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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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This study observed the activities of bromelain in the presence of various cationic surfactants at different temperatures and the conformational changes in bromelain by 1H NMR spectroscopy. We found that the bromelain activity was enhanced by tens to hundreds of micromoles per liter of the surfactant. In the presence of the surfactants, bromelain exhibited good tolerance to a range of substrate temperatures and its thermal stability was also increased. The 1H NMR experiments indicated that when the temperature was increased from 25.0 to 45.0 °C, the protons of bromelain having chemical shifts (δ) between 3.7 and 5.2 ppm moved upfield, while those having δ values between 3.2 and 3.7 ppm moved downfield. In the bromelain/cationic surfactant mixture, the values of δ for the protons in both bromelain and the cationic surfactants decreased, accompanied by the broadening of the half-peak width of the surfactant protons. These results indicated that both increasing temperature and adding a cationic surfactant made the bromelain chain more flexible and hence, increased the bromelain activity. To the best of our knowledge, this was the first time that the relationship between the protein activity and the 1H NMR data was expounded.  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   
5.
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.
目的 提高缓蚀剂在酸溶液中的缓蚀性能.方法 构建含有2-巯基苯并噻唑(MBT)以及不同浓度Cl–的Fe表面溶液模型,并进行分子动力学计算.观察缓蚀剂分子在Fe表面的吸附构型,考察不同Cl–值下缓蚀剂膜的致密化行为.提取缓蚀剂分子的均方位移(MSD)曲线,评价缓蚀剂膜的稳定性.计算水分子的密度分布和扩散系数,考察不同Cl–值下MBT缓蚀剂膜的驱水能力和水分子的迁移能力.结果 当Cl–值从0增加到25时,MBT膜的厚度(0.42~1.51 nm)和致密度(占有面积0.33~1.31 nm2)增加,缓蚀剂分子的自扩散系数减小(从1.25×10–9 m2/s到接近0),水分子的吸附峰强度(相对密度为72.3~33.9 nm–3)和扩散系数(1.495×10–9~0.627×10–9 m2/s)降低.当Cl–值从25增加到36时,则出现了相反的趋势.结论 缓蚀剂分子与Cl–之间存在协同作用,适当浓度的KCl可以提高MBT缓蚀剂在H2SO4溶液中的缓蚀性能.Cl–值为25时,MBT缓蚀效率最高.  相似文献   
8.
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   
9.
Evaporative phase transitions are widely present in industrial production and daily life such as thin film processes and crystal growth. The evaporation of the liquid layer and the thermocapillary convection affect each other and restrict each other, making the energy transfer mechanism of the evaporation interface very complicated. To understand the evaporation characteristics of water in its low-pressure pure vapor environment, a series of experimental studies were carried out on the temperature distributions and evaporating rate of water evaporation in the annular pool. The cylinder temperature of the annular liquid pool is controlled between 3℃ and 15℃, and the evaporation environment pressure ranges from 394 Pa to 1467 Pa, when the temperature measurement starts, the depth of water is 10 mm. The results show that the temperature of the vapor side on the liquid-vapor interface is higher than that of the liquid side and there is an obvious temperature jump across the vapor-liquid interface. With the decrease of the pressure ratio, the evaporation rate increases, and the interface temperature jump is enlarged. Meanwhile, with the increase of the distance from the cylinder, the local evaporation rate decreases, thus, the temperature jump decreases. At the same pressure ratio, as the cylinder temperature increases, the heat flux from vapor side decreases, the temperature jump decreases at all measurement points. Within the experimental controlled parameters, the maximum temperature jump obtained in the measurements is 2.56℃. Due to the coupling effect of evaporation cooling and thermocapillary convection, there is a uniform temperature layer with a thickness of about 2 mm under the evaporation interface. The thickness of the uniform temperature layer near the cylinder is always larger than that in the middle of the evaporation interface. In the uniform temperature layer, the thermocapillary convection induced by radial temperature gradient transfers heat from the cylinder to the liquid-vapor interface to compensate for the latent heat of evaporation. Below the uniform temperature layer, the temperature rises rapidly due to heat conduction and buoyancy convection.  相似文献   
10.
以热膨胀仪判定建窑黑瓷烧成温度的研究为例,综合运用多种测试方法对建窑黑瓷标本进行了系统研究,探讨如何从建窑黑瓷胎体重烧热膨胀曲线中筛选有效转折点的问题及其转折点的形成原因。研究表明:(1)建窑黑瓷胎体重烧热膨胀曲线上有三个转折点,分别为收缩转折点、膨胀转折点和急剧收缩点。其中第一个收缩转折点是判定其古代烧成温度的关键点。(2)建窑黑瓷胎体重烧热膨胀曲线上膨胀转折点和急剧收缩点的形成皆与其胎体中大量Fe_2O_3在高温下发生分解反应有关。该研究不仅为热膨胀仪测定建窑黑瓷烧成温度的应用研究提供判定依据,也将为科学认识古陶瓷胎体重烧热膨胀曲线上多个转折点的形成机理提供数据支持。  相似文献   
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