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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.
Surface patterning is a recent promising approach to promote performance of pressure-driven membranes in water treatment and desalination. Nevertheless, knowledge about foulant deposition mechanisms, especially at early stage of filtration, is still lacking. The applicability of particle imaging velocimetry to study fluid characteristics atop surface patterned thin-film composite membranes was investigated at different operating conditions. This work is an important first step toward reliable understanding of the impacts of topographical membrane surface modification on hydrodynamic conditions and foulant deposition mechanisms.  相似文献   
8.
王斌 《大氮肥》2021,44(1):14-16
介绍一种液体分布器检测专用工具的原理,该工具应用在尿素汽提塔后,保证了汽提塔液体分布效果,对汽提塔设备保护和节省汽耗起到关键作用。  相似文献   
9.
从宏观角度研究基于关键词的网络舆情热度有助于相关机构把握目标群体的整体舆情动态,从而实现精准施策,提升舆论引导水平.本文以新浪微博数据为例,采用因子分析方法 (Factor Analysis, FA),挖掘舆情热度内在影响因素,并通过改进Elman网络结构,利用遗传算法(Genetic Algorithm, GA)优化初始参数来构建模型对网络舆情关键词热度进行分析预测.实验结果表明,所提出的方法相较于采用原始数据集和标准Elman网络的预测结果,具有更高的预测精度,可为相关研究提供决策支持.  相似文献   
10.
晋城寺河井区煤矿采空区煤层气地面抽采关键技术研究   总被引:2,自引:0,他引:2  
随着煤层气勘探的不断深入,煤矿采空区煤层气已成为煤矿区煤层气重要资源之一。基于晋城矿区寺河井区煤矿采空区分布特征,通过地质分析、采空区煤层气成分、浓度试验和资源量模型计算等方法系统研究了煤矿采空区煤层气资源条件及地面抽采关键技术,揭示了采空区煤层气赋存规律,给出了不同赋存状态下煤层气资源量计算模型和方法,探索了煤矿采空区煤层气地面抽采关键技术。研究表明,煤矿采空区煤层气来源于煤柱及残留煤层、邻近未采煤层和围岩中的游离气和吸附气。根据吸附气和游离气资源量计算模型计算寺河井区煤层气总资源为213.016×108m3,其中游离气资源为0.102×108m3,吸附气资源为212.914×108m3。采煤方法和采空区密闭性对采空区煤层气的来源和富集程度有重要影响。针对采空区上部岩体裂隙发育特征,将采空区煤层气抽采井身结构由二开优化为三开结构,实现了二开固井封闭断裂带上部含水层,三开下入割缝套管护壁,有效解决了采空区上部含水层涌水对钻井井身稳定性影响及抽采效果等问题。在此基础上,研发了潜孔锤+压缩空气(氮气)钻井工艺,用氮气取代空气作为循环介质,形成了安全揭露含气断裂带钻井工艺技术,为采空区煤层气安全抽采探索了有效途径。  相似文献   
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