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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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为了得到螺杆泵转子直径与定子导程对泵性能的影响规律,基于Pumplinx软件对橡胶定子单头单螺杆泵进行非稳态数值计算求解,在此基础上探究了不同压差条件下无量纲参数T/D对螺杆泵流量、水力效率以及轴向力的影响进行分析并基于此进行性能优化。结果显示,随着T/D的增大,泵流量增加,轴向力基本保持不变,而水力效率先增大后减小,其最优值出现在T/D=4.5时;螺杆泵定子转子啮合区域的泄漏较为明显,且随着T/D的增大泄漏量增多。因此为了得到更高的效率,T/D宜优化至4.5;为了得到更大流量的同时不牺牲效率,T/D宜优化至5.4。此外,数值计算与试验结果较为一致,偏差不超过3.5%,表明该螺杆泵仿真方法具有参考价值。  相似文献   
4.
针对塔式起重机起重量限制器现场检验的约束条件,提出了一种利用夹绳器及施力装置配合的无载荷试重系统模型,拟解决现场难以配备标准重物及检验成本过高的问题,并通过模拟塔式起重机钢结构受力情况,分析了该理论模型系统的安全性。  相似文献   
5.
船用汽轮机后汽缸下半铸件结构复杂,质量要求高,有较高的生产难度。采用ProCAST铸造模拟软件计算铸件模数,根据模数计算设置冒口;模拟浇注过程,确保充型过程快速平稳;对铸件凝固过程模拟优化,实现顺序凝固,保证了铸件致密度。  相似文献   
6.
为指导实际双金属管精确成形工艺,基于LS-Dyna对铝/钢双金属管电磁缩径连接进行了结构场-电磁场耦合的有限元数值模拟,研究了内外管壁厚比值、内外管间隙、放电电压以及芯模对成形质量的影响规律.结果表明:内外管壁厚比值过小易引起内外管连接不紧密,比值过大易导致内管凹陷和外管开裂;随着放电电压增大或内外管间距的减小,外管缩径冲击力增大,导致内管周向应力的急剧增大和失稳起皱,同时造成外管开裂;而随着放电电压减小或内外管间距的增大,外管相对的缩径冲击力减小,内管会因无法经历一个有效的形变回弹过程导致内外管有效连接区域逐渐减小;采用弹性芯模可一定程度抑制开裂等宏观缺陷的产生,同时也能适当增加内管的回弹.最后,基于理论计算与有限元仿真获得复合管电磁成形规律和缺陷控制理论,以增大有效连接区域长度、减少宏观缺陷为目标进行优化,在施加弹性芯模的状态下,内管壁厚维持1 mm不变,外管壁厚取1.5 mm,内外管间隙取0.7 mm,放电电压取50 kV时得到的成形质量最佳.  相似文献   
7.
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   
8.
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   
9.
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   
10.
为研究废石?风砂高浓度充填料浆自流输送管道输送特性,将矿山实际充填管路进行还原,应用FLUENT软件进行输送模拟研究。结果表明:充填料浆在管道的管径方向有明显的速度梯度;随料浆流速的增大,料浆的输送沿程阻力损失基本呈线性增大;质量浓度对管输阻力的影响非常大,在充填料浆质量浓度相差2%左右时,管道单位长度的阻力损失会相差20%~30%。通过对不同骨料比的充填料浆进行数值模拟,可知废石风砂质量比为6:4的浆体稳定性和流动性相对较好,更有利于管道输送。建立了管输阻力新模型,并通过工业试验对模型进行检验,验证了新的管输阻力模型的可靠性,研究结果为该矿选取充填系统的运行参数提供了重要依据。  相似文献   
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