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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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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   
4.
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   
5.
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   
6.
社区检测(community detection)任务一直是数据挖掘领域的一个研究热点,近年来,深度学习和图链接数据呈现出多样化和复杂化的发展趋势,层次(Hierarchical)社区检测逐渐成为研究的焦点.层次社区检测任务的目标是,在将同质图中相似的节点聚集到社区中的同时,学习社区之间的层次结构关系,以更好的理解图数据结构.社区间层次关系的引入给社区检测算法带来了更复杂的建模挑战.针对该任务,已经有一些有效的启发式的方法被提出,但是受限于社区分布形态的简单假设和离散的优化学习方式,它们无法描述更复杂的图链路数据,也无法和其它有效的连续优化算法组合获得更好的结果.为了解决这个问题,本文首次尝试建模复杂的重叠式(overlapping)层次社区结构,提出简洁的节点嵌入和社区检测双任务优化模型,通过梯度更新的方式来灵活地探索节点和重叠式层次社区的隶属关系.在学习过程中,我们可以分别获得节点和社区的嵌入表示,以应用于丰富的下游任务.  相似文献   
7.
针对文本分类任务中标注数量少的问题,提出了一种基于词共现与图卷积相结合的半监督文本分类方法。模型使用词共现方法统计语料库中单词的词共现信息,过滤词共现信息建立一个包含单词节点和文档节点的大型图结构的文本图,将文本图中邻接矩阵和关于节点的特征矩阵输入到结合注意力机制的图卷积神经网络中实现了对文本的分类。实验结果表明,与目前多种文本分类算法相比,该方法在经典数据集20NG、Ohsumed和MR上均取得了更好的效果。  相似文献   
8.
刘璐  庞杰 《粮油食品科技》2021,29(2):129-134
凝胶是一种性质介于固体和液体之间的特殊分散体系,魔芋葡甘聚糖(KGM)凝胶稳定性差、强度低,物理共混能方便、快捷地改善其凝胶性质。主要综述KGM复合凝胶的网络结构变化,并介绍不同复合凝胶在食品、医药、材料工程等领域的应用。分析表明,KGM复合凝胶网络能通过氢键、席夫碱反应、形成多重网络结构和填充的方式改善其凝胶特性。  相似文献   
9.
为延长带鱼鱼丸保质期,以带鱼鱼丸为原料,分别在250、300、350 MPa压力下处理5 min,以冷藏期间鱼丸菌落总数、总挥发性盐基氮(total volatile base nitrogen,TVB-N)含量、pH值为指标,并结合感官评价、色值、凝胶强度及质地剖面分析,探究超高压处理对冷藏带鱼鱼丸保鲜效果的影响。结果表明:超高压处理可显著降低贮藏期内鱼丸菌落总数、TVB-N含量,延缓pH值的增加;超高压处理对鱼丸色泽无负面影响,同时能较好保持鱼丸冷藏期间感官特性、色值、凝胶强度、硬度及弹性。对照组和超高压组鱼丸的菌落总数分别在冷藏的第21天和第56天超出105 CFU/g;随冷藏时间延长,对照组鱼丸感官评分明显下降,贮藏14 d后产生异味,第21天时感官已不可接受;超高压组鱼丸感官评分在贮藏35 d内均无明显变化,其中300 MPa处理5 min组在冷藏49 d后感官评分仍在5 分以上,但第56天时感官不可接受。综合考虑,对带鱼鱼丸进行300 MPa超高压处理5 min,可延长其冷藏货架期约35 d。该结果可以为超高压技术在鱼糜制品保鲜中的应用提供依据。  相似文献   
10.
以玉米淀粉为原料,用流变分析、食品物性分析、差示扫描量热分析、低场核磁共振成像分析等研究冷藏过程中不同含量(相对玉米淀粉干基质量的1%、3%、5%和7%)皂荚糖胶对玉米淀粉老化特性的影响。动态流变时间扫描结果表明:随着老化时间的延长,玉米淀粉的弹性模量增加,皂荚糖胶的加入使复配体系弹性模量的变化率减小,一定程度上抑制玉米淀粉的短期老化;凝胶强度实验表明:随着冷藏时间的延长,玉米淀粉凝胶体系的硬度值增加,皂荚糖胶的加入使玉米淀粉形成质地更柔软的凝胶,硬度值明显降低;差示扫描量热测定结果表明:随着皂荚糖胶含量的增加,复配体系的老化率逐渐减小。用低场核磁水分运动性实验方法,通过5%皂荚糖胶加入前后淀粉凝胶中自由水、结合水和不易流动水含量的对比证实该胶对凝胶的水分分布有较大的影响;该研究能进一步丰富植物胶体对淀粉老化性能影响的理论。  相似文献   
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