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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   
2.
边界识别是位场数据解释中一项重要任务,可用于资源探测等领域,是目前研究的热点问题之一。对于深部异常体目标,采用传统的边界识别方法易出现模糊、发散、变形等问题,而改进的方法大多采用高阶导数,虽然能够很好地识别出深部异常体边界,但是计算复杂,易受噪声干扰。为了改善以上问题,提出了一种稳定的快速边界识别方法,仅利用符号函数和重磁垂直导数数据,即可均衡识别不同深度的目标,且避免了高阶导数的计算。通过理论模型的实验与对比,验证了方法的便捷性、有效性、抗斜磁化能力以及抗噪能力。同时,应用实测数据验证了方法在复杂重磁环境下,能够准确清晰地分辨出异常体,可节约相关研究人员的大量时间与精力,具有很好地应用前景。  相似文献   
3.
This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.  相似文献   
4.
5.
角接触球轴承在运行过程中的润滑状况至关重要,润滑油直接影响滚动轴承的接触状态。为分析角接触球轴承的润滑状况以及考虑润滑时轴承的机械特性,基于有限元和晶格玻尔兹曼方法,建立了双向流固耦合轴承仿真模型,对角接触球轴承进行动力学有限元仿真和润滑流体仿真,并与轴承拟静力学理论计算结果进行对比,验证模型的准确性。分析结果表明,保持架与滚珠接触并撞击,在轴承腔内油膜压力最大,滚珠与内圈、外圈滚道接触区分别为第二、第三大油膜压力区。润滑油受滚珠公转影响,沿着滚珠转动方向流动,实现对滚珠与内圈、外圈和保持架之间的润滑。滚珠运动和最大接触应力仿真结果与轴承拟静力学理论求解结果一致,即流固耦合仿真模型计算轴承机械特性具有较高的准确性。  相似文献   
6.
This paper focuses on the configuration design of flexure hinges with a prescribed compliance matrix and preset rotational center position. A new method for the topology optimization of flexure hinges is proposed based on the adaptive spring model and stress constraint. The hinge optimization model is formulated by maximizing the bending displacement with a spring while optimizing the compliance matrix to a prescribed value. To avoid numerical instability, an artificial spring is used as an auxiliary calculation, and a new strategy is developed for adaptively adjusting the spring stiffness according to the prescribed compliance matrix. The maximum stress of flexure hinge is limited by using a normalized P-norm of the effective von Mises stress, and a position constraint of rotational center is proposed to predetermine the position of the rotational center. In addition, to reduce the error of the stress measurement, a simple but effective filtering method is presented to obtain a complete black-and-white design. Numerical examples are used to verify the proposed method. Topology results show that the obtained flexure hinges have the prescribed compliance matrix and preset rotational center position while also meeting the stress requirements.  相似文献   
7.
针对频域法构造小波滤波器方法较少、稳定性无法保证、逼近精度不高等问题,基于天牛须搜索算法提出了一种小波滤波器直接频域逼近方法。首先根据小波滤波器电路的基本要求设计逼近有理式,然后加入电路实现所需的稳定性、正实性和初值为零的约束条件,建立小波滤波器逼近的频域优化模型。再以高斯小波和Marr小波为例,使用天牛须搜索算法求解频域逼近的数学模型得到滤波器有理式参数。在时域和频域上分别将该方法和其他频域方法进行对比,仿真和计算结果表明在相同条件下,频域逼近法具有更优的效果,五阶高斯小波和七阶Marr小波的逼近均方误差仅为3.446 8×10~(-4)和7.346 2×10~(-4)。  相似文献   
8.
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   
9.
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   
10.
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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