Repurposing of intestinal defensins as multi-target,dual-function amyloid inhibitors via cross-seeding

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.     

CFD-DEM-VDGM method for simulation of particle fluidization behavior in multi-ring inclined-hole spouted fluidized bed

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...     

Conserved Control Path in Multilayer Networks

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.     

Computational fluid dynamic-discrete element method coupling analysis of particle transport in branched networks

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 N_k22/N_k21 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).     

Comparative study on transport properties of N-, P-, and As-doped SiC nanowires: Calculated based on first principles

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.     

Cl+F2→ClF+F和F+ClF′→ClF+F′反应机理的密度泛函理论研究

用密度泛函理论（ＤＦＴ）Ｂ３ＬＹＰ方法,在６－３３１Ｇ＊基组下,计算研究了反应Ｃｌ＋Ｆ２→ＣｌＦ＋Ｆ和对称反应Ｆ＋ＣｌＦ’→ＣｌＦ＋Ｆ’的机理。求得前者的过渡态为三角形,活化能为１５．５７ｋＪ·ｍｏｌ＾－１;后者的过渡态为线形和三角形,活化能分别为１１．５２和１９６．２５ｋＪ·ｍｏｌ＾－１。结果均经过振动分析和ＩＲＣ计算验证。     

第十六届国际非线性声学会议在莫斯科市举行

第十六届国际非线性声学会议(InternationalSymposium on Nonlinear Acoustics,简称16thISNA)于2002年8月19日至23日在俄罗斯首都莫斯科市举行。来自全世界28个国家和地区约300人参加了会议,其中俄罗斯160人,美国32人,法国16人,日本11人,德国9人,英国7人,瑞典7人,….等等;中国代表有3人,他们是南京大学龚秀芬教授和王耀俊教授,江西吉安师范学院李化茂教授。ISNA是由国际非线性声学学术委员会主办的国际学术会议,每3年举行一次,自1968年以来已举办了16次,在声学和非线性声学领域具有很大的影响。本届会议由俄罗斯的莫斯科大学组织和承办。会议     

Theoretical study of (e, 2e) triple differential cross sections of pyrimidine and tetrahydrofurfuryl alcohol molecules using multi-center distorted-wave method

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.     

High efficiency giant magnetoresistive device based on two-dimensional MXene (Mn2NO2)

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.