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A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

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Cellular & Molecular Immunology 2023年第11期20卷 1379-1392页

作者： Xianyang liu Jiayu Meng Xingyun Liao yusen liu Qian Zhou Zongren Xu Shuming Yin Qingfeng Cao Guannan Su Siyuan He Wanqian Li Xiaotang Wang Guoqing Wang Dali Li Peizeng Yang Shengping Hou The First Affiliated Hospital of Chongqing Medical University ChongqingChina Chongqing Key Laboratory of Ophthalmology ChongqingChina Chongqing Eye Institute ChongqingChina Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu611731China Department of Medical Oncology Chongqing University Cancer HospitalChongqing400030China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai200241China Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing100730China

Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease.

关键词： Vogt-Koyanagi-Harada disease Whole exome sequencing De novo mutation Membrane palmitoylated protein 2 Annexin A2 ERK3/IL-17E pathway

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影像组学结合人工智能诊断颈动脉斑块及缺血性卒中的进展

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国际医学放射学杂志 2024年第2期47卷 154-159页

作者：刘雨森惠品晶(审校) 苏州大学附属第一医院神经外科-颈脑血管超声苏州215006

颈动脉粥样硬化斑块是缺血性卒中(IS)发生发展过程中的重要病理和临床诊断基础,早期评估颈动脉斑块性质有助于病人的分层管理。影像组学可以高通量提取影像数据,结合人工智能(AI)方法可以辅助评估颈动脉斑块性质、预测脑血管事件的发生... 详细信息

颈动脉粥样硬化斑块是缺血性卒中(IS)发生发展过程中的重要病理和临床诊断基础,早期评估颈动脉斑块性质有助于病人的分层管理。影像组学可以高通量提取影像数据,结合人工智能(AI)方法可以辅助评估颈动脉斑块性质、预测脑血管事件的发生发展、评估颈动脉狭窄术后的预后。就基于CT血管成像(CTA)、颈部血管超声(CDU)和高分辨MRI(HR-MRI)影像提取的影像组学特征结合AI在颈动脉斑块诊断及IS的预测、结合多种组学方法对斑块评估的研究进展进行综述,并分析影像组学应用中需要关注的问题。

关键词：脑卒中动脉粥样硬化斑块影像组学预测模型

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基于声光调制器的光学锁相环He-Ne激光稳频方法研究

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红外与激光工程 2024年第3期53卷 93-101页

作者：刘宇森王建波殷聪韩绍坤毕文文俞秋叶邹金澎北京理工大学光电学院北京100081 中国计量科学研究院北京100029 中国计量大学测试工程学院浙江杭州310018

报道了一种基于声光调制器与光学锁相环相结合的高稳定度激光稳频方法,用于提高热稳频He-Ne激光器的频率稳定度和准确度。为了克服全内腔热稳频He-Ne激光精密调谐困难的缺点,发展了基于声光调制器两次移频的频率调谐光路,有效地消除声... 详细信息

报道了一种基于声光调制器与光学锁相环相结合的高稳定度激光稳频方法,用于提高热稳频He-Ne激光器的频率稳定度和准确度。为了克服全内腔热稳频He-Ne激光精密调谐困难的缺点,发展了基于声光调制器两次移频的频率调谐光路,有效地消除声光调制器移频光束路径对衍射角θ的依赖。自行研制了具有高灵敏度与捕获带宽的光学锁相环系统,利用声光调制器的高频率响应特性实现热稳频He-Ne激光高速、准确的锁定。成功实现了热稳频He-Ne激光器偏频锁定至碘稳频HeNe激光器。实验结果表明,环路锁定后拍频频率波动在±0.2 Hz范围内,频率抖动的标准差为0.04。偏置频率为30 MHz时,系统在1 s和1000 s积分时间的相对阿伦方差分别为3.3×10^(-9)和1.4×10^(-12)。系统锁定后,压缩后的拍频线宽小于2 kHz。该研究表明,采用基于声光调制器与光学锁相环相结合的激光稳频方法可以实现亚赫兹级的激光频差控制,通过将热稳频He-Ne激光器偏频锁定至高稳定度的参考激光源可以显著提升其频率稳定度和准确度。

关键词：激光稳频声光调制器光学锁相环偏频锁定

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The Short-Term Prediction ofWind Power Based on the Convolutional Graph Attention Deep Neural Network

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Energy Engineering 2024年第2期121卷 359-376页

作者： Fan Xiao Xiong Ping Yeyang Li yusen Xu Yiqun Kang Dan liu Nianming Zhang State Grid Hubei Electric Power Research Institute Wuhan430077China College of Energy and Electrical Engineering Hohai UniversityNanjing210098China

The fluctuation of wind power affects the operating safety and power consumption of the electric power grid and restricts the grid connection of wind power on a large scale.Therefore,wind power forecasting plays a key role in improving the safety and economic benefits of the power grid.This paper proposes a wind power predicting method based on a convolutional graph attention deep neural network with multi-wind farm data.Based on the graph attention network and attention mechanism,the method extracts spatial-temporal characteristics from the data of multiple wind farms.Then,combined with a deep neural network,a convolutional graph attention deep neural network model is constructed.Finally,the model is trained with the quantile regression loss function to achieve the wind power deterministic and probabilistic prediction based on multi-wind farm spatial-temporal data.A wind power dataset in the U.S.is taken as an example to demonstrate the efficacy of the proposed model.Compared with the selected baseline methods,the proposed model achieves the best prediction performance.The point prediction errors(i.e.,root mean square error(RMSE)and normalized mean absolute percentage error(NMAPE))are 0.304 MW and 1.177%,respectively.And the comprehensive performance of probabilistic prediction(i.e.,con-tinuously ranked probability score(CRPS))is 0.580.Thus,the significance of multi-wind farm data and spatial-temporal feature extraction module is self-evident.

关键词： Format wind power prediction deep neural network graph attention network attention mechanism quantile regression

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Aluminum and Activated Alumina Powder Additions on Microwave Synthesis of Al_(4)SiC_(4)

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China's Refractories 2024年第1期33卷 44-48页

作者： WANG Li liu Shijie WEI Haoyu MA Juanjuan DONG Binbin GENG Shangrui YAN Miaoxin QIN Feng GUO yusen Henan Key Laboratory of Green Building Materials Manufacturing and Intelligent Equipemnt Luoyang Institute of Science and TechnologyLuoyang 471023China

Aiming at improving the properties of magnesia carbon materials,silicon aluminum carbide(Al_(4)SiC_(4))containing materials were prepared using industrial aluminum powder,silicon carbide powder,and graphite as raw materials,and activated alumina powder as an additive,mixing thoroughly,pressing into cylinders and then firing at 1200℃for 30 min in a carbon embedded atmosphere by the microwave method.The effects of the aluminum powder addition(20%and 24%,by mass)and activated alumina powder addition(0,3%,5%and 7%,by mass)on the microwave synthesis of Al_(4)SiC_(4) as well as the effect of the obtained Al_(4)SiC_(4) containing material on the properties of magnesia carbon bricks were studied.The results show that:compared with the samples with 20%aluminum powder,those with 24%aluminum powder generate more Al_(4)SiC_(4).With the activated alumina powder addition increasing from 0 to 7%,the amount of Al_(4)SiC_(4) generated increases first and then decreases.Compared with the sample without activated alumina powder,the samples with activated alumina powder show lower bulk density and higher apparent porosity.With the activated alumina powder addition increasing from 3%to 7%,the bulk density of the samples increases first and then decreases,while the apparent porosity of the samples shows an opposite trend.The optimal additions are 24%aluminum powder and 5%activated alumina powder,and Al_(4)SiC_(4) synthesized in this sample has a hexagonal plate structure.With the synthesized Al_(4)SiC_(4) containing material added,the magnesia carbon brick has slightly increased cold modulus of rupture,basically the same modulus of elasticity and improved oxidation resistance.

关键词： aluminum powder activated alumina powder microwave synthesis Al_(4)SiC_(4) magnesia carbon bricks

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粮食收购智能扦检系统的研究进展

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粮食储藏 2024年第2期53卷 1-7+17+9-11页

作者：李月马浩然李艺博张军党王贵锦彭倍荣云陈戈董晓欢黄泽文刘育森中储粮成都储藏研究院有限公司中国储备粮管理集团有限公司成都分公司清华大学电子科技大学成都中储粮储备有限公司中央储备粮厦门直属库有限公司中央储备粮海口直属库有限公司中央储备粮长乐直属库有限公司

当前我国涉粮企业和基层粮库普遍存在传统扦样检验自动化程度不高、劳动强度较大、检测效率较低等问题，如何利用创新技术手段提升粮食仓储“技防技控”水平，守好粮食收购入库第一关，对保障粮食安全具有重要意义。本文分析了目前粮食... 详细信息

当前我国涉粮企业和基层粮库普遍存在传统扦样检验自动化程度不高、劳动强度较大、检测效率较低等问题，如何利用创新技术手段提升粮食仓储“技防技控”水平，守好粮食收购入库第一关，对保障粮食安全具有重要意义。本文分析了目前粮食收购环节中传统扦样和质量指标检验过程存在的问题，粮食收购智能扦检系统在粮库实际应用中的必要性，并从智能制造、信息技术、机器视觉、深度学习的创新应用等方面阐述了智能扦检流程和装备的研究进展，以期为智能化粮库建设中粮食收购智能扦检系统的研究应用提供参考。

关键词：粮食收购智能扦检技防技控

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Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

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Acta Pharmaceutica Sinica B 2024年第1期14卷 87-109页

作者： Letian Song Shenghua Gao Bing Ye Mianling Yang yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong liu Peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen Research Institute of Shandong University Shenzhen 518057China The Key Laboratory of Infection and Immunity of Shandong Province Department of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a Molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous University of Madrid) Madrid 28049Spain KU Leuven Department of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

关键词： COVID-19 SARS-CoV-2 Main protease Non-covalent inhibitors Medicinal chemistry strategies

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Microwave-assisted Synthesis of Al_(4)SiC_(4) and Its Effect on Properties of MgO-C Refractories

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China's Refractories 2024年第1期33卷 14-17页

作者： WANG Li liu Shijie WEI Haoyu GUO Yanyan GENG Shangrui YAN Miaoxin QIN Feng GUO yusen Ma Juanjuan DONG Binbin Henan Key Laboratory of Green Building Materials Manufacturing and Intelligent Equipemnt Luoyang Institute of Science and TechnologyLuoyang 471023China

Al_(4)SiC_(4) was synthesized from Al powder, silicon carbide, and graphite by microwave sintering, and characterized by XRD and SEM. Then the synthesized material was added to the magnesia carbon refractory brick to study its effect on the oxidation resistance, apparent porosity, bulk density, elastic modulus, and modulus of rupture. It is found that Al_(4)SiC_(4) can be synthesized by microwave sintering at 1 300 ℃ and the addition of Al_(4)SiC_(4)-containing material as an antioxidant can enhance the oxidation resistance of the magnesia carbon refractory brick.

关键词： microwave-assisted synthesis Al_(4)SiC_(4) MgO-C refractories oxidation resistance

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培根、迪昂与判决性实验

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安徽大学学报（哲学社会科学版） 2016年第3期40卷 26-33页

作者：刘钰森华南师范大学公共管理学院哲学研究所、法国哲学与跨文化研究中心广东广州510006

迪昂所批判的判决性实验在哲学史上来自培根关于路标事例的观点。通过追溯培根路标事例的语境,可以发现,迪昂的批判对培根的观点存在一定程度的误读。对比培根和迪昂的相关著作,或许可以消除这种误读,并且发现培根与迪昂方法论背后隐含... 详细信息

迪昂所批判的判决性实验在哲学史上来自培根关于路标事例的观点。通过追溯培根路标事例的语境,可以发现,迪昂的批判对培根的观点存在一定程度的误读。对比培根和迪昂的相关著作,或许可以消除这种误读,并且发现培根与迪昂方法论背后隐含的知识论意蕴,以及他们在方法论上的相通之处。由此也能对判决性实验的认识论性质和地位做出判断。

关键词：培根迪昂判决性实验纯粹归纳整体论

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基于慢特征分析方法研究陆地表面气温变率的驱动力

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大气科学 2022年第3期46卷 520-540页

作者：朱丽飞孙诚李建平张静刘雨森宫湛秋北京师范大学全球变化与地球系统科学研究院北京100875 中国海洋大学物理海洋教育部重点实验室/海洋高等研究院/深海圈层与地球系统前沿科学中心青岛266100 青岛海洋科学与技术国家实验室海洋动力过程与气候功能实验室青岛266237

慢特征分析(SFA)方法可以从非平稳时间序列中提取出慢变的外强迫信息。近年来,SFA方法被应用于气候变化研究领域,用于探究气候变化的潜在驱动力及相关的动力学机制。本文基于SFA方法,提取全球陆地表面气温(LSAT)的慢变外强迫信息,研究全... 详细信息

慢特征分析(SFA)方法可以从非平稳时间序列中提取出慢变的外强迫信息。近年来,SFA方法被应用于气候变化研究领域,用于探究气候变化的潜在驱动力及相关的动力学机制。本文基于SFA方法,提取全球陆地表面气温(LSAT)的慢变外强迫信息,研究全球LSAT慢变驱动力的空间结构特征及低频变率的主要驱动因子。SFA方法提取的LSAT慢变驱动力与历史时期全球辐射强迫(GRF)和全球海表温度(SST)的主模态(大西洋多年代际振荡AMO、热带太平洋ENSO变率和太平洋年代际振荡PDO)有显著的相关关系,表明全球大部分地区LSAT的变率受到GRF和三个SST模态的显著影响。GRF对LSAT变率的影响有全球一致性的特征,而三个SST模态对LSAT变率的影响则呈现出明显的区域特点。此外,由于SFA方法可以有效降低原始LSAT序列中随机噪声的干扰,GRF和SST模态对LSAT变率的解释方差显著提高,进一步表明GRF和SST模态是全球LSAT低频变率主要的驱动因子。最后,利用历史海温驱动AGCM试验(即AMIP试验)的结果,验证了三个SST模态对区域LSAT变率的显著影响。

关键词：慢特征分析(SFA) 陆地表面气温驱动力低频变率 AMIP试验

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