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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   
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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   
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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   
5.
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   
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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   
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腐蚀控制是石油天然气管输过程中的一个重要问题.CO2是石油天然气管道中最常见的腐蚀介质,研究CO2腐蚀机制和防护措施具有重要科学意义和经济价值.综述了CO2的腐蚀机理,包括化学反应、电化学反应和传质过程.对现有的腐蚀理论进行了深入讨论,发现阴极反应对CO2腐蚀具有重要影响,CO2对阳极过程的影响尚未明确.在腐蚀机理的基础上,考虑管道实际工况,结合电化学实验结果阐述了各影响因素对CO2腐蚀行为的影响,并结合CO2腐蚀的影响因素讨论了常用管道防护措施的缺陷:阴极保护系统受电位影响较大,应确立新的阴极保护电位,以保证在杂散电流作用下的阴极保护效果;防护涂层容易在杂散电流干扰下发生降解,失去保护性;多数缓蚀剂对环境有害.最后,展望了未来CO2腐蚀和防护的发展方向:为进一步了解CO2腐蚀机理,需要对CO2的电化学腐蚀行为进行系统地实验测试.研究不同缓蚀剂的协同效应,使用环境友好型绿色缓蚀剂,利用新材料开发智能涂层和新型阴极保护系统,也是未来的研究方向之一.  相似文献   
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为了获取TC11钛合金拉伸性能随应变率的变化规律,对该材料开展了宽应变率范围下的单轴拉伸试验。结果表明,随着应变率从准静态增加到动态,TC11钛合金的屈服强度略有上升,而应变硬化模量下降。此外,在准静态和动态拉伸下,TC11钛合金均发生了剪切断裂,但动态断裂面上韧窝尺寸小于准静态断面上韧窝尺寸。进一步对材料在变形过程中的温升进行了分析,结果发现,高应变率下材料断裂面上更小尺寸的韧窝和材料更容易发生应变软化归因于动态加载情况下材料中产生了更高的温升。  相似文献   
9.
基于流体体积法和k-ε湍流模型对液化天然气单液滴在气流中的变形破碎情况进行模拟研究。研究不同We对液滴形态和破碎模式的影响,分析液滴形态变化过程中速度、加速度和阻力系数随时间的变化趋势,并研究不同流场下液滴变形破碎情况。结果表明,不同的We下,液滴呈现出不同的破碎模式,液滴发生剪切破碎的临界We为80左右,同一We下不同直径的液滴临界破碎时间有所不同;随着气液相对速度的We的增大,液滴的无量纲变形时间先递减后趋向于平缓;液滴变形破碎过程中,速度随着时间的延长而增加,加速度和阻力系数随着时间的延长先增后减;与普通流场相比,带挡板的流场中液滴变形破碎时间明显缩短。  相似文献   
10.
为解决基于视频流的人体关键点检测效果不佳及视频流切片后可能会发生运动模糊的问题,提出了一种改进的RetinaNet-CPN网络对人体关键点进行检测,有效解决切片后运动模糊图像的干扰并提高了人体关键点的检测准确率.视频流切片后,先用改进的RetinaNet网络检测出图片中的所有人并对每个目标框做模糊检测,对大于阈值的目标框做去模糊处理,最后用引入注意力机制的CPN网络提取关键点.将RetinaNet衡量预测框与真实框差异的IOU函数改成DIOU后,在仿真实验中目标检测AP提高了近3%;对于模糊的图片,利用匀速直线运动频谱特征估算出的模糊核与实际模糊核相差不大,对其做去模糊处理后基本能恢复出原清晰图片;同时引入注意力机制为各通道和特征层分配合理的权重,使得CPN检测AP提高近1%,AR提升0.5%.  相似文献   
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