乌牛早茶园蜡蝉类与其8种天敌空间关系的聚块样方方差分析

为了分析在不同聚块大小条件下,天敌对蜡蝉类Fulgoroidea空间上跟随关系的密切程度、聚集原因和聚集范围,为评价蜡蝉类的天敌优势种和确定样方大小提供科学依据,运用聚块样方方差分析法、灰色关联度法、空间聚集强度指数法、种群聚集均数法和ρ指数法对安徽省合肥市乌牛早茶园不同大小聚块条件下的蜡蝉类及其8种天敌进行分析。蜡蝉类与其8种天敌均方差峰值时聚块样方数的关联度分析结果表明:与蜡蝉类空间上跟随关系密切的前三位天敌依次是茶色新圆蛛Neoscona theisi(0.8010)、草间小黑蛛Erigonidium graminicolum(0.7617)和三突花蟹蛛Misumenops tricuspidatus(0.7613)。在聚块内基本样方数K为1、2、4、8时,随着聚块内基本样方数的增多,聚集分布格局时的扩散系数C不断增大,均匀和随机格局时扩散系数不断减小。聚块内基本样方数K为1、2、4、8时其相互之间的蜡蝉类及其天敌的空间分布聚集程度差异均不显著。蜡蝉类及其天敌的种群聚集均数λ多数情况均大于2,其聚集是该虫本身原因引起的,并且λ的绝对值随着聚块内基本样方数的增加而不断增大。用蜡蝉类不同大小聚块的ρ指数判断个体群聚集时的最小范围是聚块中有4个基本样方,即本文的16 m~2。为该虫抽样时确定样方大小提供了科学依据。聚块样方方差分析法是分析害虫与天敌空间关系的一种简便而又实用的方法。     

Design,synthesis, and biological evaluation of 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif inhibitors

Viral infectivity factor (Vif) is one of the accessory protein of human immunodeficiency virus type I (HIV-1) that inhibits host defense factor, APOBEC3G (A3G), mediated viral cDNA hypermutations. Previous work developed a novel Vif inhibitor 2-amino-N-(2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide (1) with strong antiviral activity. Through optimizations on the two side branches, a series of compound 1 derivatives (2–18) were designed, synthesized and tested in vitro for their antiviral activities. The biological results showed that compound 5 and 16 inhibited the virus replication efficiently with EC₅₀ values of 9.81 and 4.62 μM. Meanwhile, low cytotoxicities on H9 cells were observed for the generated compounds by the MTT assay. The structure–activity relationship of compound 1 was preliminarily clarified, which gave rise to the development of more potent Vif inhibitors.     

Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors

The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MTT assay, respectively. The results showed that neolamellarin A 1 (IC₅₀ = 10.8 ± 1.0 μM) and derivative 2b (IC₅₀ = 11.9 ± 3.6 μM) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.     

Design,synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC₅₀?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.     

SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel,CNS penetrant tricyclic M4 PAMs

This letter describes progress towards an M₄ PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M₄ PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats.     

Recent advances in natural antifungal flavonoids and their derivatives

The resistance of pathogenic fungi and failure of drug therapy increased dramatically. Numerous studies have reported the individual or synergistic antifungal potency of natural and synthesized flavonoids, especially against drug-resistant fungi. This brief review summarizes the structure and individual or synergistic antifungal activity of natural and synthesized flavonoids (literatures mainly cover the past 10 years 2009–2019), with a special focus on the antifungal spectra, structure–activity relationship and mechanisms of actions. These may contribute to a better understanding of flavonoids as multi-target agents in the treatment of mycoses and provide some ideas on the development of novel flavonoids-based antifungals.     

Structure-activity relationships of trichothecenes against COLO201 cells and Cochliobolus miyabeanus: The role of 12-epoxide and macrocyclic moieties

The novel trichothecene 12-deoxytrichodermin (3) was isolated from the fungus Trichoderma sp. 1212-03, and included with other known natural trichothecenes in a structure-activity relationship investigation against a human colon cancer cell line (COLO201) and filamentous fungus Cochliobolus miyabeanus. This revealed that the 12-epoxide functionality is critical for the cytotoxicity of simple trichothecenes trichodermin (4) and deoxynivalenol (2), while not critical for the cytotoxicity of roridin J (6) and epiisororidin E (8). In contrast, 12-epoxide is essential for the antifungal activity.     

南昌市城镇空间扩展与景观生态风险的耦合关系

为探究城镇用地空间扩展对景观生态风险的影响,以南昌市为例,运用遥感、GIS及数理统计的方法,借助城镇扩展强度指数研究了南昌市2000—2017年城镇空间扩展的时空变化特征,构建了景观生态风险指数,以3 km×3 km的单元网格进行系统采样,探究城镇扩展下南昌市景观格局的动态变化和景观生态风险,最后基于地理加权回归(GWR)模型,定量分析2000—2017年南昌市城镇空间扩展与景观生态风险之间的耦合关系。结果表明:(1)2000—2017年,南昌市城镇用地增加了247.56 km~2,年均扩展速率达17.75 km~2,其中2000—2005年扩展最快,呈现出剧烈扩展的态势,扩展强度达到0.55。城镇扩展主要沿正北和西北方向扩展,分布在青山湖区、南昌县、新建区等,总体上呈快速扩展趋势;(2)南昌市景观格局以耕地为主,建设用地快速扩张,耕地、林地、草地面积持续减少,土地利用的景观格局指数反映此期间人类活动的干扰程度加剧,景观斑块数量增加,整体破碎度提高。借助地统计分析方法,计算得到南昌市景观生态风险由2000年的0.1354上升至2017年的0.1420,景观生态风险呈逐渐升高的趋势;(3)2000—2017年,城镇用地面积与景观生态风险、城镇空间扩展强度指数和景观生态险变化值之间,都呈现负相关影响,后者相关性在减弱。回归系数的空间分布上,由中部向外逐渐升高,低值位于城镇扩展较快的南昌市区,城镇的快速扩展使城镇用面积大幅增加,景观破碎度、损失度降低,景观生态风险随之降低;高值出现在进贤县、安义县等经济发展缓慢的地区,城镇用地扩展幅度小,扩展边界斑块破碎度大,分离度上升,景观生态风险增加。研究结果为促进城市建设与生态环境保护的相互协调,正确评价人类活动对城市生态系统的影响,以及南昌市的可持续发展和科学管理提供借鉴。