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41.
Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases, including Alzheimer''s disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). While significant efforts have been made to develop different prevention strategies and preclinical hits for these diseases, conventional design strategies of amyloid inhibitors are mostly limited to either a single prevention mechanism (amyloid cascade vs. microbial infection) or a single amyloid protein (Aβ, hIAPP, or hCT), which has prevented the launch of any successful drug on the market. Here, we propose and demonstrate a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins, human α-defensin 6 (HD-6) and human β-defensin 1 (HBD-1), as multiple-target, dual-function, amyloid inhibitors. Both HD-6 and HBD-1 can cross-seed with three amyloid peptides, Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC), to prevent their aggregation towards amyloid fibrils from monomers and oligomers, rescue SH-SY5Y and RIN-m5F cells from amyloid-induced cytotoxicity, and retain their original antimicrobial activity against four common bacterial strains at sub-stoichiometric concentrations. Such sequence-independent anti-amyloid and anti-bacterial functions of intestinal defensins mainly stem from their cross-interactions with amyloid proteins through amyloid-like mimicry of β-sheet associations. In a broader view, this work provides a new out-of-the-box thinking to search and repurpose a huge source of antimicrobial peptides as amyloid inhibitors, allowing the blocking of the two interlinked pathological pathways and bidirectional communication between the central nervous system and intestines via the gut–brain axis associated with neurodegenerative diseases.Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases. Here, we proposed a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins as multiple-target, dual-function amyloid inhibitors. 相似文献
42.
The simulation of particle fluidization behavior in a complex geometry with a large number of particles is challenging owing to the complexity of unstructured c... 相似文献
43.
Bingbo Wang Xiujuan Ma Cunchi Wang Mingjie Zhang Qianhua Gong Lin Gao 《Entropy (Basel, Switzerland)》2022,24(7)
The determination of directed control paths in complex networks is important because control paths indicate the structure of the propagation of control signals through edges. A challenging problem is to identify them in complex networked systems characterized by different types of interactions that form multilayer networks. In this study, we describe a graph pattern called the conserved control path, which allows us to model a common control structure among different types of relations. We present a practical conserved control path detection method (CoPath), which is based on a maximum-weighted matching, to determine the paths that play the most consistent roles in controlling signal transmission in multilayer networks. As a pragmatic application, we demonstrate that the control paths detected in a multilayered pan-cancer network are statistically more consistent. Additionally, they lead to the effective identification of drug targets, thereby demonstrating their power in predicting key pathways that influence multiple cancers. 相似文献
44.
An understanding of the particle transport characteristics in a branched network helps to predict the particle distribution and prevent undesired plugging in various engineering systems.Quantitative analysis of particle flow characteristics is challenging in that experiments are expensive and particle flow is difficult to detect without disturbing the flow.To overcome this difficulty,man-made fractal tree-like branched networks were built,and a coupled computational fluid dynamic and discrete element method model was applied.A series of numerical simulations was carried out to analyze the influence of fractal structure parameters of networks on the particle flow characteristics.The joint influence of inertial,shunt capacity and superposition from upstream branches on particle flow was investigated.The injection position at the inlet determined the particle velocity and its future flow path.The particle density ratio,particle size and bifurcation angle had a greater influence on the shunting of K2 branches than that in the K1 level and Nk22/Nk21 reached a maximum at 60°.Compared with a network with an even number of branches,there was a preferential branch when the branch number was odd.The preferential branch effect or asymmetry degree of the level(K2)branches had a more significant impact on particle shunting than that from the upstream branches(K1). 相似文献
45.
Comparative study on transport properties of N-, P-, and As-doped SiC nanowires: Calculated based on first principles 下载免费PDF全文
According to the one-dimensional quantum state distribution, carrier scattering, and fixed range hopping model, the structural stability and electron transport properties of N-, P-, and As-doped SiC nanowires(N-SiCNWs, P-SiCNWs, and As-SiCNWs) are simulated by using the first principles calculations. The results show that the lattice structure of NSiCNWs is the most stable in the lattice structures of the above three kinds of doped SiCNWs. At room temperature,for unpassivated SiCNWs, the doping effect of P and As are better than that of N. After passivation, the conductivities of all doped SiCNWs increase by approximately two orders of magnitude. The N-SiCNW has the lowest conductivity. In addition, the N-, P-, As-doped SiCNWs before and after passivation have the same conductivity–temperature characteristics,that is, above room temperature, the conductivity values of the doped SiCNWs all increase with temperature increasing.These results contribute to the electronic application of nanodevices. 相似文献
46.
47.
Theoretical study of (e, 2e) triple differential cross sections of pyrimidine and tetrahydrofurfuryl alcohol molecules using multi-center distorted-wave method 下载免费PDF全文
We report theoretical studies of electron impact triple differential cross sections of two bio-molecules,pyrimidine and tetrahydrofurfuryl alcohol,in the coplanar asymmetric kinematic conditions with the impact energy of 250 eV and ejected electron energy of 20 eV at three scattering angles of-5°,-10°,and-15°.Present multi-center distorted-wave method well describes the experimental data,which was obtained by performing(e,2e)experiment.The calculations show that the secondary electron produced by the primary impact electron is strongly influenced by the molecular ionic multi-center potential,which must be considered when the low energy electron interacts with DNA analogues. 相似文献
48.
Xiaolin Zhang Pengwei Gong Fangqi Liu Kailun Yao Jian Wu Sicong Zhu 《Frontiers of Physics》2022,17(5):53510
Due to the unique electronic structure of half-metals, characterized by the conductivity of majority-spin and the band gap of minority-spin, these materials have emerged as suitable alternatives for the design of efficient giant magnetoresistive (GMR) devices. Based on the first-principles calculations, an excellent GMR device has been designed by using two-dimensional (2D) half-metal Mn2NO2. The results show that Mn2NO2 has sandwiched between the Au/nMn2NO2 (n = 1, 2, 3)/Au heterojunction and maintains its half-metallic properties. Due to the half-metallic characteristics of Mn2NO2, the total current of the monolayer device can reach up to 1500 nA in the ferromagnetic state. At low voltage, the maximum GMR is observed to be 1.15 × 1031 %. Further, by increasing the number of layers, the ultra-high GMR at low voltage is still maintained. The developed device is a spintronic device exhibiting the highest magnetoresistive ratio reported theoretically so far. Simultaneously, a significant negative differential resistance (NDR) effect is also observed in the heterojunction. Owing to its excellent half-metallic properties and 2D structure, Mn2NO2 is an ideal energy-saving GMR material. 相似文献
49.
介绍了两种制备磁流变弹性体的硫化方法即高温硫化和辐射硫化. 研究中采用动态力学分析仪(DMA)测量了样品的动态力学特性.特别是对样品的磁流变效应和耐久性进行了详细的测试. 实验结果表明,经过辐射硫化的样品具有更大的零场模量和磁致模量,以及更好的磁流变效应和耐久性. 为了解释这些结果,文章对样品的体积形变和增塑剂渗出都作了详细的分析. 在硫化过程中样品的体积保持稳定是辐射硫化样品具有大磁致模量的重要原因,而增塑剂渗透性小也是辐射硫化样品具有高磁流变效应和耐久性的重要因素. 相似文献
50.
In this paper, we study the epidemic spreading in scale-free networks and propose a new susceptible-infected-recovered (SIR) model that includes the effect of individual vigilance. In our model, the effective spreading rate is dynamically adjusted with the time evolution at the vigilance period. Using the mean-field theory, an analytical result is derived. It shows that individual vigilance has no effect on the epidemic threshold. The numerical simulations agree well with the analytical result. Furthermore, we investigate the effect of individual vigilance on the epidemic spreading speed. It is shown that individual vigilance can slow the epidemic spreading speed effectively and delay the arrival of peak epidemic infection. 相似文献