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Intelligent nanotherapeutic strategies for the delivery of CRISPR system

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药学学报:英文版 2023年第6期13卷 2510-2543页

作者： Chao Chen Wu Zhong Shiyu Du Yayao Li Yunfei Zeng Kunguo Liu jingjing yang Xiaoxiang Guan Xin Han Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province School of MedicineHunan Normal UniversityChangsha 410013China Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.

关键词： CRISPR system Intelligent delivery Gene editing Endogenous responsive Exogenous control Nanotherapeutic platforms Gene therapy Diseases correction

Comparison of DUS testing and SNP fingerprinting for variety identification in cucumber

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Horticultural Plant Journal 2022年第5期8卷 575-582页

作者： Jian Zhang jingjing yang Shenzao Fu Jun Ren XiaoFei Zhang Changxuan Xia Hong Zhao Kun yang Changlong Wen Beijing Vegetable Research Center(BVRC) Beijing Academy of Agricultural and Forestry SciencesNational Engineering Research Center for VegetablesBeijing 100097China Beijing Key Laboratory of Vegetable Germplasms Improvement Beijing 100097China Institute of Vegetables and Flowers Chinese Academy of Agricultural SciencesBeijing 100081China State Key Laboratory of Vegetable Germplasm Innovation Tianjin 300192China

Variety identification plays an important role in protecting the intellectual property of varieties,ensuring seed quality,and encouraging breeding innovation.Currently,morphological evaluation in the field,such as distinctness,uniformity,and stability(DUS)testing,and DNA fingerprinting in the laboratory using molecular markers are two dominant methods used for variety identification.Few studies have compared the results of these approaches,and the relationship between the two methods is obscure.In this study,134 dominant cucumber varieties were evaluated using 50 DUS testing traits and genotyped by 40 single nucleotide polymorphisms(SNPs).The 40 SNPs were developed in our previous study and arewell suited for variety identification.In the DUS testing,significant positive or negative correlations among 50 DUS traits were observed,and 20 core traits,including 15 fruit traits,were further selected to increase field inspection efficiency.This suggested that fruit shape plays an important role in variety identification.The ratio of fruit length/diameter was themost important trait,explaining 9.2%of the phenotypic variation.In the DNA fingerprinting test,the 40 SNPs were highly polymorphic and could distinguish all of the 134 cucumber varieties,and 14 core SNPs were selected to improve the identification rate.Interestingly,the population structure analysis of 134 cucumber varieties by phenotypic data in the DUS test was in accordance with the genotypic data from the DNA fingerprinting,indicating that all varieties could be divided into the same four subgroups:European type,North China type,South China type,and hybrids of the North China and South China types.Moreover,linear correlativity of distinguishment for each pair of varieties was observed between the DUS test and the DNA fingerprinting.These results indicated that these two methods have good application in future research,especially for the scaled-up analysis of hundreds of varieties.

关键词： Cucumber DUS test SNP fingerprinting Variety identification

Overexpression of MdFRK2 enhances apple drought resistance by promoting carbohydrate metabolism and root growth under drought stress

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Horticultural Plant Journal 2023年第5期9卷 884-897页

作者： jingjing yang Ruiling Zhan Lan Wang Junqiao Li Baiquan Ma Fengwang Ma Mingjun Li Key Laboratory of Molecular Module-Based Breeding of High Yield and Abiotic Resistant Plants in Universities of Shandong College of AgricultureLudong UniversityYantaiShandong 264025China State Key Laboratory of Crop Stress Biology for Arid Areas/Shaanxi Key Laboratory of Apple College of HorticultureNorthwest A&F UniversityYanglingShaanxi 712100China Key Laboratory of Fruit Tree Research in Ganzi Academy of Agricultural Sciences KangdingSichuan 626000China

Soluble sugars function not only as the energy and structural blocks supporting plants,but also as osmoregulators and signal molecules during plant adaptation to water deficit.Here,we investigated drought resistance in transgenic apple(Malus×domestica)overexpressing MdFRK2,a key gene regulating fructose content and sugar metabolism.There is no obvious phenotypic difference between MdFRK2-overexpressing transgenic plants and WT plants under the well-watered condition.However,the transgenic plants and the grafted plants using MdFRK2-overexpressing rootstock exhibited improved tolerance to drought stress.Overexpression of MdFRK2 significantly promoted the growth of root system under drought stress.RNA sequencing showed that under drought stress,genes involved in sugar metabolism,transcription regulation,signal transduction or hormone metabolism were differentially expressed in MdFRK2 transgenic plants.Consistent with the gene expression profile,the activities of enzyme(SDH,FRK and NI)involved in sugar metabolism in the roots of MdFRK2 transgenic plants were significantly higher than those of untransformed control plants after drought stress.Under drought stress,overexpression of MdFRK2 promoted the accumulation of IAA,and decreased the contents of ABA and CK in apple root system.In conclusion,these results suggest that MdFRK2 can promote the growth of apple roots under drought stress by regulating sugar metabolism and accumulation,hormone metabolism and signal transduction,and then resist drought stress.

关键词： Malus×domestica MdFRK2 Drought stress Sugar Auxin Signal transduction Transcriptome

Entrainment of Astrocytic and Neuronal Ca^(2+) Population Dynamics During Information Processing of Working Memory in Mice

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Neuroscience Bulletin 2022年第5期38卷 474-488页

作者： Zhu Lin Feng You Ting Li Yijia Feng Xinyue Zhao jingjing yang Zhimo Yao Ying Gao Jiang-Fan Chen The Molecular Neuropharmacology Laboratory and the EyeBrain Research Center State Key Laboratory of OphthalmologyOptometry and Visual ScienceSchool of Optometry and Ophthalmology and Eye HospitalWenzhou Medical UniversityWenzhou 325035China

Astrocytes are increasingly recognized to play an active role in learning and memory,but whether neural inputs can trigger event-specific astrocytic Ca^(2+)dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca^(2+)dynamics in animals performing tasks.Here,using fiber photometry,we showed that population astrocytic Ca^(2+)dynamics in the hippocampus were gated by sensory inputs(centered at the turning point of the T-maze)and modified by the reward delivery during the encoding and retrieval phases.Notably,there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca^(2+)dynamics with a 3-s phase difference.Furthermore,there was a robust synchronization of astrocytic Ca^(2+)at the population level among the hippocampus,medial prefrontal cortex,and striatum.The inter-locked,bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.

关键词： Working memory Ca^(2+)dynamics Astrocyte Neuron Fiber photometry Hippocampus

Time-course transcriptome landscape of achene development in lettuce

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Horticultural Plant Journal 2022年第1期8卷 99-109页

作者： Chen Luo Shenglin Wang Kang Ning Zijing Chen jingjing yang Yixin Wang Meixia Qi Qian Wang Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops Department of Vegetable ScienceCollege of HorticultureChina Agricultural UniversityBeijing 100193China

Lettuce(Lactuca sativa L.),which belongs to the large Asteraceae(Compositae)family,breeds by sexual reproduction and produces seeds.Actually,lettuce seeds are achenes,which are defined as fruits.However,few studies have described the morphological characteristics of the lettuce achenes,and genes essential for achene development are largely unknown in lettuce.To investigate the gene activity during achene development and determine the possible mechanisms that influence achene development in lettuce,we performed a time-course transcriptome analysis of lettuce achenes.A total of 27,390 expressed genes were detected at the five achene development stages.We investigated the gene expression patterns during achene development and identified the enriched biological processes at the corresponding stages.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed a variety of transcriptomic similarities and differences at different achene development stages.Further,transcription factors and phytohormones were found to play important roles during achene development.Finally,we proposed a working model to illustrate the gene expression modules and possible molecular mechanisms underlying achene development.Our time-course transcriptome data also provide a foundation for future functional studies to reveal the genetic control of achene development in lettuce.

关键词： Lettuce Achene development Transcriptome Fruit Seed Transcription factor

非物质文化遗产保护传承的实践研究及对策分析——以河南省为例

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河南社会科学 2024年第4期32卷 87-93页

作者：杨静静河南中医药大学管理学院河南郑州450046

非物质文化遗产是中华优秀传统文化的重要组成部分,其保护传承工作意义重大。系统把握非物质文化遗产的历史价值、文化价值、经济价值、社会价值等多重价值,是推动非物质文化遗产创造性转化、创新性发展的有力支撑。河南历史文化积淀深... 详细信息

非物质文化遗产是中华优秀传统文化的重要组成部分,其保护传承工作意义重大。系统把握非物质文化遗产的历史价值、文化价值、经济价值、社会价值等多重价值,是推动非物质文化遗产创造性转化、创新性发展的有力支撑。河南历史文化积淀深厚,孕育了丰富的非物质文化遗产,具有种类丰、分布广、价值高和影响大的特点,在加强非物质文化遗产保护传承中形成了一系列卓有成效的实践探索,但同时也面临文化土壤流失、传承后继乏人、传播效能不佳等问题,今后应从挖掘价值、焕发生命力,善作善为、增强保护力,厚植基础、激活原动力,传承教育、注入新活力,守正创新、提升竞争力,数字赋能、提升传播力,加强宣传、扩大影响力七个方面,在融合创新中激发非遗保护传承的动力活力,在推动文化新辉煌中有更大作为。

关键词：非物质文化遗产保护传承价值对策

In vitro and in vivo efficacy of Molnupiravir against Zika virus infections

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Virologica Sinica 2023年第4期38卷 639-642页

作者： Zhuang Wang Shaokang yang Qingsong Dai Xiaojia Guo Yuexiang Li Wei Li Xiaotong yang jingjing yang Xintong Yan Huimin Tao Chongda Luo Song Li Xingjuan Chen Ruiyuan Cao Wu Zhong Institute of Medical Research Northwestern Polytechnical UniversityXi'an710072China National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing100850China College of Chemical and Pharmaceutical Engineering Hebei University of Science and TechnologyShijiazhuang050018China Song Li's Academician Workstation of Hainan University(School of Pharmaceutical Sciences) Yazhou BaySanya572000China School of Medicine Tsinghua UniversityBeijing100084China

Dear Editor,Zika virus(ZIKV)is a mosquito-borne,positive-stranded RNA virus first identified in 1947 in monkeys and later identified in humans in 1952(Faye et al.,2014).It is among the“TORCH”group of microorganisms ... 详细信息

关键词： TORCH infections vivo

Tilorone confers robust in vitro and in vivo antiviral effects against severe fever with thrombocytopenia syndrome virus

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Virologica Sinica 2022年第1期37卷 145-148页

作者： jingjing yang Yunzheng Yan Qingsong Dai Jiye Yin Lei Zhao Yuexiang Li Wei Li Wu Zhong Ruiyuan Cao Song Li School of Pharmaceutical Sciences Hainan UniversityHaikou570228China National Engineering Research Centre for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing100850China

Dear Editor,Severe fever with thrombocytopenia syndrome virus(SFTSV),an emerging pathogen,is a tick-borne bunyavirus belonging to the genus Bandavirus in the family Phenuiviridae(Kuhn et al.,2020).This pathogen was first identified in China during the heightened surveillance of acute febrile illness in 2009,and has been reported to cause several outbreaks in eastern Asia areas,including China,Japan,and Korea(Yu et al.,2011).

关键词： al. fever acute

HSV-2-encoded miRNA-H4 Regulates Cell Cycle Progression and Act-Dinduced Apoptosis in HeLa Cells by Targeting CDKL2 and CDKN2A

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Virologica Sinica 2019年第3期34卷 278-286页

作者： yang Zhao jingjing yang Yan Liu Jianyong Fan Huilan yang Guangzhou School of Clinical Medicine Southern Medical UniversityGuangzhou 510010China Department of Dermatology General Hospital of Southern Theatre Command of PLAGuangzhou 510010China

MicroRNAs(miRNAs)encoded by latency-associated transcript are associated with both latent and acute stages of herpes simplex virus 2(HSV-2)infection.In this study,miRNA-H4-5p and miRNA-H4-3p were ectopically expressed in HeLa cells to explore potential cellular targets of viral miRNAs and demonstrate their potential biological functions.The results showed that miRNA-H4-5p could reverse apoptosis induced by actinomycin D(Act-D)and promote cell cycle progression,but miRNA-H4-3p had no such obvious functions.Bioinformatics analysis,luciferase report assay,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and Western blotting demonstrated that miRNA-H4-5p could bind to the 3-′untranslated region(UTR)of cyclin-dependent kinase inhibitor 2A(CDKN2A)and cyclin-dependent kinase-like 2(CDKL2)to negatively regulate their expression.We verified that these two targeted genes were associated with cell apoptosis and cell cycle.Furthermore,in HeLa cells infected with HSV-2,we detected significantly reduced expression of CDKN2A and CDKL2 and demonstrated the negative regulation effect of miRNA-H4-5p on these two target genes.Our findings show that viral miRNAs play a vital role in regulating the expression of the host's cellular genes that participate in cell apoptosis and progression to reshape the cellular environment in response to HSV-2 infection,providing further information on the roles of encoded herpesvirus miRNAs in pathogen-host interaction.

关键词： Herpes simplex virus 2(HSV-2) MicroRNAs(miRNAs) Anti-apoptosis-Cell cycle progression Pathogen-host interaction