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Small molecule compound induces chromatin de-condensation and facilitates induced pluripotent stern cell generation

Journal of Molecular Cell Biology 2014年第5期8卷 409-420页

作者： Xiaoyuan Wei Yueting Chen Yongyu Xu YangZhan Ru Zhang Min Wang qiuhong hua Haifeng Gu Fajun Nan Xin Xie Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-based Bio-medicine School of Life Sciences and Technology Tongji University Shanghai 200092 China CAS Key Laboratory of Receptor Research the National Center for Drug Screening Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China State Key Laboratory of Drug Research the National Center for Drug Screening Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

The revolutionary induced pluripotent stem cell (iPSC) technology provides a new means for cell replacement therapies and drug screening. Small molecule compounds have been found extremely useful to improve the generation of iPSCs and understand the reprogramming mechanism. Here we report the identification of a novel chemical, CYT296, which improves OSKM-mediated induction of iPSCs for >10 folds and enables efficient reprogramming with only Oct4 in combination with other small molecules. The derived iPSCs are genuinely pluripotent and support the development of two ‘All-iPSC’ mice by tetraploid complementation. CYT296 profoundly impacts heterochromatin formation without affecting cell viability. MEFs treated with CYT296 exhibit de-condensed chromatin structure with markedly reduced loci containing heterochromatin protein 1α (HP1α) and H3K9me3, which is very similar to the chromatin configuration in embryonic stem cells (ESCs). Given that an open chromatin structure serves as a hallmark of pluripotency and has to be acquired to fulfill reprogramming, we propose that CYT296 might facilitate this process by disrupting condensed chromatin, thereby creating a more favorable environment for reprogramming. In agreement of this idea, shRNA targeting HP1α also promotes the generation of iPSCs. Thus current findings not only provide a novel chemical for efficient iPSC induction, but also suggest a new approach to regulate somatic cell reprogramming by targeting chromatin de-condensation with small molecules.

关键词：小分子化合物多能干细胞异染色质诱导凝聚染色质结构船尾凯尔特人

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Methuselah regulates longevity via dTOR: a pathway revealed by small-molecule ligands

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分子细胞生物学报:英文版 2015年第3期7卷 280-282页

作者： Junjie Wang Zhilong Wang Zhenghong Zhang qiuhong hua Min Wang Changjie Shi Lei Xue Ru Zhang Xin Xie Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-based Bio-medicineSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China CAS Key Laboratory of Receptor Research the National Center for Drug ScreeningShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Dear Editor,G protein-coupled receptors(GPCRs),the largest and the most versatile family of membrane receptors,respond to a wide range of extracellular stimuli and control various physiological *** potential role of GPCRs in lifespan control has been highlighted by the study in Drosophila with mutations in a class B GPCR encoded by methuselah(mth).

关键词： functions versatile ligands

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Association between Low Ambient Temperature and the Severity of Acute Ischemic Stroke

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Journal of Clinical and Nursing Research 2024年第5期8卷 83-94页

作者： Xinyi huang Liming Shu Su Xiao qiuhong Jiang Shiliang Yang hualiang Liang hua Hong Liang Luo Department of Critical Care Medicine The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518107GuangdongChina Department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510260GuangdongChina The Second Xiangya Hospital of Central South University Changsha 410011HunanChina Department of Neurology National Key Clinical Department and Key Discipline of NeurologyThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080GuangdongChina Department of General Practice Shenshan Central HospitalSun Yat-Sen Memorial HospitalSun Yat-Sen UniversityShanweiChina 516600GuangdongChina School of Public Health Sun Yat-sen UniversityGuangzhou 510080GuangdongChina

Objective:To explore the relationships among ambient temperature,ischemic stroke severity,and blood ***:Meteorological data(2005–2015)were collected from the Guangzhou Meteorological Data *** stroke patients from the Department of Neurology of the First Affiliated Hospital,Sun Yat-sen University were retrospectively evaluated,each winter from 2005 to *** demographics,baseline measurements,and National Institute of Health Stroke Scale(NIHSS)score were ***:Three hundred sixty-two patients were *** median latency from symptom onset to admission was 2 d(IQR:1–3 d).During recruitment,the highest and lowest temperatures were 39℃and 1.3℃,*** was the most common comorbidity(75.1%).NIHSS scores at admission and discharge were higher in the cold-exposed group than in the controls regardless of the average temperature at *** addition,systolic and diastolic blood pressure values at admission were higher in the cold-exposed group than in the *** stratified by hypertensive status,the average and minimum temperatures at admission were negatively associated with systolic and diastolic blood pressure values in hypertensive *** in the average and minimum temperatures at symptom onset were associated with more severe ***:Ischemic stroke patients with symptom onset in winter had higher systolic blood pressure values and more serious neurologic deficits upon admission.

关键词： Low ambient temperature Stroke Blood pressure Severity

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基于产教融合的高职院校跨区跨校在线开放课程建设研究

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连云港职业技术学院学报 2019年第3期32卷 62-65页

作者：华秋红无锡城市职业技术学院会计学院

高职院校在线开放课程的目标是推进教育改革,提高人才培养质量。基于产教融合的高职院校跨区跨校在线开放课程"1+M+N"协同建设策略研究,加强了校企深度融合、产学研一体的课程开发共建机制,集合了高职院校优秀骨干教师协同行业企业专家... 详细信息

高职院校在线开放课程的目标是推进教育改革,提高人才培养质量。基于产教融合的高职院校跨区跨校在线开放课程"1+M+N"协同建设策略研究,加强了校企深度融合、产学研一体的课程开发共建机制,集合了高职院校优秀骨干教师协同行业企业专家,制定符合行业、企业标准的在线开放课程标准,构建立体化的课程内容,在专业应用能力提升的基础上,形成在线开放式课程评价指标体系,为推动高职院校在线开放课程的建设提供了新的思路。

关键词：产教融合跨区跨校在线开放课程 “1+M+N”协同建设

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小鼠不同脑区星形胶质细胞小分子诱导转分化和基因表达差异的研究

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中国细胞生物学学报 2020年第9期42卷 1551-1559页

作者：曾鹏花秋红石昌杰张儒上海市信号转导与疾病研究重点实验室同济大学生命科学与技术学院上海200092

该文旨在比较小分子化合物诱导小鼠不同脑区星形胶质细胞向神经元转分化的特性,并利用转录组测序技术分析小鼠不同脑区星形胶质细胞的基因表达差异。以新生小鼠皮层和海马的星形胶质细胞作为起始细胞,通过小分子化合物VCR诱导其向神经... 详细信息

该文旨在比较小分子化合物诱导小鼠不同脑区星形胶质细胞向神经元转分化的特性,并利用转录组测序技术分析小鼠不同脑区星形胶质细胞的基因表达差异。以新生小鼠皮层和海马的星形胶质细胞作为起始细胞,通过小分子化合物VCR诱导其向神经元转分化,利用免疫荧光染色检测转分化过程中细胞形态的变化以及神经元的比例,通过转录组测序比较两种星形胶质细胞的基因表达差异,并对差异基因进行荧光定量PCR验证及GO富集分析。结果表明,皮层星形胶质细胞经VCR诱导转分化为神经元的能力要显著优于海马星形胶质细胞;转录组测序发现,两种星形胶质细胞有12658个基因存在差异表达,GO分析结果表明,在皮层星形胶质细胞中高表达的基因更多地参与细胞分裂的过程,推测差异显著基因GAD2、EYA2、GSX2、INSM1以及GNG3是与转分化相关的基因。该研究对星形胶质细胞向神经元转分化的机制研究具有借鉴意义。

关键词：星形胶质细胞小分子转分化转录组测序

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高职会计核心课程混合学习现状及系统构建策略研究——以无锡城市职业技术学院为例

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山东商业职业技术学院学报 2020年第2期20卷 37-40,56页

作者：胡静华秋红陆艺潘佳妮无锡城市职业技术学院江苏无锡214000

以无锡城市职业技术学院会计专业为研究对象,采用问卷调查和访谈的方法对其开展的混合学习现状进行调研,通过对收集数据的描述性分析探究其存在的问题,从学生、教师、平台资源、学院管理层面分析其原因,并提出构建高职会计专业核心课程... 详细信息

以无锡城市职业技术学院会计专业为研究对象,采用问卷调查和访谈的方法对其开展的混合学习现状进行调研,通过对收集数据的描述性分析探究其存在的问题,从学生、教师、平台资源、学院管理层面分析其原因,并提出构建高职会计专业核心课程混合学习系统的有效策略,从而提升学院教学效果以及教改的科研水平。

关键词：混合学习系统构建有效策略

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Tectonic implications of the subduction of the Kyushu-Palau Ridge beneath the Kyushu,southwest Japan

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Acta Oceanologica Sinica 2021年第3期40卷 70-83页

作者： Chenglong Xia Yanpeng Zheng Baohua Liu Qingfeng hua Long Ma Xianfeng Li qiuhong Xie College of Marine Geosciences Ocean University of ChinaQingdao 266100China Laboratory for Marine Geology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China Hubei Key Laboratory of Marine Geological Resources China University of GeosciencesWuhan 430074China National Deep Sea Center Qingdao 266237China Key Laboratory of Marine Geology and Metallogeny First Institute of OceanographyMinistry of Natural ResourcesQingdao 266061China

The Kyushu-Palau Ridge(KPR),a remnant arc on the Philippine Sea Plate(PSP),is subducting beneath the Kyushu,southwest *** by the subducting KPR,the Kyushu subduction zone corresponding to the KPR is significantly different from Shikoku subduction zone in terms of gravity anomalies,seismicity,the stress state,and the subducting slab *** negative free-air and Bouguer gravity anomalies are observed in a prolonged area of KPR,southeast of the Miyazaki Plain,indicating that this is where KPR overlaps the overriding *** gravity anomaly in this area is much lower than that in other areas where the inferred KPR extends,suggesting that the subduction of the buoyant KPR may cause the lower mantle density to *** earthquakes have occurred in Hyuga-nada region where the KPR subducts than in Shikoku forearc and other areas in the Kyushu forearc,indicating that the subduction of the KPR enhances the local coupling between the subducting and overriding *** centroid moment tensor(CMT)mechanism of earthquakes shows that stress is concentrated in the accumulated crust beneath the Kyushu forearc corresponding to the KPR,and the shallow thrusting events in the obducting plate are caused by the KPR *** buoyant KPR,with a large volume of low-density sediments,was responsible for the differences of the subduction depth and dip angle of the subducting Philippine Sea(PS)slab between northern Kyushu and *** seismic gaps and the sudden change of the dipping angle of the subducting PS slab indicate that slab tear may have occurred along the west side of the KPR beneath southwest Kyushu.A two-tear model was proposed,and the subduction of the buoyant KPR was believed to play an important role in the slab tear.

关键词： Kyushu-Palau Ridge gravity anomaly seismicity slab morphology slab tear

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张福利教授基于“中和观”论甲亢、甲减的因机证治

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四川中医 2024年第2期42卷 19-22页

作者：常铭熙张健王秋虹李富震张福利黑龙江中医药大学黑龙江哈尔滨150040 中国中医科学院广安门医院内分泌科北京100053

甲亢、甲减为当今常见的甲状腺功能紊乱疾病,在临床治疗中常有因“干预太过”或“干预不及”而出现甲亢、甲减二者间“相互转化”的情况,故维持机体“内稳态”、使甲状腺功能达到“中和”状态是现代临床亟待解决的问题。“中和观”为我... 详细信息

甲亢、甲减为当今常见的甲状腺功能紊乱疾病,在临床治疗中常有因“干预太过”或“干预不及”而出现甲亢、甲减二者间“相互转化”的情况,故维持机体“内稳态”、使甲状腺功能达到“中和”状态是现代临床亟待解决的问题。“中和观”为我国古代重要的世界观与方法论,对中医学辨治体系的发展起着统立之功。张福利教授以中医经典和传统哲学理论为依托,结合自身临证经验,认为甲亢、甲减发生的因机之本在于中气失和所致的气化失司,以相反相成法为构架的组方配伍为求复“中和”的重要门径,阴阳调平、升降回环即为甲亢、甲减的辨治之本。

关键词：中和甲亢甲减气化相反相成法

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The prolonged effect of glucagon-like peptide 2 pretreatment on growth performance and intestinal development of weaned piglets

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Journal of Animal Science and Biotechnology 2016年第4期7卷 579-587页

作者： qiuhong Deng Gang Jia hua Zhao Zheng li Chen Xiao ling Chen Guang mang Liu Kang ning Wang Animal Nutrition Institute Sichuan Agricultural University College of Animal Medicine Sichuan Agricultural University

Background： Glucagon-like peptide 2 （GLP-2） is a potent epithelium-specific intestinal growth factor. The aim of this study was to demonstrate the prolonged effect of GLP-2 on the growth performance of weaned piglets. Forty piglets weaned at the age of 28 d with an average BW of 6.8 ＋ 0.4 kg were assigned to four treatments：（i） non- challenged control; （ii） LPS-challenged control; （iii） LPS ＋ low GLP-2; and （iv） LPS ＋ high GLP-2. Piglets in groups （i）, （ii）, and （iv） were s.c. injected with PBS supplemented with human [Gly2]GLP-21-34 at doses of 0, 2 and 10 nmol/kg BW per day for seven consecutive days. BW, gain：feed ratio （G：F）, and plasma GLP-2 levels were determined on d 0 7, and 14 after weaning. Piglets were challenged with i.p. administration of Escherichia coil lipopolysaccharide （LPS） at a dose of 100 pg/kg on d 14 to induce intestinal damage. Twenty-four hours later, intestinal tract samples were collected to assess intestinal morphology and quantify enzyme activity. Results： Plasma GLP-2 levels decreased after weaning, but in the high GLP-2 group, plasma GLP-2 was maintained on d 7 and even increased to a level higher than the preweaning level on d ]4 （P 〈 0.05）. High GLP-2 treatment significantly increased the duodenal, jejunal and ileal weight, as well as the gross weight of the small intestine （SI）, and the SI weight index （P 〈 0.05）. LPS caused villous atrophy and disrupted intestinal morphology in the duodenum, jejunum and ileum. GLP-2 also significantly increased the villus height and the villus height/crypt depth ratio （VCR） of the duodenum, jejunum, and ileum （P 〈 0.05）. Histological examination revealed that in GLP-2-treated groups, the integrity of the villus was maintained, and the villus was protected against LPS-induced damage. GLP-2 significantly increased the activity of alkaline phosphatase （AKP）, y-glutamyltranspeptidase （y-G-i-）, and pancreatic lipase in the duodenum and jejunum （P 〈 0.05）. GLP-2 treatment also significantly increased th

关键词： Escherichia coil lipopolysaccharide Glucagon-like peptide-2 Growth performance Intestinal enzymes Smallintestinal morphology Weaned piglets

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语言相关的发育性疾病早期语言特征分析

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中华实用儿科临床杂志 2022年第4期37卷 279-283页

作者：韦秋宏刘晓代英魏华程茜重庆医科大学附属儿童医院儿童保健科/儿童发育疾病研究教育部重点实验室/国家儿童健康与疾病临床医学研究中心/儿童发育重大疾病国家国际科技合作基地/儿科学重庆市重点实验室重庆400014

目的探讨发育水平相当的孤独症谱系障碍(ASD)、全面发育迟缓(GDD)、发育性语言障碍(DLD)儿童的语言特征,为疾病早期识别提供依据。方法回顾性分析2018年1月至2020年1月于重庆医科大学附属儿童医院就诊的719例儿童病例资料,其中ASD 382例... 详细信息

目的探讨发育水平相当的孤独症谱系障碍(ASD)、全面发育迟缓(GDD)、发育性语言障碍(DLD)儿童的语言特征,为疾病早期识别提供依据。方法回顾性分析2018年1月至2020年1月于重庆医科大学附属儿童医院就诊的719例儿童病例资料,其中ASD 382例,DLD 198例,GDD 139例。采用χ^(2)检验比较3组儿童的发育水平分布的差异,方差分析比较3组儿童的发育情况,采用相关性分析语言和非语言发育水平的相关关系,控制发育水平后,采用t检验比较ASD和GDD、ASD和DLD儿童的语言能力及儿童的表达性与接受性、视觉相关性语言水平的差异。结果ASD、GDD、DLD儿童非语言发育水平差异有统计学意义(χ^(2)=414.64,P0.05);发育边缘的ASD与DLD相比,ASD的接受性、视觉相关性更差(t=-4.64、-4.60,均P0.05);发育轻度落后的ASD与GDD相比,ASD的接受性、视觉相关性更差(t=-4.11、-4.68,均P0.05)。结论在儿童早期,发育异常的ASD儿童以接受性和视觉相关性语言落后为主要表现,发育正常的DLD表达性语言落后明显,GDD语言能力全面落后,以接受性为著;在发育边缘及轻度异常时,接受性、视觉相关语言的显著落后对诊断ASD有参考价值,在发育水平较好或过低情况下,ASD、DLD、GDD语言发育落后情况相似。

关键词：孤独症谱系障碍发育性语言障碍全面发育迟缓语言特征

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