The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore,ADMET, Molecular Docking and Molecular Dynamics Study

Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6.     

海洋养殖柔性网衣结构水动力特性研究进展

发展深水网箱养殖是保障我国粮食及食品安全的长远战略,也是缓解近海网箱养殖环境胁迫力、拓展食物生产空间的必然选择。发展深水网箱养殖首先需要面对的突出挑战是养殖设施在外海恶劣海况下的安全性问题。网衣是深水网箱的主体结构,由于其自身具有高柔性、小尺度的特点,在波浪和水流作用下易出现大位移和大变形的极端响应。当前,网衣结构分析技术已成为我国深水网箱养殖工程技术的薄弱环节,一定程度上制约当前海上养殖网箱向大型化和深水化发展。因此,网衣水动力特性研究对于深远海网箱养殖的发展具有重要意义。本研究系统介绍了计算网衣水动力荷载的主要方法及其适用范围。同时,对网衣动态响应数值计算中的主流建模技术进行了总结和分析。最后,根据目前网衣水动力特性研究中存在的热点问题,提出了网衣流固耦合分析、生物污损分析、数字孪生技术等前沿发展方向,为网衣水动力学分析向数字化、精准化发展提供参考。     

考虑陀螺效应的动力总成悬置系统分析和优化

应用陀螺力学理论,对传统动力总成悬置系统的无阻尼动力学方程进行修正,引入陀螺矩阵,得到新的动力学方程。对新的动力总成悬置系统动力学模型进行计算分析,研究了陀螺矩阵对频域、时域响应的影响。使用遗传算法分别对修改前后的方程进行优化计算,并进行比较分析。结果表明,对于低转速发动机,曲轴转动的陀螺效应不明显,而对于高转速的发动机,陀螺效应不能忽略,应以考虑陀螺力矩的方程为基础进行设计分析。     

西藏日喀则地区马铃薯气候适宜度模型分析及其时空变化特征研究

基于日喀则地区7个国家气象站1980—2021年逐日气象数据,分析构建了高原马铃薯气温(T)、光照(S)、水分(W)、气候(C)适宜度评价模型并对其时空变化特征进行分析,结果发现：近42年日喀则地区S平均值为0.82,呈逐年弱下降趋势,T、W、C适宜度平均值分别为0.79、0.64、0.61,均呈逐年上升趋势;马铃薯全生育期的光热资源都在最合理区域(S、T≥0.7),满足了其长发育需求。W在播种～出苗期(W=0.62)、开花～成熟期(W=0.44)呈现较低水平,是制约日喀则地区马铃薯生长发育的最主要因素;T、S空间分布较均匀,且呈现自西向东、自南北向中递增趋势,W空间分布不均匀。桑珠孜区—南木林县一带地区为马铃薯综合气候适宜度高值区(C>0.6),适宜大力发展马铃薯产业。由本文建立的日尺度气候适宜度评价模型得出的年际变化和区域特征结果与实际情况比较一致,为了解气候变化下日喀则马铃薯生长发育适宜度的时空变化提供依据。     

土壤处理对西洋参根际线虫数量动态的影响及对防治茎线虫根腐病的效果

 Root rot of American ginseng (Panax quinquefolium) caused by Ditylenchus destructor is a novel disease found recently in Beijing area. The effects of three soil treatments (fumigating with chloropicrin, chloropicrin + lvfeng organic manure and nematicide fosthiazate) on the number of rhizospheric nematodes, survived plants, root yield and root rot of 3-year ginseng plant were compared. The effects were also investigated at the second year after treatment. The results indicated that the number of parasitic nematodes in rhizosphere of treated soil reached the peak value in late June to early July as the soil temperature raised in the growing season. Compared with the regular treatment, the number of plant parasitic nematodes was reduced while non-plant parasitic nematodes increased. The number of non-plant parasitic nematodes in the soil treated with chloropicrin + lvfeng organic manure was 2 times than that treated with chloropicrin only. The ratio of non-parasitic to parasitic nematodes of three treatments was higher than the control. Percent of survived plants was 94.8%-96.4% and diseased root was decreased obviously. The control efficacy was more than 89% at the first year after treatment. The survived plants and plot yield of ginseng increased significantly and the control efficacy was around 40% at the second year. The best of the three treatments was by chloropicrin + organic manure.     

黄河流域旱涝灾害的时空分布特征

本文以月降水距平为指标,根据黄河流域典型台站４０年的降水资料,对黄河流域旱涝灾害的时空分布特征进行了分析,并进行了区域划分。     

汽车麦克弗森滑柱式悬架多刚体模型的建立及仿真

以多刚体系统动力学的拉格朗日方法时汽车麦克弗森滑柱式悬架进行研究,根据结构特点建立其多刚体模型,进行了理论分析和计算机仿真。分析及算例结果表明．所建立的多刚体模型精确,采用的拉格朗日方法易行,仿真精度较高,是汽车悬架精确分析的理想方法。     

Modelling population dynamics and response to management options in the poultry red mite Dermanyssus gallinae (Acari: Dermanyssidae)

The poultry red mite Dermanyssus gallinae is a major pest and widespread ectoparasite of laying hens and other domestic and wild birds. Under optimal conditions, D. gallinae can complete its lifecycle in less than 10 days, leading to rapid proliferation of populations in poultry systems. This paper focuses on developing a theoretical model framework to describe the population dynamics of D. gallinae. This model is then used to test the efficacy and residual effect of different control options for managing D. gallinae. As well as allowing comparison between treatment options, the model also allows comparison of treatment efficacies to different D. gallinae life stages. Three different means for controlling D. gallinae populations were subjected to the model using computer simulations: mechanical cleaning (killing once at a given time all accessible population stages), sanitary clearance (starving the mite population for a given duration, e.g. between flocks) and acaricide treatment (killing a proportion of nymphs and adults during the persistence of the treatment). Simulations showed that mechanical cleaning and sanitary clearance alone could not eradicate the model D. gallinae population, although these methods did delay population establishment. In contrast, the complete eradication of the model D. gallinae population was achieved by several successive acaricide treatments in close succession, even when a relatively low treatment level was used.     

不同轮作模式下小麦禾谷孢囊线虫的发生动态和种群密度

轮作是防治小麦禾谷孢囊线虫的重要农业措施,为了明确青海省春麦区不同轮作模式对小麦禾谷孢囊线虫的控制效果,采用田间大区试验法对生产中应用的6种轮作模式进行了研究。结果表明:不同轮作模式下,小麦禾谷孢囊线虫种群密度变化差异极显著,其中小麦与马铃薯、油菜、蚕豆轮作两年或以上能有效降低小麦禾谷孢囊线虫种群密度,土壤中的孢囊量减少39.31%~84.39%,单孢虫口数量减少73.21%~95.35%,虫口密度减少83.76%~97.82%;不同作物间,小麦与马铃薯或蚕豆的轮作效果(虫口密度减少74.39%~79.37%)显著优于小麦与油菜的轮作效果(虫口密度减少67.16%)。在同一地块相同条件下,种植油菜、蚕豆、马铃薯、小麦4种作物,小麦禾谷孢囊线虫均能正常孵化,4月底土壤中的2龄幼虫(J2)量增加,5月上旬达到高峰期,5月中旬开始,土壤中的J2、孢囊量、虫口密度和单孢虫口数量均急剧下降,6月至7月份下降幅度小,趋于稳定;田间空孢囊率于5月中旬至6月中旬急剧增加,7月份趋于稳定,8月份以前,4种作物田禾谷孢囊线虫的孵化动态和种群密度变化趋势一致,8月中旬,小麦田随着新孢囊脱落到土壤中,禾谷孢囊线虫种群密度开始上升,小麦收获后土壤中的孢囊量比播种前增加28.62%,虫口密度增加41.30%;而油菜、蚕豆、马铃薯田土壤中的孢囊量比播种前减少32.27%~48.36%,虫口密度减少70.91%~81.73%,8月中旬至10月份小麦田禾谷孢囊线虫种群密度极显著高于油菜、蚕豆、马铃薯田。     

中国六省土地沙漠化敏感性时空格局与趋势分析

以我国新疆维吾尔自治区、青海省、内蒙古自治区、甘肃省、宁夏回族自治区和陕西省六省区为研究区,分析了1990年、2000年、2005年、2010年4个时期的土地沙漠化敏感性空间格局分布和时间动态变化特征,探讨变化成因并采用CA-Markov耦合模型对土地沙漠化敏感性格局变化趋势进行预测。结果表明:中国六省四期土地沙漠化敏感性格局相似,各级敏感区按分布面积大小排序为:轻度敏感区域 > 中度敏感区域 > 高度敏感区域 > 不敏感区域 > 极敏感区域。极敏感区域主要分布在土壤质地为流动沙地的沙漠区域,不敏感区域主要分布在高山、湖泊附近;人口增多、人为活动强度增加的区域敏感性程度增高;建立治沙工程的区域敏感性降低。对2020年土地沙漠化敏感性格局预测结果显示,相比2010年,极敏感区域在原有的基础上向外围扩张了7 120.04 km²,增幅为4.63%。本文通过分析中国六省土地沙漠化敏感性时空格局与趋势,为中国土地沙漠化防治分区策略制定和划分沙漠化扩展屏障区提供科学依据。