Synthesis and radiopharmacological characterization of 2beta-carbo-2'-[18F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane ([18F]MCL-322) as a PET radiotracer for imaging the dopamine transporter (DAT)

The fluoroalkyl-containing tropane derivative 2beta-carbo-2'-fluoroethoxy-3beta-(4-bromo-phenyl)tropane (MCL-322) is a highly potent and moderately selective ligand for the dopamine transporter (DAT). The compound was labeled with the short-lived positron emitter (18)F in a single step by nucleophilic displacement of the corresponding tosylate precursor MCL-323 with no-carrier-added [(18)F]fluoride. The positron emission tomography (PET) radiotracer 2beta-carbo-2'-[(18)F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane [(18)F]MCL-322 was obtained in decay-corrected radiochemical yields of 30-40% at a specific radioactivity of 1.6-2.4Ci/mumol (60-90GBq/mumol) at the end-of-synthesis (EOS). Small animal PET, ex vivo and in vivo biodistribution experiments in rats demonstrated a high uptake in the striatum (3.2% ID/g) 5min after injection, which increased to 4.2% ID/g after 60min. The uptake in the cerebellum was 1.8% ID/g and 0.6% ID/g after 5min and 60min post-injection, respectively. Specific binding to DAT of [(18)F]MCL-322 was confirmed by blocking experiments using the high affinity DAT ligand GBR 12909. The radiopharmacological characterization was completed with metabolite and autoradiographic studies confirming the selective uptake of [(18)F]MCL-322 in the striatum. It is concluded that the simple single-step radiosynthesis of [(18)F]MCL-322 and the promising radiopharmacological data make [(18)F]MCL-322 an attractive candidate for the further development of a PET radiotracer potentially suitable for clinical DAT imaging in the human brain.     

稻水象甲(Lissorhoptrus oryzophilus Kuschel)滞育征候群中的飞行行为

１９９４－１９９６年对浙江省双季稻区稻水象甲（ＬｉｓｓｏｒｈｏｐｔｒｕｓｏｒｙｚｏｐｈｉｌｕｓＫｕｓｃｈｅｌ）飞行行为的研究表明,稻水象甲飞行扩散的行为特征是：（１）长时间的起飞准备和不高的起飞成功率,每晚的迁出率只有三分之一左右,（２）卵巢,飞行肌呈季节性消长而无局地飞行（ｔｒｉｖｉａｌｆｌｉｇｈｔ）;（３）飞行速度不高,飞行能力不强,且风力稍大便无法起飞,一般情况下不会形成远距离自然扩散,因此     

Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons

Increasing evidence supports that the mitochondrial dysfunction, mainly caused by abnormal changes in mitochondrial proteins, plays a pivotal role in glutamate-induced excitotoxicity, which is closely associated with the pathogenesis of acute and chronic neurodegenerative disorders, such as stroke and Alzheimer's disease. In this study, post-treatment of cerebellar granule neurons with bis(7)-tacrine significantly reversed declines in mitochondrial membrane potential, ATP production, and neuronal cell death induced by glutamate. Moreover, this reversal was independent of NMDA antagonism, acetylcholinesterase inhibition, and cholinergic pathways. Using two-dimensional differential in-gel electrophoresis, we conducted a comparative analysis of mitochondrial protein patterns. In all, 29 proteins exhibiting significant differences in their abundances were identified in the glutamate-treated group when compared with the control. The expression patterns in 22 out of these proteins could be reversed by post-treatment with bis(7)-tacrine. Most of the differentially expressed proteins are involved in energy metabolism, oxidative stress, and apoptosis. In particular, the altered patterns of four of these proteins were further validated by Western blot analysis. Our findings suggest that multiple signaling pathways initiated by the altered mitochondrial proteins may mediate glutamate-induced excitotoxicity and also offer potentially useful intracellular targets for the neuroprotection provided by bis(7)-tacrine.     

Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

Proton pump inhibitors(PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease(GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls(HCs) using 16 S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPIuser and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae,Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on shortterm PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.     

三江源地区雪豹保护优先区规划

为了将有限资源合理投放到关键区域, 实现物种保护成效的最大化, 找出质量最好的栖息地及它们之间的迁徙通道是制定保护规划的第一步。本研究以三江源的雪豹(Panthera uncia)栖息地为对象, 基于野外调查数据和高分辨率卫星遥感数据, 利用物种分布模型、保护规划模型和连通度分析工具, 找出了三江源地区雪豹的核心栖息地分布和潜在迁徙通道位置, 分析了目前保护中的潜在威胁, 并提出了针对三江源西、中、东三块区域的不同保护对策。结果表明: (1)三江源西部核心栖息地比较小而破碎, 但迁徙通道较多且没有明显窄点, 未来应关注青藏线的潜在阻碍作用, 同时应防范道路沿线的野生动物盗猎; (2)中部区域横跨玉树-杂多-囊谦的雪豹栖息地是三江源最大的核心雪豹栖息地, 在连通其他种群中也处于中心地位, 应通过种群监测确定其健康稳定, 对开发、偷猎等威胁防微杜渐, 保持其源种群的作用; (3)东部区域人口密度高, 受人类活动的影响最大, 需保证阿尼玛卿、年保玉则两块核心栖息地的质量, 并重点监测甘德县境内的省道处雪豹的迁徙通道是否畅通。三江源地区雪豹栖息地总体质量较好, 建议将维持核心源种群的稳定性, 保持种群间迁徙通道的畅通作为三江源的雪豹景观保护工作的整体目标。未来应充分利用天地一体化监测手段, 开展重要保护物种栖息地状况的评估和预警, 尤其是非保护地区域物种核心栖息地的开发建设活动。     

玫瑰色微球菌A-04的红色素鉴定及稳定性分析

从石油污染的土壤和水样中筛选出一株玫瑰色微球菌A-04 Micrococcus roseus,对其所产红色色素进行了分离,并初步鉴定了色素种类,基于对影响A-04色素稳定性的单因素分析基础之上,采用3因素3水平响应面分析法,进一步对影响色素稳定性的主要因素进行了优化分析。结果表明A-04所产红色色素为类胡萝卜素,对该菌株的色素稳定性的单因素条件分析,色素对环境条件的耐受性较好,在80℃、pH5. 0～8. 0等条件下依然能长时间保持鲜红而不褪色。经响应面优化分析表明:温度、pH和溶剂是影响该色素稳定性的主要因素,温度与溶剂的交互作用对色素稳定性的影响也较为明显。pH5. 0～8. 0之间时,在80℃范围内,温度越低,同时溶剂的极性越大,越有利于维持色素的稳定性。本研究结果为该色素的实际开发和应用奠定了基础。     

6A型肺炎球菌结合物分子大小对小鼠免疫原性的影响

目的 比较不同分子大小的6A型肺炎球菌(serotype 6A Streptococcus Pneumoniae )结合物和佐剂吸附在小鼠体内免疫原性的影响。方法 通过乙酸水解降低6A型荚膜多糖的相对分子质量制备成水解物,水解物经1-氰基-4-二甲胺基吡啶四氟硼酸盐(CDAP)活化并与破伤风类毒素己二酸酰肼衍生物TT AH 结合,制备成结合物。用Sepharose 4 Fast Flow 纯化结合物,并根据化学检测结果将结合物分为 K D 0.0~0.2、 K D 0.2~0.4、 K D 0.4~0.6等3个组分,每个组分分别以磷酸铝佐剂吸附,将吸附前后的各个组分按照每针次每只小鼠0.2 μg分别免疫小鼠,并采用ELISA检测结合物在小鼠体内的抗体水平。结果 3种不同相对分子质量吸附前后的结合物在小鼠体内均能产生较高水平的抗体,各组2、3针之间具有明显的加强效应。在吸附组和未吸附组中,3种不同分子大小的结合物在小鼠体内产生抗体水平无明显差异。各组分佐剂吸附后的结合物血清抗体滴度高于未吸附组,但这种差异无统计学意义( P > 0.05)。结论 结合物的分子大小对小鼠体内抗体水平的产生没有明显影响;磷酸铝佐剂吸附对于不同分子大小的结合物在小鼠体内的免疫原性有一定的增强效应,但这种增强效应差异无统计学意义。     

雌雄子午沙鼠的认知行为及其神经内分泌水平的差异

本研究通过对雌雄子午沙鼠进行新物体识别和社会认知实验,运用免疫组化方法检测其相关脑区合成催产素（OT）、加压素（AVP）和多巴胺（DA）能的神经元数量,采用酶联免疫试验（ELISA）方法检测了其血清中OT、AVP的水平,探究了雌雄子午沙鼠的两性认知差异及其神经内分泌水平的差异。结果表明,雌雄子午沙鼠对新物体的探究时间均要显著高于旧物体,雌雄子午沙鼠的辨别指数无显著差异（P＞0.05）;雄性子午沙鼠随着探究次数的增加对重复刺激鼠a的探究时间不断减少,对陌生刺激鼠b的探究时间显著高于刺激鼠a（P＜0.05）;雌性子午沙鼠没有此趋势。雄性子午沙鼠OT能神经元数量在下丘脑室旁核(PVN)和视上核(SON)均要显著少于雌性（P＜0.05）;雄性个体DA能神经元数量在黑质显著高于雌性（P＜0.01）;然而雄性个体DA能神经元数量在腹侧被盖区显著少于雌性（P＜0.01）;雌雄子午沙鼠血清OT、AVP水平均无显著差异。综上所述,雌雄子午沙鼠对新物体的识别能力无显著差异,然而雄性子午沙鼠的社会认知能力强于雌性。在神经内分泌水平上,雌雄子午沙鼠PVN和SON中OT能神经元数量、黑质和腹侧背盖区的DA能神经元数量均呈现出了两性差异。