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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
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针对直流配电网母线电压稳定性问题,设计了一种变增益线性扩张状态观测器(variable gain linear extended state observer,VGLESO),有效地解决了传统高增益线性扩张状态观测器(linear extended state observer extended state observer,LESO)在运行初始阶段输出存在峰值的问题。在此基础上进一步提出了一种变增益滑模自抗扰控制策略,将其应用到直流配电网AC-DC双向变流器控制系统中的电压外环。变增益滑模自抗扰控制策略在不需要增加额外电流传感器的情况下,就能够实现对系统总扰动的快速跟踪和补偿,有效地抑制了母线电压波动,提高了系统的动态响应。从理论上证明了VGLESO和变增益滑模自抗扰控制策略的稳定性。最后通过MATLAB/Simulink验证了该控制策略的可行性与正确性。 相似文献
4.
Eugene Metakovsky Laura Pascual Patrizia Vaccino Viktor Melnik Marta Rodriguez-Quijano Yulia Popovych Sabina Chebotar William John Rogers 《International journal of molecular sciences》2021,22(4)
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.
Md Saifur Rahman Md Badrul Alam Young Kyun Kim Mst Hur Madina Ismail Fliss Sang Han Lee Jin Cheol Yoo 《International journal of molecular sciences》2021,22(10)
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
6.
Kyunghee Kim Jisue Kim Hyoungseob Kim Gun Yong Sung 《International journal of molecular sciences》2021,22(4)
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
7.
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
8.
针对飞行器轴承信号单一且噪声多、需要针对性特征以及需要高可解释性的问题,开发了涵盖具有自适应噪声的完全集合经验模态分解(CEEMDAN)、自动特征工程以及随机森林的故障诊断模型,模型核心为自动进行特征生成以及提取的特征工程。通过该特征工程能够根据不同对象的信号差异,自动提取出不同对象的有效特征,具备对象间的通用性,且该特征工程可根据样本量的不同调整有效特征的数量,丰富特征空间,具备灵活的可扩展性。验证表明,该涵盖自动特征工程的模型的故障分类准确率为95.32%,可较好地在大样本量下区分压缩机轴承上的不同故障。 相似文献
9.
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
10.
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