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Smooth muscle cell-specific genetic targeting by Myh11-driven Cre(ER)knockin mice

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Science china(Life Sciences) 2024年第10期67卷 2280-2282页

作者： Enci Wang Ximeng han Haixiao Wang Kathy O.Lui Bin Zhou Lixin Wang Department of Vascular Surgery Zhongshan HospitalFudan UniversityShanghai 200032China Department of Cardiology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Pediatric Research Institute The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027China Department of Chemical Pathology and Li Ka Shing Institute of Health SciencesPrince of Wales HospitalThe Chinese University of Hong KongHong Kong 999077China New Cornerstone Investigator Institute State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Department of Vascular Surgery(Xiamen) Zhongshan hospitalFudan UniversityXiamen 361015China

Dear editor,Site specific recombinases have been widely used for genome engineering in cardiovascular research(Fu et al.,2.2.;Huang et al.,2.2.;Xue et al.,2.2.).In particular,Cre is the most broadly used recombinase for cell type-specific lineage tracing and gene manipulation in *** smooth muscle cell(SMC)-specific targeting,several SMC promoters including Myh11(smooth muscle myosin heavy chain),Acta2.smooth muscle a-2.actin),and SM2.a(Tagln)have been used to drive Cre or CreER.

关键词： cardiovascular manipulation

Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers

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Molecular Plant 2024年第9期17卷 1472-1483页

作者： Qi Yao Rundong Shen Yang Shao Yifu Tian Peijin han Xuening Zhang Jian-Kang Zhu Yuming Lu shanghai Collaborative Innovation center of Agri-Seeds Joint Center for Single-Cell BiologySchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China shanghai center for Plant Stress Biology Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 201602China University of the chinese Academy of Sciences BeijingChina College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China

Geneupregulation through genome editing is important for plant research and *** insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with ***,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene *** address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice *** in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript ***-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant *** approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic ***,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene ***,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.

关键词： genome editing short transcriptional enhancers gene upregulation crop breeding

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泛基因组研究揭示柑橘亚科物种的起源和传播

科学通报 2024年第8期69卷 965-967页

作者：韩斌邓秀新中国科学院分子植物科学卓越创新中心上海200233 华中农业大学果蔬园艺作物种质创新与利用全国重点实验室武汉430070

柑橘是全球广泛种植的果树之一.我国柑橘栽培历史悠久,公元前370年的《禹贡》一书就有记载.柑橘种类繁多,长期的选择与利用导致柑橘品种类型和用途多样,既有常见的栽培类型橘、柚、甜橙、柠檬、枸橼、金柑等,也有用作砧木的野生或半野... 详细信息

柑橘是全球广泛种植的果树之一.我国柑橘栽培历史悠久,公元前370年的《禹贡》一书就有记载.柑橘种类繁多,长期的选择与利用导致柑橘品种类型和用途多样,既有常见的栽培类型橘、柚、甜橙、柠檬、枸橼、金柑等,也有用作砧木的野生或半野生资源如枳、酸橙等;既可鲜食,也可加工,还可药用.

关键词：栽培类型柑橘品种半野生酸橙《禹贡》金柑柑橘栽培砧木

Allelic reprogramming of chromatin states in human early embryos

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national Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu center for Reproductive Medicine Shandong University CAS key laboratory of {2. Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of chinese Academy of Sciences CUHK-SDU Joint laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong key laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University center for Reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K2.me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K2.me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K2.me3 chromatin accessibility

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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national Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing key laboratory of {2. Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical Science Wenzhou Medical University Institute of Life Sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2.cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of {2. major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated􀀖􀄮􀀏􀀙􀄮􀀏􀀚􀄮􀀏􀀔􀀕􀄮􀀐􀀷􀁈􀁗􀁕􀁄􀁋􀁜􀁇􀁕􀁒􀁛􀁜􀁏􀁄􀁗􀁈􀁇􀀃􀀥􀁌􀁏􀁈􀀃􀀤􀁆􀁌􀁇􀀃􀁌􀁑􀀃􀀦􀁋􀁒􀁏􀁈􀁖􀁗􀁄􀁖􀁌􀁖

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 151-161页

作者： Teng Liu Ren-Xue Wang Jun han Zhong-Die Li Jonathan ASheps Li-Juan Zheng Xiao-Xiao Xu Victor Ling Jian-She Wang Department of Pediatrics Shanghai Medical CollegeFudan UniversityThe Center for Pediatric Liver DiseasesChildren’s Hospital of Fudan UniversityShanghaiChina BC Cancer Agency VancouverBritish Columbia V5Z 1L3Canada University of Victoria-genome BC Proteomics center University of VictoriaVictoriaBritish Columbia V8Z 7X8Canada shanghai key {2. of Birth Defect ShanghaiChina

Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in ***:Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-MS).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different *** areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further ***:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.2. m)were significantly lower than those of healthy controls(14.02.1.74 m,p2..Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a ***:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.

关键词： Bile acids MDR3 BSEP PFIC Liquid chromatography-mass spectrometry

Achieving high carrier mobility and low lattice thermal conductivity in GeTe-based alloys by cationic/anionic co-doping

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Rare Metals 2024年第6期43卷 2784-2795页

作者： Xiao-Qiang Wang Xiao-Quan Hu Jun-Yan Lin Chu-Bin Li Xiao-Tong Yu Qi-Yong Chen Li-Li Xi Qi-Shuo Yang han Li Ji-Ye Zhang Shuan-Kui Li Kai Guo School of Physics and Materials Science Guangzhou UniversityGuangzhou 510006China Research center for Advanced Information Materials(CAIM) Huangpu Research&Graduate School of Guangzhou UniversitySino-Singapore Guangzhou Knowledge CityGuangzhou510555China School of Materials Science and Engineering Shanghai UniversityShanghai 200444China Materials genome Institute Shanghai UniversityShanghai 200444China School of Mechanical and Mining Engineering University of QueenslandBrisbaneQLD 4072Australia key laboratory of Si-Based Information Materials&Devices and Integrated Circuits Design Department of Education of Guangdong ProvinceGuangzhou 510006China

TheⅣ-Ⅵcompound GeTe is considered as a promising alternative to the toxic PbTe for high-efficiency mid-temperature thermoelectric ***,pristine GeTe suffers from a high concentration of Ge vacancies,resulting in an excessively high hole concentration(>1×10^(2.)cm^(-3)),which greatly limits its thermoelectric *** address this issue,CuBiTe_(2.alloying is introduced to increase the formation energy of Ge vacancies in GeTe,thereby inhibiting the high carrier *** carrier scattering caused by the electronegativity difference between different elements is suppressed due to the similar electronegativity of Cu and Ge atoms.A relatively high hole mobility is obtained,which ultimately leads to a high power ***,by introducing Se as an alloying element at the anionic site in GeTe,dense point defects with mass/strainfield fluctuations are *** contributes to the strengthening of phonon scattering,thereby reducing the lattice thermal conductivity from 1.44 W·m^(-1)·K^(-1)for pristine GeTe to 0.2. W·m^(-1)·K^(-1)for Ge_(0.95)Cu_(0.05)Bi_(0.05)Te_(0.9)Se_(0.15)compound at 62. K.

关键词： GeTe Carrier mobility CuBiTe_(2.alloying Lattice thermal conductivity Thermoelectric properties

Prediction of ultimate tensile strength of Al-Si alloys based on multimodal fusion learning

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Materials genome Engineering Advances 2024年第1期2卷 104-119页

作者： Longfei Zhu Qun Luo Qiaochuan Chen Yu Zhang Lijun Zhang Bin Hu Yuexing han Qian Li State key laboratory of Advanced Special Steels&{2. key laboratory of Advanced Ferrometallurgy&School of Materials Science and Engineering Shanghai UniversityShanghaiChina School of Computer Engineering and Science Shanghai UniversityShanghaiChina College of Materials Science and Engineering Chongqing UniversityChongqingChina State key laboratory of Powder Metallurgy Central South UniversityChangshaChina CSMET Group Co. Ltd.ShanghaiChina Zhejiang laboratory HangzhouChina national Engineering Research center for Magnesium Alloy Chongqing UniversityChongqingChina national key {2. of Advanced Casting Technologies Chongqing UniversityChongqingChina

Exploring the“composition-microstructure-property”relationship is a long-standing theme in materials ***,complex interactions make this area of research *** on the image processing and machine learning techniques,this paper proposes a multimodal fusion learning framework that comprehensively considers both composition and microstructure in prediction of the ultimate tensile strength(UTS)of Al-Si ***,the composition and image information are collected from the literature and supplementary experi-ments,followed by the image segmentation and quantitative analysis of eutectic Si ***,the quantitative analysis results are combined with other features for three-step feature screening,and 12.key features are ***,four machine-learning models(i.e.,decision tree,random forest,adaptive boosting,and extreme gradient boosting[XGBoost])are used to predict the UTS of Al-Si *** results show that the quantitative analysis method proposed in this paper is superior to Image-Pro Plus(IPP)software in some *** XGBoost model has the best prediction performance with R^(2.=***,five mixed features and their critical values that significantly affect UTS are *** study provides enlightenment for the prediction of UTS of Al-Si alloys from composition and microstructure,and would be applicable to other alloys.

关键词： Al-Si alloys image processing machine learning multimodal property prediction

Inhibitory Effect of IGF1R siRNA on the growth of human liver cancer SMMC772. cell xenograft in nude mice

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The chinese-German Journal of Clinical Oncology 2008年第5期7卷 272-276页

作者： Jian Niu Haixin Qian Xiangnong Li zeguang han Department of General Surgery The First Affiliated Hospital Xuzhou Medical College Xuzhou 221004 China Department of General Surgery The First Affiliated Hospital Soochow University Suzhou 215006 China chinese national {2. genome Research center at shanghai Shanghai 201203 China

Objective： To investigate the effect of insulin-like growth factor 1 receptor （IGF1R） small interfering RNA （siRNA） on the growth of human liver cancer SMMC772. cell xenograft in nude mice. Methods： siRNA targeting IGF1R was designed, and plasmid SMMC772.-1GF1R-siRNA was constructed and transfected into SMMC772. cells （SMMC772.-1GF1R-siRNA cells）; the cells transfected with SMMC772.-1GF1 R-mutation （SMMC772.-1GF1 R-mutation cells） were used as negative con- trol, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density （MVD） in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay. Results： The tumor volume was significantly smaller in SMMC772.-1GF1R-siRNA group than in SMMC772.-1GF1R-mutation and SMMC772. groups （P 〈 0.05）. Necrosis and cell apoptosis were found in SMMC772.- IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC772.-1GF1R-siRNA group than in SMMC772.-1GF1R-mutation and SMMC772. groups （P 〈 0.05）. MVD was significantly lower in SMMC772.-1GF1R-siRNA group than in SMMC772.-1GF1R-mutation and SMMC772. groups （11.3 ± 4.4 vs. 36.7 ± 7.6 and 2..4 ±6.5, P 〈 0.05）. The apoptosis rate of tumor cells was significantly higher in SMMC772.-1GF1R-siRNA group than in SMMC772.-1GF1R-mutation and SMMC772. groups [（50.2.± 6.4）% vs. （5.4 ± 1.0）% or （6.0 ±2.1）%, P〈0.05]. Conclusion： IGF1R siRNA can inhibit the growth of SMMC772. cell xenograft in nude mice.

关键词： RNA interference human insulin-like growth factor 1 receptor microvessel density gene expression