Quantified 123I-Thyroid Scan based classification of hyperthyroidism

The original thyroid scan (TS) was widely used to identify typical imaging patterns, suggesting the widely accepted main following clinical diagnoses: Grave's disease, Toxic adenoma, [hetero]-nodular goiters and thyroiditis. With the diffusion of sensitive TSH assays, considerable advances in the comprehension of the molecular mechanisms of hormonosynthesis, and new quantification possibilities especially using ¹²³I, the TS is a textbook of molecular imaging. The image can be finely quantified with, not only as regards the Uptake (¹²³IUp) and related parameters but also, the quantification of the spatial targeting leading to a Spatial Target Index (STI). Using this new molecular ¹²³I-TS, TSH values, and when required, correlation to Multiparametric Ultrasounds (MPUS), we generated a basic classification system of hyperthyroidism, with well-defined indexed criteria (C11-1 to C17-3), that allows reporting 24 distinct etiologies. Selected criteria involve TS and contrast patterns, precocious ¹²³IUp (p¹²³IUp), maximal TSH-dependent physiological Uptake, lobar concentration, Uptake and concentration ratios, STI, ^99mTc-MIBI TS and correlative MPUS. This approach allows to identify 4 subtypes of Graves’ disease, including hyperplastic, nodular and common GD variants entangled with Hashimoto's struma, 4 subtypes of Thyroid Functional Autonomy, including Disseminated Functional Autonomy, that cannot be diagnosed with other conventional procedures. Criteria C14-1 to C17-3 report on hyperthyroidism and iodine overload, factitia, main thyroiditis presentations and rare central or tumoral etiologies of hyperthyroidism. This classification, based on ¹²³I-TS molecular imaging, leads to unprecedented diagnostic finesse and paves the way for a personalized theranostic approach in thyroid pathology. Further development towards artificial intelligence networks is under study.     

Discovery of a potent and selective adenylyl cyclase type 8 agonist by docking-based virtual screening

Adenylyl cyclases (ACs), which are responsible for catalyzing the conversion of adenosine triphosphate (ATP) into the second messenger cyclic adenosine monophosphate (cAMP), play a critical role in cell signal transduction. In this study, a combined approach involving docking-based virtual screening, with the combination of homology modeling followed by an in-vitro, and cell-based biological assay have been performed for discovering a class of novel potent and selective isoform adenylyl cyclase type 8 (AC8) agonist. The computer-aided virtual screening was used to identify fourteen virtual cluster compounds as potential hits which were further subjected to rigorous bioassays. A novel hit compound VHC-7 (ethyl 3-(2,4-dichlorobenzyl)-2-oxoindoline-3-carboxylate) was identified as a highly potent selective AC8 agonist with EC₅₀ value of 0.1052 ± 0.038 µM. Remarkably, the molecule herein reported can be explored further to discover greater number of hit compounds with better pharmacokinetic properties as well as to serve as a promising novel hit agonist of AC8 for the treatment of various central nervous system disorders and its associated diseases.     

RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ～40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ～90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).     

Synthesis and biological evaluation of novel 3-benzylcoumarin-imidazolium salts

A series of novel 3-benzylcoumarin-imidazolium salts were prepared and evaluated in vitro against a panel of human tumor cell lines. The results showed that the existence of 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. Notably, compound 38 was found to be the most potent derivative with IC₅₀ values of 2.04–4.51 μM against five human tumor cell lines, while compound 34 were more selective to SW-480 cell lines with IC₅₀ value 40.0-fold lower than DDP. Mechanism of action studies indicated that compound 38 can cause the G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cell lines.     

基于综合评价法的洞庭湖区绿地生态网络构建

绿地生态网络对于改善区域生态空间破碎化、生物多样性降低、生态系统服务供需不平衡及保障区域生态安全具有重要意义。本研究以洞庭湖区为例,在3S技术支持下,从生态系统服务功能、潜在生物多样性、形态空间格局的角度综合评价和识别生态源地及计算栅格单元的基本生态阻力;利用夜间灯光指数修正基本生态阻力;运用最小累积阻力模型识别生态廊道;构建加权评价模型,对源地的聚合度、离散度及廊道的生态连接贡献度进行评价;利用结构特征指数对综合网络、“源-汇”潜在网络及规划网络进行对比分析和评价。结果表明: 源地空间分布不均衡,林地、灌丛与水域三者面积之和占源地总面积的95.9%,位于研究区中部的洞庭湖湿地生态风险较高;源地离生态网络系统中心位置越近及到其他源地的平均最小累积阻力越小,聚合及离散的优势越强;高生态质量源地周围的中、高生态质量源地分布越密集,其聚合度、离散度越高;廊道离高生态质量的源地越近,表现为生态连接贡献度越大;林地、灌丛,尤其是河道在自然生态系统与人类社会系统之间起着非常重要的生态连接作用;“源-汇”规划绿道对“源-汇”潜在生态廊道形成了良好补充,与“源-汇”潜在网络相比,综合网络的α、β、γ、ρ指数分别提高123.1%、25.8%、26.2%、74.6%;与“源-汇”规划网络相比,α、β、γ、ρ指数分别提高了190.0%、31.1%、32.5%、114.6%。本研究结果能为洞庭湖区绿地生态网络构建、国土空间规划提供参考。     

两种生态系统服务价值评估方法比较研究——以四川省金堂县三星镇土地整治工程为例

乡镇土地整治是建设中国美丽乡村的重要途径,对当地生态环境带来正面和负面影响,如何准确评价其生态效益是国家开展土地整治和美丽乡村建设需要面临的重要科学问题。以中国西南部丘陵地区典型乡镇——四川省金堂县三星镇的土地整治工程为例,对比分析了生态系统服务价值当量修正法和单项服务评价法评估土地整治生态效益的异同,以期确定适合我国西南部丘陵地区乡镇土地整治生态效益评估的合理方法。研究结果表明:单项服务评价法的评估结果(生态系统服务价值约300万元)比当量修正法(生态系统服务价值约290万元)高3.5%。当量修正法评估的各项生态系统服务价值增量由高到低依次为:调节服务价值支持服务价值供给服务价值文化服务价值;单项服务评价法评估的生态系统服务价值增量大小排序为:调节服务价值支持服务价值文化服务价值供给服务价值。方法依据和参数的选取不同,导致评估结果具有显著差异,主要表现在单项服务评价法测算的维持养分循环价值、美学景观价值分别是当量修正法的46.90倍和6.94倍,当量修正法测算的水文调节价值是单项服务评价法的5.93倍。单项服务评价法针对各项生态系统服务特征,灵活地选取差异化评估方法,因而其评估结果更准确、真实地反映了生态效益价值。建议运用单项服务评价法评估我国西南部丘陵地区乡镇土地整治的生态效益。     

生态保护项目绩效评估的技术方法体系

自20世纪90年代以来,以各种形式的生态补偿政策和工程项目为代表的生态保护项目在全球广泛实施。1998年长江大洪水之后,我国也陆续实施了天然林保护工程、退耕还林还草工程、京津风沙源治理工程、森林生态效益补偿基金、退田还湖还湿工程、生态转移支付等一系列生态保护项目。近年来,政府、研究人员和社会各界越来越重视这些项目产生的生态、经济和社会效益。不过,我国生态保护项目绩效评估还处于起步阶段,主要体现在定量化不足、研究设计不严密、基准线选取不规范、评估方法过于简易、因果推理证据不足、评估结果可信度较差。不管是从学术研究、国家战略,还是实际生态管理的角度,都迫切需要推动和完善我国生态保护项目的绩效评估。结合过去十多年的理论和案例研究经验,对绩效评估的研究设计、基准线选取、评估方法、以及评估分析中面临的问题和挑战进行了系统地归纳与梳理,以期为进一步开展生态保护项目绩效评估提供技术参考。     

城市尺度的城乡建设用地潜力及空间格局匹配评价——以南昌市为例

随着经济快速发展和城镇化进程不断加快,土地开发强度日益增大,导致生态环境不断恶化,分析城乡建设用地承载能力及空间格局匹配情况,对解决土地利用不合理、生态破坏等问题具有重要意义。以江西省南昌市为例,首先从生态安全、自然条件、社会经济等方面构建指标体系,采用层次分析法和限制系数评价模型,进行城乡建设用地开发适宜性评价,然后测算城乡建设用地承载力、可承载城乡建设用地丰度;最后与现状城乡建设用地进行空间匹配度分析,并探讨可承载临界值、丰度与空间匹配度的相关性。结果表明：南昌市城乡建设用地最适宜区、较适宜区、较不适宜区和不适宜区面积分别为1466.19、1346.01、353.69 km²和3770.70 km²;研究区城乡建设用地可承载临界值和可承载潜力分别为41.25%和24.05%,各县（区）值差异较大,各县（区）可承载临界值和可承载潜力范围分别为19.43%-98.71%和5.65%-49.83%,可承载城乡建设用地丰度情况良好,各县（区）值介于0.19-1.50之间;研究区各县（区）空间匹配度范围为67.41%-99.25%;相关分析显示,空间匹配度与城乡建设用地可承载临界值和可承载城乡建设用地丰度均呈正相关关系。研究可为南昌市城乡建设用地合理开发利用和国土空间优化提供依据。