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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   
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为提高超声相干平面波复合(CPWC)成像质量,本文提出了基于环形统计矢量(CSV)的加权算法。该算法以延时信号相位为环形统计样本,通过样本平均合矢量建立反映相位分布一致性程度的相干因子。进一步地,根据波束形成及相干因子构建数量的不同,提出了全孔径环形统计矢量(tCSV)加权算法。结果表明,相比于CPWC,CSV和tCSV的散射靶点分辨率和囊肿的对比度分别提高了至少23.67%和27.69%,CNR值降低至多39.37%。与相干因子(CF)和符号相干因子(SCF)相比,虽然CSV和tCSV算法在分辨率和对比度上最大分别比之减小约12.83%和88.31%,但抑制背景噪声和保留目标靶点回波幅值的能力较强,且CNR值比之提高了约20%,其成像质量具有更好地鲁棒性。  相似文献   
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The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity.  相似文献   
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The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.  相似文献   
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磁感应断层成像作为一种新的检测成像技术,在脑出血等疾病的临床诊断和连续检测中具有重要的应用价值。 磁感应 断层成像系统由激励线圈和检测线圈两种线圈组成,其中激励线圈只有一个,而检测线圈在以往的研究中多达十几个甚至几十 个。 由于空间限制以及线圈之间的相互干扰,如何在不损失成像准确度的情况下最大程度减少线圈的个数具有重要的研究意 义。 针对此问题,本文提出了仅使用 5 个检测线圈,分别检测两个相互垂直方向磁场信息的双向检测成像方法。 进行了含有半 径为 15 mm 的单个异质体和半径分别为 7 和 15 mm 的两个异质体的复杂头部模型仿真实验和异质体检测的仿体实验,结果均 表明双向检测成像方式不仅可以抵消检测线圈个数减少带来的影响,而且具有更高的抗噪性能和成像准确度,从而为推动 MIT 的实际应用奠定了技术基础。  相似文献   
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为了提高渐开线齿廓谐波齿轮的啮合性能,利用柔轮装配变形的包络精确算法获得了设计截面内共轭齿廓离散点,基于渐开线特征对共轭齿廓离散点拟合,得出刚轮渐开线齿廓.考虑柔轮锥度变形的影响,建立了侧隙优化控制模型,对不同径向位移下柔轮截面的变位系数进行了优化.部分柔轮截面在减小齿廓工作段高的基础上再选择合理变位系数,设计出满足空间啮合要求的渐开线齿廓谐波齿轮,并通过运动仿真分析对设计结果进行了验证.结果表明,相对于设计截面,最大径向位移增大的截面通过减小变位系数可避免干涉,最大径向位移减小的截面通过增大变位系数可获得良好啮合性能;变位系数调整量与该截面至设计截面间的距离成近似线性关系.对最大径向位移减小幅度较大而引起干涉的柔轮后端截面,需减小柔轮齿高并合理改变变位系数,才可获得良好的啮合性能.相比平面齿廓,所设计的空间齿廓能增大啮合区间和齿廓接触面积,较大幅度提升传动性能.  相似文献   
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电力企业智能招聘系统对电力企业招贤纳才,提高电力企业市场竞争力具有至关重要的作用。本文将卷积神经网络作用于智能招聘系统原始图像,采用K均值聚类算法对图像进行识别,同时对招聘系统的用户管理模块、信息检索模块、求职管理模块以及安全验证模块进行了设计与实现。将深度学习的经典算法卷积神经网络应用于智能招聘系统中使得智能招聘系统的安全性、智能性得到了很大程度的提升,对智能招聘系统的设计具有一定的实用价值。  相似文献   
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The presence of Mn(II) in water exceeding the permitted concentration limits declared by the World Health Organization (WHO) influences individuals, animals, and the ecosystem negatively. Therefore, there is a necessity for an efficient material to eliminate this potentially toxic element from wastewater. We herein focused on the adsorptive removal of Mn(II) ions from polluted aqueous media using natural Egyptian glauconite clay (G) and its nanocomposites with modified chitosan (CS). We applied modified chitosan with glutaraldehyde (GL), ethylenediaminetetraacetic acid (EDTA), sodium dodecyl sulfate (SDS), and cetyltrimethyl ammonium bromide (CTAB). The utilized nanocomposites were referred to as GL-CS/G, EDTA-GL-CS/G, SDS-CS/G, and CTAB-CS/G, respectively. The point of zero charge values of the materials were estimated. The adsorption properties of the G clay and its nanocomposites toward the removal of Mn(II) ions from polluted aqueous media as well as the adsorption mechanism were explored using a batch technique. The glauconite (G) and its nanocomposites: GL-CS/G, CTAB-CS/G, EDTA-GL-CS/G, and SDS-CS/G, exhibited maximum adsorption capacity values of 3.60, 24.0, 26.0, 27.0, and 27.9 mg g?1, respectively. The adsorption results fitted well the Langmuir isotherm and pseudo-second-order kinetic models. The estimated thermodynamic parameters: ΔH° (from 1.03 to 5.55 kJ/mol) and ΔG° (from ? 14.5 to ? 18.8 kJ/mol), indicated that Mn(II) ion adsorption process was endothermic, spontaneous, and physisorption controlled. Furthermore, the obtained adsorption results are encouraging and revealing a great potentiality for using the modified adsorbents as accessible adsorbents for Mn(II) ion removal from polluted aqueous solutions, depending on their reusability, high stability, and good adsorption capacities.

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