Research on Interactions between Alternative Splicing and DNA Methylation

选择性剪接是真核生物中基因表达的一种重要的调控机制，也是高等生物中蛋白质多样性的主要来源。最近的研究工作揭示了表观遗传学(如组蛋白修饰)在调控选择性剪接方面的重要作用。DNA甲基化是一种重要的表观遗传学修饰，它与肿瘤发生密切相关。人们推测DNA甲基化也可能参与选择性剪接的调控，但是目前尚无任何实验证据。 近年来大量生物学实验的数据积累，形成了当前数以万计的生物信息数据库。本论文通过对数据库的检索，筛选出6个基因，这些基因的选择性剪接和DNA甲基化状态同时在分化前和分化后的人类胚胎干细胞（hESC）之间发生相应的变化。后来，我们通过在不同的细胞系及小鼠组织中的实验发现选择性剪接和DNA甲基化之...Alternative splicing is a crucial mechanism for gene regulation and also a major source for protein diversity in higher eukaryotes. Recent studies indicate an important role for epigenetics (e.g. histone modifications) in alternative splicing regulation. Although it is highly likely that DNA methylation, one of principal epigenetic factors which plays a significant role in tumor genesis, may also ...学位：理学硕士院系专业：生命科学学院生物学系_生物化学与分子生物学学号：2172008115264

葡萄糖感应器及其AMPK活性和细胞代谢状态的调控机理

葡萄糖是细胞的主要能量来源,它通过糖酵解和/或氧化代谢产生ATP。葡萄糖水平下降将激活AMP活化蛋白激酶(AMP-activated protein kinase-AMPK),数十年来,人们一直认为这是由于AMP或ADP的上升,或者说能量水平的下降引起的。厦门大学生命科学学院林圣彩研究团队与英国Dundee大学D.Grahame Hardie团队合作报道了一种通过感知胞内葡萄糖代谢中间物果糖-1,6-二磷酸(FBP)的下降来触发AMPK活化的机制:FBP水平下降,便不再占据其催化酶——醛缩酶(aldolase)上的催化位点,后者直接改变了溶酶体膜上的质子泵v-ATPase和与其相结合的\"Ragulator\"的构象,进而让携带有能磷酸化并激活AMPK的上游激酶LKB1的AXIN蛋白质转移到溶酶体膜表面,在此形成了能激活AMPK的复合体(该复合体也是由林圣彩实验室发现并鉴定-Cell Metabolism,2013,2014),从而激活AMPK,同时抑制了促进细胞进行生物合成和生长的激酶-mTORC1。重要的是,他们从中也颠覆性地发现细胞能量水平在葡萄糖水平急速下降期间仍保持不变,且AMPK上的AMP结合位点对于此时AMPK的活化不是必需的。该研究不仅发现了醛缩酶这一糖酵解酶的新功能:调控AMPK的葡萄糖感受器,还深刻地揭示了葡萄糖的本质:既是能量和物质来源,也是直接调控细胞生物合成和生长状态的信号,对多种代谢型疾病的发生、癌症与代谢关系的认知与治疗、卡路里限制与健康长寿等的认知具有重大意义。相关研究论文在2017年8月3日发表于《自然》[NATURE,548(7665):112-116,August 2017]

The Development of a New Type of Medical Rehabilitation Brace for Lower Limbs

本文阐述了一种新型医用下肢康复支具的研制过程。该装置主要由承重装置、负重装置、负重调节装置以及压力检测装置等结构组成,具有调节、设定以及控制负重载荷等功能,可使行内固定术后的下肢骨折患者早期进行负重、行走功能锻炼,促进其骨折愈合及肢体功能康复,减少术后并发症,具有一定的实用价值。The paper expounded the development of a new type of medical rehabilitation brace for lower limbs. The device was mainly composed of different structures including the hip weight-bearing device, the foot weight-bearing device, the weight-bearing adjustment device and the pressure detection device. The brace was designed to allow patients to carry out weight-bearing exercises and walking exercises in early postoperative period after receiving internal fixation of lower limb fracture. It could also promote fracture healing and functional recovery of lower limbs and reduce postoperative complications, which is of certain clinical value

连续硬膜外阻滞对婴幼儿血流动力学的影响

摘　要　探讨硬膜外阻滞麻醉对婴幼儿循环功能的影响: 前瞻性选择2岁以下小儿施行连续硬膜外阻滞麻 醉,定时测定阻滞前后收缩压、舒张压、平均动脉压、心率、每搏输出量、分钟心输出量、射血速率指数、心室射血 时间、肺液指数等9项指标及阻滞平面,其中阻滞平面达胸4 ( T4)和胸6 ( T6 )各10例;结果表明阻滞平面达T4和T6 两组患儿硬膜外阻滞后,除心率减慢之外,其他指标无明显改变, 提示连续硬膜外阻滞麻醉对婴幼儿血流动力 学无明显影响

Apoptosis induced by a novel intestinal metabolite of ginseng saponin in human hepatocellular carcinoma BEL-7402 cells

目的探讨一种新的人参稀有皂苷20-O-(β-D-吡喃葡萄糖)-20(S)-原人参二醇皂苷(IH-901)对人肝癌BEL-7402细胞的增殖抑制效果和诱导凋亡作用。方法以0、6.25、12.5、25、50、75、100μmol/L的IH-901作用于体外培养的BEL-7402细胞,通过MTT法检测IH-901对细胞生长的抑制作用,相差显微镜观察细胞形态变化,AO/EB的荧光核染色观察凋亡细胞形态,流式细胞术检测细胞周期和细胞凋亡。结果MTT实验显示IH-901抑制BEL-7402细胞的生长,呈时间及浓度依赖的方式;显微镜下观察到典型的凋亡形态变化和生化特征:细胞固缩,核染色质凝聚,出现凋亡小体;AO/EB的荧光核染色后,观察到典型的凋亡细胞;流式细胞仪可以检测到凋亡峰,且细胞被阻滞在G0/G1期。结论IH-901能通过诱导细胞凋亡的方式有效地抑制人肝癌BEL-7402细胞的生长,稀有人参皂苷IH-901可能成为一种潜在的抗肝癌药物。Objective To investigate the effects of 20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol(IH-901) on the human hepatocellular carcinma BEL-7402 cells in terms of inhibition of proliferation and induction of apoptosis.Methods BEL-7402 Cells in cultural medium in vitro were given 0,6.25,12.5,25,50,75,and 100 μmol/L IH-901.The inhibitory rate of cells was measured by MTT assay,morphology of cell apoptosis was observed by AO/EB fluorescent staining,cell apoptotic rate and cell phase were detected by flow Cytometry(FCM).Results The results indicated that IH-901 could inhibit the proliferation of BEL-7402 cells significantly.The suppression was both in a time-and dose-dependent manner.Morphological examination of IH-901-treated samples showed cells with chromatin condensation,cell shrinkage,and all typical characteristics of apoptotic cells.Marked morphological changes of cell apoptosis was observed very clearly by AO/EB fluorescent staining.The increase in the apoptotic sub-G1 fraction in a concentration-dependent manner and cell cycle arrest at the G0/G1 phase were detected by FCM.Conclusion The results demonstrate that IH-901 dramatically suppresses BEL-7402 cell growth by inducing programed cell death.These results may provide a pivotal mechanism for the use of IH-901 in the prevention and treatment of human hepatocellular carcinoma BEL-7402 cells,the antiproliferation,and the apoptosis厦门市科技创新基金重点项目(3502Z20062008