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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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砂卵石地层是一种典型的力学不稳定地层及强磨蚀性地层,盾构在该类地层中掘进通常会面临刀盘、刀具磨损严重,盾构推力与刀盘扭矩偏高且波动幅度大、地层变形不易控制等问题。砂卵石地层盾构掘进效率的高低及地层控制的好坏,刀盘选型及刀具配置是关键。以北京地铁新机场线“磁各庄站~1#风井”盾构区间为工程依托,利用PFC3D数值模拟及现场测试相结合的手段,研究刀盘开口率、刀具组合高差、先行刀刀间距等参数对盾构掘进效率及地层变形的影响。研究结果表明:相同掘进参数下大开口率辐条式刀盘比小开口率辐板式刀盘具有更好的掘进速度,小开口率辐板式刀盘掘进时引起的地表变形更小,对周围地层的扰动范围也更小;先行刀与切削刀的组合高差为70 mm时盾构掘进效率较高且扭矩较低;先行刀刀间距设定为300 mm时,盾构有较好的掘进效率和较低的刀盘扭矩。工程实践表明;要实现砂卵石地层盾构长距离高效掘进,大开口率辐条式刀盘设计及大高差梯次化刀具布置是基础,高贯入度、低转速的掘进控制是关键。研究结果可为类似工程的盾构刀盘选型与刀具布设提供借鉴。  相似文献   
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   
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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.
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.
晶体结构研究是研究固体材料物理化学性质的基础,而筛选晶体结构通常基于能量最低原理,采用密度泛函理论计算结构能量需要大量计算资源及服务时间.为此本文提出了面向材料结构预测的深度学习方法,加快材料晶体结构的预测.本文从数据集优化、模型训练策略、算法优化等方面进行了深入研究,确定了应用于材料结构预测中深度学习的网络参数和优化算法.将确定的深度学习框架用于寻找Si单晶、TiO2和CaTiO3化合物的基态稳定结构,实验结果表明,利用本研究提出的深度学习方法预测的晶体结构与实验室制备材料结构相吻合.  相似文献   
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电池充电造成的电池损耗对企业运营成本影响较大,以不同SOC区间内一次充电造成的电池容量衰退成本模型估计电池损耗成本,研究了车辆途中可多次进入充电站充电的路径优化问题,在考虑运输成本、制冷成本、货损成本、充电时间成本、惩罚成本的基础上,将电动冷藏车的电池损耗成本纳入总成本最小的目标函数,并建立了线性规划数学模型。采用增加粒子间共享信息类型的改进粒子群算法对该模型进行求解。将改进粒子群算法应用于构造的算例中,得到包括充电策略在内的车辆最优路径方案和最小运营成本,结果表明充电上限为80%的车辆路径方案可得到最低的运营成本,同时与标准粒子群算法求得的计算结果进行了比较分析,证明该改进粒子群算法在求解该问题上的可行性。  相似文献   
9.
提出一种基于强化学习的生成对抗网络(Reinforcement learning-based Generative Adversarial Networks,Re-GAN)能耗预测方法.该算法将强化学习与生成对抗网络相结合,将GAN(Generative Adversarial Nets)中的生成器以及判别器分别构建为强化学习中Agent(生成器)以及奖赏函数.在训练过程中,将当前的真实能耗序列作为Agent的输入状态,构建一组固定长度的生成序列,结合判别器及蒙特卡洛搜索方法进一步构建当前序列的奖赏函数,并以此作为真实样本序列后续第一个能耗值的奖赏.在此基础之上,构建关于奖赏的目标函数,并求解最优参数.最后使用所提算法对唐宁街综合大楼公开的建筑能耗数据进行预测试验,实验结果表明,所提算法比多层感知机、门控循环神经网络和卷积神经网络具有更高的预测精度.  相似文献   
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针对最小化完工时间的作业车间调度问题(JSP),提出改进麻雀搜索算法(ISSA).首先设计有效的编码转换方式,形成JSP离散决策空间与麻雀搜索算法(SSA)连续搜索空间的对应关系.然后,针对SSA在求解后期易陷入局部最优,利用量子计算、正余弦搜索和警戒者数量递减策略对SSA进行改进,同时引入多邻域搜索和高斯扰动策略以弥补SSA在求解离散问题时深度发掘能力不足的弊端.最后,进行FT、LA系列10个测试问题、6种算法和2个应用实例的对比实验.结果表明,ISSA在求解JSP时,能获得更好的最小值、平均值和寻优成功率,验证了ISSA求解JSP的有效性.  相似文献   
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