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1.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease. 相似文献
2.
Sobha Karuthedom George Lucia Laukov Ren Weiss Vladislav Semak Birgit Fendl Victor U. Weiss Stephanie Steinberger Günter Allmaier Carla Tripisciano Viktoria Weber 《International journal of molecular sciences》2021,22(8)
Growing interest in extracellular vesicles (EVs) has prompted the advancements of protocols for improved EV characterization. As a high-throughput, multi-parameter, and single particle technique, flow cytometry is widely used for EV characterization. The comparison of data on EV concentration, however, is hindered by the lack of standardization between different protocols and instruments. Here, we quantified EV counts of platelet-derived EVs, using two flow cytometers (Gallios and CytoFLEX LX) and nanoparticle tracking analysis (NTA). Phosphatidylserine-exposing EVs were identified by labelling with lactadherin (LA). Calibration with silica-based fluorescent beads showed detection limits of 300 nm and 150 nm for Gallios and CytoFLEX LX, respectively. Accordingly, CytoFLEX LX yielded 40-fold higher EV counts and 13-fold higher counts of LA+CD41+ EVs compared to Gallios. NTA in fluorescence mode (F-NTA) demonstrated that only 9.5% of all vesicles detected in scatter mode exposed phosphatidylserine, resulting in good agreement of LA+ EVs for CytoFLEX LX and F-NTA. Since certain functional characteristics, such as the exposure of pro-coagulant phosphatidylserine, are not equally displayed across the entire EV size range, our study highlights the necessity of indicating the size range of EVs detected with a given approach along with the EV concentration to support the comparability between different studies. 相似文献
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This work describes the procedure used to define the measurement uncertainties of horizontal two-phase air-water flow experiments conducted to determine influences due to pipe diameter on pressure gradient on such flows. These experiments were performed with 4 different pipe diameters, always using the same test section length, therefore varying the length-to-diameter (L/D) ratio. Several parameters were measured, such as volumetric/mass flow rate, pressures, temperatures and pressure drop; other parameters were calculated, such as the superficial velocities of each fluid, as well as their corresponding properties. The main parameters studied were the flow patterns for different velocity configurations and the two-phase pressure drop to be used for model improvement, thus the importance of uncertainties analysis. The sources of uncertainty were defined, detailed, systematically studied and quantified. Also, the reproducibility capacity of the experimental setups were analysed through the uncertainty analysis and proving them to be able for future similar studies. The flow maps with their uncertainties could help understand the thresholds for each defined flow pattern region, and the plots of two-phase pressure drop variation with diameter confirmed the homogeneous model as a possible approach to calculate pressure drop if the uncertainties are considered. 相似文献
5.
建立了高效液相色谱-高分辨质谱法分析鉴定拉萨大黄化学成分。选用Agilent Zorbax SB-C18柱(150 mm×4.6 mm×5 μm),以乙腈和水为流动相进行梯度洗脱,流速0.5 mL/min;采用电喷雾离子源,在正、负离子模式下对拉萨大黄提取物进行一级和多级全扫描质谱分析。综合分析化合物的色谱和质谱行为,并结合对照品、文献和数据库等相关数据鉴定化合物。在负离子模式下,鉴定出63种化合物;正离子模式下,鉴定出54种化合物。所检测到的化合物包括22种鞣质类、28种茋类、6种黄酮类、3种苯丙酸类、2种苯丁酮类和2种有机酸类,其中有53种化合物为在该药材中首次发现,且未发现蒽醌类成分。该方法快速、灵敏,不仅提高了拉萨大黄复杂基质中微量化合物的鉴定效率,同时实现了对拉萨大黄提取物中不同类型化合物的分析鉴别,为进一步阐明拉萨大黄的药效物质基础及质控标准提供了科学依据。 相似文献
6.
拉臂机构作为拉臂式垃圾车的关键部位,直接决定整车的可靠运行与人员操作体验,文中在分析拉臂机构的力学特性基础上,计算出在装卸工况下的载荷,利用有限元分析软件,对拉臂机构关键部位进行静态有限元分析与模态分析,分析结果表明拉臂机构符合动态性能要求,但其工作时强度不足,需对此进行结构优化。通过对拉臂机构进行局部修改,采取必要的辅助措施,使其达到符合静态性能要求的目的。在满足拉臂机构静动态性能要求上,装箱工况最大应力降低了23.3%,卸箱工况最大应力降低了24.9%,较好地达到了提高拉臂机构安全性能的目的。 相似文献
7.
针对某一体式夹紧器工作原理,以及根据打开周期、有无气缓冲、气缓冲形式、负载因素不同,定义不同工况,制定一体式夹紧器下盖冲击的测试方案。可调节工装设计为模拟不同负载工况提供了便捷条件;搭建测试和信号采集平台,获得夹紧器在不同工况条件下冲击力和动态性能——爬行、反弹、撞击;确定下盖冲击力主要影响因素——打开周期、负载、气缓冲效果,并对其敏感性进行量化分析。通过工况1,4的数据记录对比得出,现有的缓冲结构可以减少160%~290%的下盖冲击力。实验结论为V63夹紧器设计和气缓冲设计提供依据,为V63夹紧器标准工况应用条件提供量化分析数据支撑。 相似文献
8.
针对激光聚变冲击波速度测量的需求,设计了一种集被动式扫描高温计和主动式冲击波速度测量于一体的复合冲击波速度测量系统。通过采用多种耐辐射光学玻璃材料,实现了共用光路的400~700 nm耐辐射消色差设计;通过采用自动控制干涉仪简化了系统操作;主动测速系统通过切换不同焦距的中继成像镜头,实现了不同放大倍率的切换。系统的物方视场为φ2.0 mm,主动式测速系统的放大倍率为10×,20×,30×,静态实验干涉条纹平直,调制度达到0.69以上,物方分辨率达到4.72μm。该系统在激光聚变装置上能够实现冲击波速度的动态测量。 相似文献
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