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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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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   
4.
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   
5.
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   
6.
Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several AuI and AuIII complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds.  相似文献   
7.
为了提升煤矿车辆异常行为检测水平,设计了基于红外遥感信息的煤矿车辆异常行为检测方法。该方法引入清晰度权重以及拉伸系数实现红外遥感图像中目标煤矿车辆部位的局部增强,利用均值漂移算法跟踪增强后的红外遥感图像中目标煤矿车辆,依据煤矿车辆跟踪结果提取煤矿车辆运动方向、运动速度以及运动方向3项异常行为检测参数,采用加权融合方法处理煤矿车辆异常行为检测参数的状态函数,融合结果高于所设定阈值时,煤矿车辆存在异常行为,否则煤矿车辆为正常行驶状态。实验结果表明,该方法可利用煤矿车辆位置、车辆行驶速度以及车辆方向变化检测煤矿车辆异常行为,具有较高的应用性。  相似文献   
8.
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   
9.
长期以来顶板灾害在我国煤矿灾害事故中发生起数和死亡人数始终占据首位,是困扰煤矿安全生产的主要难题。笔者开展了顶板岩性、矿压显现特征和顶板灾害案例统计分析,结果表明:我国回采工作面顶板灾害主要表现为片帮冒顶、顶板大面积突然垮落和大面积切顶压架3种类型。系统分析了各类型顶板灾害的发生特点及致灾原因:片帮冒顶多发生于松软煤岩体,采煤方法不合理及管理不当的工作面;顶板大面积突然垮落一般为坚硬顶板大面积悬顶、瞬时垮落所致;大面积切顶压架主要发生在薄基岩浅埋深工作面或顶板累积下沉量大引起顶板在煤壁处断裂的工作面。针对我国顶板灾害监测与防治,建立了工作面顶板灾害全景监测预警技术架构,即采用微震监测系统监测远场顶板活动,采用矿压监测系统监测近场顶板运动,采用三维激光扫描技术监测煤壁片帮时空演化,通过监测数据系统分析,动态掌握采场围岩的活动规律和支架工况,实现顶板灾害监测预警。提出了工作面开采全过程的顶板灾害综合防治技术体系,在工作面开采前确定合理采煤方法,合理工作面布置方式,科学开采参数及优化设备选型配套,这是防治顶板灾害的核心技术;在开采过程中保持支架良好的工况辅以顶板弱化技术,进而实现工作面顶板灾害防治。  相似文献   
10.
刘璐  庞杰 《粮油食品科技》2021,29(2):129-134
凝胶是一种性质介于固体和液体之间的特殊分散体系,魔芋葡甘聚糖(KGM)凝胶稳定性差、强度低,物理共混能方便、快捷地改善其凝胶性质。主要综述KGM复合凝胶的网络结构变化,并介绍不同复合凝胶在食品、医药、材料工程等领域的应用。分析表明,KGM复合凝胶网络能通过氢键、席夫碱反应、形成多重网络结构和填充的方式改善其凝胶特性。  相似文献   
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