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1.
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.
基于分形几何理论,考虑微凸体因应变硬化而造成弹塑性变形阶段硬度随变形量变化而变化,建立结合面第一、第二弹塑性变形阶段单次加载刚度分形模型。推导出在计入硬度变化的情况下,单个微凸体在弹塑性变形阶段法向接触刚度与接触面积之间的关系式,进而得出结合面在弹塑性变形阶段法向接触刚度与接触面积、接触载荷之间量纲为一的关系式,并通过仿真分析得出相关参数对结合面法向接触刚度的影响。仿真结果显示:考虑硬度变化时,结合面量纲一法向接触刚度的值与法向实际接触载荷、实际接触面积之间存在关系;结合面法向接触刚度随着分形维数D的增大而增大;分形维数一定时,结合面法向接触刚度随表面长度尺度参数G值增大而增大。  相似文献   
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为研究雷达功率组件金刚石微通道热沉的加工难题,开展了飞秒激光加工多晶金刚石微流道的工艺研究,仿真模拟了飞秒激光作用于金刚石表面的温度场分布,以及诱导去除过程,理论与实验研究了金刚石的烧蚀阈值,系统研究了激光能量、扫描速度、扫描次数、焦点位置等参量及其优化工艺参数对金刚石微槽尺寸的影响规律。结果表明:当飞秒激光功率大于0.3 W时,激光作用于金刚石的最高温度超过材料去除的气化温度,温度最高位置处于光斑中心,功率不会改变温度场的分布情形;飞秒激光加工金刚石的烧蚀阈值为1.80 J/cm2,金刚石微槽深度与激光功率、扫描次数正相关,与扫描速度负相关,与正负离焦量基本成对称分布关系,而金刚石微槽表面宽度则变化不明显;在激光功率为5 W,扫描速度为100 mm/s,扫描次数为30,离焦量为-0.5 mm的优化参数下,加工出的金刚石微槽结构形状规则,截面侧壁锥度控制在3°以内,表面无残渣、裂纹、崩边等缺陷,且内部也无裂纹等缺陷,加工一致性较高,实现了微通道的 “冷”加工,可满足雷达功率组件金刚石热沉对微通道的高质量加工要求。  相似文献   
5.
The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.  相似文献   
6.
In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.  相似文献   
7.
Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.  相似文献   
8.
研究Nb元素对Cr-Ni-Mo系合金在不同渗碳热处理工艺下组织和性能的影响。结果表明,不同渗碳工艺下Nb元素对表面硬度及表面残留奥氏体含量、非马组织影响不大。但是,通过Nb元素细化晶粒的试验钢,在较长的渗碳工艺下能使得有效硬化层深加深10%且获得更细的表层马氏体片层组织。  相似文献   
9.
对激光选区熔化(Selective laser melting,SLM)成形马氏体时效钢进行固溶及500 ℃时效不同时间的热处理,分析时效时间对其组织性能的影响。结果表明:SLM 18Ni300钢经固溶+时效处理后,其组织为马氏体、逆转变奥氏体和Ni3(Mo, Ti)析出相,随时效时间增加,析出相数量逐渐增加并聚集长大,同时逆转变奥氏体含量增大。随时效时间的增加,其硬度和强度逐渐增加达到峰值后下降,而伸长率不断增加。SLM 18Ni300钢的最佳时效工艺为500 ℃×4 h。  相似文献   
10.
分别从热力学和动力学方面研究了低碳含钛微合金钢凝固过程选分结晶对TiN夹杂物析出的影响。热力学分析表明,液相线温度以上不会有TiN析出;由于凝固过程凝固前沿Ti、N元素富集,凝固分数达到0.377时,凝固前沿固相中开始析出TiN;凝固末期,Ti和N的富集程度进一步增大,固液相中均有TiN析出。动力学分析表明,随着冷却速度的降低,凝固过程TiN夹杂物的尺寸显著增加,当冷速高于50 K/s时,TiN的理论半径为5.5 μm,当冷速低于5 K/s时,TiN的理论半径在17.5 μm以上;固相中析出的TiN为纳米级别。铸坯中TiN析出物主要尺寸为1~5 μm,且大尺寸夹杂主要在铸坯厚度方向的1/4处和中心处析出,这表明铸坯中的大尺寸夹杂物是在凝固过程中析出的。  相似文献   
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