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

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

The primary investigation of the value of whole body diffusion weighted imaging in diagnosis of metastatic tumor

背景与目的:随着临床上晚期肿瘤病例的增多,为了解治疗前、后全身转移瘤的大小及数量变化的实际情况,以往多采用分部位进行CT和(或)Mr扫描,少部分有条件的患者采用PET检查,但这些方法可能存在过多地暴露于射线、检查时间过长及经济负担过重等问题。因此,我们探讨磁共振的全身弥散加权成像(WHOlE bOdy dIffuSIOn WEIgHTEd IMAgIng,WbdWI)方法对肿瘤及转移灶的检出准确性及其临床应用的可行性。方法:对68例临床已发现原发肿瘤及多个转移灶或发现多个肿瘤病灶,但原发灶不明确的患者进行WbdWI检查,其中男性49例;女性19例。平均年龄61岁。68例均与CT和(或)MrI的检查结果进行比较,其中17例与PET的检查结果相比较。对病灶的检出率,以病灶长径大小分为:<1CM,≥1~<2CM,≥2~<3CM及≥3CM以上4组进行计数分析,同时,对不同部位间的病灶检出情况进行分析。结果:WbdWI对4组病灶的检出率分别为30%、78%、96%及100%。在各个部位的敏感性和准确性中以骨骼最高。对位于肺部小于1CM的病灶和位于颈部、盆腔小于2CM的淋巴结的诊断存在一定困难。结论:WbdWI对大范围的肿瘤病灶筛查是安全、简便、有效和经济的检查新方法。随着技术参数的进一步完善,WbdWI在发现和诊断全身多发肿瘤方面,具有良好的发展潜力。因此,本技术有望作为一种新的、效果好于PET的全身检查技术。Background and purpose:With the increased number of advanced tumors,it is important to evaluate the actual pre-and post-treatment changes in metastatic diseases,such as tumor size and tumor quantity.Previously,CT and/or MRI scan were usually applied,only a few patients could pay for PET(positron emition tomography).But there were several problems we should face,including redundantly exposure to radiation,too long verification time and heavy financial burden.Therefore we evaluated the application of whole body diffusion weighted imaging in diagnosing of tumor and metastatic tumor.Methods:sixty-eight patients(49 male,19 female,age from 29 to 84 years with mean age of 61 years) with a variety of tumors were investigated by combined CT and/or MRI scan,seventeen patients were compared with positron emition tomograph(PET).All tumors were classified into four groups,according to longest diameter of <1 cm,≥1-<2 cm,≥2-<3 cm and ≥3 cm.At the same time,the positive detection rates between different parts of the lesions were analyzed.Results:The detection rate of the four groups were 30%,78%,96% and 100%,respectively.The skeletal system had the highest sensitivity and accuracy in every part of body.There was difficulty in diagnosing lung cancer with longest diameter less than 1 cm as well as tumors located in neck and pelvic with longest diameter less than 2 cm.Conclusion:Whole body diffusion weighted imaging is secure,convenient,effective and economic for screening wide-ranging tumor focus.After improvement of parameters,WBDWI could be as a new effective whole body examination technique.厦门市科技计划项目(No:3502Z20074017

红树林共生真菌Paecilomyces sp· Tree 1-7代谢产物的研究

用硅胶柱色谱及重结晶等方法,并根据理化性质和光谱数据从一株红树林共生真菌Paecilomycessp.Tree 1-7中分离鉴定了四个化合物,分别为secalon ic ac id A(1),tenellic ac id A(2),大黄素(3),大黄酚(4)。并首次对化合物1和2进行了抗人的肝癌细胞hepG2的活性测试。结果显示,化合物1有很强的抗肿瘤活性,IC50=2.0μg/m l,化合物2的抗肿瘤活性IC50=62.1μg/m l

福建绞股蓝皂苷的优化提取及其抗肝癌活性

绞股蓝素有"南方人参"美誉,含有与人参皂苷相同骨架达玛烷型结构的三萜皂苷。通过不同体积分数乙醇溶液优化提取绞股蓝皂苷,测定其抗癌活性,为后续活性化合物的分离奠定基础。利用HPLC分析绞股蓝的皂苷成分并确定提取绞股蓝皂苷的乙醇体积分数,正交实验优化提取方法,进而MTT法测定提取的绞股蓝皂苷抗肝癌活性。HPLC分析确定用体积分数75%乙醇溶液提取绞股蓝总皂苷(GYP),体积分数45%乙醇提取极性绞股蓝皂苷(GYP1),体积分数90%乙醇提取弱极性绞股蓝皂苷(GYP2);正交实验结果表明在70℃水浴中以30质量的体积分数45%乙醇加热提取12 h为最佳条件提取GYP1,在60℃水浴中以30质量的体积分数90%乙醇加热提取6 h为最佳条件提取GYP2;利用MTT法测定GYP、GYP1和GYP2对肝癌细胞的抑制作用,GYP和GYP2对肝癌细胞SMCC7721具有抗癌活性,半抑制率IC50值分别为(165.83±14.12)μg/mL和(113.97±9.26)μg/mL,GYP1没有抗癌活性,表明绞股蓝抗癌药效成分主要是由弱极性绞股蓝皂苷发挥功效

企业补贴:为何成为“唐僧肉”

背景材料:2012年11月至2013年3月,国家审计署对2011年、2012年中央财政本级和转移支付给天津、河北、辽宁、吉林、黑龙江等18个省、直辖市能源节约利用(21110款)、可再生能源(21112款)和资源综合利用(21113款)节能环保类三个款级科目资金(以下简称“三款科目“资金)进行了审计,延伸审计项目5044个,涉及资金621.09亿元,分别占项目总数和资金总额的60.57%、75.85%。本次审计发现