Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC₅₀ = 12.25 µM) with comparable activity with the positive control remdesivir (IC₅₀ = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC₅₀ = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC₅₀ = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested M^pro to be its primary viral protein target. More potent anti-SARS CoV-2 M^pro inhibitors can be developed according to our findings presented in the present investigation.     

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 M^pro with IC₅₀ value of 0.47 μM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 M^pro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related M^pro inhibitors.     

东北典型农区土地利用变化的生态效应研究——以公主岭市为例

在人为活动占优势的景观内,不同土地利用方式和强度产生的生态效应是不同的,并且可以直观地反映在生态系统的结构和组成上。因此,本文利用Landsat TM和MSS遥感数据,以具有相对完整的自然生态过程的小流域作为评价单元,借助GIS空间分析和地统计分析功能,从景观生态学角度提出了景观生态指数来反映LUCC变化所带来的生态效应。研究发现,公主岭市1975—1986年间由于土地利用/土地覆被变化造成的生态风险不断增加,随后逐渐减小,到2000年局部地区又有所回升,这种变化与该地区土地利用类型的变化,特别是耕地、林地和草地的变化趋势呈高度相关,说明该地区土地利用/土地覆被变化对生物多样性及生态安全具有重要影响。     

农牧交错带不同封育时间对植物特征值及多样性的影响

为研究我国北方农牧交错带不同封育时间对干旱、半干旱草原植物特征值及多样性的影响,同时探索农牧交错带草原封育周期,本研究选取位于我国农牧交错带的宁夏盐池人工封育草原为研究对象,采用样方调查法,于每年7-8月份(植物生长季节)对封育区植被生长状况进行调查,调查内容包括:植物名称、植物种数、株数、盖度、高度、地上生物量(鲜重)等。运用生态学、地统计学原理,结合Biodiversity Pro、Microcal Origin等生态学统计软件对外业数据进行处理、分析,结果表明:封育2-3年后植物群落优势种优势地位得到巩固,而一些伴生种则在竞争中消失;封育区植物特征值在封育2-3年后达到最大,如地上生物量(鲜重)在封育3年达到最大值,为6907.75kg/hm2,此后呈下降趋势;封育区主要植物重要值及植物物种多样性均在封育2-3年后出现最大值,此后也不同程度地呈下降趋势。     

带状砂沟模式下土壤入渗过程模拟研究

[目的] 探究土壤质地类型和砂沟结构参数对土壤入渗过程的影响,为砂沟集雨工程设计、运行和管理提供科学依据。 [方法] 基于HYDRUS-2D/3D软件,建立带状砂沟模式下土壤水分运动数学模型,利用室内试验验证模拟带状砂沟模式下土壤入渗过程的可靠性。在此基础上,模拟分析不同影响因素下带状砂沟模式下土壤累积入渗量和湿润锋运移变化过程。 [结果] 模拟结果与实测数据无显著性差异且一致性良好,表明所建模型及其求解方法能够有效获取带状砂沟模式下不同时刻土壤累积入渗量和湿润锋运移距离数值;均质土壤填充带状砂沟存在明显的增渗效应。原土质地、砂沟距、砂沟宽和砂沟深均对增渗率有较大影响,增渗率随原土饱和导水率和砂沟距的增大而减小,随砂沟宽和砂沟深的增大而增大;土壤湿润锋轮廓呈下低上高的U形,随时间的延长,U形侧边湿润锋逐渐靠近砂沟交汇面,顶部平台逐渐消失;原土质地对湿润锋运移距离影响较大,湿润体随原土饱和导水率的增大而增大;砂沟深对湿润锋的形态和分布影响较大,随砂沟深度的增大,U字体型垂向拉伸,左侧湿润深度显著增大,右侧湿润深度变化微弱;砂土质地、砂沟距和砂沟宽对湿润锋运移距离影响较小。[结论] 带状砂沟土体构型能够显著提高土壤入渗能力,土壤质地类型和砂沟结构参数对土壤累积入渗量和湿润锋运移距离均有不同程度影响。     

First Identification of 12β-Deoxygonyautoxin 5 (12α-Gonyautoxinol 5) in the Cyanobacterium Dolichospermum circinale (TA04) and 12β-Deoxysaxitoxin (12α-Saxitoxinol) in D. circinale (TA04) and the Dinoflagellate Alexandrium pacificum (Group IV) (120518KureAC)

Saxitoxin and its analogues, paralytic shellfish toxins (PSTs), are potent and specific voltage-gated sodium channel blockers. These toxins are produced by some species of freshwater cyanobacteria and marine dinoflagellates. We previously identified several biosynthetic intermediates of PSTs, as well as new analogues, from such organisms and proposed the biosynthetic and metabolic pathways of PSTs. In this study, 12β-deoxygonyautoxin 5 (12α-gonyautoxinol 5 = gonyautoxin 5-12(R)-ol) was identified in the freshwater cyanobacterium, Dolichospermum circinale (TA04), and 12β-deoxysaxitoxin (12α-saxitoxinol = saxitoxin-12(R)-ol) was identified in the same cyanobacterium and in the marine dinoflagellate Alexandrium pacificum (Group IV) (120518KureAC) for the first time from natural sources. The authentic standards of these compounds and 12α-deoxygonyautoxin 5 (12β-gonyautoxinol 5 = gonyautoxin 5-12(S)-ol) were prepared by chemical derivatization from the major PSTs, C1/C2, produced in D. circinale (TA04). These standards were used to identify the deoxy analogues by comparing the retention times and MS/MS spectra using high-resolution LC-MS/MS. Biosynthetic or metabolic pathways for these analogues have also been proposed based on their structures. The identification of these compounds supports the α-oriented stereoselective oxidation at C12 in the biosynthetic pathway towards PSTs.     

臭氧结合氮气气调储藏对稻谷品质的影响

为探讨臭氧(O3)预处理结合氮气(N2)气调对稻谷储藏品质的影响,以4种不同方式(O3/N2、O3/Air、对照/N2、对照/Air)对稻谷进行处理,并在14℃和相对湿度75％的储藏条件下,对储藏期间稻谷微生物指标、理化特性和感官评分等进行研究.结果表明,臭氧预处理显著降低了稻谷中细菌、霉菌和酵母菌菌落数(P＜0.05...     

Effects of pirenzepine on expression of MMP-2 and TIMP-2 in stroma of sclera in chick myopic eyes

AIM:To observe the effect of intravitreal injection of pirenzepine on form-deprivation myopia in chicks. METHODS:Forty-one day old chicks were randomly divided into 4 groups:normal control group, form deprivation group, vehicle control group and pirenzepine injection group. The right eyes of all chicks were used as experimental eyes. The deprived eyes in vehicle control group and pirenzepine injection group received daily intravitreal injection of vehicle control solution(0.01 mol/L PBS) and pirenzepine(1%in PBS), respectively. Optical examinations such as refraction, axial length and equatorial diameter were made at the end of the 5th day. The mRNA and protein levels of matrix metalloproteinase 2(MMP-2) and tissue inhibitor of metalloproteinase-2(TIMP-2), and the activity of MMP-2 were detected by RT-PCR, Western blotting and zymography analysis,respectively. RESULTS:Refraction, axial length and equatorial diameter of the eyes in pirenzepine injection group were significantly lower than those in form deprivation group and vehicle control group(P<0.05), but those were higher(P<0.05) and the eyes were relatively myopic as compared with normal control group. The mRNA expression, protein le vels and activity of MMP-2 in pirenzepine group were significantly higher than those in normal control group(P<0.01), and were significantly lower than those in form deprivation group and vehicle control group(P<0.01, P<0.01). The mRNA and protein levels of TIMP-2 in pirenzepine group were significantly lower than those in normal control group(P<0.01), and was significantly higher than those in form deprivation group and vehicle control group(P<0.01, P<0.01). CONCLUSION:Intravitreal injection of pirenzepine may partly prevent form-deprivation myopia by modulating the expression of MMP-2 and TIMP-2 in the fibrous layer of sclera.     

Interaction of NR2D subunit of NMDA receptor with MOCA

AIM: To identify the potential proteins interacting with NR2D subunit of NMDA receptor by yeast two-hybrid screening and to investigate the role of NR2D in excitotoxicity of the retina.METHODS: The Clontech GAL4 yeast two-hybrid system was used to screen the mouse brain cDNA library, and the bait plasmid containing C-terminus of NR2D was constructed. Physical interaction between 2 proteins was verified by co-immunoprecipitation assay. The subcellular localization of 2 proteins in the mouse retina was observed under microscope with immunofluorescence.RESULTS: Modifier of cell adhesion (MOCA) was identified as a new protein interacting with NR2D. MOCA and NR2D were co-expressed in the mouse retina. CONCLUSION: MOCA specifically interacts with NR2D, which provides the experimental basis for identifying the role of glutamate excitotoxicity in the retina neurodegeneration.     

茄子新品种青茄2号的选育

青茄2号是以H2005-8-4-3为母本,以X2005-1-7-9为父本选育的茄子一代杂种。中晚熟,始花节位为第7~8节,生育期171d(天)左右;果实卵圆形,纵径17.6cm,横径11.3cm,果皮绿色,果面光滑,单果质量为0.49kg,平均每667m2产量可达5000kg。田间对黄萎病、青枯病、绵疫病和病毒病的抗性与对照新乡糙青茄相当。适于河南省平顶山、漯河、郑州、驻马店、信阳以及各地喜好绿茄地区栽培。