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Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12i^(Max)

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Science China(Life Sciences) 2024年第3期67卷 555-564页

作者： jilong ren Tang Hai Yangcan Chen Ke Sun Zhiqiang Han Jing Wang Chongyang Li Qingwei Wang Leyun Wang Huabing Zhu Dawei Yu Wei Li Shanjiang Zhao State Key Laboratory of Animal Nutrition Key Laboratory of Animal GeneticsBreeding and Reproduction of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China State Key Laboratoryf Stem Cell and Reproductive Biology Instituteof ZooogyChinese Academyof SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Beijing Farm Animal Research Center Institute of ZoologyChinese Academy of SciencesBeijing 100101China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated gene(Cas) system is continually optimized to achieve the most efficient gene editing effect. The Cas12i^(Max), a Cas12i variant, exhibits powerful DNA editing activity and enriches the gene editing toolbox. However, the application of Cas12i^(Max)in large domestic animals has not yet been reported. To verify the efficiency and feasibility of multiple gene editing in large animals, we generated porcine fibroblasts with simultaneous knockouts of IGF2, ANPEP, CD163,and MSTN via Cas12i^(Max)in one step. Phenotypically stable pigs were created through somatic cell nuclear transfer technology. They exhibited improved growth performance and muscle quality. Furthermore, we simultaneously edited three genes in bovine fibroblasts. A knockout of MSTN and PRNP was created and the amino acid Q-G in CD18 was precisely substituted. Meanwhile, no off-target phenomenon was observed by sum-type analysis or off-target detection. These results verified the effectiveness of Cas12i^(Max)for gene editing in livestock animals and demonstrated the potential application of Cas12i^(Max)in the field of animal trait improvement for agricultural production.

关键词： Cas12i^(Max) gene editing livestock multiple trait improvement

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Long-term effects of gravel―sand mulch on soil organic carbon and nitrogen in the Loess Plateau of northwestern China

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Journal of Arid Land 2015年第1期7卷 46-53页

作者： Yang QIU ZhongKui XIE YaJun WANG Sukhdev S MALHI jilong ren Cold and Arid Regions Environmental and Engineering Research Institute Chinese Academy of Sciences Northeast Agricultural Research Foundation (NARF)

Gravel-sand mulch has been used for centuries to conserve water in the Loess Plateau of north- western China. In this study, we assessed the influence of long-term （1996-2012） gravel-sand mulching of cultiv- ated soils on total organic carbon （TOC）, light fraction organic carbon （LFOC）, microbial biomass carbon （MBC）, total organic nitrogen （TON）, particulate organic carbon （POC）, mineral-associated organic carbon （MOC）, perma- nganate-oxidizable carbon （KMnO4-C）, and non-KMnO4-C at 0-60 cm depths. Mulching durations were 7, 11 and 16 years, with a non-mulched control. Compared to the control, there was no significant and consistently positive effect of the mulch on TOC, POC, MOC, KMnO4-C and non-KMnO4-C before 11 years of mulching, and these organic C fractions generally decreased significantly by 16 years. LFOC, TON and MBC to at a 0-20 cm depth in- creased with increasing mulching duration until 11 years, and then these fractions decreased significantly between 11 and 16 years, reaching values comparable to or lower than those in the control. KMnO4-C was most strongly correlated with the labile soil C fractions. Our findings suggest that although gravel-sand mulch may conserve soil moisture, it may also lead to long-term decreases in labile soil organic C fractions and total organic N in the study area. The addition of manure or composted manure would be a good choice to reverse the soil deterioration that occurs after 11 years by increasing the inputs of organic matter.

关键词： gravel mulch mulching duration permanganate-oxidizable carbon light fraction organic carbon microbial biomass carbon

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数字化转型背景下高校图书馆数字基座的构建探索:以复旦大学图书馆为例

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图书馆杂志 2024年第3期43卷 41-49页

作者：薛崧苗青张计龙伏安娜任磊赵敏复旦大学图书馆

高校图书馆数字基座是一种支撑图书馆数字化转型的数字基础设施,其核心结构由数据中心、业务中心、基础服务中心、物联中心和AI服务中心组成,为业务转型和服务创新提供数据能力、通用业务能力和数字技术应用能力的支撑。本文以复旦大学... 详细信息

高校图书馆数字基座是一种支撑图书馆数字化转型的数字基础设施,其核心结构由数据中心、业务中心、基础服务中心、物联中心和AI服务中心组成,为业务转型和服务创新提供数据能力、通用业务能力和数字技术应用能力的支撑。本文以复旦大学图书馆数字基座的建设和成效为例,探索高校图书馆数字基座的建设思路、策略和方法,提出数字基座的建设需要在数字化转型战略指引下,适度超前规划并完善总体信息技术架构;围绕用户需求,从平台工具、数据资源、运营机制、场景创新、标准规范等方面进行系统性的构建和持续演进。

关键词：高校图书馆数字化转型数字基座数据管理

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Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs

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Protein & Cell 2020年第2期11卷 97-107页

作者： Rui Fu Dawei Yu jilong ren Chongyang Li Jing Wang Guihai Feng Xuepeng Wang Haifeng Wan Tianda Li Libin Wang Ying Zhang Tang Hai Wei Li Qi Zhou State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Blastocyst complementation by pluripotent stem cell(PSC)injection is believed to be the most promising method to generate xenogeneic organs.However,ethical issues prevent the study of human chimeras in the late embryonic stage of development.Primate embryonic stem cells(ESCs),which have similar pluripotency to human ESCs,are a good model for studying interspecies chimerism and organ generation.However,whether primate ESCs can be used in xenogenous grafts remains unclear.In this study,we evaluated the chimeric ability of cynomolgus monkey(Macaca fascicularis)ESCs(cmESCs)in pigs,which are excellent hosts because of their many similarities to humans.We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos,in which domesticated cmESCs(D-ESCs)injected into pig blastocysts differentiated into cells of all three germ layers.In addition,we obtained two neonatal interspecies chimeras,in which we observed tissue-specific D-ESC differentiation.Taken together,the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model,with a chimeric ratio of 0.001-0.0001 in different neonate tissues.We believe this work will facilitate future developments in xenogeneic organogenesis,bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

关键词： embryonic stem cells,blastocyst complementation cynomolgus monkey pig interspecies chimera organ reconstruction

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Single-cell RNA Sequencing Reveals Thoracolumbar Vertebra Heterogeneity and Rib-genesis in Pigs

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Genomics, Proteomics & Bioinformatics 2021年第3期19卷 423-436页

作者： Jianbo Li Ligang Wang Dawei Yu Junfeng Hao Longchao Zhang Adeniyi C.Adeola Bingyu Mao Yun Gao Shifang Wu Chunling Zhu Yongqing Zhang jilong ren Changgai Mu David M.Irwin Lixian Wang Tang Hai Haibing Xie Yaping Zhang State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Animal Science Chinese Academy of Agricultural SciencesBeijing 100193China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Core Facility for Protein Research Institute of BiophysicsChinese Academy of SciencesBeijing 100101China State Key Laboratory for Molecular and Developmental Biology CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650223China Department of Laboratory Medicine and Pathobiology University of TorontoTorontoOntario M5S1A8Canada Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China

Development of thoracolumbar vertebra(TLV)and rib primordium(RP)is a common evolutionary feature across vertebrates,although whole-organism analysis of the expression dynamics of TLV-and RP-related genes has been lacking.Here,we investigated the single-cell transcriptome landscape of thoracic vertebra(TV),lumbar vertebra(LV),and RP cells from a pig embryo at 27 days post-fertilization(dpf)and identified six cell types with distinct gene expression signatures.In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development.Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA103′-UTR sequence specific to osteoblasts of LV cells,which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition.Thus,this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution,which serves as a comprehensive view on the transcriptional profile of animal embryo development.

关键词： scRNA-seq Thoracolumbar vertebra transition Rib-genesis Osteogenesis Angiogenesis

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扫描电镜下的HFW焊缝原位拉伸试验

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物理测试 2024年第1期42卷 14-21页

作者：聂向晖杨周瑾张继龙张辉任涛中国石油集团工程材料研究院有限公司陕西西安710077 石油天然气冀东工程质量监督站河北唐山063299 中国石油集团长庆油田采油八厂陕西西安710016

利用扫描电镜(SEM)下的原位拉伸试验对HFW焊缝不同部位的微观形貌变化进行观察,在试验过程中试样变形主要集中在热影响区,大量的滑移和颈缩变形在热影响区发生,裂纹在热影响区形核,并垂直于拉伸方向扩展,直至试样断裂。HFW焊缝试样的断... 详细信息

利用扫描电镜(SEM)下的原位拉伸试验对HFW焊缝不同部位的微观形貌变化进行观察,在试验过程中试样变形主要集中在热影响区,大量的滑移和颈缩变形在热影响区发生,裂纹在热影响区形核,并垂直于拉伸方向扩展,直至试样断裂。HFW焊缝试样的断裂为延性断裂,裂纹呈穿晶型,其形成过程包括:试样弹性伸长、晶内滑移开动、试样缩颈变形、滑移台阶形成和试样开裂。在滑移变形和颈缩的交互作用下,滑移变形不断积累,这是造成裂纹形成及试样断裂的主要原因。

关键词：原位拉伸缩颈滑移变形裂纹

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The efficacies and biomarker investigations of antiprogrammed death-1 (anti-PD-1)-based therapies for metastatic bone and soft tissue sarcoma

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Cancer Biology & Medicine 2022年第6期19卷 910-930页

作者： Jia Lu Ting Li Zhichao Liao Hui Yu Yongtian Zhao Haixiao Wu Zhiwu ren Jun Zhao Ruwei Xing Sheng Teng Yun Yang Xiangchun Li Kexin Chen Jonathan Trent jilong Yang Department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Infection Management Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Key Laboratory of Molecular Cancer Epidemiology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China YuceBio Technology Co. Ltd.Shenzhen 518172China Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Sarcoma Multidisciplinary Program Sylvester Comprehensive Cancer CenterThe University of MiamiMiamiFL 33136USA

Objective:Sarcomas are a group of rare malignancies with various subtypes.Patients with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies,including anti-programmed death-1(PD-1)-based therapies.Methods:We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15,2016 to December 30,2019.These patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional treatments.Furthermore,8 patients underwent panel DNA and whole transcript sequencing.Results:Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only group.The median follow-up time was 5.77 months.The median progression-free survival was 7.59 months,the overall response rate was 16.7%and the disease control rate was 55.6%.Based on whole exome and transcript sequencing data,there was no association between TMB,TNB,MSI,HLA-LOH,and PD-L1 expressions and sarcoma types with clinical responses.Immunotherapy efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity(ITH)in progressive disease(PD)patients and lower ITH in partial response(PR)and stable disease patients.A higher percentage of immune cell infiltration,especially monocytes,was observed in PR patients.Active stromal gene expression was increased in PD patients but decreased in PR patients.Enrichment analysis revealed that an increased TGF-βsignaling pathway was reversely correlated with anti-PD-1 efficacy,while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 efficacy.Conclusions:Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and well-tolerated.ITH,monocyte ratio,stroma subtypes,and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.

关键词： Sarcoma PD-1 PD-L1 immunotherapy angiogenesis safety efficacy biomarker

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Geochemistry and Zircon U-Pb Geochronology of Early Paleozoic S-type Granites in the Eastern Qilian Block,Northwest China

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Acta Geologica Sinica(English Edition) 2021年第2期95卷 439-458页

作者： LIU Xiuting LI Binkai HAN jilong ren Erfeng GAO Donglin DU Yongsheng ren Qianhui ZHANG Yan Key Laboratory of Comprehensive and Highly Efficient Utilization of Salt Lake Resources Qinghai Institute of Salt LakesChinese Academy of SciencesXining 810008China Key Laboratory of Salt Lake Geology and Environment of Qinghai Province Qinghai Institute ofSalt LakesChinese Academy of SciencesXining 810008China University ofChinese Academy of Sciences Beijing 100049China College of Chemical and Pharmaceutical Engineering(Hebei) University of Science and TechnologyShijiazhuang 050018China Department of Geological Engineering Qinghai UniversityXining 810016China Department of Water Conservancy and Electric Power Qinghai UniversityXining 810016China Qinghai Province Nonferrous Metals Third Geological Exploration Institute Xining 810012China

The Qilian Block(QB)is a Precambrian micro-continent located in the northeastern Qinghai–Tibet Plateau.Prevalent Lower Paleozoic granitic magmatic rocks crop out in the QB.A new integrated study of zircon U-Pb ages and systematic whole-rock geochemical data for the Xindian,Dongjiazhuang and Xiaogaoling granites in the eastern segment of the QB constrains their emplacement ages,petrogenesis,and regional evolutionary history.U-Pb dating reveals that the Xindian granite was emplaced 454 Ma,and both the Dongjiazhuang and Xiaogaoling granites were emplaced ca.440 Ma.Geochemical study shows that all granites belong to the high-K calc-alkaline to shoshonitic series and are S-type granites formed by partial melting of continental crust,mainly metagraywacke.We infer that these ca.454–445 Ma granites formed in a syn-collisional setting during the continental collisional between the Qaidam and Qilian blocks.

关键词： geochemistry geochronology petrogenesis syn-collision Qilian Block NW China

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Roles of low?density lipoproteinreceptor?related protein 1 in tumors

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Chinese Journal of Cancer 2016年第1期35卷 4-11页

作者： Peipei Xing Zhichao Liao Zhiwu ren Jun Zhao Fengju Song Guowen Wang Kexin Chen jilong Yang Department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute and HospitalTianjin 30060P.R.China National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and HospitalTianjin 30060P.R.China Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Institute and HospitalTianjin 30060P.R.China.

Low-density lipoprotein receptor-related protein 1(LRP1,also known as CD91),a multifunctional endocytic and cell signaling receptor,is widely expressed on the surface of multiple cell types such as hepatocytes,fibroblasts,neurons,astrocytes,macrophages,smooth muscle cells,and malignant cells.Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression.For example,LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase(MMP)-2and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor,the serine/threonine protein kinase signaling pathway,and the expression of Caspase-3.LRPI-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion.In addition,LRP1 has been shown to be down-regulated by microRNA-205 and methylation of LRP1CpG islands.Furthermore,a novel fusion gene,LRP1-SNRNP25,promotes osteosarcoma cell invasion and migration.Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

关键词： Low-density lipoprotein receptor-related protein 1, Tumorigenesis, Invasion, migration, Proliferation,apoptosis, Signaling pathway, MicroRNA, Fusion gene

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Alternative Fuzzy Cluster Segmentation of Remote Sensing Images Based on Adaptive Genetic Algorithm

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Chinese Geographical Science 2009年第1期19卷 83-88页

作者： WANG Jing TANG jilong LIU Jibin ren Chunying LIU Xiangnan FENG Jiang Key Laboratory for Wetland Ecology and Vegetation Restoration of National Environmental Protection Northeast Normal University Changchun 130024 China Key Laboratory of Vegetation Ecology of Education Ministry Institute of Grassland Science Northeast Normal University Changehun 130024 China Changehun University of Seienee and Technology Changchun 130022 China Urban and Town Plan and Design Institute of Jilin Province Changehun 130061 China Northeast Institute of Geography and Agroecology Chinese Academy of Sciences Changchun 130012 China School of Information Engineering China University of Geosciences Beijing 100083 China

Remote sensing image segmentation is the basis of image understanding and analysis. However,the precision and the speed of segmentation can not meet the need of image analysis,due to strong uncertainty and rich texture details of remote sensing images. We proposed a new segmentation method based on Adaptive Genetic Algorithm(AGA) and Alternative Fuzzy C-Means(AFCM) . Segmentation thresholds were identified by AGA. Then the image was segmented by AFCM. The results indicate that the precision and the speed of segmentation have been greatly increased,and the accuracy of threshold selection is much higher compared with traditional Otsu and Fuzzy C-Means(FCM) segmentation methods. The segmentation results also show that multi-thresholds segmentation has been achieved by combining AGA with AFCM.

关键词：自适应遗传算法图像分解运动 AFCM 模糊技术遥感技术

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