Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)

Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC₅₀ = 0.074 ± 0.0026 μM) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research.     

Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors

Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations.     

人工锌指核酸酶突变EGFP基因的功能分析

锌指核酸酶技术在基因定点修饰中具有效率高和特异性好等特点,并成功应用于数十种生物。目前,该技术是否能应用羊上尚未报道。为了敲除转基因山羊标记基因 (EGFP),构建了一对针对EGFP外显子上的锌指核酸酶表达载体,将其电转染至转EGFP基因胎儿成纤维细胞中,研究了锌指核酸酶突变EGFP基因的效率和方式,利用基因显微注射单细胞获得获得的转基因 (EGFP) 细胞系作为锌指核酸酶的靶细胞。结果显示,通过锌指核酸酶的突变作用,转染后的细胞发绿色荧光比例下降,测序结果显示在EGFP外显子中插入1个碱基G,导致编码EGFP基因的阅读框改变,从而起到基因突变的作用。结果表明,文中构建的锌指核酸酶对EGFP基因有突变作用,可以为以后获得无标记基因供核细胞进行体细胞核移植生产克隆羊奠定基础。     

砀山酥梨不同程度缺铁叶片生长素抑制蛋白基因表达分析

以‘砀山酥梨’为材料,采用酶联免疫分析法(ELISA),测定叶片中内源IAA的含量.依据已构建的缺铁叶片SSH文库中生长素抑制蛋白(ARP)基因片段的序列信息,应用RACE技术克隆其cDNA全长,通过实时荧光定量(qRT-PCR)技术,分析ARP基因的相对表达量.结果表明:(1)ARP基因cDNA全长为707 bp,其中开放阅读框为351 bp,编码116个氨基酸,推测的蛋白质分子量为12.82 kD;该蛋白可能定位于微体,属于非分泌型、非跨膜蛋白类,并具有ARP基因家族的保守结构域.(2)在不同程度缺铁叶片中ARP基因的表达量存在差异,随着缺铁程度的增加,表达量显著升高,同时叶片中内源IAA含量逐渐降低.据此推测,ARP基因可能负反馈调节缺铁黄化叶片中IAA的水平,从而调控叶片的生长发育.     

磷石膏浸提液对豌豆种子生理及幼苗生长的影响

利用不同浓度的磷石膏浸提液处理豌豆种子,测定豌豆种子淀粉酶活性、可溶性糖、种子生命力、吲哚乙酸含量、吲哚乙酸氧化酶活性和发芽率、苗高、植株鲜重。结果表明:磷石膏浸提液处理后,豌豆种子可溶性糖含量和吲哚乙酸含量分别比对照增加6.7%～43.3%和9.4%～40.8%。豌豆幼芽中α-淀粉酶活性和吲哚乙酸氧化酶活性分别比对照高出8%～64%和15.2%～30.9%;发芽率、苗高和植株鲜重分别比对照提高10%以上。表明磷石膏能促进豌豆萌发和生长。     

新疆12种黄芩属植物叶表皮微形态结构的研究

应用光学显微镜和扫描电镜技术对新疆12种黄芩属植物叶片上的微形态特征进行观察。结果表明:该属植物叶的上表皮细胞形状及垂周壁式样有多种形式;而下表皮细胞形状均为不规则形,垂周壁式样均为深波形,不具分类学意义,但叶片两面分布的气孔器,在不同种间气孔大小、气孔密度、气孔指数、气孔外拱盖内缘等方面都存在着显著差异;其表皮角质层纹饰和表皮毛的微形态也各有不同;大多数植物叶片表面具腺点,其大小、分布及疏密程度也有不同。植物叶表皮上的这些微形态特征,可为探讨本属种间的分类学及亲缘关系提供一定的佐证。     

桂西南喀斯特山地蚬木幼龄植株的天然更新

分析了桂西南喀斯特山地蚬木幼龄植株的结构特征、空间分布格局和生长动态,以及影响其种群更新的环境因子.结果表明: 该区域的幼龄蚬木种群为稳定型,种群空间分布格局呈集群型分布;幼龄植株的地径和株高生长趋势相同,且地径随株高的增长而增加,实生苗的地径和株高生长受到种群密度的抑制;群落乔木和灌木层对蚬木幼龄植株的更新有重要影响,而草本层的影响不显著;岩石裸露率对蚬木天然更新未产生显著影响,不同坡度、坡位上蚬木幼龄植株的株高和地径的差异极显著,不同坡向植株的密度、株高和地径差异极显著.蚬木的天然更新受到物种的生物学特性,种内、种间竞争,生境异质性及人为干扰等因素的综合影响.     

A genetic adaptive pattern＊low hemoglobin concentration in the himalayan highlanders

Mean hemoglobin （Hb） concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders （Tibetans, Sherpas, and Ladakhis） was compared with lowlanders （Chinese Han, Indian Tamils） lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness （CMS）. Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.     

华西雨屏区香樟人工林土壤表层细根生物量和碳储量

2010年11月-2011年12月, 研究了华西雨屏区31年生香樟人工林土壤表层(0～30 cm)细根生物量及碳储量.结果表明: 香樟人工林土壤0～30 cm层细根总生物量(活根+死根)和碳储量的平均值分别为1592.29 kg·hm^-2和660.68 kg C·hm^-2,其中活细根贡献率分别为91.1%和91.8%.随着土壤深度的增加,香樟1～5级活细根和死细根的生物量及碳储量均显著减少;随着根序等级的升高,香樟活细根生物量及碳储量显著增加.香樟细根总生物量及碳储量均在秋季最高、冬季最低,死细根生物量及碳储量为冬季最高、夏季最低;1级根和2级根生物量及碳储量均在夏季最高、冬季最低,而3~5级根则为秋季最高、冬季最低.土壤养分和水分的空间异质性是导致细根生物量和碳储量变化的主要原因.     

预见性护理在烟花炮竹致眼外伤患儿中的应用研究

目的 探讨预见性护理对眼外伤患儿预后的影响.方法 将60例符合研究条件的眼外伤患儿随机分为对照组和观察组各30例,对照组予常规的护理措施,观察组在常规护理基础上给予预见性的护理措施,并观察两组患儿治疗的依从性、满意度及视力恢复情况.结果 观察组患儿治疗的依从性、满意度、视力恢复均优于对照组(P<0.05),差异有统计学意义.结论 对眼外伤的患儿实施预见性的护理,能提高患儿治疗的依从性,提高视力及满意度,降低致残、致盲率,从而提高患儿的生活质量.