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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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孙玉明  徐蒙  李文慧  王静  张华  王玉林 《质谱学报》2021,42(6):1100-1112
建立了高效液相色谱-高分辨质谱法分析鉴定拉萨大黄化学成分。选用Agilent Zorbax SB-C18柱(150 mm×4.6 mm×5 μm),以乙腈和水为流动相进行梯度洗脱,流速0.5 mL/min;采用电喷雾离子源,在正、负离子模式下对拉萨大黄提取物进行一级和多级全扫描质谱分析。综合分析化合物的色谱和质谱行为,并结合对照品、文献和数据库等相关数据鉴定化合物。在负离子模式下,鉴定出63种化合物;正离子模式下,鉴定出54种化合物。所检测到的化合物包括22种鞣质类、28种茋类、6种黄酮类、3种苯丙酸类、2种苯丁酮类和2种有机酸类,其中有53种化合物为在该药材中首次发现,且未发现蒽醌类成分。该方法快速、灵敏,不仅提高了拉萨大黄复杂基质中微量化合物的鉴定效率,同时实现了对拉萨大黄提取物中不同类型化合物的分析鉴别,为进一步阐明拉萨大黄的药效物质基础及质控标准提供了科学依据。  相似文献   
4.
为了解决高精度的直线时栅位移传感器依赖空间超精密刻线和刻线不均匀等问题,提出一种采用多参数协同调制的新型直线时栅位移传感器。该传感器通过在PCB基板上布置阵列的激励线圈和特定形状的感应线圈,通过调制感应的面积和线圈的参数,感应出电行波信号,经过整形后用高频时钟脉冲插补得到位移量。通过仿真分析设计与样机实验,得出实验结果表明,在不改变空间极距的情况下,使得分辨力在信号源头上提高1倍且有±68μm的测量精度。  相似文献   
5.
张涛    霍然  刘景  李逸鸿  霍黎明 《陕西电力》2021,(9):1-7,55
智能软开关(SOP)可控制潮流、提供无功补偿,进而改善配电网电压、降低网损。因此,针对可再生能源大规模接入配电网后电能质量下降问题,采用K-means算法构建风-光典型场景,同时建立了基于SOP、可投切电容器的含高渗透率分布式电源的主动配电网优化运行模型。该模型以电压偏差、系统网损最小以及系统运行成本最低为目标,综合考虑了能源利用率及系统运行稳定性。最后利用基于参考点的非支配排序方法的多目标优化算法(NSGA-III)进行求解,输出Pareto最优解集,并采用改进的IEEE 33节点系统对所建立模型的有效性进行了验证。  相似文献   
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Fe-based bulk metallic glasses (BMGs) with high boron content have potential application as a coating material used in the framework for storing spent nuclear fuels to support their safe long-term disposal. The high glass forming ability (GFA) and large supercooled liquid region are therefore required for such Fe-based BMGs in either the glassy powder fabrication or the subsequent coating spraying. In order to meet these requirements, the influence of Nb content on the GFA of Fe57Cr10Zr8B18Mo7−xNbx (x=1–5, at.%) alloys was investigated, as Nb has positive roles in GFA and thermal stability of BMGs. The results indicate that a fully amorphous phase in the as-cast samples with 3 mm in diameter is obtained for both the Fe57Cr10Zr8B18Mo5Nb2 and Fe57Cr10Zr8B18Mo4Nb3 alloys. The corresponding supercooled liquid regions of the two BMGs are 78 K and 71 K, respectively. The mechanism for improving their GFA was analyzed based on the principle of metal solidification, the parameters for glass formation and thermal properties of the alloys. The compression strength and Vicker’s hardness of the two BMGs are 1,950 MPa and 1,310 HV, 2,062 MPa and 1,180 HV, respectively. The developed BMGs with high B content, good GFA, and very high hardness can be used as coating materials to the framework for spent nuclear fuels.

  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   
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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   
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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