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蛋白质组氨酸磷酸化修饰的调节及功能作用

生物化学与生物物理进展 2024年第10期51卷 2694-2704页

作者：刘萧然邢美宁应万涛军事科学院军事医学研究院生命组学研究所医学蛋白质组全国重点实验室北京蛋白质组研究中心国家蛋白质科学中心(北京)北京102206

组氨酸磷酸化(pHis)在原核和真核生物的生命活动中发挥重要调控作用,并与包括恶性肿瘤在内的多种病理过程相关。pHis修饰中磷酰胺键在高温和低pH下容易断裂,其高度不稳定性导致对pHis修饰的鉴定和研究进展缓慢。近年来,磷酸化蛋白质组... 详细信息

组氨酸磷酸化(pHis)在原核和真核生物的生命活动中发挥重要调控作用,并与包括恶性肿瘤在内的多种病理过程相关。pHis修饰中磷酰胺键在高温和低pH下容易断裂,其高度不稳定性导致对pHis修饰的鉴定和研究进展缓慢。近年来,磷酸化蛋白质组学新技术的发展以及pHis特异性抗体的出现,推动了p His修饰蛋白底物的鉴定和功能研究。首次在哺乳动物细胞中鉴定到超过700个pHis修饰蛋白,并陆续发现黏着斑激酶(FAK)和磷酸甘油酸变位酶1(PGAM1)等蛋白质的pHis修饰能促进肿瘤发展。本文主要探讨组氨酸激酶和组氨酸磷酸酶在调控特定蛋白质pHis修饰中的关键机制及其功能,以期为pHis修饰蛋白的生物学功能研究奠定基础。

关键词：蛋白质磷酸化组氨酸激酶组氨酸磷酸酶组氨酸磷酸化

考虑弱势群体疏散行为特征的高层住院楼疏散仿真及优化

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科学技术与工程 2024年第2期24卷 715-722页

作者：刘晓然丰慧曾德民张略淼北京建筑大学理学院北京102616 北京建筑大学土木与交通工程学院北京100044

为有效提高高层住院楼内人员安全疏散效率,选取某综合医院高层住院楼为研究对象,重点考虑高层住院楼内弱势群体疏散行为特征,结合视域分析法对住院楼内部空间进行适弱化分析,应用AnyLogic软件对建筑内部人员开展多情景疏散仿真。结果表... 详细信息

为有效提高高层住院楼内人员安全疏散效率,选取某综合医院高层住院楼为研究对象,重点考虑高层住院楼内弱势群体疏散行为特征,结合视域分析法对住院楼内部空间进行适弱化分析,应用AnyLogic软件对建筑内部人员开展多情景疏散仿真。结果表明,进行紧急疏散时,建筑内的空间布局会诱使疏散压力集中在建筑内某一区域;依据住院楼内人员的生理和行为特征进行分类,将不同类别人员组合并进行分梯疏散,最优方案下整体疏散效率提高了15.95%。可见考虑弱势群体的疏散行为特征,对人员进行合理的分组分梯疏散能有效提高高层住院楼整体疏散效率。

关键词：高层住院楼空间句法弱势群体疏散行为 Anylogic 分组分梯

乌鲁木齐地区育龄女性脊髓性肌萎缩症携带者筛查胚胎植入前诊断及产前诊断情况分析

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中国妇幼保健 2024年第3期39卷 417-421页

作者：刘翛然武爽韩锐新疆医科大学第一附属医院新疆乌鲁木齐830054 新疆生殖免疫临床医学研究中心

目的了解乌鲁木齐地区脊髓性肌萎缩症(SMA)的人群携带率,对乌鲁木齐地区孕前女性进行携带者筛查,并召回携带者配偶进行检测,对筛查出的高风险夫妻行单基因病胚胎遗传学检测(PGT-M),对曾生育过SMA患儿的高风险夫妻行产前诊断,为该地区SM... 详细信息

目的了解乌鲁木齐地区脊髓性肌萎缩症(SMA)的人群携带率,对乌鲁木齐地区孕前女性进行携带者筛查,并召回携带者配偶进行检测,对筛查出的高风险夫妻行单基因病胚胎遗传学检测(PGT-M),对曾生育过SMA患儿的高风险夫妻行产前诊断,为该地区SMA的一级预防和二级预防提供指导。方法选取2020年1月—2023年7月在新疆医科大学第一附属医院就诊的选择做SMA携带者筛查的育龄期女性7 158例为研究对象,均无SMA表型及相关疾病史。携带者筛查用PCR-熔解曲线法,检测SMN1基因E7、E8的拷贝数,统计乌鲁木齐地区育龄期女性SMA携带者频率;用二代测序的方法对高风险夫妻的胚胎进行PGT-M;对高风险胎儿,用多重连接依赖式探针扩增(MLPA)的方法进行产前诊断。结果在7 158例育龄期女性中,共检出117例SMA携带者,携带频率为1.63%(1/61);检出双方均为携带者的夫妇1对,而PGT-M技术为这对高风险夫妻选择出未携带突变的整倍体囊胚1枚,携带父源突变单拷贝的整倍体囊胚1枚;产前诊断夫妻的胎儿SMN1基因E7、E8均为2个拷贝数,胎儿出生后随访1年发育未见异常。结论初步获得乌鲁木齐地区育龄女性SMA携带率为1.63%;对于明确缺失类型和基因型的SMA携带者夫妻,PGT-M技术能够阻断SMA致病基因向后代的传递;对于高风险胎儿,MLPA可给出明确诊断,阻止SMA患儿的出生。该研究有效完成了SMA的一级预防和二级预防,对乌鲁木齐地区出生缺陷防控具有重要意义。

关键词：脊髓性肌萎缩症携带者筛查胚胎植入前诊断产前诊断

肝癌细胞中NME1功能研究及调控的pHis修饰底物发现

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现代生物医学进展 2024年第13期24卷 2401-2407页

作者：刘萧然邢美宁陈沛渝孙薇应万涛军事科学院军事医学研究院生命组学研究所、医学蛋白质组全国重点实验室、北京蛋白质组研究中心、国家蛋白质科学中心(北京) 北京102206 广东药科大学药学院广东广州510006

目的:研究核苷二磷酸激酶1(Nucleoside diphosphate kinase A,NME1)在肝癌细胞HCCLM3中的功能作用及其调控的组氨酸磷酸化(Histidine phosphorylation,pHis)修饰底物。方法:采用划痕愈合实验和Transwell小室实验以及蛋白质组学和磷酸化... 详细信息

目的:研究核苷二磷酸激酶1(Nucleoside diphosphate kinase A,NME1)在肝癌细胞HCCLM3中的功能作用及其调控的组氨酸磷酸化(Histidine phosphorylation,pHis)修饰底物。方法:采用划痕愈合实验和Transwell小室实验以及蛋白质组学和磷酸化蛋白质组学分析方法,对NME1敲除后细胞表型与分子水平变化进行分析。结果:在肝癌细胞中敲除组氨酸激酶NME1能降低细胞运动能力,全蛋白组差异分析发现NME1敲除后差异表达蛋白主要参与细胞底物黏附调控、细胞周期调节及蛋白激酶活性调控等生命活动过程。Western blot检测发现敲除NME1表达使细胞整体pHis修饰水平显著下调。随后使用整合pHis修饰位点鉴定策略,即通过双甲基标记、强阳离子交换色谱(Strong cation exchange,SCX)分离磷酸化修饰肽段与非修饰肽段、铜珠(Cu-iminodiacetic acid,Cu-IDA)富集组氨酸肽段以及质谱检测等过程,首次在肝癌细胞系中鉴定到242个pHis修饰位点及206个pHis修饰蛋白。大约25%的pHis修饰蛋白为首次发现,其中NME1敲低组pHis修饰水平显著下调的蛋白有(Cell adhesion molecule 3,CADM3)、(Cytochrome C,CYCS)、(Glyceraldehyde-3-phosphate dehydrogenase,GAPDH)及(Phosphofructokinase,PFKM)等近30个,表明NME1可能通过这些蛋白及代谢酶的组氨酸磷酸化修饰水平的变化影响肿瘤细胞间的黏附及代谢能力。结论:肿瘤细胞中NME1表达水平的变化会影响肿瘤细胞的运动能力,细胞内pHis修饰水平的失调可能全面参与疾病进程。

关键词：肝细胞癌 NME1 组氨酸磷酸化细胞表型蛋白质组学磷酸化蛋白质组学

Tracked robot with underactuated tension-driven RRP transformable mechanism:ideas and design

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Frontiers of Mechanical Engineering 2024年第1期19卷 85-104页

作者： ran XU Chao liu School of Mechanical Electronic and Control EngineeringBeijing Jiaotong UniversityBeijing 100044China Key Laboratory of Vehicle Advanced Manufacturing Measuring and Control Technology(Ministry of Education)Beijing Jiaotong UniversityBeijing 100044China

Robots with transformable tracked mechanisms are widely used in complex terrains because of their high adaptability,and many studies on novel locomotion mechanisms have been conducted to make them able to climb higher *** underactuated transformable mechanisms for tracked robots could decrease the number of actuators used while maintaining the flexibility and obstacle-crossing capability of these robots,and increasing their cost ***,the underactuated tracked robots have appreciable research *** this paper,a novel tracked robot with a newly proposed underactuated revolute‒revolute‒prismatic(RRP)transformable mechanism,which is inspired by the sit-up actions of humans,was *** newly proposed tracked robot has only two actuators installed on the track pulleys for moving and does not need extra actuators for ***,it could concentrate the track belt’s tension toward one side,and the unbalanced tension would drive the linkage mechanisms to change its *** this method,the proposed underactuated design could change its external shape to create support points with the terrain and move its center of mass actively at the same time while climbing obstacles or crossing other kinds of terrains,thus greatly improving the climbing capability of the *** geometry and kinematic relationships of the robot and the crossing strategies for three kinds of typical obstacles are *** the basis of such crossing motions,the parameters of links in the robot are designed to make sure the robot has sufficient stability while climbing ***-crossing dynamic simulations were run and analyzed to prove the feasibility of the robot.A prototype was built and *** show that the proposed robot could climb platforms with heights up to 33.3%of the robot’s length or cross gaps with widths up to 43.5%of the robot’s length.

关键词： mechanical design tracked robot underactuated mechanisms RRP mechanism obstacle crossing strategy

Prediction for permeability index of blast furnace based on VMD-PSO-BP model

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Journal of Iron and Steel Research International 2024年第3期31卷 573-583页

作者： xiao-jie liu Yu-jie Zhang Xin Li Zhi-feng Zhang Hong-yang Li ran liu Shu-jun Chen School of Metallurgy and Energy North China University of Science and TechnologyTangshan 063210HebeiChina Chengde Branch HBIS Group Co.Ltd.Chengde 067000HebeiChina

The permeability index is one of the important production indicators to monitor the operation of blast *** is crucial to grasp the trends of changes in the new permeability index in *** the complex vibration spectrum of the permeability index,a prediction model of the permeability index based on the VMD-PSO-BP(variational mode decomposition-particle swarm optimization-back propagation)method was ***,the key factors that affect the permeability index of blast furnace were studied from multiple ***,the permeability index was divided into multiple sub-modes based on the difference of frequency bands by the VMD algorithm,and a PSO-BP prediction model was established for each ***,the prediction results of each sub-mode were summed to obtain the final *** results show that the composite prediction accuracy by using the VMD algorithm is 3%higher than that of the traditional prediction method,which has better applicability.

关键词： Big data-Blast furnace Air permeability Variational mode decomposition Particle swarm optimization Back propagation Model prediction

Prescribed-time stabilization and inverse optimal control of stochastic high-order nonlinear systems

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Science China(Information Sciences) 2024年第2期67卷 144-156页

作者： ran liu Hui WANG Wuquan LI School of Mathematics and Statistics Science Ludong University

This paper investigates the prescribed-time state-feedback stabilization and prescribed-time inverse optimality problems for stochastic high-order nonlinear systems. First, a time-varying controller is designed by developing scaled quartic Lyapunov functions, which can guarantee that the system has a unique strong solution almost surely on the prescribed interval for any system initial conditions and that the states and the control converge to the origin in a mean-square form within the prescribed time. Then, the controller is redesigned to address the problem of prescribed-time inverse optimal mean-square stabilization. Finally,a concrete example is provided to confirm the efficiency of the proposed design schemes.

关键词： stochastic high-order nonlinear systems prescribed-time stabilization the scaled design inverse optimality

Optimization study of spherical tuyere based on BP neural network and new evaluation index

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Building Simulation 2024年第2期17卷 223-234页

作者： Mengchao liu ran Gao Yi Wang Angui Li School of Building Services Science and Engineering Xi’an University of Architecture and TechnologyXi’an710055China

The energy consumption of heating,ventilation,and air conditioning(HVAC)systems holds a significant position in building energy usage,accounting for about 65%of the total energy ***,with the advancement of building automation,the energy consumption of ventilation systems continues to *** study focuses on improving the performance of spherical tuyeres in HVAC *** primarily utilizes neural networks and multi-island genetic algorithms(MIGA)for multi-parameter *** employing methods such as structural parameterization,accurate and fast computational fluid dynamics(CFD)simulations,a minimized sample space,and a rational optimization strategy,the time cycle of the optimization process is ***,a new comprehensive evaluation index is proposed in this research to describe the performance of spherical tuyeres,which can be used to more accurately assess spherical tuyeres with different *** results show that by establishing a neural network prediction model and combining it with the multi-island genetic algorithm,a novel spherical tuyere design was successfully *** optimized novel spherical tuyeres achieved a 27.05%reduction in the spherical tuyeres effective index(STEI)compared to the traditional spherical ***,the resistance decreased by 15.68%,and the jet length increased by 7.57%.The experimental results demonstrate that our proposed optimization method exhibits high accuracy,good generalization capability,and excellent agreement at different Reynolds numbers.

关键词： spherical tuyeres STEI CFD ventilation

Rapid prediction of damaged ship roll motion responses in beam waves based on stacking algorithm

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Journal of Hydrodynamics 2024年第2期36卷 394-405页

作者： Xin-ran liu Ting-qiu Li Zi-ping Wang School of Naval Architecture Ocean and Energy Power EngineeringWuhan University of TechnologyWuhan430063China

Accurate modeling for highly non-linear coupling of a damaged ship with liquid sloshing in waves is still of considerable interest within the computational fluid dynamics(CFD)and AI *** paper describes a data-driven Stacking algorithm for fast prediction of roll motion response amplitudes in beam waves by constructing a hydrodynamics model of a damaged ship based on the dynamic overlapping grid CFD *** general idea is to optimize various parameters varying with four types of classical base models like multi-layer perception,support vector regression,random forest,and hist gradient boosting *** offers several attractive properties in terms of accuracy and efficiency by choosing the standard DTMB 5415 model with double damaged compartments for *** is clearly demonstrated that the predicted response amplitude operator(RAO)in the regular beam waves agrees well with the experimental data available,which verifies the accuracy of the established damaged ship hydrodynamics *** high-quality CFD samples,therefore,implementation of the designed Stacking algorithm with its optimal combination can predict the damaged ship roll motion amplitudes effectively and accurately(e.g.,the coefficient of determination 0.9926,the average absolute error 0.0955 and CPU 3s),by comparison of four types of typical base models and their various ***,the established Stacking algorithm provides one potential that can break through problems involving the time-consuming and low efficiency for large-scale lengthy CFD simulations.

关键词： Ship motion damaged ship computational fluid dynamics(CFD) machine learning stacking algorithm