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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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针对车身三维模型中焊枪头与焊点附近的钣金件之间空间间隙检查过程复杂、检查结果不准确等问题,提出了焊枪头与钣金件空间间隙的自动检查方法。在特征识别算法和包围盒技术的基础上获得焊点特征、钣金件特征和螺母特征等分析要素;基于三维模型的投影算法和距离测量算法计算钣金件的拓扑面与虚拟焊枪之间的距离,与安全阈值比较,筛选出与焊枪发生干涉的危险平面、孔和螺母;对焊接空间不足的焊点进行标注并截图。利用二次开发环境所提供的函数库编程实现了上述算法,通过运行实例以及企业的实际使用,验证了自动检查系统的可行性。  相似文献   
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在生物、医学研究采用两血管阻断法(2-VO)建立脑缺血模型过程中,由于对动脉的非量化结扎,导致模型建立的重复性较差,组内个体差异较大且死亡率较高.本文以金属应变计为核心元件设计了血管阻断拉力仪,实现对结扎力的量化检测.从体外、体内两个层面以及体内的细胞分子水平、组织器官水平和整体水平进行生物学实验验证.结果表明:该拉力仪线性度、灵敏度受金属应变计基底参数、胶接工艺、电路参数、外观结构等因素影响;与非仪器结扎组比较,脑缺血模型动物死亡率降低了42.22%.实验动物脑血流量下降程度与结扎力递增呈对应关系;海马组织苏木素-伊红(HE)染色后光镜检测发现神经元排列松散,神经元数量减少乃至消失,神经元胞浆染色变淡及齿状回出现神经元固缩.不同结扎力组间比较显示,1.5 N组内大鼠海马组织形态个体差异最小;Morris水迷宫结果显示,与假手术组比,1.5 N结扎组、2.5 N结扎组大鼠逃避潜伏期显著增加(P0.05),且1.5 N结扎组大鼠站台穿越次数显著下降(P0.05),出现了明显的学习记忆障碍.证伪了实验室前期实验中2-VO大鼠结扎力越大,结扎效果越佳的理论.得出结扎力标准偏差越小结扎效果越好,且结扎力量化可控的结论.该血管阻断拉力仪应用于医药学基础实验研究具有重要意义.  相似文献   
5.
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   
6.
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   
7.
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   
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In flotation, metal ions possess significant roles that are usually fulfilled by either selectively activating or depressing the target minerals. Despite that tremendous efforts have been made to address the roles of metal ions in flotation, it still lacks a comprehensive review, especially to compare various ions instead of focusing on a specific one. This review begins by elaborately categorizing the factors involved in affecting the roles of metal ions in flotation. After that, well-accepted mechanisms are updated and discussed from the ore type. Furthermore, typical approaches to explore the underlying mechanisms are emphasized, including traditional techniques such as micro-flotation, contact angle measurement, zeta potential measurement, and other recent prevailing methodologies, like computational method, solution chemistry calculation, and cyclic voltammetry. This work will pave the way to promote flotations via activities like selectively adding/reducing metal ions, choosing reagents, and regulating the slurry chemistry.  相似文献   
9.
Metal organic frameworks (MOFs) containing zirconium secondary building units (SBUs) in UiO-67 and related MOFs, are highly active for neutralizing both the chemical warfare agents and simulants, such as dimethyl methylphosphonate (DMMP). However, two recent publications gave conflicting reports of DMMP reaction with UiO-67 under ultra high vacuum (UHV) conditions, with one reporting chemisorption and reaction (Wang et al., J Phys Chem C, 2017, 121, 11261–11272) and the other reporting only physisorption and reversible desorption (Ruffley et al., J Phys Chem C, 2019, 123, 19748–19758) from very similar temperature programmed desorption experiments. We show that the discrepancy between these experiments may be explained by different levels of missing linker defects in the UiO-67 samples. We present density functional theory calculations showing that SBU sites having two-adjacent missing linkers exhibit reaction barriers that are about 30 kJ/mol lower than SBU sites having a single missing linker. We also show that topology of the undercoordinated sites plays an important role in the reaction barrier under UHV conditions.  相似文献   
10.
为了解决醇胺法燃烧后捕集二氧化碳再生能耗过高的问题,研究了一种向胺溶液中添加金属离子以降低其CO2解吸能耗的方法,称之为金属离子络合物热缓冲自热利用技术。以广泛商业化应用的单乙醇胺(MEA)溶液为研究载体,并在MEA溶液中分别添加金属离子铜或镍, 通过建立含有金属离子的MEA捕集CO2体系的化学反应模型,解释金属离子热缓冲剂效应的内在机理。机理显示在MEA-金属离子-CO2-H2O体系中,金属-MEA络合物作为一种有效的反应热缓冲剂,将有机胺吸收CO2过程中释放的反应热(放热反应)存储于金属络合物的解离键能中(吸热反应),在CO2高温解吸中通过其络合放热反应将储存的能量释放出来用于CO2解吸,形成自热再生低能耗CO2捕集技术,从而降低了MEA再生的能耗。本文进行了综合的实验测定来评价金属离子对MEA溶液捕集CO2过程的性能提升影响,包括CO2反应热、解吸速率、吸收-解吸循环负载、汽液平衡溶解度等。实验结果表明铜离子或镍离子作为添加剂,能增加MEA的CO2平衡循环负载14%~20%或7%~10%,同时能够降低MEA的CO2反应热值6.6%~24%或6.0%~20%。  相似文献   
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