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1.
Peter K. Windsor Stephen P. Plassmeyer Dominic S. Mattock Jonathan C. Bradfield Erika Y. Choi Bill R. Miller III Byung Hee Han 《International journal of molecular sciences》2021,22(6)
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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针对激光聚变冲击波速度测量的需求,设计了一种集被动式扫描高温计和主动式冲击波速度测量于一体的复合冲击波速度测量系统。通过采用多种耐辐射光学玻璃材料,实现了共用光路的400~700 nm耐辐射消色差设计;通过采用自动控制干涉仪简化了系统操作;主动测速系统通过切换不同焦距的中继成像镜头,实现了不同放大倍率的切换。系统的物方视场为φ2.0 mm,主动式测速系统的放大倍率为10×,20×,30×,静态实验干涉条纹平直,调制度达到0.69以上,物方分辨率达到4.72μm。该系统在激光聚变装置上能够实现冲击波速度的动态测量。 相似文献
4.
Eugene Metakovsky Laura Pascual Patrizia Vaccino Viktor Melnik Marta Rodriguez-Quijano Yulia Popovych Sabina Chebotar William John Rogers 《International journal of molecular sciences》2021,22(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.
Md Saifur Rahman Md Badrul Alam Young Kyun Kim Mst Hur Madina Ismail Fliss Sang Han Lee Jin Cheol Yoo 《International journal of molecular sciences》2021,22(10)
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.
Kyunghee Kim Jisue Kim Hyoungseob Kim Gun Yong Sung 《International journal of molecular sciences》2021,22(4)
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.
为提高城市排水防涝能力,满足国家、地方政策及标准要求,老城区低标排水系统提标改造需求日益迫切。但许多老城区存在现状条件复杂、地下公用管线多、道路狭窄、施工条件苛刻等问题,提标改造难度较大。文中以上海市宝山区月浦城区雨水排水系统提标改造工程为例,详细介绍工程设计方案,结合Info Works ICM排水模型对系统内积水风险、管网水力条件进行分析,结果表明:提标改造后的管网系统在3年一遇设计降雨时,可保证城区内无积水产生,系统内大部分管道的水力坡度与管道坡度接近,基本未出现非满管或超载的情况;在100年一遇的设计降雨时,城区内积水深度普遍在0.15 m以下。针对排水系统改造中的重点、难点,提出充分利用现状设施、合理选择顶管与开槽埋管相结合的施工方案、减少骑马井数量、利用已建雨水管道收集路面雨水、合理确定井位管位,减小管线搬迁工程量等解决方案,同时,对关键节点进行具体分析。案例可为其他老城区的雨水排水系统提标改造工程提供一定的借鉴。 相似文献
8.
《矿业科学技术学报(英文版)》2021,31(1):103-110
Longwall gateroad entries are subject to changing horizontal and vertical stress induced by redistribution of loads around the extracted panel. The stress changes can result in significant deformation of the entries that may include roof sag, rib dilation, and floor heave. Mine operators install different types of supports to control the ground response and maintain safe access and ventilation of the longwall face. This paper describes recent research aimed at quantifying the effect of longwall-induced stress changes on ground stability and using the information to assess support alternatives. The research included monitoring of ground and support interaction at several operating longwall mines in the U.S., analysis and calibration of numerical models that adequately represent the bedded rock mass, and observation of the support systems and their response to changes in stress. The models were then used to investigate the impact of geology and stress conditions on ground deformation and support response for various depths of cover and geologic scenarios. The research results were summarized in two regression equations that can be used to estimate the likely roof deformation and height of roof yield due to longwall-induced stress changes. This information is then used to assess the ability of support systems to maintain the stability of the roof. The application of the method is demonstrated with a retrospective analysis of the support performance at an operating longwall mine that experienced a headgate roof fall. The method is shown to produce realistic estimates of gateroad entry stability and support performance, allowing alternative support systems to be assessed during the design and planning stage of longwall operations. 相似文献
9.
小尺寸涡轮钻具主要用于深部高温硬岩地层钻进,对我国油气、干热岩等深部能源矿藏的地质调查具有重要意义,在石油行业中小井眼钻井、老井加深及连续油管钻修井等方面具有较好的应用前景。目前,国内尚无248;73 mm小尺寸涡轮钻具,为推进涡轮钻具系列化,对248;73 mm小尺寸涡轮钻具的涡轮节中常规级定转子叶片及制动级定转子叶片进行设计优化,旨在研制长度短、转矩适中、转速适中、压降小、功率高及效率高的248;73 mm小尺寸涡轮钻具,使248;73 mm小尺寸涡轮钻具尽快在我国实现现场应用。设计出符合性能要求的3种常规定转子叶型方案和5种制动级叶型方案,通过理论分析及数值模拟,选出最优的常规定转子叶型及制动级叶型方案,并提出常规涡轮级与制动涡轮级复配的5种涡轮节结构方案,同时对涡轮节结构进行了性能分析及方案优选,优选的涡轮节方案在流量5.5 L/s,工作转速1 500~2 500 r/min时,输出转矩为109~140 N·m,平均压降为11.5 MPa,制动转矩为185.5 N·m,可满足小井眼钻井对248;73 mm小尺寸涡轮钻具的输出性能要求。 相似文献
10.
介绍螺纹锁紧环换热器管箱密封结构特点,分析其载荷传递方式,总载荷最终通过主螺纹传递到管程筒体。目前螺纹锁紧环换热器主螺纹设计中是假设将总载荷平均分配,再对螺纹进行强度校核,但每扣螺纹实际承受载荷是不均匀的。以某螺纹锁紧环换热器为例,参照GB/T 34019—2017《超高压容器》中关于螺纹载荷分布的计算校核方法,计算主螺纹的载荷分布并校核。结果表明:螺纹载荷分布计算结果与有限元模拟相吻合,前四扣螺纹承担超过总载荷的50%,主螺纹校核合格。为螺纹锁紧环结构设计中考虑螺纹承受载荷不均匀的强度校核提供一种可借鉴的方法。 相似文献