Discovery of small molecule inhibitors of tyrosine kinase RET

RET（TheREarrangedduringTransfection）是一种受体酪氨酸激酶，与细胞增殖、迁移、分化及神经嵴细胞的生存、肾脏器官的形成、精子发生等过程的信号转导有关。其异常表达、突变和重组与多种癌症的发生发展密切相关，如乳突状甲状腺癌、多发性内分泌腺瘤病2型、髓样甲状腺癌、嗜铬细胞瘤和甲状腺旁腺瘤等。在肺癌方面，RET基因的异常重组KIF5B-RET和CCDC6-RET与约1~2%的肺腺癌相关，其中KIF5B-RET更是占到了其中70~90%的比例，CCDC6-RET约占10~25%。然而，至今还没有特异性的RET小分子抑制剂的报道，因此发展高活性、高选择性的RET抑制剂具有十...The REarranged during Transfection (RET) receptor protein was one of the first Receptor tyrosine kinases (RTKs) that play a role in neoplasia. Expressed primarily in neural crest-derived and urogenital cells, RET is thought to be involved in the signal transduction required for proliferation, migration, differentiation and survival of neural crest cells, kidney organogenesis and spermatogenesis. A...学位：理学硕士院系专业：生命科学学院_转化医学学号：2162014115259

Isatis tinctoria L. combined with co-stimulatory molecules blockade inhibits accelerated rejection caused by al-lo-primed CD4+ memory T cells in mice

由记忆性T细胞介导的加速性排斥反应是器官移植中诱导移植物长期耐受的主要障碍，传统的一线免疫抑制剂如钙调蛋白抑制剂类药物多数针对效应性T细胞的作用发挥功能，这些药物对记忆性T细胞介导的加速排斥反应作用效果较差。在之前的研究中，我们发现从传统中药板蓝根中提取出的高级不饱和脂肪酸化合物单体K能够有效抑制小鼠初次心脏移植模型中的急性排斥反应。此外，单体K与共刺激分子阻断剂联用可以有效延长同种异体抗原预致敏受体小鼠受体心脏移植物的生存期。在这项研究中，我们进一步探究了单体K在同种异体来源CD4+记忆性T细胞过继转移小鼠心脏移植模型中对同种异体移植物排斥的抑制作用。我们的研究结果表明，单体K与共刺激分子阻...Accelerated rejection caused by memory T cells is one of the major barriers to induce long term survival of allograft in transplantation. Traditional immunosuppressants target on effector T cells often have poor effect on alloreactive memory T cells. In previous studies, we discovered that compound K, a synthesized analogue of highly unsaturated fatty acids from Isatics tinctoria L., was effective...学位：理学硕士院系专业：医学院_药理学学号：2452010115335

Study on the marine algicidal bacteria and their algicidal substances

赤潮是一种严重的全球性海洋灾害，近年来赤潮发生次数增多，发生区域扩大，赤潮危害加剧。海洋细菌在赤潮生消过程中有着极其重要的作用，而近年来细菌杀藻现象的发现为微生物防治赤潮提供了可能途径，菌藻关系研究已经成为当前赤潮研究的重点和热点。 本论文研究了一株有毒甲藻——塔玛亚历山大藻（ATGD98-006）藻际细菌的群落组成；验证了FDA活性染色法应用于本研究中主要的实验藻种——塔玛亚历山大藻藻细胞活性检测的可行性，并用于后续的杀藻活性试验；从东海海域分离并筛选到多株能杀死塔玛亚历山大藻的海洋细菌，对其进行了生理生化及分子鉴定，研究了细菌的杀藻方式、杀藻谱，并选取杀藻效果较好的两株细菌从藻细胞生理生...The apparent increasing occurrence of harmful algal blooms (HABs) throughout the world has led to extensive researches to mitigate the blooms, as a result, some management strategies have been developed. Outbreak and termination of HABs in marine environment was affected by physical and chemical factors, and biological factors as well. Of the factors that regulate the red tide dynamics, algal-bact...学位：理学博士院系专业：生命科学学院生物化学与生物技术系_微生物学学号：2012005140313

A case of lymphedema in both lower extremities

治疗双下肢淋巴水肿患者1例。采用针刺中脘、水分、水道、足三里、阴陵泉、三阴交、阳陵泉、太冲、太溪穴,配以TdP局部照射,改善局部血液循环,促进淋巴液的回流,从而有效减轻双下肢水肿。疗程短,效果显著,无痛苦,无副作用。Patient suffering from lymphedema in both lower extremities was treated,acupuncture was carried out at Zhōngwǎn(中脘 CV 12),Shuǐfēn(水分 CV 9),ShuǐDào(水道 ST 28),Zúsānlǐ(足三里 ST 36),Yīnlíngquán(阴陵泉 SP 9),Sānyīnjiāo(三阴交 SP 6),Yánɡlínɡquán(阳陵泉 GB 34),Tàichōng(太冲 LR 3) and Tàixī(太溪穴 KI 3),and local TDP irradiation was also carried out to improve local blood circulation and promote lymph fluid backflow,and thus effectively alleviate lymphedema in both lower extremities.The treatment courses were short and painless,and no adverse eff ect was detected

Taxonomic diversity of fish community in the waters surrounding the Taishan Islands of Fujian Province

根据2012年~2013年在台山列岛周边海域进行的4个航次底拖网调查资料,并结合该海域的历史资料系统整理了台山列岛周边海域鱼类总名录,使用PRIMER 5.0软件计算了该海域鱼类的分类多样性指数,研究了分类多样性指数的季节变化。结果显示,台山列岛周边海域共记录鱼类2纲20目81科150属208种,以鲈形目种类占绝对优势;2012年~2013年调查记录到鱼类2纲11目40科63属77种。台山列岛周边海域鱼类的平均分类差异指数(△~+)和分类差异变异指数(∧~+)的理论平均值分别为63.14和378.4。鱼类分类多样性指数(△)秋季最高,春、夏季次之,冬季最低;鱼类分类差异指数(△~*)秋季最高,春季次之,夏、冬季较低。研究结果表明,春季鱼类种类数最多,夏、秋季次之,冬季最少,水温和饵料决定了研究海域鱼类种类组成。According to the data collected from four seasonal trawling surveys between 2012 and 2013 in the waters surrounding the Taishan Islands,we made a list of fish species in this area and calculated its taxonomic diversity by PRIMER 5. 0. We identified 208 fish species including 2 classes,20 orders,81 families and 150 genera in the waters around Taishan Islands,with Perciformes being the major order. According to the survey data from 2012 to 2013,77 fish species including 2 classes,11 orders,40 families and 63 genera were identified. The average taxonomic distinctness( △~+) and variation in taxonomic distinctness( ∧~+) of fish species listed in that area were 63. 14 and 378. 4,respectively. The taxonomic diversity( △) and taxonomic distinctness( △~*) were higher in autumn and spring than in summer and winter. It is concluded that the species in spring was more than that in summer and autumn,and was the least in winter. Water temperature and food were the main factors which affect fish species composition.国家自然科学基金项目(41106073);; 福建省科技计划项目(2012Y0072);; 福建省海洋与渔业厅科技项目[(2012)013号

南方红豆杉内生真菌的初步研究

从共生理论出发,对采自福建省龙岩山区的药用植物南方红豆杉的内生真菌进行分离。从南方红豆杉的树叶、短茎和树皮中共分离得到107株内生真菌。抗菌、抗氧化和抗肿瘤活性检测结果显示,其中有8株菌对1种或者几种指示菌有一定的抗菌活性,占供测菌株的7.48%;有40株菌对HElA细胞有较强的细胞毒活性,占供测菌株的37.38%;有2株菌对dPPH·有机自由基有较强清除活性,占供测菌株的1.87%。从南方红豆杉内生真菌XylArIAlES SP.的固体发酵产物中初步分离并鉴定出化合物10,11-dIHydrOXynErOlIdOl,该化合物表现出了一定的抗氧化作用。说明南方红豆杉植物中含有丰富的菌种资源,具有开发生物活性物质的潜力

Molecular Ecology Research Progress for Soil Denitrification and Research Status for Its Influencing Factors

反硝化作用是在微生物参与下的土壤氮循环中的一个重要过程,反硝化作用强弱直接影响着氮素的利用。反硝化微生物是一大生理类群,广泛分布于细菌、真菌和古菌中,经典的16S rrnA方法不适合反硝化细菌的生态学研究。利用功能基因,结合现代分子生物学技术,已成为反硝化研究的常用方法。主要介绍了变性梯度凝胶电泳、末端标记限制性片段长度多态性技术、实时荧光定量PCr、反转录PCr以及最近发展起来的高通量测序技术和功能单细胞分离技术在反硝化生态研究中的应用,并综述了土壤反硝化作用的研究进展及其影响因素,对反硝化未来的研究技术和方向进行了展望。Denitrification,a microbial redox process in which nitrogen oxides are reduced stepwise to gaseous products,is an important step in nitrogen cycling,especially in the soil environments.Denitrifying microbes possess a series of enzymes encoded by various functional denitrifying genes.The classic 16S rRNA molecular method is not suitable for the study of diversity and abundance of denitrifying bacteria,since denitrifying microorganisms are a large physiological group of microbes widely distributed in bacteria,fungi and archaea.It is easier to distinguish microbes with different ecological functions by investigating specific functional genes.The application of modern molecular techniques,including denaturing gradient gel electrophoresis(DGGE),terminal restriction fragment length patterns(T-RFLP),real-time fluorescent quantitative PCR(qPCR),and reverse transcription-PCR(RT-PCR)techniques,as well as the newly developed high-throughput sequencing technique and functional single-cel(lFSC)isolation method in denitrification ecological research are reviewed in this paper.Compared with the traditional methods,high-throughput sequencing technique could provide more reliable results to directly understand the denitrifying communities,and would contribute to the identification of new denitrification pathways when combined with FSC isolation method.The progress of molecular ecology research on soil denitrification mechanism and its influencing factors are also reviewed.In addition,the main influencing factors including temperature,pH,carbon and nitrogen sources and dissolved oxygen are discussed in relation to the denitrification activity.Finally,some new directions in the denitrification research are proposed in this paper.国家自然科学基金(31000254); 福建省自然科学基金(2012J05070); 中国科学院知识创新工程重要方向项目(KZCX2-YW-Q02-04); 科技部国际科技合作专项(2011DFB91710

The importance and potential application of allelopathy in red-tide control

作者简介: 杨小茹(1980),女,博士研究生,E-mail :[email protected];通讯作者(责任作者),E-m ail [email protected][中文文摘]简要概述了化感作用的定义、化感物质的种类及其作用机理,描述了化感物质在赤潮控制中的作用;集中综述了水生植物、微藻和细菌所产生的化感物质对赤潮生物的抑制或杀灭作用.强调了化感作用在赤潮调控中具有重要的意义和广阔应用前景,对化感作用的深入研究将可能开发出新型的赤潮控制技术. [英文文摘]This paper summarizes the definition of allelopathy, including the categories, functions and mechanisms of allelochemicals in red tide succession, as well as the allelopathic growth inhibition of phytoplankton by different aquatic plants, microalgae and microbes. Considering that allelopathy is one of the mechanisms thought to control red tides, the authors emphasize that future research should mainly focus on the isolation and identification of new allelochemicals and the mechanisms of allelopathy. Intensive study of allelopathy should provide new red tide control methods.国家高技术研究发展计划项目(No2008AA09Z408);国家自然科学基金(No30370276);国家海洋局海洋生态系统与生物地球化学重点实验室开放基金(NoLMEB200601);高等学校博士学科点专项科研基金(No20050384002

Impact of simulated tide and vegetation on the wetland greenhouse gases fluxes

以福建省九龙江入海口的滩涂潮间带作为研究对象,通过原位采样和室内人工微宇宙实验,利用静态箱-气相色谱法,研究了潮汐植被对湿地CH4、CO2和n2O 3种重要温室气体通量的影响.结果表明,3种温室气体通量在模拟潮汐和植被作用下表现出明显的差异.模拟潮汐对CH4和n2O通量的影响没有明显的规律,总量上都表现为排放;对CO2通量具有显著影响,退潮时抑制,表现为吸收,涨潮时促进,表现为排放.植被促进CH4的排放,对CO2通量影响无明显规律,对n2O通量表现为抑制作用.植被除了自身对温室气体直接作用外,还通过改变沉积物的理化性质影响微生物活动,进而影响温室气体通量.综合分析,植被对温室气体通量的影响要比模拟潮汐作用明显.To evaluate the effects of environmental factors on the greenhouse gases( GHGs) fluxes,sediment samples from the Mangrove Nature Reserve of Jiulong River estuary were collected and homogenized evenly before microcosm experiments.Tide and vegetation types were simulated in the microcosm.A static chamber technique was used to measure the fluxes of three important greenhouse gases,i.e.CH4,CO2and N2O.Three vegetation types were simulated in the microcosm according to the plant coverage patterns in the estuary,i.e.unvegetated,Spartina alterniflora and native mangrove plant Kandelia obovata,while tide was simulated by using peristaltic pump controlled by a timing device.Results showed that the fluxes of three GHGs responded differently to simulated tide and vegetation.The simulated tide seemed to have no impact on the emission of CH4and N2O,and all the treatments showed positive values in total fluxes,indicating general possibility of release.CO2flux was inhibited during the falling tide and promoted during the rising tide,resulting in the negative and positive value during the falling and rising tide,respectively.Vegetation showed positive effect and negative effect on CH4and N2O emission,respectively,and no significant difference was observed on CO2flux between different vegetation types.Except for the direct effect on gas flux,plants also influenced the sediment microorganisms by altering the sediment physicochemical properties.Through comprehensive analysis,the impact of vegetation was more significant compared with the simulated tide.国家自然科学基金(No.31000254); 福建省自然科学基金(No.2012J05070); 中国科学院知识创新工程重要方向项目(No.KZCX2-YW-Q02-04); 科技部国际科技合作专项(No.2011DFB91710)~

基于生物信息学途径评估 UBE2 家族及 UBE2T 基因在肺腺癌中的表达及临床意义

【目的】探究泛素结合酶E2家族和泛素结合酶E2T（UBE2T）在肺腺癌中的表达情况及其与临床病理特征之间的关系。【方法】利用linkedomics平台进行UBE2C、UBE2M、UBE2S、UBE2T、UBE2V2 mRNA表达水平与肺腺癌临床特征之间的关系分析，对总生存时间（OS）（Cox回归检验）、总分期（Kruskal-WallisH检验）、T分期（Kruskal-WallisH检验）、N分期（Kruskal-WallisH检验）及M分期（Wilcox秩和检验）进行差异比较。运用肿瘤基因组图谱（TCGA）数据库获取UBE2T基因在肺腺癌组织和癌旁组织中的表达信息，将结果进行两独立样本t检验。利用GSEA软件进行KEGG通路及富集分析。【结果】UBE2C、UBE2M、UBE2S、UBE2T、UBE2V2 mRNA表达量与肺腺癌的临床病理特征存在相关关系。其中，UBE2T高表达者其OS较短，TNM分期较晚者UBE2T呈高表达，差异均具有统计学意义（P<0.05）。UBE2T mRNA表达量在肺腺癌中明显升高（P<0.01）。基因富集结果显示高表达的UBE2T与细胞周期（FDR=0），剪接体（FDR=0），DNA修复（FDR=0）及糖代谢等36个信号通路密切相关（FDR<0.05）。UBE2家族的UBE2C、UBE2M、UBE2S、UBE2T、UBE2V2 mRNA均与肺腺癌的临床病理特征存在相关关系，其中UBE2T的表达水平与临床分期及预后的关系最为密切，且与肿瘤细胞糖酵解通路密切相关。【结论】UBE2家族与肺腺癌临床病理特征相关。UBE2T mRNA有望成为肺腺癌新的生物标志物