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2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu peng Minru Liao Wenke Jin Wei liu Zixiang Li Zhichao fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

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DVsc:An Automated Framework for Efficiently Detecting Viral Infection from Single-cell Transcriptomics Data

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 189-200页

作者： fei Leng Song Mei Xiaolin Zhou Xuanshi liu Yefeng Yuan Wenjian Xu Chongyi Hao Ruolan Guo Chanjuan Hao Wei Li peng Zhang Beijing Key Laboratory for Genetics of Birth Defects Beijing Pediatric Research Institute/MOE Key Laboratory of Major Diseases in Children/Rare Disease CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Institute of Biomedical Engineering University of TorontoTorontoM5S 3G9Canada

Single-cell RNA sequencing(scRNA-seq)has emerged as a valuable tool for studying cellular heterogeneity in various fields,particularly in virological *** studying the viral and cellular transcriptomes,the dynamics of viral infection can be investigated at a single-cell ***,limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs,and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been ***,we introduce DVsc,an open-source framework for precise quantitative analysis of viral infection from single-cell transcriptomics *** applied to approximately 200 diverse clinical samples that were infected by more than 10 different viruses,DVsc demonstrated high accuracy in systematically detecting viral infection across a wide array of cell *** innovative bioinformatics pipeline could be crucial for addressing the potential effects of surreptitiously invading viruses on certain illnesses,as well as for designing novel medicines to target viruses in specific host cell subsets and evaluating the efficacy of *** supports the FASTQ format as an input and is compatible with multiple single-cell sequencing ***,it could also be applied to sequences from bulk RNA sequencing *** is available at http://62.***.32.33:5000/DVsc.

关键词： Single-cell RNA sequencing Viral transcriptome Cellular transcriptome Viral infection Quantitative analysis Bulk RNA sequencing

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Cryo-EM structure of cannabinoid receptor CB1-β-arrestincomplex

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Protein & Cell 2024年第3期15卷 230-234页

作者： Yuxia Wang Lijie Wu Tian Wang Junlin liu fei Li Longquan Jiang Zhongbo fan Yanan Yu Na Chen Qianqian Sun Qiwen Tan Tian Hua Zhi-Jie liu iHuman Institute ShanghaiTech UniversityShanghai 201210China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Institute of Molecular and Clinical Medicine Kunming Medical UniversityKunming 650500China

Dear Editor,G protein-coupled receptors(GPCRs)play a vital role in regulating almost every aspect of human physiology,making up more than one-third of marketed drug targets(Santos et al.,2017).GPCRs orchestrate their signalling through interactions with three distinct downstream protein families:G proteins,G protein-coupled receptor kinases(GRKs),and arrestins(Santos et al.,2017).While G protein-mediated signalling is initiated upon GPCR stimulation,activated GPCRs return to their basal levels through a GRK-and arrestin-regulated desensitization process(Santos et al.,2017).In addition to modulating receptor desensitization,β-arrestin also regulates downstream events that are distinct from classical G protein signalling(Ahn et al.,2020).

关键词： stimulation return

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Biphase-to-monophase structure evolution of Na_(0.766+x)Li_(x)Ni_(0.33-x)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) toward ultradurable Na-ion batteries

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Carbon Energy 2024年第9期6卷 66-79页

作者： Mengting liu Zhiwei Cheng Xu Zhu Haojie Dong Tianran Yan Liang Zhang Lu Zheng Hu-Rong Yao Xian-Zuo Wang Lianzheng Yu Bing Xiao Yao Xiao peng-fei Wang State Key Laboratory of Electrical Insulation and Power Equipment School of Electrical EngineeringCenter of Nanomaterials for Renewable EnergyXi'an Jiaotong UniversityXi'anShaanxiChina Jiangsu Key Laboratory of Advanced Negative Carbon Technologies Institute of Functional Nano&Soft Materials(FUNSOM)Soochow UniversitySuzhouJiangsuChina Fujian Provincial Key Laboratory of Quantum Manipulation and New Energy Materials College of Physics and EnergyFujian Normal UniversityFuzhouFujianChina Wenzhou Key Laboratory of Sodium-Ion Batteries Institute for Carbon NeutralizationWenzhou University Technology InnovationWenzhouZhejiangChina

Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 ***,their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation,complicated electrochemical phase transition,and unsatisfactory cycling ***,we propose an efficient structural evolution strategy from biphase to monophase of Na_(0.766+x)Li_(x)Ni_(0.33-x)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) through Li+*** role of Li+substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal(TM)cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery *** a result,the thermodynamically robust O_(3)-Na_(0.826)Li_(0.06)Ni_(0.27)Mn_(0.5)Fe_(0.1)Ti_(0.07)O_(2) cathode delivers a high capacity of 139.4 mAh g^(-1) at 0.1 C and shows prolonged cycling life at high rates,with capacity retention of 81.6%at 5 C over 500 *** work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials,contributing to the development of long-life sodium-ion batteries.

关键词： electrochemistry Li+substitution Na-ion batteries O_(3)phase phase transition

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Carbon nanotube films with ultrahigh thermal-shock and thermalshock-fatigue resistance characterized by ultra-fast ascending shock testing

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Nano Research 2024年第8期17卷 6777-6784页

作者： Mingquan Zhu Shijun Wang Yunxiang Bai Feng Gao Zhenxing Zhu Congying Wang peng Zhang Hao Jin Hui Zhang Luqi liu Zhiping Xu Xinghong Zhang fei Wei Zhong Zhang CAS Key Laboratory of Nanosystem and Hierarchical Fabrication CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical EngineeringTsinghua UniversityBeijing 100084China Department of Engineering Mechanics Tsinghua UniversityBeijing 100084China National Key Laboratory of Science and Technology on Advanced Composites in Special Environments Center for Composite Materials and StructuresHarbin Institute of TechnologyHarbin 150001China CAS Key Laboratory of Mechanical Behavior and Design of Materials Department of Modern MechanicsUniversity of Science and Technology of ChinaHefei 230027China

The exploration of material failure behavior not only involves defining its limits and underlying mechanisms but also entails devising strategies for improvement and protection in extreme ***'ve pioneered an advanced multi-scale,high-speed ascending thermal shock testing platform capable of inducing unprecedented heat shocks at rates surpassing 105℃/*** meticulous examination of the thermal shock responses of carbon nanotube(CNT)films,we've achieved remarkable *** employing an innovative macro-scale synchronous tightening and relaxing approach,we've attained a critical temperature differential in CNT films that exceeds an exceptional 2500℃—surpassing any previously reported metric for highperformance,thermal-shock-resistant ***,these samples have demonstrated exceptional resilience,retaining virtually unchanged strength even after enduring 10,000 thermal shock cycles at temperatures exceeding 1000℃.Furthermore,our research has revealed a novel thermal shock/fatigue failure mechanism that fundamentally diverges from conventional theories centered on thermal stress.

关键词： carbon nanotubes failure behavior thermal shock characterization

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Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer

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Cancer Innovation 2024年第4期3卷 67-86页

作者： Yuan‐yuan Sun Hai‐cheng Gao peng Guo Na Sun Chan peng Zhi‐hua Cheng Jing Gu Jin‐yi liu fei Han Department of Clinical Pharmacy Jilin University School of Pharmaceutical SciencesChangchunChina Institute of Toxicology College of Preventive MedicineArmy Medical UniversityChongqingChina Department of Hepatobiliary Surgery Third Affiliated Hospital of Chongqing Medical UniversityChongqingChina Breast and Thyroid Surgery Southwest HospitalArmy Medical UniversityChongqingChina College of Pharmaceutical Sciences Southwest UniversityChongqingChina Vascular Surgery Department General Surgery CenterFirst Hospital of Jilin UniversityChangchunChina Department of Toxicology School of Public HealthChongqing Medical UniversityChongqingChina Laboratory of Reproductive Biology Chongqing Medical UniversityChongqingChina

Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival *** identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently ***:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in *** UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic ***‐of‐function assays were performed to examine the *** ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular ***:NR3C2 was identified as a potentially important molecule in ***3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these *** operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC *** NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC *** results have been confirmed both with database analysis and real‐world clinical samples on a tissue *** number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in *** NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application ***3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell ***3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially si

关键词： diagnosis and prognosis expression regulation function immune cell infiltration non‐small cell lung cancer NR3C2 therapeutic target tumor microenvironment

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Unexpected divergence in magnetoreceptor MagR from robin and pigeon linked to two sequence variations

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Zoological Research 2024年第1期45卷 69-78页

作者： Shun Wang peng Zhang fan fei Tianyang Tong Xiujuan Zhou Yajie Zhou Jing Zhang Mengke Wei Yanqi Zhang Lei Zhang Yulong Huang Lin Zhang Xin Zhang Tiantian Cai Can Xie Institutes of Physical Science and Information Technology Anhui UniversityHefeiAnhui 230039China High Magnetic Field Laboratory Hefei Institutes of Physical ScienceChinese Academy of SciencesScience IslandHefeiAnhui 230031China Science Island Branch of Graduate School University of Science and Technology of ChinaHefeiAnhui 230036China Department of Anatomy Anhui Medical UniversityHefeiAnhui 230032China Department of Mechanical and Aerospace Engineering University at BuffaloState University of New YorkBuffaloNY 14260 USA International Magnetobiology Frontier Research Center Science IslandHefeiAnhui 230031China

Birds exhibit extraordinary mobility and remarkable navigational skills,obtaining guidance cues from the Earth’s magnetic field for orientation and long-distance *** species also show tremendous diversity in navigation strategies,with considerable differences even within the same taxa and among individuals from the same *** highly conserved iron and iron-sulfur cluster binding magnetoreceptor(MagR)protein is suggested to enable animals,including birds,to detect the geomagnetic field and navigate ***,MagR is also implicated in other functions,such as electron transfer and biogenesis of iron-sulfur clusters,raising the question of whether variability exists in its biochemical and biophysical features among species,particularly *** the current study,we conducted a comparative analysis of MagR from two different bird species,including the migratory European robin(Erithacus rubecula)and the homing pigeon(Columba livia).Sequence alignment revealed an extremely high degree of similarity between the MagRs of these species,with only three sequence ***,two of these variations underpinned significant differences in metal binding capacity,oligomeric state,and magnetic *** findings offer compelling evidence for the marked differences in MagR between the two avian species,potentially explaining how a highly conserved protein can mediate such diverse functions.

关键词： Homing and migration Animal navigation Magnetoreceptor(MagR) Diverse navigation pattern Conserved protein

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基于红外辐射测温法的焊头动态高速真温测量系统研制

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光谱学与光谱分析 2024年第3期44卷 836-842页

作者：萧鹏台泓冰向茂林王伟宸张帆哈尔滨工业大学黑龙江哈尔滨150001 中国航天科工集团第四研究院北京100038 中国空空导弹研究院控制所河南洛阳471009

温度是用来表征物体特性的一个重要的基本参数,被广泛应用于金属加工、生产生活、航空航天等各个领域,温度测量的准确与否对每个行业都有着至关重要的影响。随着电子设备的尺寸不断微型化以及各种可穿戴智能设备的普及和发展,小型化成... 详细信息

温度是用来表征物体特性的一个重要的基本参数,被广泛应用于金属加工、生产生活、航空航天等各个领域,温度测量的准确与否对每个行业都有着至关重要的影响。随着电子设备的尺寸不断微型化以及各种可穿戴智能设备的普及和发展,小型化成为了电子元件技术水平的一个重要技术指标,所以电子元器件也一直朝着小尺寸、高集成化方向发展,而其焊接温度的波动引起的产品良品率也在不断降低。因此,如何实现电子元器件焊接过程中焊头温度的实时获取,已成为众多相关企业急需研究的课题。基于晶体管式焊接电源的工作特点,从分析焊头的结构特性入手,利用焊头的红外光谱辐射特性,设计了一种激光瞄准式的光学系统,采用朗伯体法对焊头进行温度测量,从而得到焊头工作时的实时真温。整个温度测量系统由硬件系统部分和软件系统部分构成。其中,硬件系统包括光学系统的设计、 I/V转换及放大电路和上位机的高速数据采集系统。软件系统主要包括上位机系统界面的设计。上位机软件采用LabVIEW进行程序设计,主要包括AD采集卡的配置与驱动、数据滤波、零点测量、温度标定、温度计算、实时温度曲线和数据存储。在系统建立、软件调试完毕后,采用标准空腔黑体炉对测温系统进行了校准。首先,利用整体黑体法对焊头工作时的发射率进行了试验,结果表明,在氧化和非氧化状态下,其发射率与文献数据基本一致。然后利用该发射率值,计算出了焊头上小孔的空腔黑体发射率。最后,利用恒流晶体管式焊接电源进行了系统稳定性和重复性实验。分析该方法的不确定度,得出该方法的总体不确定度在3%以内。通过对测温系统的标定和配置,该系统还可以应用在其他需要高速精确测温的场景。

关键词：焊头温度黑体法测温快速测量红外光谱发射率

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A graph-based pan-genome of Brassica oleracea provides new insights into its domestication and morphotype diversification

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Plant Communications 2024年第2期5卷 261-278页

作者： Ning Guo Shenyun Wang Tianyi Wang Mengmeng Duan Mei Zong Liming Miao Shuo Han Guixiang Wang Xin liu Deshuang Zhang Chengzhi Jiao Hongwei Xu Liyang Chen Zhangjun fei Jianbin Li fan liu State Key Laboratory of Vegetable Biobreeding National Engineering Research Center for VegetablesBeijing Key Laboratory of Vegetable Germplasm ImprovementKey Laboratory of Biology and Genetics Improvement of Horticultural Crops(North China)Beijing Vegetable Research CenterBeijing Academy of Agriculture and Forestry ScienceBeijing 100097China Jiangsu Key Laboratory for Horticultural Crop Genetic Improvement Vegetable Research InstituteJiangsu Academy of Agricultural ScienceNanjingJiangsuChina Smartgenomics Technology Institute Tianjin 301700China Boyce Thompson Institute IthacaNYUSA

The domestication of Brassica oleracea has resulted in diverse morphological types with distinct patterns of organ *** we report a graph-based pan-genome of *** constructed from high-quality genome assemblies of different *** pan-genome harbors over 200 structural variant hotspot regions enriched in auxin-andflowering-related *** genomic analyses revealed that early domestication of *** focused on leaf or stem *** resulting from agricultural practices and variety improvement were detected among different ***-sweep and pan-genome analyses identified an auxin-responsive small auxin up-regulated RNA gene and a CLAV-ATA3/ESR-RELATED family gene as crucial players in leaf–stem differentiation during the early stage of *** domestication and the BoKAN1 gene as instrumental in shaping the leafy heads of cabbage and Brussels *** pan-genome and functional analyses further revealed that variations in the BoFLC2 gene play key roles in the divergence of vernalization andflowering characteristics among different morphotypes,and variations in thefirst intron of BoFLC3 are involved infine-tuning theflowering process in *** study provides a comprehensive understanding of the pan-genome of *** and sheds light on the domestication and differential organ development of this globally important crop species.

关键词： Brassica oleracea graph-based pan-genome structural variants SV domestication morphotype diversification

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Establishing VIGS and CRISPR/Cas9 techniques to verify RsPDS function in radish

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Journal of Integrative Agriculture 2024年第5期23卷 1557-1567页

作者： Jiali Ying Yan Wang Liang Xu Tiaojiao Qin Kai Xia peng Zhang Yinbo Ma Keyun Zhang Lun Wang Junhui Dong Lianxue fan Yuelin Zhu Liwang liu National Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization/Key Laboratory of Horticultural Crop Biology and Genetic Improvement(East China)of Ministry of Agriculture and Rural Affairs/College of Horticulture Nanjing Agricultural UniversityNanjing210095China College of Horticulture and Landscape Architecture Yangzhou UniversityYangzhou 225009China College of Life Sciences Nanjing Agricultural UniversityNanjing 210095China

Virus-induced gene silencing(VIGS)and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein(CRISPR/Cas)systems are effective technologies for rapid and accurate gene function verification in modern plant ***,the investigation of gene silencing and editing in radish remains *** this study,a bleaching phenotype was generated through the knockdown of RsPDS using tobacco rattle virus(TRV)-and turnip yellow mosaic virus(TYMV)-mediated gene silencing *** TYMV-mediated gene silencing efficiency was higher than the TRV-based VIGS system in *** expression level of RsPDS was significantly inhibited using VIGS in'NAU-067'radish *** rootless seedlings of‘NAU-067'were infected with Agrobacterium rhizogenes using the 2300GN-Ubi-RsPDS-Cas9 vector with two target *** adventitious roots were blue with GUs staining,and four of these adventitious roots were edited at target sequence 1 of the RsPDS gene as indicated by Sanger ***,albino lines were generated with ***-mediated transformation of radish *** base substitutions and three base deletions occurred at target sequence 2 in Line 1,and three base insertions and three base substitutions occurred at target sequence 1 in Line *** study shows that VIGS and CRISPR/Cas9 techniques can be employed to precisely verify the biological functions of genes in radish,which will facilitate the genetic improvement of vital horticultural traits in radish breeding programs.

关键词： Raphanus sativus L. VIGS CRISPR/Cas9 Agrobacterium rhizogenes A.tumefaciens RsPDS

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