height under non-compression and that under compression condition) of benzaldehyde and 4-HQ were 0.19 and 0.13, respectively. By this application of the peak compression technique to the mixture, both enhanced peak height and good separation were obtained in one run cycle. This peak compression technique was introduced to determine benzaldehyde from semicarbazide-sensitive amine oxidase-catalyzed enzymetic reaction in order to illustrate the applicability of this technique to the real sample. As a result, the peak was compressed effectively, and 4.94-fold, 19.3-fold and 5.74-fold enhancement in peak height, plate number and signal to noise ratio were also achieved, respectively.

关键词：压缩技术高效液相色谱模型化合物脲甲醛迁移速度羟基喹啉压缩条件运行周期

Genomic divergence in cotton germplasm related to maturity and heterosis

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Journal of Integrative Plant Biology 2019年第8期61卷 929-942页

作者： Shoupu He gaofei Sun Longyu Huang Daigang Yang Panhong Dai Dayun Zhou Yuzhen Wu Xiongfeng Ma Xiongming Du Shoujun wei Jun Peng Meng Kuang Research Base State Key Laboratory of Cotton BiologyAnyang Institute of TechnologyAnyang 455000China Institute of Cotton Research of the Chinese Academy of Agricultural Sciences Anyang 455000China Department of Computer Science and Information Engineering/Data Mining Institute Anyang Institute of TechnologyAnyang 455000China

Commercial varieties of upland cotton(Gossypium hirsutum)have undergone extensive breeding for agronomic traits,such as fiber quality,disease resistance,and *** breeding programs have widely used Chinese upland cotton source germplasm(CUCSG)with excellent agronomic traits.A better understanding of the genetic diversity and genomic characteristics of these accessions could accelerate the identification of desirable ***,we analyzed 10,522 high-quality singlenucleotide polymorphisms(SNP)with the CottonSNP63 K microarray in 137 cotton accessions(including 12 hybrids of upland cotton).These data were used to investigate the genetic diversity,population structure,and genomic characteristics of each population and the contribution of these loci to *** subgroups were identified,in agreement with their knownpedigrees,geographical distributions,and times since *** each group,we identified lineagespecific genomic divergence regions,which potentially harbor key alleles that determine the characteristics of each group,such as early maturity-related *** of the distribution of heterozygous loci,among 12 commercial cotton hybrids,revealed a potential role for these regions in *** study provides insight into the population structure of upland cotton ***,the overlap between lineagespecific regions and heterozygous loci,in the high-yield hybrids,suggests a role for these regions in cotton heterosis.

关键词： upland cotton fiber quality genetic diversity