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Immune checkpoint inhibitors:breakthroughs in cancer treatment

Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi zhang Shuwei Chen Xianyang Wang qing Xi Han Shen Rongxin zhang Laboratory of Immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China Department of Biology School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most *** such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical *** antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic ***,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune ***,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 ***,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under ***-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of *** review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： Immunotherapy cancer ICIs PD-1 CTLA-4

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Influence characteristics of water penetration on fibre-reinforced polymer/rigid polyurethane foam interface of the composite cross-arm considering natural ageing

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High Voltage 2024年第1期9卷 81-93页

作者： Jun Xie Zhe Zhou Ziqian Liu Haonan Tian Sigang zhang qing Xie Hebei Provincial Key Laboratory of Power Transmission Equipment Security Defense North China Electric Power UniversityBaodingChina State Grid Gansu Electric Power Company LanzhouChina

Fibre-reinforced polymer(FRP)/rigid polyurethane foam(RPUF)interface is susceptible to moisture intrusion in addition to natural ageing during *** study investigated the influence of moisture intrusion on the FRP/RPUF interface under natural ageing using experiments and molecular dynamics(MD)*** absorption,shear strength,and leakage current tests were used to clarify the changes in the interface *** degradation mechanism of moisture intrusion at the interface under natural ageing was revealed by MD simulation and *** results show that the natural ageing of interfacial materials will slightly reduce the quality of the interface but will reduce the water resistance of the material and promote the process of water intrusion into the *** addition,water mainly invades the interface through *** water penetration,the interfacial bonding strength and insulation performance significantly *** and hydrolysis of interfacial materials are the main reasons for decreased interfacial *** can cause irreversible damage to the interface,increasing interface defects and water *** vicious cycle of material hydrolysis is the ultimate cause of interfacial *** polar molecules produced by this process and the water absorbed by the interface caused the degradation of the interface insulation performance.

关键词： interface polyurethane interfacial

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MK3综掘机岩巷大断面快速掘进技术研究

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煤炭技术 2011年第4期30卷 81-82页

作者：张海清淮南矿业集团矿业工程公司安徽淮南232001

结合顾北矿南翼Y型通风浅部边界巷MK3综掘作业线施工情况,阐述了MK3综掘作业线的施工工艺、劳动组织、技术保障、设备改进等,并针对施工中出现的问题提出了建议,对MK3综掘作业线快速掘进及推广具有一定的借鉴意义。

关键词：岩巷机械化快速掘进

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Odorant receptor orthologues from moths display conserved responses to cis-jasmone

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Insect Science 2024年第4期31卷 1107-1120页

作者： Xiao-qing Hou Zhongqiang Jia Dan-Dan zhang Guirong Wang Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureSynthetic Biology Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenGuangdong ProvinceChina State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijingChina Department of Biology Lund UniversityLundSweden

In insects,the odorant receptor(OR)multigene family evolves by the birth-and-death evolutionary model,according to which the OR repertoire of each species has undergone specific gene gains and losses depending on their chemical environment,resulting in taxon-specific OR lineage radiations with different sizes in the phylogenetic *** the general divergence in the gene family across different insect orders,the ORs in moths seem to be genetically conserved across species,clustered into 23 major clades containing multiple orthologous groups with single-copy gene from each *** hypothesized that ORs in these orthologous groups are tuned to ecologically important compounds and functionally ***-Jasmone is one of the compounds that not only primes the plant defense of neighboring receiver plants,but also functions as a behavior regulator to various *** test our hypothesis,using Xenopus oocyte recordings,we functionally assayed the orthologues of BmorOR56,which has been characterized as a specific receptor for *** results showed highly conserved response specificity of the BmorOR56 orthologues,with all receptors within this group exclusively responding to *** is supported by the dN/dS analysis,showing that strong purifying selection is acting on this ***,molecular docking showed that the ligand binding pockets of BmorOR56 orthologues to cis-jasmone are *** together,our results suggest the high conservation of OR for ecologically important compounds across Heterocera.

关键词： cis-jasmone evolutionary conservation functional characterization molec-ular docking moths purifying selection

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IPv6技术在智慧消防信息网络中的应用

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消防科学与技术 2019年第5期38卷 661-663页

作者：张庆海南京工业职业技术学院

采用IPv6的低速无线个域网技术与IPv4网络相融合,实现消防传感与控制的目的。在构建全IP消防通信网络结构的基础上,重点给出6LoWPAN网络的硬件节点和软件设计方案,并进行组网测试。测试结果表明,通信终端可以完成数据采集与传输,经对数... 详细信息

采用IPv6的低速无线个域网技术与IPv4网络相融合,实现消防传感与控制的目的。在构建全IP消防通信网络结构的基础上,重点给出6LoWPAN网络的硬件节点和软件设计方案,并进行组网测试。测试结果表明,通信终端可以完成数据采集与传输,经对数据包进行抓取和分析,证明IPv6与IPv4网络可以互通。该设计可实现覆盖范围广、建设成本低、智能化程度高的全IP消防信息网络。

关键词： IPv6 6LowPAN 智慧消吩无线通信网络

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Constitutive Behavior of the Interface between UHPC and Steel Plate without Shear Connector:From Experimental to Numerical Study

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Computer Modeling in Engineering & Sciences 2024年第8期140卷 1863-1888页

作者： Zihan Wang Boshan zhang Hui Wang qing Ai Xingchun Huang School of Naval Architecture Ocean and Civil EngineeringShanghai Jiao Tong UniversityShanghai200240China Department of Bridge Engineering Tongji UniversityShanghai200092China

The application of ultra-high performance concrete(UHPC)as a covering layer for steel bridge decks has gained widespread *** employing a connection without a shear connector between the steel plate and UHPC,namely,the sandblasted interface and the epoxy adhesive with sprinkled basalt aggregate interface,the installation cannot only be simplified but also the stress concentration resulting from the welded shear connectors can be *** study develops constitutive models for these two interfaces without shear connectors,based on the interfacial pull-off and push-out *** validation,three-point bending tests on the steel-UHPC composite plates are *** results indicated that the proposed bilinear traction-separation model for the sandblasted interface and the trapezoidal traction-separation model for the epoxy adhesive with sprinkled basalt aggregate interface can generally calibrate the interfacial ***,the utilization of the experimentally determined pure shear strength underestimates the load-carrying capacity of the composite plates in the case of three-point bending *** recalling the Mohr-Coulomb criterion,this underestimation is attributed to the enhancement of the interface shear strength by the presence of normal stress.

关键词： Cohesive zone model interfacial behavior finite element simulation UHPC steel plate

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The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development

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Genes & Diseases 2024年第5期11卷 252-271页

作者： qing Ma Guang Chen Ying Li Zhenming Guo Xue zhang NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Urology The Fourth Hospital of Harbin Medical UniversityHarbinHeilongjiang 150000China Department of Child and Adolescent Health School of Public HealthHarbin Medical UniversityHarbinHeilongjiang 150000China Institute for Regenerative Medicine Shanghai East HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China

Malformations of cortical development(MCD)are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental *** kinds of MCD are caused by genetic *** is the common cause of intellectual disability and intractable *** rapid advances in imaging and sequencing technologies,the diagnostic rate of MCD has been increasing,and many potential genes causing MCD have been successively ***,the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted ***,in this review,we outline important events of cortical *** we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR ***,we briefly discuss the diagnostic methods,disease models,and therapeutic strategies for *** information will facilitate further research on *** the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

关键词： Epilepsy Gene mutation Genetics Malformations of cortical development PI3K/PTEN/AKT/mTOR pathway

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论19世纪法国犹太人的职业转型

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史学集刊 2023年第3期 59-69页

作者：张庆海俞杰华南师范大学历史文化学院广东广州510631

19世纪法国犹太人的职业发展实现了法兰西民族化和现代化的转型,并与法国经济发展的总体特征达成高度契合,犹太人成为法国企业家的重要代表。首先,犹太人在大革命之后即融入法国工业化进程中,其突出表现是犹太人群体的城市化,这是近代... 详细信息

19世纪法国犹太人的职业发展实现了法兰西民族化和现代化的转型,并与法国经济发展的总体特征达成高度契合,犹太人成为法国企业家的重要代表。首先,犹太人在大革命之后即融入法国工业化进程中,其突出表现是犹太人群体的城市化,这是近代法国犹太人融入法兰西民族并实现职业转型的开端和条件;其次,犹太人企业家的经营领域发生了重大变化:从传统高利贷及旧货交易经营模式拓展到近代法国几乎所有经济领域,尤其在金融、工业和服务业等行业具有独特的地位,树立起成功的犹太人企业家群体形象;再次,犹太人企业家在经济领域取得成功,却因为他们的族裔背景受到了类似于“原罪”一般的否定,被作为法国资本主义制度的腐朽象征而备受攻讦,甚至连法国都被种族主义者污蔑为“犹太法国”。

关键词：近代法国犹太人企业家城市化金融资本家

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Evaluation of lightning-induced overvoltage on a 10 kV distribution line based on electromagnetic return-stroke model using finite-difference time-domain

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High Voltage 2024年第2期9卷 356-366页

作者： Pan Duan Lianfang zhang Xiaogang Huang Jian Sun Yue Qi qing Yang School of Automation Chongqing University of Posts and TelecommunicationsChongqingChina Chongqing Power Co Tongnan BurChongqingChina China Southern Power Grid Science Research Institute GuangzhouChina State Key Laboratory of Power Transmission Equipment&System Security and New Technology Chongqing UniversityChongqingChina

Accurate simulation of lightning-induced overvoltage for overhead distribution lines is helpful to prevent lightning trip *** electromagnetic return-stroke model was used to represent lightning and then a 3D finite-difference time-domain(FDTD)method was adopted to simulate the lightning-induced overvoltage on a distribution line without a field-line coupling *** lightning-induced overvoltage behave for different ground conductivity and varying distance between the distribution line and the lightning channel was *** results showed that the overvoltage waveforms at the centre point of the line corresponding to lightning strikes on the lossy ground and an ideal ground(σ=∞)were similar;however,the peak amplitudes of the waveform were affected by soil conductivity at a close *** relationship between magnitude of the overvoltage and distance can be described by a second-order exponential decay ***,the overvoltage calculated using the proposed model was compared with those obtained based on Agrawal's model and measurements made using the newly developed intelligent insulator on *** these comparisons,it could be concluded that the FDTD method with the electromagnetic return-stroke model produces reasonably accurate results of the attenuated oscillation waveform,which can better reproduce the overvoltage on operational distribution lines.

关键词： lightning distribution return

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Tailoring electron vortex beams with customizable intensity patterns by electron diffraction holography

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Opto-Electronic Advances 2024年第2期7卷 14-21页

作者： Pengcheng Huo Ruixuan Yu Mingze Liu Hui zhang Yan-qing Lu Ting Xu National Laboratory of Solid-State Microstructures and Collaborative Innovation Center of Advanced Microstructures Nanjing UniversityNanjing 210093China College of Engineering and Applied Sciences Key Laboratory of Intelligent Optical Sensing and Manipulation and Jiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjing 210093China

An electron vortex beam(EVB) carrying orbital angular momentum(OAM) plays a key role in a series of fundamental scientific researches, such as chiral energy-loss spectroscopy and magnetic dichroism spectroscopy. So far, almost all the experimentally created EVBs manifest isotropic doughnut intensity patterns. Here, based on the correlation between local divergence angle of electron beam and phase gradient along azimuthal direction, we show that free electrons can be tailored to EVBs with customizable intensity patterns independent of the carried OAM. As proof-of-concept, by using computer generated hologram and designing phase masks to shape the incident free electrons in the transmission electron microscope, three structured EVBs carrying identical OAM are tailored to exhibit completely different intensity patterns. Furthermore, through the modal decomposition, we quantitatively investigate their OAM spectral distributions and reveal that structured EVBs present a superposition of a series of different eigenstates induced by the locally varied geometries. These results not only generalize the concept of EVB, but also demonstrate an extra highly controllable degree of freedom for electron beam manipulation in addition to OAM.

关键词： electron vortex beam orbital angular momentum diffraction holography

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