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Precise genome-editing in human diseases:mechanisms,strategies and applications

Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei li Kaiyu Zhou tiange li Nathan J.VanDusen Yimin Hua Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic disease.Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo applications.Nonetheless,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target effects.In this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and applications.First,we discuss the landmark events in the history of precise genome-editing.Second,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome.Third,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and RNPs.Finally,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

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Food Science and Human Wellness 2024年第1期13卷 124-136页

作者： Han Gong tiange li Dong liang Jingxin Gao Xiaohan liu Xueying Mao Key Laboratory of Functional Dairy Ministry of EducationCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control College of Food Science and TechnologyHenan Agricultural UniversityZhengzhou 450002China Applied Nutrition I China National Center for Food Safety Risk AssessmentBeijing 100022China

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

关键词： Cow’s milk allergy Milk fat globule membrane Gut microbiota Short-chain fatty acid G protein-coupled receptor Regulatory T cell

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Maternal obesity exacerbates the responsiveness of offspring BALB/c mice to cow's milk protein-induced food allergy

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Food Science and Human Wellness 2023年第3期12卷 920-928页

作者： Jingxin Gao tiange li Dong liang Han Gong liang Zhao Xueying Mao Key Laboratory of Functional Dairy Ministry of EducationCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China Henan Engineering Technology Research Center of Food Processing and Circulation Safety Control College of Food Science and TechnologyHenan Agricultural UniversityZhengzhou 450002China Applied Nutrition I China National Center for Food Safety Risk AssessmentBeijing 100022China

Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.

关键词： Cow's milk allergy Maternal obesity Offspring Intestinal barrier Immune response

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A Correct Smoothed Particle Method to Model Structure-Ice Interaction

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Computer Modeling in Engineering & Sciences 2019年第7期120卷 177-201页

作者： Yang liu Yue Qiao tiange li College of Shipbuilding Engineering Harbin Engineering UniversityHarbin150001China China Ship Research and Development Academy Beijing100101China Department of Civil and Environmental Engineering University of CaliforniaBerkeleyCA 94720USA

This paper studies the effect of ice resistance on the icebreaking capacity and speed of an icebreaking vessel.We combine an improved Correct Smoothed Particle Method(CSPM)with a material low-speed collision fracture model to numerically simulate the continuous icebreaking and rolling process of crushed.Using this model,we investigate the icebreaking resistance and immersion resistance during the icebreaking process,taking into account the fluid(water)as the elastic boundary support and the fluid-solid coupling interaction.We compare the icebreaking resistance and broken ice fracture shapes obtained by the numerical calculation with the theoretical analytical results,and thus validate the improved CSPM method.Further,we compare the immersion resistance results from our simulation against that from Puntigliano[Puntigliano,Hamburgische Schiffbau-Versuchsanstalt GmbH(1995)],and demonstrate that the proposed method can accurately predict ice resistance.

关键词： SPH ice resistance fluid-structure interaction numerical simulation ventilation phenomenon

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A 4H-SiC semi-super-junction shielded trench MOSFET: p-pillar is grounded to optimize the electric field characteristics

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Journal of Semiconductors 2022年第12期43卷 79-87页

作者： Xiaojie Wang Zhanwei Shen Guoliang Zhang Yuyang Miao tiange li Xiaogang Zhu Jiafa Cai Rongdun Hong Xiaping Chen Dingqu lin Shaoxiong Wu Yuning Zhang Deyi Fu Zhengyun Wu Feng Zhang College of Physical Science and Technology Xiamen UniversityXiamen 361005China Key Laboratory of Semiconductor Material Sciences Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China Shenzhen Research Institute of Xiamen University Shenzhen 518057China Jiujiang Research Institute of Xiamen University Jiujiang 332000China

A 4H-SiC trench gate metal-oxide-semiconductor field-effect transistor(UMOSFET)with semi-super-junction shiel-ded structure(SS-UMOS)is proposed and compared with conventional trench MOSFET(CT-UMOS)in this work.The advantage of the proposed structure is given by comprehensive study of the mechanism of the local semi-super-junction structure at the bottom of the trench MOSFET.In particular,the influence of the bias condition of the p-pillar at the bottom of the trench on the static and dynamic performances of the device is compared and revealed.The on-resistance of SS-UMOS with grounded(G)and ungrounded(NG)p-pillar is reduced by 52%(G)and 71%(NG)compared to CT-UMOS,respectively.Additionally,gate ox-ide in the GSS-UMOS is fully protected by the p-shield layer as well as semi-super-junction structure under the trench and p-base regions.Thus,a reduced electric-field of 2 MV/cm can be achieved at the corner of the p-shield layer.However,the quasi-intrinsic protective layer cannot be formed in NGSS-UMOS due to the charge storage effect in the floating p-pillar,resulting in a large electric field of 2.7 MV/cm at the gate oxide layer.Moreover,the total switching loss of GSS-UMOS is 1.95 mJ/cm2 and is reduced by 18%compared with CT-UMOS.On the contrary,the NGSS-UMOS has the slowest overall switching speed due to the weakened shielding effect of the p-pillar and the largest gate-to-drain capacitance among the three.The proposed GSS-UMOS plays an important role in high-voltage and high-frequency applications,and will provide a valuable idea for device design and circuit applications.

关键词： breakdown voltage specific on-resistance silicon carbide switching energy loss super-junction-shield(SS) trench gate MOSFET grounded(G) ungrounded(NG)

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A Deep Learning-Based Computational Algorithm for Identifying Damage Load Condition: An Artificial Intelligence Inverse Problem Solution for Failure Analysis

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Computer Modeling in Engineering & Sciences 2018年第12期117卷 287-307页

作者： Shaofei Ren Guorong Chen tiange li Qijun Chen Shaofan li College of Shipbuilding Engineering Harbin Engineering UniversityHarbinChina Department of Civil and Environmental Engineering University of CaliforniaBerkeleyCAUSA.

In this work,we have developed a novel machine(deep)learning computational framework to determine and identify damage loading parameters(conditions)for structures and materials based on the permanent or residual plastic deformation distribution or damage state of the structure.We have shown that the developed machine learning algorithm can accurately and(practically)uniquely identify both prior static as well as impact loading conditions in an inverse manner,based on the residual plastic strain and plastic deformation as forensic signatures.The paper presents the detailed machine learning algorithm,data acquisition and learning processes,and validation/verification examples.This development may have significant impacts on forensic material analysis and structure failure analysis,and it provides a powerful tool for material and structure forensic diagnosis,determination,and identification of damage loading conditions in accidental failure events,such as car crashes and infrastructure or building structure collapses.

关键词： Artificial intelligence(AI) deep learning forensic materials engineering plastic deformation structural failure analysis.

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旅游网站机器人客服身份披露和服务属性对顾客满意度的交互影响研究

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旅游科学 2024年第3期38卷 44-61页

作者：张初兵李天歌常颖天津财经大学商学院天津300222

基于技术的发展,旅游网站机器人客服对话质量显著提高,在互动方面和人工客服具有高度相似性。顾客是否知晓机器人客服的真实身份会影响满意度。然而,现有研究较少结合服务属性探究旅游网站机器人客服身份披露对顾客满意度的影响机制。... 详细信息

基于技术的发展,旅游网站机器人客服对话质量显著提高,在互动方面和人工客服具有高度相似性。顾客是否知晓机器人客服的真实身份会影响满意度。然而,现有研究较少结合服务属性探究旅游网站机器人客服身份披露对顾客满意度的影响机制。基于此,文章利用两个实验讨论了机器人客服身份披露和服务属性对顾客满意度的交互作用及内在机制。结果表明:在享乐属性的服务中,无身份披露(vs.有身份披露)的机器人客服更能提高顾客的满意度;在实用属性的服务中,身份披露对满意度作用不显著。同时,能力感知在其中发挥中介作用。研究结论不仅丰富了与机器人客服身份披露相关的研究,也为旅游网站机器人客服身份披露提供了理论指导。

关键词：旅游网站机器人客服身份披露服务属性能力感知

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自强还是自嘲:智能语音助手幽默语言风格对用户失败容忍度的影响

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财经论丛 2024年第3期 91-101页

作者：张初兵李天歌常颖张卓苹天津财经大学商学院天津300222

幽默语言因其能够显著提升沟通效果,正逐渐成为智能对象设计中的重要考虑因素之一。然而以往学者在智能语音助手服务失败时,对于如何有效利用幽默语言风格来提升用户失败容忍度缺乏系统深入的探讨。本研究以智能语音助手服务补救为情境... 详细信息

幽默语言因其能够显著提升沟通效果,正逐渐成为智能对象设计中的重要考虑因素之一。然而以往学者在智能语音助手服务失败时,对于如何有效利用幽默语言风格来提升用户失败容忍度缺乏系统深入的探讨。本研究以智能语音助手服务补救为情境,基于良性冲突理论,通过三个实验,验证了幽默语言风格对用户失败容忍度的影响。结果表明:相较于自强型幽默,自嘲型幽默能够使用户产生更高的失败容忍度,同时揭示了幽默欣赏在其中的中介作用路径。此外,当智能语音助手扮演伙伴角色时,自强型幽默和自嘲型幽默对幽默欣赏及失败容忍度的影响无显著差异;而当其扮演仆人角色时,自嘲型幽默更能通过幽默欣赏影响用户的失败容忍度。

关键词：自强型幽默自嘲型幽默幽默欣赏失败容忍度角色类型

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基于鲁棒增广e约束法的综合能源系统多目标多阶段供能优化配置方法

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电网技术 2024年第7期48卷 2723-2733,I0013,I0014,I0015页

作者：李天格胡志坚谈竹奎王扬胡号郝丹宁郑琳武汉大学电气与自动化学院湖北省武汉市430072 贵州电网有限责任公司电力科学研究院贵州省贵阳市550005

综合能源园区供能优化配置是实践现代能源体系建设、实现能源高效清洁利用的重要技术手段,然而现有规划配置方法存在多能耦合转换模型各异、忽视建设时序性与缺乏多维目标选优上的不足。为此,该文建立综合能源系统多目标多阶段供能优化... 详细信息

综合能源园区供能优化配置是实践现代能源体系建设、实现能源高效清洁利用的重要技术手段,然而现有规划配置方法存在多能耦合转换模型各异、忽视建设时序性与缺乏多维目标选优上的不足。为此,该文建立综合能源系统多目标多阶段供能优化配置模型,该模型为一个多目标混合整数线性优化问题。为实现多目标问题的高效求解,提出了基于鲁棒增广e约束法(robust augmented e-constraint method,AUGMECON-R)的Pareto解集求解方法,并结合综合权重与逼近理想解排序法(technique for order preference by similarity to ideal solution,TOPSIS),选取最契合园区多维评价偏好的建设方案。通过算例仿真验证了所提模型和算法的有效性,该模型能适用于各地各类型园区的供能优化配置决策。

关键词：综合能源系统规划多维目标多阶段模型鲁棒增广e约束法

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基于荧光共振能量转移效应的荧光传感器在真菌毒素检测中的应用

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食品科学 2024年第11期45卷 293-300页

作者：卢美君王田林李天歌乔明武马燕黄现青范家霖宋莲军河南农业大学食品科学技术学院河南郑州450002 河南省科学院同位素研究所有限责任公司河南郑州450002

真菌毒素对人和动物具有剧毒和致癌性,且预防和控制其对食品造成的污染较为困难,因此人们对真菌毒素的关注度越来越高。检测食品中的真菌毒素十分必要,传统检测方法的检测结果准确、可靠,但所需设备昂贵、检测时间长,不符合快速检测真... 详细信息

真菌毒素对人和动物具有剧毒和致癌性,且预防和控制其对食品造成的污染较为困难,因此人们对真菌毒素的关注度越来越高。检测食品中的真菌毒素十分必要,传统检测方法的检测结果准确、可靠,但所需设备昂贵、检测时间长,不符合快速检测真菌毒素的要求。因此,需要开发出快速、灵敏、准确且经济的真菌毒素检测方法。基于荧光共振能量转移(fluorescence resonance energy transfer,FRET)效应的荧光传感器由于操作简单、反应速度快、结果可靠且成本低而广泛应用于检测行业。本文主要介绍了基于FRET效应荧光传感器的检测机制,综述了该传感器在真菌毒素检测中的应用情况,提出了目前荧光传感器仍存在的问题并对其未来的发展趋势进行了展望,以期为新型荧光传感器的设计及真菌毒素检测时灵敏度的优化提供参考。

关键词：真菌毒素荧光传感器荧光共振能量转移检测

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