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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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随着科学技术的快速发展与进步,当今社会要求学生学习知识水平越来越高,要求其学习范围更为广泛。因此目前学生仅依凭英语课堂学习还远远不够,很多时候根本无法适应社会发展的需要,所以培养学生自学能力就显得非常重要。由此提出开发一款英语自学系统为英语爱好者提供自学英语平台。文章立足于Web网络,依托B/C结构,应用ASP.NET和数据库进行相互融入技术;然后从功能模块,数据库等设计详细分析本系统设计;最后从聊天室、BBS论坛、以及留言板等方面来实现本系统的在线沟通与交流,从而完成了本系统研究。该系统不但能使学生学习英语不受时空限制,而且对于提升他们学习英语效果与使用英语能力均有很大帮助。 相似文献
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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
6.
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
7.
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
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Recently, a number of classification techniques have been introduced. However, processing large dataset in a reasonable time has become a major challenge. This made classification task more complex and expensive in calculation. Thus, the need for solutions to overcome these constraints such as field programmable gate arrays (FPGAs). In this paper, we give an overview of the various classification techniques. Then, we present the existing FPGA based implementation of these classification methods. After that, we investigate the confronted challenges and the optimizations strategies. Finally, we highlight the hardware accelerator architectures and tools for hardware design suggested to improve the FPGA implementation of classification methods. 相似文献
9.
命名实体识别的目的是识别文本中的实体指称的边界和类别。在进行命名实体识别模型训练的过程中,通常需要大量的标注样本。本文通过实现有效的选择算法,从大量样本中选择适合模型更新的样本,减少对样本的标注工作。通过5组对比实验,验证使用有效的选择算法能够获得更好的样本集,实现具有针对性的标注样本。通过设计在微博网络数据集上的实验,验证本文提出的基于流的主动学习算法可以针对大量互联网文本数据选择出更合适的样本集,能够有效减少人工标注的成本。本文通过2个模型分别实现实体的边界提取和类别区分。序列标注模型提取出实体在序列中的位置,实体分类模型实现对标注结果的分类,并利用主动学习的方法实现在无标注数据集上的训练。使用本文的训练方法在2个数据集上进行实验。在Weibo数据集上的实验展示算法能从无标签数据集中学习到文本特征。在MSRA数据集上的实验结果显示,在预训练数据集的比例达到40%以上时,模型在测试数据集上的F1值稳定在90%左右,与使用全部数据集的结果接近,说明模型在无标签数据集上具有一定的特征提取能力。 相似文献
10.
糖尿病视网膜病变是世界上致盲率最高的眼科疾病,早期诊断可以显著降低患者失明的概率。深度学习方法可以提取医学图像的隐含特征,并完成图像的检测任务,因此应用深度学习实现糖尿病视网膜病灶检测成为研究热点。主要从数据集介绍、全监督检测方法、非完全监督检测方法、小样本问题的处理和模型可解释性五个方面进行详细总结,重点整理各类方法的基本思想、网络结构形式、改进方案及优缺点总结等内容,结合当前检测方法所面临的挑战,对其未来研究方向进行展望。 相似文献