一种大型设备多自由度自动对接方法

提出一种新颖的大型设备多自由度自动对接方法,该方法采用基于“三叉形”分划板的高精度CCD自准直仪来测量垂直与水平方向的二维小角度,采用单线阵CCD器件来测量轴向滚动、垂直、水平方向三自由度偏差,在嵌入式计算机的控制下通过测量这五个自由度偏差来调整设备姿态,直至对接完成。建立了五个自由度偏差的数据模型,并设计出包括CCD自准直仪、CCD接收处理装置、嵌入式计算机和执行机构的自动对接系统。该方法速度快、测量精度高,能实现大型设备的精确定位和自动对接,其角度测量精度为0.5″。     

AUV回收对接前景视场立体匹配算法研究

针对研发的自主水下机器人(Autonomous Underwater Vehicle,AUV)回收对接中前景视场三维重建的需求以及提高导航定位精度与对接成功率,提出了一种改进的CENSUS变换与最小生成树相结合的立体匹配算法.该立体匹配算法针对水下图像弱纹理及重复纹理区域多的问题,利用图像的梯度强度及颜色信息融合作为C...     

In Silico Structural Modeling and Analysis of Interactions of Tremellomycetes Cytochrome P450 Monooxygenases CYP51s with Substrates and Azoles

Cytochrome P450 monooxygenase CYP51 (sterol 14α-demethylase) is a well-known target of the azole drug fluconazole for treating cryptococcosis, a life-threatening fungal infection in immune-compromised patients in poor countries. Studies indicate that mutations in CYP51 confer fluconazole resistance on cryptococcal species. Despite the importance of CYP51 in these species, few studies on the structural analysis of CYP51 and its interactions with different azole drugs have been reported. We therefore performed in silico structural analysis of 11 CYP51s from cryptococcal species and other Tremellomycetes. Interactions of 11 CYP51s with nine ligands (three substrates and six azoles) performed by Rosetta docking using 10,000 combinations for each of the CYP51-ligand complex (11 CYP51s × 9 ligands = 99 complexes) and hierarchical agglomerative clustering were used for selecting the complexes. A web application for visualization of CYP51s’ interactions with ligands was developed (http://bioshell.pl/azoledocking/). The study results indicated that Tremellomycetes CYP51s have a high preference for itraconazole, corroborating the in vitro effectiveness of itraconazole compared to fluconazole. Amino acids interacting with different ligands were found to be conserved across CYP51s, indicating that the procedure employed in this study is accurate and can be automated for studying P450-ligand interactions to cater for the growing number of P450s.     

Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus

Quercetin, the primary dietary flavonol, exerts a strong inhibitory effect on calcineurin (CN), a unique Ca²⁺/calmodulin-dependent serine/threonine protein phosphatase. Using fluorescence spectroscopy (FS) we showed quercetin strongly bound to calcineurin catalytic subunit (CNA) with a ratio of 1:1; we also showed that calcineurin regulatory subunit (CNB) weakened this binding. In addition, the secondary structure of CNA was much tighter in the presence of quercetin. An FS study with CNA truncated mutant CNAa showed that the binding area for quercetin was reduced to the catalytic domain of CNA. Furthermore, fluorescence resonance energy transfer (FRET) results and molecular docking indicated three potential binding sites for quercetin, which were located at a region between the active centre of CNA and the CNB binding domain, a similar binding area to that of cyclosporin A and tacrolimus. Interestingly, this region was also important for CN substrate recognition.     

红曲桔霉素致毒机理的网络药理学分析

为探讨红曲中桔霉素导致毒性的内在机理,通过搜索Swiss Target Prediction、Similarity ensemble approach、Comparative Toxicogenomics Database和GeneCards数据库,利用Metascape、Kobas 3.0、Cytoscape 3.7.2和AutoDock软件,开展了网络药理学分析。结果显示,通过筛选去重获得桔霉素与“liver toxicity”和“kidney toxicity”相关的潜在靶点110个,GO 富集分析功能条目496条,其中涉及分子功能、生物过程和细胞组成的条目分别为97、354和45条。KEGG信号通路富集靶点数和显著性均较高的是肿瘤MicroRNA通路、肿瘤通路、乙型肝炎等通路。桔霉素可能通过TP53、CASP3、MAPK3和ALB等关键靶点导致肝肾毒性。分子对接实验证明,桔霉素与靶点可以结合,揭示了桔霉素导致肝肾毒性的潜在作用靶点和信号通路,为进一步研究桔霉素致毒机理和健康防护提供理论参考。     

油茶籽乙醇提取物代谢物组成及其抗炎活性

为探究油茶籽油抗炎机制,采用超高效液相色谱-串联质谱技术检测分析了15?个批次油茶籽乙醇提取物中所有小分子代谢物,并通过“蓝精灵”实验评估油茶籽乙醇提取物对果蝇肠炎的抑制活性,将油茶籽乙醇提取物中小分子代谢物与抗炎活性进行相关性分析并与脂氧合酶进行分子对接,筛选鉴定其关键代谢产物,最后通过“蓝精灵”实验进行验证。结果表明：油茶籽乙醇提取物具有良好的果蝇肠炎抑制活性,抑制率为15.06%～61.71%,其代谢物主要包括多酚类、氨基酸类、有机酸类、核苷酸类、糖类、脂类等,发现7?种多酚类化合物以前未在油茶籽中报道过。初步筛选出具有良好抗肠炎活性的代谢物为：鸦胆子素B、丹参新酮、8-香叶草氧基补骨脂素、异芒果苷、5,7,4’-三羟基-6-异戊烯基异黄酮、山柰苷和山柰酚-3-O-芸香糖苷。5,7,4’-三羟基-6-异戊烯基异黄酮是首次被证实具有抗炎活性,0.1 mg/mL给药量时,果蝇肠炎抑制率为64%,远大于阳性对照柳氮磺胺吡啶（27.99%）。本研究为进一步探究油茶籽提取物内外抗肠炎活性及其机制奠定了基础。     

Insights into the Interaction of LVV-Hemorphin-7 with Angiotensin II Type 1 Receptor

Hemorphins are known for their role in the control of blood pressure. Recently, we revealed the positive modulation of the angiotensin II (AngII) type 1 receptor (AT1R) by LVV-hemorphin-7 (LVV-H7) in human embryonic kidney (HEK293) cells. Here, we examined the molecular binding behavior of LVV-H7 on AT1R and its effect on AngII binding using a nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) assay in HEK293FT cells, as well as molecular docking and molecular dynamics (MD) studies. Saturation and real-time kinetics supported the positive effect of LVV-H7 on the binding of AngII. While the competitive antagonist olmesartan competed with AngII binding, LVV-H7 slightly, but significantly, decreased AngII’s k_D by 2.6 fold with no effect on its B_max. Molecular docking and MD simulations indicated that the binding of LVV-H7 in the intracellular region of AT1R allosterically potentiates AngII binding. LVV-H7 targets residues on intracellular loops 2 and 3 of AT1R, which are known binding sites of allosteric modulators in other GPCRs. Our data demonstrate the allosteric effect of LVV-H7 on AngII binding, which is consistent with the positive modulation of AT1R activity and signaling previously reported. This further supports the pharmacological targeting of AT1R by hemorphins, with implications in vascular and renal physiology.     

基于“234”现代学徒制人才培养模式的研究与实践

2015年,教育部下发了关于现代学徒制项试点建设要求,经过5年多实践,探索出 “234”现代学徒制人才培养模式,即培养主体“两融合”(学院与企业两个主体深度融合)；培养方式“三对接”(课程内容与岗位标准相对接,教学过程与生产过程相对接,学历证书与职业资格证书相对接)；培养过程“四阶段”(企业认知、基础学习；岗位训练、工学结合；学徒实践、工学交替；顶岗实习、考核入职)。通过培养模式创新,学生学习主动性明显增强,人才培养质量显著提高。