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Applications of human organoids in the personalized treatment for digestive diseases

Signal Transduction and Targeted Therapy 2022年第10期7卷 3837-3866页

作者： Qinying Wang Fanying Guo Yutao Jin yanlei ma Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina School of Clinical Medicine Shanghai Medical CollegeFudan UniversityShanghaiChina

Digestive system diseases arise primarily through the interplay of genetic and environmental influences;there is an urgent need in elucidating the pathogenic mechanisms of these diseases and deploy personalized *** and long-established model systems rarely reproduce either tissue complexity or human physiology faithfully;these shortcomings underscore the need for better *** represent a promising research model,helping us gain a more profound understanding of the digestive organs;this model can also be used to provide patients with precise and individualized treatment and to build rapid in vitro test models for drug screening or gene/cell therapy,linking basic research with clinical *** the past few decades,the use of organoids has led to an advanced understanding of the composition of each digestive organ and has facilitated disease modeling,chemotherapy dose prediction,CRISPR-Cas9 genetic intervention,high-throughput drug screening,and identification of SARS-CoV-2 targets,pathogenic ***,the existing organoids of the digestive system mainly include the epithelial *** order to reveal the pathogenic mechanism of digestive diseases,it is necessary to establish a completer and more physiological organoid *** organoids and advanced techniques to test individualized treatments of different formulations is a promising approach that requires further *** review highlights the advancements in the field of organoid technology from the perspectives of disease modeling and personalized therapy.

关键词： diseases treatment digestive

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Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1573-1584页

作者： Cheng Kong Xuebing Yan Yongqiang Liu Linsheng Huang Yefei Zhu Jide He Renyuan Gao matthew F.Kalady Ajay Goel Huanlong Qin yanlei ma Department of Gastrointestinal Surgery Shanghai Tenth People's HospitalTongji UniversityShanghaiChina Research Institute of Intestinal Diseases Tongji University School of MedicineShanghaiChina Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Oncology Affiliated Hospital of Yangzhou UniversityYangzhou UniversityYangzhouChina sDepartment of Coloreaal Surgery Digestive Disease and Surgery InstituteCleveland ClinicClevelandOHUSA Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Comprehensive Cancer CenterDuarteCAUSA Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiChina

Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain *** performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory *** were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation *** tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and *** samples were analyzed by metabolic assay *** samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass *** observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from *** diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/*** colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut *** together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.

关键词： colitis lymphoid consequences

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PTPRO represses colorectal cancer tumorigenesis and progression by reprogramming fatty acid metabolism

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Cancer Communications 2022年第9期42卷 848-867页

作者： Weixing Dai Wenqiang Xiang Lingyu Han Zixu Yuan Renjie Wang yanlei ma Yongzhi Yang Sanjun Cai Ye Xu Shaobo Mo Qingguo Li Guoxiang Cai Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032P.R.China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032P.R.China Department of Surgery Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 528406P.R.China

Background:Abnormal expression of protein tyrosine phosphatases(PTPs)has been reported to be a crucial cause of *** a member of PTPs,protein tyrosine phosphatase receptor type O(PTPRO)has been revealed to play tumor suppressive roles in several cancers,while its roles in colorectal cancer(CRC)remains to be ***,we aimed to explore the roles and mechanisms of PTPRO in CRC initiation and ***:The influences of PTPRO on the growth and liver metastasis of CRC cells and the expression patterns of different lipid metabolism enzymes were evaluated in vitro and in *** and biological experiments were conducted to uncover the underpinning mechanisms of dysregulated de novo lipogenesis and fatty acidβ-***:PTPRO expression was notably downregulated in CRC liver metastasis compared to the primary cancer,and such a downregulation was associated with poor prognosis of patients with *** silencing significantly promoted cell growth and liver *** with PTPRO wild-type mice,PTPROknockout mice developed more tumors and harbored larger tumor loads under treatment with azoxymethane and dextran sulfate *** set enrichment analysis revealed that PTPRO downregulation was significantly associated with the fatty acid metabolism *** of fatty acid synthesis abrogated the effects of PTPRO silencing on cell growth and liver *** experiments indicated that PTPRO silencing induced the activation of the AKT serine/threonine kinase(AKT)/mammalian target of rapamycin(mTOR)signaling axis,thus promoting de novo lipogenesis by enhancing the expression of sterol regulatory element-binding protein 1(SREBP1)and its target lipogenic enzyme acetyl-CoA carboxylase alpha(ACC1)by activating the AKT/mTOR signaling ***,PTPRO attenuation decreased the fatty acid oxidation rate by repressing the expression of peroxisome proliferator-activated receptor alpha(PPARα)and its downstream enzyme

关键词： AKT colorectal cancer fatty acid oxidation fatty acid synthesis lipid metabolism liver metastasis mTOR PTPRO tumorigenesis

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GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies

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Signal Transduction and Targeted Therapy 2020年第1期5卷 965-978页

作者： Weixing Dai Ye Xu Shaobo Mo Qingguo Li Jun Yu Renjie Wang yanlei ma Yan Ni Wenqiang Xiang Lingyu Han Long Zhang Sanjun Cai Jun Qin Wen-Lian Chen Wei Jia Guoxiang Cai Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina Department of Surgery Johns Hopkins University School of MedicineBaltimoreMD 21287USA The Children’s Hospital School of MedicineZhejiang UniversityZhejiangChina The Key Laboratory of Stem Cell Biology CAS Center for Excellence in Molecular Cell ScienceInstitute of Health SciencesShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China University of Hawaii Cancer Center HonoluluHI 96813USA School of Chinese Medicine Hong Kong Baptist UniversityKowloon TongHong KongChina

Cancer cells are usually characterized by hyperactive glucose metabolism,which can often lead to glucose scarcity;thus,alternative pathways to rewire cancer metabolism are ***,we demonstrated that GLUT3 was highly expressed in colorectal cancer(CRC)and negatively linked to CRC patient outcomes,whereas GLUT1 was not associated with CRC *** glucoselimiting conditions,GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide ***,GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting ***,low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 ***,high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing ***,the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.

关键词： GLUT3 vitamin AMPK

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职业教育研究的历史演进与趋势展望——2006—2018年全国教育科学规划职业教育类课题的量化分析

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职业技术教育 2019年第15期40卷 45-50页

作者：马彦蕾刘杨廊坊燕京职业技术学院廊坊065200 聊城市教育和体育局

通过对2006-2018年间全国教育科学规划职业教育类立项课题从立项类别、地域分布、责任单位分布、课题负责人及研究内容等方面进行量化分析,发现:职业教育类课题立项虽然逐年增加,但总数和所占比例总体偏低;立项课题区域分布不平衡;高校... 详细信息

通过对2006-2018年间全国教育科学规划职业教育类立项课题从立项类别、地域分布、责任单位分布、课题负责人及研究内容等方面进行量化分析,发现:职业教育类课题立项虽然逐年增加,但总数和所占比例总体偏低;立项课题区域分布不平衡;高校在职业教育研究中占据优势地位;职业教育研究偏向应用型研究,轻视基础理论研究。为此,建议加强不同区域之间的合作创新;增强不同类型责任单位之间的合作交流;加大对职业教育科研的支持力度,加强职业教育基础理论研究。

关键词：职业教育研究全国教育科学规划课题历史演进未来趋势

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延安时期中国共产党的妇女劳动观探析——以《中国妇女》为例

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咸阳师范学院学报 2022年第6期37卷 103-107页

作者：孔岩马彦蕾延安大学文学院陕西延安716000

延安时期中国共产党的妇女劳动观是马克思主义劳动观在延安时期的新发展。《中国妇女》月刊是延安时期中央妇委创立的妇女刊物,其刊载文章和插图都显示了党对劳动的重视,蕴含着中国共产党的妇女劳动观。从延安时期的历史背景入手,探析... 详细信息

延安时期中国共产党的妇女劳动观是马克思主义劳动观在延安时期的新发展。《中国妇女》月刊是延安时期中央妇委创立的妇女刊物,其刊载文章和插图都显示了党对劳动的重视,蕴含着中国共产党的妇女劳动观。从延安时期的历史背景入手,探析延安时期中国共产党妇女劳动观在《中国妇女》中的体现及其重要指导作用。

关键词：妇女劳动观《中国妇女》延安时期

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工业电气自动化中数字技术的应用

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现代工业经济和信息化 2018年第6期8卷 41-42页

作者：苏厚博马岩磊中国电建集团贵阳勘测设计研究院有限公司贵州贵阳550081 河南新中建设工程有限公司河南郑州450000

探讨工业电气自动化中数字技术的特点,分析工业电气自动化中数字技术的应用缺陷,研究工业电气自动化中数字技术优化方案。

关键词：工业电气自动化数字技术

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基于空间回归模型的道路交通事故影响因子分析

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测绘地理信息 2023年第3期48卷 126-131页

作者：马艳磊朱欣焰岳瀚郑业晴高飞武汉大学测绘遥感信息工程国家重点实验室湖北武汉430079 广州大学地理科学与遥感学院公共安全地理信息分析中心广东广州510275

为分析影响交通事故的主要道路影响因子,选取道路结构、道路附属设施、交通基础设施等方面的16个解释变量,考虑交通事故分布的过度分散性、零膨胀性及空间相关性,构建空间滞后-零膨胀负二项回归模型,并利用赤池信息准则(Akaike informat... 详细信息

为分析影响交通事故的主要道路影响因子,选取道路结构、道路附属设施、交通基础设施等方面的16个解释变量,考虑交通事故分布的过度分散性、零膨胀性及空间相关性,构建空间滞后-零膨胀负二项回归模型,并利用赤池信息准则(Akaike information criterion,AIC)和贝叶斯信息准则(Bayesian information criterion,BIC)、模型残差的空间依赖性检验等指标将其与常用的普通最小二乘(ordinary least square,OLS)等回归模型进行对比。结果显示,所提模型的拟合效果最优;车道数、道路宽度、平均车速等因子对交通事故的发生具有显著影响。

关键词：交通事故影响因子空间滞后-零膨胀负二项回归模型

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堆石料在不同应力路径下的颗粒破碎特性

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人民黄河 2015年第1期37卷 137-139,145页

作者：樊怀华刘大才刘恩龙马颜磊中国有色金属工业昆明勘察设计研究院云南昆明650051 中国市政工程西南设计研究总院有限公司四川成都610081 四川大学水利水电学院水力学与山区河流开发保护国家重点实验室四川成都610065

采用大三轴试验设备,对直径为300 mm、高为600 mm的圆柱体堆石料试样进行了三种不同应力路径的固结排水试验,包括常规三轴压缩试验、等平均应力试验及等向压缩试验,探讨不同应力路径下堆石料的颗粒破碎特性,常规三轴压缩试验围压为200、... 详细信息

采用大三轴试验设备,对直径为300 mm、高为600 mm的圆柱体堆石料试样进行了三种不同应力路径的固结排水试验,包括常规三轴压缩试验、等平均应力试验及等向压缩试验,探讨不同应力路径下堆石料的颗粒破碎特性,常规三轴压缩试验围压为200、400、800、1 200 k Pa,等平均应力试验平均应力为200、400、600、800 k Pa。试验结果表明,应力路径对堆石料的颗粒破碎特性有很大的影响。常规三轴压缩试验的应力—应变关系近于双曲线,低围压时试样先剪缩后剪胀、高围压时剪缩;等平均应力试验的应力—应变曲线呈应变软化型,体变表现为先体缩后剪胀。计算得到的颗粒破碎指数表明,等平均应力试验的颗粒破碎最为严重,等向压缩试验的颗粒破碎轻微。

关键词：堆石料三轴试验应力路径颗粒破碎

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Local magnetic moment oscillation around an Anderson impurity on graphene

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 192-201页

作者： Shuai Li Zhen ma Jin-Hua Gao School of Science Hebei University of Science and Technology School of Electronics and Information Zhengzhou University of Light Industry School of Physics and Wuhan National High magnetic Field Center Huazhong University of Science and Technology

We theoretically investigate the spin resolved Friedel oscillation （FO） and quasiparticle interference （QPI） in graphene induced by an Anderson *** the impurity becomes magnetic,the resulted FO becomes spin dependent,which gives rise to a local magnetic moment oscillation with an envelop decaying as r-2in real space in the doping ***,at half filling,the electron density and local magnetic moment will not oscillate but decay as *** spin resolved FO has both sublattice and spin ***,the local magnetic moment decay at half filling only occurs at one sublattice of graphene,which is quite like the phenomenon observed in the STM experiment (***ález-Herrero et al.,Science 352,437 （2016）).We further give an analytic formula about such spin dependent FO based on the stationary phase ***,we study the interference of quasiparticles around the magnetic impurity by calculating the spin dependent Fourier-transformed local density of states （FT-LDOS）.Our work gives a comprehensive understanding about the local magnetic moment oscillation around an Anderson impurity on graphene.

关键词： Friedel oscillation local magnetic moment graphene Anderson impurity

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