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Alternative splicing of inner-ear-expressed genes

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Frontiers of Medicine 2016年第3期10卷 250-257页

作者： Yanfei Wang Yueyue Liu Hongyun Nie Xin Ma zhigang xu Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology School of Life Sciences Shandong University Jinan 250100 China School of Control Science and Engineering Shandong University Jinan 250061 China

Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 （Cdh23） gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23（＋ 68） is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnmal, which encodes for the a subunit of the Ca2＋-activated K~ channel （BK channel）, has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer Cov） mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

关键词： alternative splicing inner ear hearing loss hair cells

The PDZ-Containing Unconventional Myosin XVIIIA Regulates Embryonic Muscle Integrity in Zebrafish

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Journal of Genetics and Genomics 2014年第8期41卷 417-428页

作者： Jianmeng Cao Shangqi Li Ming Shao Xiaoning Cheng zhigang xu Deli Shi School of Life Sciences Shandong University Sorbonne Universite's UPMC Univ Paris 06UMR 7622Laboratory of Developmental BiologyF-75005 ParisFrance CNRS UMR 7622Laboratory of Developmental BiologyF-75005 ParisFrance

Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.

关键词： Myosin XVIIIA MYO18A Unconventional myosin Myofiber Muscle Dystrophin Dystroglycan Zebrafish

In situ synthesis of a porous high-Mn and high-Al steel by a novel two-step pore-forming technique in vacuum sintering

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Journal of Materials Science & Technology 2020年第4期39卷 82-88页

作者： Chuanbing Zhuang zhigang xu Shangyu Huang Yu Xia Chuanbin Wang Qiang Shen Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China Hubei Collaborative Innovation Center for Automotive Components Technology Wuhan University of TechnologyWuhan 430070China School of Materials Science and Engineering Wuhan University of TechnologyWuhan 430070China State Key Lab of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Hubei Engineering Research Center for Green Precision Materials Forming Wuhan University of TechnologyWuhan 430070China

In this work, a novel in-situ two-step pore-forming process in vacuum sintering(ITPVS) technique combining low-temperature processing to produce open pores through the interdiffusion among the intrinsic components in the base steel, and subsequent high-temperature processing to further improve the porosities by the sublimation of Mn via previously formed open pores, was proposed to produce a lab-scale porous Fe Mn Al steel. For the first time, a high-Mn and high-Al steel with open and overall porosities of ~59.6 vol.% and ~63.7 vol.%(percent in volume, vol.%) was synthesized by isothermal holding of the quaternary elemental Fe/Mn/Al/C powder mixture at 640℃ for 1 h and the subsequent sintering at 1200℃ for 1 h. Elemental Al partly incorporated into/reacted with α-Fe and α-Mn after sintering at640℃ for 1 h, leading to the overall and open porosities promoting by ~26.6 vol.% and ~25.6 vol.%. After sintering at 1200℃, Fe Mn Al steel with increased porosities mainly comprising of austenite and α-Fe obtained. The compression strength and corresponding strain of the 1200℃-sintered porous specimen without crack on the surface was ~75 MPa and ~25%. The ITPVS technique takes advantage of using the intrinsic components like Al, Mn and Fe in steels to produce porous structure. This is beneficial to avoiding the contamination of the Fe Mn Al steel matrix caused by the employment of the foreign pore-forming agents.

关键词： Porous metal High manganese steel Two-stage sintering Reaction-diffusion Sublimation method

Indocyanine Green-Conjugated Magnetic Prussian Blue Nanoparticles for Synchronous Photothermal/Photodynamic Tumor Therapy

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Nano-Micro Letters 2018年第4期10卷 324-338页

作者： Peng xue Ruihao Yang Lihong Sun Qian Li Lei Zhang zhigang xu Yuejun Kang Faculty of Materials and Energy Institute for Clean Energy and Advanced Materials Southwest University Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices State Key Laboratory of Silkworm Genome Biology Southwest University

Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.

关键词： Combination therapy Prussian blue nanoparticles Photothermal therapy Photodynamic therapy Indocyanine green

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集成学习框架下的车辆跟驰行为建模

哈尔滨工业大学学报 2024年第3期56卷 46-55页

作者：李立李仕琪徐志刚李光泽汪贵平长安大学电子与控制工程学院西安710064 长安大学信息工程学院西安710064

为了提高复杂行驶环境下车辆跟驰行为预测精度,提出了一种集成学习框架下融合理论驱动模型和数据驱动模型的车辆跟驰行为建模方法。基于stacking集成学习框架,选择理论驱动的智能驾驶模型(IDM)、考虑车辆队列和周围行驶条件因素的数据... 详细信息

为了提高复杂行驶环境下车辆跟驰行为预测精度,提出了一种集成学习框架下融合理论驱动模型和数据驱动模型的车辆跟驰行为建模方法。基于stacking集成学习框架,选择理论驱动的智能驾驶模型(IDM)、考虑车辆队列和周围行驶条件因素的数据驱动的长短时记忆(LSTM)网络和门控循环单元(GRU)网络作为跟驰行为特征的一级学习算法,选择3种线性和8种非线性回归方法作为备选二级学习算法来融合一级学习器的输出特征。通过对比使用实际车辆轨迹数据计算的模型预测精度,确定了最优模型。研究结果表明:包含车辆队列和周围行驶条件变量的数据驱动跟驰模型比IDM模型的预测精度更高;多数情况下采用非线性二级学习算法的融合跟驰模型的预测精度高于IDM模型、数据驱动跟驰模型以及采用线性二级学习算法的融合跟驰模型;分别采用GBRT回归和随机森林回归作为二级学习算法的IDM-LSTM-stacking模型和IDM-GRU-stacking模型具有最高的预测精度;外界干扰下的融合跟驰模型稳定性优于单一的理论和数据驱动跟驰模型。集成学习为驾驶行为建模提供了新方法。

关键词：交通工程跟驰模型集成学习理论驱动模型数据驱动模型

Facile microwave-assisted synthesis of 1H-pyrazino[1,2-a]quinoxaline-1,5(6H)-dione derivatives via a nucleophilic substitution reaction

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Science China Chemistry 2015年第7期58卷 1239-1242页

作者： Xiaoyan Zhang Guiting Song Hailei Cui zhigang xu Jin Zhu Zhongzhu Chen Key Laboratory of the Ministry of Education for Advanced Catalysis Materials Department of Chemistry and Life Science Zhejiang Normal University Key Laboratory for Asymmetric Synthesis and Chiral Technology of Sichuan Province Chengdu Institute of Organic Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences Drug Discovery Center of Innovation Chongqing University of Arts and Sciences

A series of compounds containing the 1H-pyrazino[1,2-a]quinoxaline-1,5(6H)-dione scaffold have been synthesized using a one-pot procedure under microwave irradiation. This new strategy allowed for the facile synthesis of target compounds in good yields and could be readily applied to the construction of diverse libraries of compounds for high throughput screening in medicinal chemistry.

关键词：微波辅助合成亲核取代反应酮衍生物吡嗪喹喔啉轻便高通量筛选化合物

中国粮食安全保障的农地规模经营逻辑——基于农户与地块双重规模经济的分析视角

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管理世界 2024年第5期40卷 106-120页

作者：徐志刚章丹程宝栋南京农业大学经济管理学院南京农业大学金善宝农业现代化发展研究院北京林业大学经济管理学院

粮食安全保障是维护国家安全与社会稳定的重要内容和基础。农地规模经营可提升劳动生产率与收入,但其土地产出率及粮食安全效应却因规模经济与规模不经济之争一直存在争议。本文创新性地从农户规模经济和地块规模经济两个维度解析规模经... 详细信息

粮食安全保障是维护国家安全与社会稳定的重要内容和基础。农地规模经营可提升劳动生产率与收入,但其土地产出率及粮食安全效应却因规模经济与规模不经济之争一直存在争议。本文创新性地从农户规模经济和地块规模经济两个维度解析规模经济,抓住规模经营机械化和雇工化特点,再度审视粮食“规模-单产”关系。本文构建刻画机械化和雇工化对“规模-单产”关系影响逻辑的分析框架,借助对水稻和玉米的农艺和要素特点的比较分析,阐释了不同粮食作物因为耕地资源可获性和农艺及劳动投入特征差异导致机械作业标准化程度与雇工道德风险劳动质量差异,并影响农户和地块规模经济及“规模-单产”关系的经济逻辑。基于全国4省农户与地块抽样调查数据,实证研究表明:(1)水稻和玉米地块层面“规模-单产”均呈“倒U型”关系,但农户层面“规模-单产”关系,水稻为“倒U型”,玉米则为“U型”;(2)中国农业发展现阶段机械技术模式下的规模经营机械化和雇工化在粮食生产农户规模与地块规模影响单产过程中发挥着重要的中介作用。机械作业效率和技术进步有增产效应,但会受地块规模经济约束;雇工专业分工的高劳动质量增产效应会被道德风险低劳动质量影响抵消,但机械化可缓解雇工道德风险问题。调节粮食“规模-单产”关系必须结合机械化和雇工化,从审视粮食生产农艺和资源、技术约束入手。研究结论可为推动劳动生产率与土地产出率协同增长,协调农民增收和保障粮食安全关系提供新的理论指导依据。

关键词：粮食安全土地产出率规模经济机械化雇工化

Polydopamine(PDA)-activated cobalt sulfide nanospheres responsive to tumor microenvironment(TME)for chemotherapeutic-enhanced photothermal therapy

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Chinese Chemical Letters 2021年第3期32卷 1055-1060页

作者： Mengmeng Hou Yuanxin Zhong Lei Zhang zhigang xu Yuejun Kang Peng xue School of Materials and Energy Southwest UniversityChongqing 400715China State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqing 400716China

Most recently,cobalt sulfide(CoS)nanospheres(NSs)have been demonstrated as an ideal high-efficient photothermal agent for tumor elimination.Howeve r,the surface of CoS NSs is lack of functio nal chemical groups or active radicals to incorporate therapeutic agents,which tremendously hinders their versatile utilization in medical field.Here,surface activation of CoS NSs was realized through the growth of polydopamine(PDA)in situ via alkaline-triggered polymerization.Upon the formation of CoS@PDA NSs,thiol-polyethylene glycol(SH-PEG)and chemotherapeutic agent of doxorubicin(DOX)were loaded onto the particle surface by means ofπ-πelectrostatic interaction and Michael addition reactions.Assynthesized CoS@PDA/PEG/DOX(CoPPD)NSs exhibited an admirable photothermal property and high loading capacity of DOX(44.6%).Furthermore,drug release can be accelerated under a more acidic pH condition mimicking tumor microenvironment(TME),ascribed to the protonation of amino group in DOX molecules.Finally,a strong chemotherapeutic-enhanced photothermal therapeutic effect was demonstrated toward solid tumor under near-infrared(NIR)light irradiation without causing significant systemic toxicity.In this regard,this paradigm may offer valuable guidance for the design of multifunctional CoS-based nanoagents for medical treatment.

关键词： Cobalt sulfide nanospheres Polydopamine Tumor microenvironment Drug delivery Combination therapy

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智能网联环境下车载终端的发展现状与挑战

汽车安全与节能学报 2024年第3期15卷 295-308页

作者：张永升李逸椆王亮徐志刚中车戚墅堰机车车辆工艺研究所股份有限公司常州213011 电子科技大学信息与软件工程学院成都610054 清华大学车辆与运载学院北京100084 长安大学信息工程学院陕西西安710000

随着智能网联技术的快速发展,智能网联汽车装配的智能车载终端功能也相应扩展。经过数十年的进步,智能车载终端系统在多个领域取得了显著的发展,并在自动驾驶领域展现出巨大的潜力。该文从智能车载终端在智能网联环境中的现状入手,描述... 详细信息

随着智能网联技术的快速发展,智能网联汽车装配的智能车载终端功能也相应扩展。经过数十年的进步,智能车载终端系统在多个领域取得了显著的发展,并在自动驾驶领域展现出巨大的潜力。该文从智能车载终端在智能网联环境中的现状入手,描述了智能车载终端系统的架构,并回顾了在车间通信和车路协同赋能下车载终端系统的发展历程;对5G时代车联网无线通信技术的创新对智能车载终端发展的重大影响做了深入分析,并详细回顾了在协同驾驶与控制、边缘计算与雾计算、数字孪生等领域的最新研究成果,同时指出了智能车载终端在信息安全和自动驾驶测试领域面临的挑战。

关键词：自动驾驶技术车载单元网联化智能网联车辆通信