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Correction of a CADASIL point mutation using adenine base editors in hiPsCsandbloodvessel organoids

Journal of Genetics and Genomics 2024年第2期51卷 197-207页

作者： Jingwen Wang Lei Zhang guanglan wu Jinni wu Xinyao Zhou Xiaolin Chen Yongxia Niu Yiren Jiao Qianyi Liu Puping Liang Guang Shi Xueqing wu Junjiu Huang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Key Laboratory of Reproductive Medicine of Guangdong Province The First Affiliated Hospital and School of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Center of Reproductive Medicine Children's Hospital of Shanxi and Women Health Center of ShanxiTaiyuanShanxi 030013China

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.

关键词： CADASIL Induced pluripotent stem cells Adenine base editors AAV Blood vessel Organoid

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Cost-effective generation of A-to-G mutant mice by zygote electroporation of adenine base editor ribonucleoproteins

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Journal of Genetics and Genomics 2020年第6期47卷 337-340页

作者： Hongwei Sun Shengyao Zhi Guifang wu guanglan wu Tianqi Cao Hu Hao Zhou Songyang Puping Liang Junjiu Huang MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging Research SYSU-BCM Joint Research CenterSchool of Life SciencesSun Yat-sen UniversityGuangzhou510275China Department of Paediatrics The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou510655China Key Laboratory of Reproductive Medicine of Guangdong Province School of Life Sciencesand the First Affiliated HospitalSun Yat-sen UniversityGuangzhou510275China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou510060China Verna and Marrs Mclean Department of Biochemistry and Molecular Biology Baylor College of MedicineOne Baylor PlazaHoustonTX77030USA

More than 32,000 pathogenic single nucleotide polymorphisms(SNPs)have been identified in the human genome(Gaudelli et al.,2017).Genetically modified mice with pathogenic SNPs are good models for studies of disease pathogenesis and the development of new ***,an efficient,high-throughput method for the generation of mouse models with SNPs is needed.

关键词： al. editor pathogenesis

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VMMAO-YOLO:an ultra-lightweight and scale-aware detector for real-time defect detection of avionics thermistor wire solder joints

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Frontiers of Mechanical Engineering 2024年第3期19卷 77-92页

作者： Xiaoqi YANG Xingyue LIU Qian wu Guojun WEN Shuang MEI guanglan LIAO Tielin SHI School of Mechanical Engineering and Electronic Information China University of GeosciencesWuhan 430074China State Key Laboratory of Digital Manufacturing Equipment and Technology Huazhong University of Science and TechnologyWuhan 430074China

The quality of the exposed avionics solder joints has a significant impact on the stable operation of the inorbit ***,the previously reported inspection methods for multi-scale solder joint defects generally suffer low accuracy and slow detection ***,a novel real-time detector VMMAO-YOLO is demonstrated based on variable multi-scale concurrency and multi-depth aggregation network(VMMANet)backbone and“one-stop”global information gather-distribute(OS-GD)*** with infrared thermography technology,it can achieve fast and high-precision detection of both internal and external solder joint ***,VMMANet is designed for efficient multi-scale feature extraction,which mainly comprises variable multi-scale feature concurrency(VMC)and multi-depth feature aggregation-alignment(MAA)*** can extract multi-scale features via multiple fix-sized and deformable convolutions,while MAA can aggregate and align multi-depth features on the same order for feature *** allows the low-level features with more spatial details to be transmitted in depth-wise,enabling the deeper network to selectively utilize the preceding inference *** VMMANet replaces inefficient highdensity deep convolution by increasing the width of intermediate feature levels,leading to a salient decline in *** OS-GD is developed for efficacious feature extraction,aggregation and distribution,further enhancing the global information gather and deployment capability of the *** a self-made solder joint image data set,the VMMAOYOLO achieves a mean average precision mAP@0.5 of 91.6%,surpassing all the mainstream YOLO-series ***,the VMMAO-YOLO has a body size of merely 19.3 MB and a detection speed up to 119 frame per second,far superior to the prevalent YOLO-series detectors.

关键词： defect detection of solder joints VMMAO-YOLO ultra-lightweight and high-performance multiscale feature extraction VMC and MAA modules OS-GD

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地铁盾构施工地表建筑物监测与BP变形预测

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山西建筑 2022年第16期48卷 156-159页

作者：吴广兰邵阳学院城乡建设学院湖南邵阳422000

地铁隧道盾构法施工不可避免地扰动周边土体,甚至会造成地表沉陷、周边建筑物损坏等事故。以地铁盾构下穿地面运营铁路段为例,基于盾构施工对地表变形影响机理分析,设计采用TM30测量机器人自动化监测方案。监测结果表明,盾构施工过程中... 详细信息

地铁隧道盾构法施工不可避免地扰动周边土体,甚至会造成地表沉陷、周边建筑物损坏等事故。以地铁盾构下穿地面运营铁路段为例,基于盾构施工对地表变形影响机理分析,设计采用TM30测量机器人自动化监测方案。监测结果表明,盾构施工过程中工程总体安全,但地面铁路轨枕出现变形预警,需要进行有效的跟踪监测并采取合理措施。为此,基于BP模型进行结构变形预测,结果能较好的预测地表变形,为工程施工方案决策提供重要参考。

关键词：地铁盾构法自动化监测预测 BP模型

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建筑深基坑变形监测及FLAC数值模拟分析

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山西建筑 2023年第19期49卷 86-89页

作者：吴广兰邵阳学院土木与建筑工程学院湖南邵阳422000

深基坑是高层建筑的关键工程。以某商住楼工程为例,基于基坑开挖方式、支护方式及变形规律分析设计了监测方案,并应用于工程实践得到系统的监测数据。同时,利用FLAC3D对基坑开挖各类变形进行模拟计算,将围护结构位移、地表沉降等主要变... 详细信息

深基坑是高层建筑的关键工程。以某商住楼工程为例,基于基坑开挖方式、支护方式及变形规律分析设计了监测方案,并应用于工程实践得到系统的监测数据。同时,利用FLAC3D对基坑开挖各类变形进行模拟计算,将围护结构位移、地表沉降等主要变形监测数据与模拟结果进行对比分析,表明FLAC3D数值模拟结果与实测数据结果相近、规律一致,即模拟结果具有可信度。然后分析了两者出现差异的原因,为提升数值模拟结果的准确性提供了建议,提出了工程安全防护措施,对于类似工程施工监测、变形预测和安全防护具有重要意义。

关键词：基坑变形监测 FLAC3D 数值模拟围护结构

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西南生态脆弱区重大建设工程渣场的生态修复技术和策略

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应用与环境生物学报 2024年第4期30卷 848-860页

作者：齐芳丁建林崔嘉琪蒲光兰向双吴彦刘庆中国科学院山地生态恢复与生物资源利用重点实验室生态恢复与生物多样性保育四川省重点实验室中国科学院成都生物研究所成都610213 四川农业大学林学院成都611130 中国科学院茂县山地生态系统定位研究站茂县623299 中国科学院大学北京100049

西南地区是我国长江上游重要的生态屏障区和国家重大建设工程的重要实施区.该区域雨水丰沛、地势陡峭,工程建设产生大量弃渣,不仅占用大面积的临时性和永久性土地,还极易造成水土流失、滑坡泥石流等次生灾害,生态环境极端脆弱.为保障区... 详细信息

西南地区是我国长江上游重要的生态屏障区和国家重大建设工程的重要实施区.该区域雨水丰沛、地势陡峭,工程建设产生大量弃渣,不仅占用大面积的临时性和永久性土地,还极易造成水土流失、滑坡泥石流等次生灾害,生态环境极端脆弱.为保障区域生态安全,亟须进行科学治理.基于西南地区的地质历史、气候条件和人地矛盾等实际,总结西南脆弱生态区渣场生态修复技术的研究进展.目前建设工程产生渣土的来源主要为道路修建、水电站建设、矿山开采和山区城镇基础建设等四大类项目.渣场修复作为一个系统工程,通常按照“土地整理—土壤重构—植被建设—景观再造—生态演替”的序列进行,修复技术主要分为土壤系统构建技术和植物群落构建技术两大板块.土壤系统的构建关键在于坡面整理保持水土,生土熟化和土壤改良,理化、微生物和植物措施修复重金属污染等方面.植物群落构建技术主要由选择先锋物种激发植物存活、群落配置促进持续演替、土壤种子库有效利用、植物配置促进成土等技术组成.针对目前渣场生态修复中存在的修复目标定位不清、土壤修复技术单一、物种适应难、生物入侵、群落演替难以为继等主要问题和难点,提出以区分不同生境梯度、不同生态系统类型和修复目标为核心依据的解决思路.在此基础上,展望了未来渣场修复技术、创新管理模式以及区域差异化治理策略等优化途径.(图2表4参82)

关键词：渣场土壤改良修复目标植物筛选群落配置

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以应用能力为核心的测绘人才培养模式改革

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科教导刊 2022年第32期 74-76页

作者：陈佳艺黄雄伟王亮吴广兰邵阳学院城乡建设学院湖南邵阳422000

文章以应用型大学转型为契机,校企合作为平台,结合专业特点,紧盯社会需求,构建以应用能力为核心,产学深度融合的高素质应用型人才培养模式。测绘工程专业一直致力于完善人才培养体系,重视学生应用能力和创新技能的培养,构建了产学融合... 详细信息

文章以应用型大学转型为契机,校企合作为平台,结合专业特点,紧盯社会需求,构建以应用能力为核心,产学深度融合的高素质应用型人才培养模式。测绘工程专业一直致力于完善人才培养体系,重视学生应用能力和创新技能的培养,构建了产学融合的多元化实践教学环境,注重过程考核,优化创新人才的成长环境,并通过努力取得了一定的成效。

关键词：测绘工程校企合作应用能力创新培养模式

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Microstructural evolution,mechanical properties and corrosion behavior of as-cast Mg-5Li-3Al-2Zn alloy with different Sn and Y addition

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Journal of Materials Science & Technology 2021年第13期72卷 16-22页

作者： Xiang Peng Shihao Xu Dehua Ding guanglan Liao Guohua wu Wencai Liu Wenjiang Ding Ding National Engineering Research Center of Light Alloy Net Forming and State Key Laboratory of Metal Matrix Composite School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Influences of Sn and Y on the microstructure,mechanical properties,and corrosion behavior of as-cast Mg-5 Li-3 Al-2 Zn(LAZ532)alloy were *** addition of Sn and Y refines grains and results in the formation of Mg2 Sn and Al2 Y phases,thus improving the mechanical properties of alloy by second phase strengthening and grain refinement ***-cast LAZ532 alloy shows typical filiform corrosion morphology,and the addition of Sn and Y does not change the corrosion mode of *** LAZ532-0.8 Sn-1.2 Y alloy shows excellent mechanical properties with yield strength of 166.2 MPa,ultimate tensile strength of 228.6 MPa and elongation of 14.8%,and exhibits the best corrosion resistance with the smallest corrosion current density and the lowest anodic dissolution rate.

关键词： Mg-Li alloy Sn Y Mechanical properties Corrosion behavior

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Automated X-ray recognition of solder bump defects based on ensemble-ELM

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Science China(Technological Sciences) 2019年第9期62卷 1512-1519页

作者： SU Lei WANG LingYu LI Ke wu JingJing LIAO guanglan SHI TieLin LIN TingYu Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment and Technology Jiangnan UniversityWuxi 214122China State Key Laborotary of Digital Manufacturing Equipment and Technology Huazhong University of Science and TechnologyWuhan 430074China School of Mechanical Engineering Zhejiang UniversityHangzhou 310027China National Center for Advanced Packaging Wuxi 214028China

Solder bumps realize the mechanical and electrical interconnection between chips and substrates in surface mount components,such as flip chip, wafer level packaging and three-dimensional integration. With the trend to smaller and lighter electronics,solder bumps decrease in dimension and pitch in order to achieve higher I/O density. Automated and nondestructive defect inspection of solder bumps becomes more difficult. Machine learning is a way to recognize the solder bump defects online and overcome the effect caused by the human eye-fatigue. In this paper, we proposed an automated and nondestructive X-ray recognition method for defect inspection of solder bumps. The X-ray system captured the images of the samples and the solder bump images were segmented from the sample images. Seven features including four geometric features, one texture feature and two frequency-domain features were extracted. The ensemble-ELM was established to recognize the defects intelligently. The results demonstrated the high recognition rate compared to the single-ELM. Therefore, this method has high potentiality for automated X-ray recognition of solder bump defects online and reliable.

关键词： automated recognition solder bump X-ray ensemble-ELM

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Investigation on color variation of Morpho butterfly wings hierarchical structure based on PCA

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Science China(Technological Sciences) 2012年第1期55卷 16-21页

作者： JIANG Xuan SHI TieLin ZUO HaiBo YANG XueFeng wu WenJun LIAO guanglan State Key Laboratory of Digital Manufacturing Equipment and Technology Huazhong University of Science and TechnologyWuhan 430074China

Morpho butterfly wings show brilliant blue color,which has a close relationship with the hierarchical micro/nano structures on the surface of *** liquids such as methanol,ethanol and isopropanol with different refractive indexes drop onto the scales,the reflectance of wings would *** main peaks of reflectance shift to the right and the scales turn to *** the liquids volatilizes completely,the scales revert to the original blue *** typical micro/nano struc-tures of Morpho butterfly wing scales are modeled,and the reflectance variation in the course of dropping liquids is ***,the principal component analysis(PCA) method is employed to analyze the experimental and simulation reflec-tance data,extract principal components and reduce *** a result,the curves mapping the reflectance variation are clearly shown in the coordinate system consisting of three principal *** typical color variation of scales during the dropping process could be monitored,and different kinds of liquids could be obviously distinguished according to the dis-tributed regions of mapping *** study provides guidance to environmental media detecting as well as data processing,and enhances the fabrication and application of the mimic Morpho butterfly wings micro/nano structures.

关键词： Morpho butterfly hierarchical structure color variation principal components analysis

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