Synthesis and biological evaluation of 18F labeled fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives for sigma-1 receptor imaging

We report the synthesis and evaluation of a series of fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives as potential σ₁ receptor ligands. In vitro competition binding assays showed that 1-(1,3-benzodioxol-5-ylmethyl)-4-(4-(2-fluoroethoxy)benzyl)piperazine (6) exhibits low nanomolar affinity for σ₁ receptors (K_i = 1.85 ± 1.59 nM) and high subtype selectivity (σ₂ receptor: K_i = 291 ± 111 nM; K_iσ₂/K_iσ₁ = 157). [¹⁸F]6 was prepared in 30–50% isolated radiochemical yield, with radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic ¹⁸F^? substitution of the corresponding tosylate precursor. The log D_{pH 7.4} value of [¹⁸F]6 was found to be 2.57 ± 0.10, which is within the range expected to give high brain uptake. Biodistribution studies in mice demonstrated relatively high concentration of radiotracers in organs known to contain σ₁ receptors, including the brain, lungs, kidneys, heart, and spleen. Administration of haloperidol 5 min prior to injection of [¹⁸F]6 significantly reduced the concentration of radiotracers in the above-mentioned organs. The accumulation of radiotracers in the bone was quite low suggesting that [¹⁸F]6 is relatively stable to in vivo defluorination. The ex vivo autoradiography in rat brain showed high accumulation of radiotracers in the brain areas known to possess high expression of σ₁ receptors. These findings suggest that [¹⁸F]6 is a suitable radiotracer for imaging σ₁ receptors with PET in vivo.     

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, ^99mTc sestamibi and ^99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. ¹²³I has a similar energy as ^99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an ¹²³I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with ¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog ¹²⁷I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: ¹²³I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111 GBq/μmol; 400–3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significant myocardial uptake (2.01 ± 0.48%ID/g) and high heart to liver (2.98 ± 0.93), heart to lung (4.11 ± 1.04) and heart to blood (8.37 ± 3.97) ratios. At 24 h p.i., the majority of ¹²³I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: ¹²³I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics.     

Open-Channel Structures of the Human Glycine Receptor α1 Full-Length Transmembrane Domain

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太湖流域生态风险评价

随着城镇的急剧扩张和经济的快速增长,流域生态环境遭到极大冲击和破坏,致使生态系统出现资源退化、环境恶化与灾害风险加剧的趋势,生态环境面临前所未有的挑战.从复合生态系统入手,深入分析流域内各生态系统要素之间的相互作用与影响机制,综合考虑多风险源、多风险受体和生态终点共存情况下的风险大小,从风险源危险度、生境脆弱度及受体损失度三方面构建了流域生态风险评价技术体系,并选取太湖流域为实证区域,对太湖流域2000年、2008年两个时期生态风险的时空演化特征进行评价与分析.结果表明:太湖流域生态风险指数介于0.015-0.253之间,以中等和较低生态风险为主.至2008年,高、较高生态风险所占面积逐渐扩大,已由2000年的5.66％、13.42％增加至6.05％、18.42％,主要集中在流域北部的常州市区、江阴市大部分地区以及无锡市区.     

广西马山岩溶植被年龄序列的群落特征

石漠化地区是我国西南植被恢复和生态重建的重点和难点地区。通过对马山县岩溶植被年龄序列(石漠、草丛、灌丛、小乔林和成熟林)5个演替阶段15个样地(20 m×50 m)的系统取样调查,研究了停止人为干扰后岩溶植被的更新、演替及群落特征的变化。结果表明:沿石漠、草丛、灌丛、小乔林、成熟林的顺向演替发展,群落各层次的覆盖度存在显著差异(P<0.05),乔木层覆盖度以成熟林最大,灌木层覆盖度以小乔林最高,而草本层覆盖度以灌丛最高;重要值≥10.00的科、属、种最大值出现在小乔林;不同演替阶段群落不同层次的结构明显不同,乔木层的植物密度存在显著差异(P<0.05),以小乔林最高;成熟林灌木层的植物密度显著低于小乔林和草丛(P<0.05),与石漠和灌丛差异不显著(P>0.05);森林阶段草本层的植物密度显著低于灌丛、草丛和石漠(P<0.05);群落的物种丰富度随着顺向演替发展而增加,但不同演替阶段不同层次的丰富度变化不同,草本层的物种丰富度以草丛阶段最大,成熟林最小;灌木层的丰富度以小乔林阶段最大,石漠阶段最小;乔木层的丰富度以小乔林最大,成熟林有所下降;不同演替阶段群落草本层的生态优势度无显著差异(P>0.05),而灌木层和乔木层均存在显著差异(P<0.05)。岩溶植被恢复可分为恶劣物理环境阈值和顶极种缺乏的阈值两个阶段,每一个阶段内由不同功能特征的驱动种和关键种决定着群落的演替方向和速度,越接近演替后期,顶极种越丰富,群落驱动种和关键种向高级、大型和长寿植物发展的趋势越明显。     

圈养大熊猫野化培训期的生境选择特征

大熊猫(Ailuropoda melanoleuca)是我国特有的珍稀物种,也是世界上最濒危的野生动物之一。为了将人工繁育的部分大熊猫个体重引入其历史分布区或复壮野生种群,中国保护大熊猫研究中心从2003年开始进行圈养大熊猫的野外放归工作,通过野化培训以提高圈养大熊猫适应和选择野外环境的能力。对野化培训大熊猫"淘淘"的生境选择研究表明:该野化培训大熊猫幼仔经常活动于新笋密度较大的区域[生境与对照:(2.68±1.14)对(1.58±0.66)],却避开成竹密度过大[(9.91±2.51)对(12.18±4.68)]、竹子较高[(4.57±1.09) m对(4.98±0.66) m]以及枯死竹过多[(2.52±0.86)对(3.39±1.33)]的区域;喜欢活动于离水源[(1.59±0.67)对(2.19±0.87)]和隐蔽场所较近[(5.37±2.14) m对(8.35±7.76)m],以及距离乔木较远[(3.09±0.69) m对(2.70±0.42) m]和郁闭度较低[(1.85±0.57)对(2.10±0.47)]的区域(P < 0.05),新笋密度大小是该栖息地在整个野化培训期间是否被利用的最重要因素。该野化培训大熊猫幼仔保持着与带仔母兽相近的生境选择特征,对竹子环境的选择也与卧龙野生大熊猫相似,野化培训对该大熊猫幼仔产生了积极的作用。野化培训大熊猫幼仔形成的家域和核域面积分别为9.21 hm² 和1.93 hm²,占野化培训圈面积的51.95%和10.89%,其中家域面积仅有卧龙野生大熊猫的1.4%-2.4%,所以在以后的野化培训过程中需要采取增加野化培训圈中环境丰富度等方式,促进野化培训大熊猫形成较大的家域面积。     

潮虫消耗木本植物凋落物的可选择性试验

近年来,越来越多的学者关注外来植物入侵对土壤生态功能的影响效应及其相应反馈机制的探索与研究,然而本地原生土壤生物群落对不同入侵程度下的外来植物种以及本地原生植物种之间是否存在消耗差异却尚不明了.通过等足目潮虫的选择性喂养试验来测试10个本地种、5个非入侵性外来种和5个强入侵性外来种之间的适口性差异,试图求证外来植物的入侵性是否与植物落叶被消耗率呈现必然联系.数据分析结果显示潮虫对本地种、非入侵性外来种和入侵性外来种的消耗并无显著差异;而潮虫对不同生活型下木本植物的取食却存在显著差异,即灌木消耗率显著高于乔木.其次,通过植物初始性状指标(包括木质素、纤维素、半纤维素、碳、氮含量)与相应消耗率的相关比较,消耗量总体上与植物凋落物的氮含量呈正相关关系(R2 =0.358).由此,研究结论强调植物落叶的降解速率并不一定与植物入侵性或入侵阶段呈绝对相互关连,但是氮含量,抑或各种形式的植物氮元素成分都可能在一定程度上参与并影响着外来植物的入侵进程.     

生态系统生产总值核算:概念、核算方法与案例研究

生态系统产品与服务功能是人类生存与发展的基础。生态系统生产总值(GEP)可以定义为生态系统为人类福祉和经济社会可持续发展提供的产品与服务价值的总和,包括生产系统产品价值、生态调节服务价值和生态文化服务价值。生态系统生产总值核算的基本任务有3个,即核算生态系统产品与服务的功能量、确定生态系统产品与服务的价格、核算生态系统产品与服务的价值量。生态系统生产总值核算可以用于揭示生态系统为经济社会发展和人类福祉的贡献,分析区域之间的生态关联,评估生态保护成效和效益。以贵州省为例,探讨了生态系统生产总值核算的应用方法,评价了贵州省生态系统为贵州和其他地区人们福祉和支撑经济社会发展所提供的产品和服务及其经济价值总和。评价结果显示,贵州省2010年全省生态系统生产总价值为20013.46亿元,人均GEP 57526元,是当年该省国民生产总值和人均GDP的4.3倍。研究表明,生态系统生产总值的核算可以反映生态系统对经济社会发展的支撑作用,并为建立生态系统保护效益与成效的考核机制提供基础。     

桔梗种子萌发对低温、干旱及互作胁迫的响应

以药用植物桔梗种子为材料,研究了低温、干旱及其互作对种子萌发和幼苗生长的影响,旨在探索在春寒干旱条件下其种子萌发对策及生态适应性,为桔梗野生种群恢复及人工栽培群体构建提供依据.结果表明,温度、干旱及其互作对桔梗种子萌发和幼苗生长均有显著影响.0-10％ PEG水分条件下,在变温10/20℃及恒温15-25℃下桔梗种子能够良好萌发(10％ PEG、20℃除外),而15％ PEG可显著抑制萌发.低温(10℃)下种子萌发始时间延迟,发芽率降低.随干旱胁迫程度的增加,10℃发芽率呈先升后降趋势,而其它温度下,发芽率和发芽指数均呈下降趋势.随温度的降低,幼苗根长、茎长及鲜重均呈下降趋势,且幼根生长对温度变化更为敏感.