IOP-lowering effect of isoquinoline-5-sulfonamide compounds in ocular normotensive monkeys

Rho-associated coiled coil-formed protein kinase (ROCK) inhibitors are under development as a new class of antiglaucoma agents. Based on the potent ROCK inhibitor H-1152, previously developed by us, we explored the possibility of related compounds as antiglaucoma agents and synthesized seven types of H-1152-inspired isoquinoline-5-sulfonamide compounds (H-0103–H-0107, H-1001, H-1005). Although all of these compounds potently inhibited ROCK (IC₅₀ = 18–48 nM), only H-0104 and H-0106 exerted strong intraocular pressure (IOP)-lowering effects into the eyes of monkeys. These results suggested the possibility that there is no direct relationship between ROCK inhibition and IOP-lowering effects, indicating that the initial screening of compounds based on ROCK inhibitory activity may be an unsuitable strategy for developing antiglaucoma agents with potent IOP-lowering effects.     

基于灰色关联度分析的辽西地区典型种植模式评价

不同种植模式评价是当今种植制度研究中的热点之一,针对辽西地区自然特点和种植模式混杂多样的现状,在多年试验研究和专家问卷调查的基础上,采用灰色关联度分析方法对辽西地区6种典型种植模式进行了评价。结果表明:无论是在等权关联度下还是在侧重生态环境指标或经济指标的变权重下,南果梨+南瓜种植模式与参考模式的关联度均为最大,分别为0.867、0.920和0.841,南果梨+花生种植模式次之,说明南果梨+南瓜‖花生的林粮间作模式的生态和经济效益最好,是辽西地区发展种植业的最佳模式,玉米/大豆间作模式的关联度最小,分别为0.848、0.901和0.821,这种模式的生态和经济效益最差。该研究结果对保护辽西地区生态环境,发展多熟立体农业,推动该区域的社会经济与环境的协调发展提供了理论依据。     

An investigation into the solution structure of the single-stranded DNA undecamer 5′d AAGTGTGATAT by means of nuclear Overhauser enhancement measurements

A 500-MHz ¹H-NMR study on the single-stranded DNA undecamer (11-mer) 5d AAGTGTGATAT is presented. Using a combination of one-dimensional pre-steady-state nuclear Overhauser enhancement (NOE) measurements and two-dimensional homonuclear J-correlated spectroscopy, virtually complete resonance assignments are obtained. The relative magnitudes of the intra- and internucleotide NOEs indicate that the overall structure of the single-stranded 11-mer is a right-handed B-type helix with extensive base stacking. Within this overall structure there is quite a large degree of variability, as exemplified by variations in glycosidic bond and sugar pucker conformations, most likely determined by base sequence.Abbreviations NOE nuclear Overhauser effect - COSY twodimensional homonuclear J-correlated spectroscopy - 11-mer undecamer - EDTA sodium ethylenediamine tetraacetate - HPLC nigh-pressure liquid chromatography - DSS 4,4-dimethylsilapentane-1-sulfonate     

生态恢复中灌丛保育效应研究进展

灌木作为干旱半干旱地区植被的主要组成部分,对于维持生态系统稳定性和发挥生态服务功能具有重要作用。灌丛保育效应可以减轻限制性因子对目标植物生长和繁殖的不利影响,促进退化生境植物物种自然更新和植被恢复。本文综述了近20年有关灌丛保育效应研究和应用的主要成果,从微生境改善、肥岛形成、防御和抵抗作用发挥、有益微生物引入和协助繁殖体传播或保存以及种间竞争网络格局改变等方面阐述灌丛保育效应的促进机制,并从非生物环境、生物干扰、生活史阶段和生长繁殖策略等方面分析影响灌丛保育效应发挥的关键因素。从完善灌丛保育效应的理论机制和开展多因素共同作用下多植物物种相互作用关系模型构建角度,对灌丛保育效应的研究进行了展望。     

On the path to extinction: Inbreeding and admixture in a declining grey wolf population

Allee effects reduce the viability of small populations in many different ways, which act synergistically to lead populations towards extinction vortexes. The Sierra Morena wolf population, isolated in the south of the Iberian Peninsula and composed of just one or few packs for decades, represents a good example of how diverse threats act additively in very small populations. We sequenced the genome of one of the last wolves identified (and road‐killed) in Sierra Morena and that of another wolf in the Iberian Wolf Captive Breeding Program and compared them with other wolf and dog genomes from around the world (including two previously published genome sequences from northern Iberian wolves). The results showed relatively low overall genetic diversity in Iberian wolves, but diverse population histories including past introgression of dog genes. The Sierra Morena wolf had an extraordinarily high level of inbreeding and long runs of homozygosity, resulting from the long isolation. In addition, about one‐third of the genome was of dog origin. Despite the introgression of dog genes, heterozygosity remained low because of continued inbreeding after several hybridization events. The results thus illustrate the case of a small and isolated wolf population where the low population density may have favoured hybridization and introgression of dog alleles, but continued inbreeding may have resulted in large chromosomal fragments of wolf origin completely disappearing from the population, and being replaced by chromosomal fragments of dog origin. The latest population surveys suggest that this population may have gone extinct.     

阴式全子宫切除术和腹腔镜下全子宫切除术的临床对比分析

目的:比较阴式全子宫切除术与腹腔镜下全子宫切除术的临床治疗效果。方法:回顾性分析2014年6月-2015年6月我院收治的137例子宫良性病变患者的临床病历资料,按照手术方式将其分为阴式组(行阴式全子宫切除术)和腹腔镜组(行腹腔镜下全子宫切除术),比较两组患者的术中、术后临床指标及术后并发症情况。结果:阴式组手术时间及术中出血量均少于腹腔镜组,差异有统计学意义(P0.05)。阴式组肛门排气时间、下床活动时间以及住院时间均短于腹腔镜组,住院总费用低于腹腔镜组,差异有统计学意义(P0.05)。两组患者并发症发生情况差异无统计学意义(P0.05)。结论:阴式全子宫切除术较腹腔镜下全子宫切除术而言,具有手术创伤小、术后恢复快的特点,值得临床推广。     

灾难之殇：负向外生冲击的教育损失——以1976年唐山大地震为例

文章使用2005年全国1%人口抽样调查数据,运用双重差分（DiD）模型和工具变量下的局部平均处理效应（LATE-IV）方法,研究了唐山大地震对个体受教育水平和在劳动力市场中表现的影响。研究发现,唐山大地震使得个体受教育年限减少0.14-0.21年,可看作地震的短期教育损失;此外,唐山大地震使得个体受教育年限的减少进而带来的收入损失约为3.51%-4.77%,带来的人力资本损失约占2005年唐山地区生产总值的0.30%-0.41%,可看作地震的长期教育损失。     

The effect of grasses on the quality of transmitted radiation and its influence on the growth of white clover Trifolium repens

Summary Plants of white clover Trifolium repens were grown under the canopies of three grass species, Lolium perenne, Agrostis tenuis and Holcus lanatus, and under simulated canopies of black polythene and controls were exposed to unfiltered natural radiation. The canopies were adjusted so that they transmitted equal intensities of Photosynthetically Active Radiation (P.A.R.). The ratio of red to far red radiation () was unchanged under the black polythene canopies but was reduced under canopies of Lolium and Agrostis and even more so under Holcus. The effect of canopy filtered radiation on the growth of clover was greatly to reduced internode length, mean number of nodes, the number of branched nodes and the number of rooted nodes and greatly to increase petiole length. The effect of canopies of Holcus was greater than that of the other grass species both in its effect on and on the responses of the clover plant to its shade.     

Synthesis of a dimeric monosaccharide lipid A mimic and its synergistic effect on the immunostimulatory activity of lipopolysaccharide

Bacterial endotoxin lipopolysaccharide (LPS) is a potent immune stimulant, with the recognition of LPS and its active principal lipid A mediated by the Toll-like receptor 4 (TLR4)/MD-2 receptor complex. Due to the broad downstream implications of TLR4-mediated signalling, TLR4 ligands show great potential for immunotherapeutic manipulations. In this paper a dimeric monosaccharide lipid A mimic (3) has been designed as a potential TLR4 ligand. The chemical synthesis and the preliminary biological studies are described. Compound 3 shows a significant synergistic effect on LPS-induced ICAM-1 expression in human monocytic THP-1 cells.