Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

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.     

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Effect of lamellar spacing on microstructural instability and creep behavior of a lamellar TiAl alloy

Finer lamellar spacing in the lamellar structure of a Ti–45Al–2Nb–2Mn + 0.8 vol.%TiB₂ (45XD) alloy does improve the primary creep resistance. However, the unstable nature of the fine plate contributes largely to the degradation of the lamellar structure and a rapid increase in the tertiary creep rate, indicating that a fine lamellar structure has a detrimental effect on the long-term creep.     

In-Plane Cracking Behavior and Ultimate Strength for 2D Woven and Braided Melt-Infiltrated SiC/SiC Composites Tensile Loaded in Off-Axis Fiber Directions

The tensile mechanical properties of ceramic matrix composites (CMC) in directions off the primary axes of the reinforcing fibers are important for the architectural design of CMC components that are subjected to multiaxial stress states. In this study, two-dimensional (2D)-woven melt-infiltrated (MI) SiC/SiC composite panels with balanced fiber content in the 0° and 90° directions were tensile loaded in-plane in the 0° direction and at 45° to this direction. In addition, a 2D triaxially braided MI SiC/SiC composite panel with a higher fiber content in the ±67° bias directions compared with the axial direction was tensile loaded perpendicular to the axial direction tows (i.e., 23° from the bias fibers). Stress–strain behavior, acoustic emission, and optical microscopy were used to quantify stress-dependent matrix cracking and ultimate strength in the panels. It was observed that both off-axis-loaded panels displayed higher composite onset stresses for through-thickness matrix cracking than the 2D-woven 0/90 panels loaded in the primary 0° direction. These improvements for off-axis cracking strength can in part be attributed to higher effective fiber fractions in the loading direction, which in turn reduces internal stresses on weak regions in the architecture, e.g., minicomposite tows oriented normal to the loading direction and/or critical flaws in the matrix for a given composite stress. Both off-axis-oriented panels also showed relatively good ultimate tensile strength when compared with other off-axis-oriented composites in the literature, both on an absolute strength basis as well as when normalized by the average fiber strength within the composites. Initial implications are discussed for constituent and architecture design to improve the directional cracking of SiC/SiC CMC components with MI matrices.     

Effect of the addition of fluoride on the conditional solubility of alumina in LiCl-KCl eutectic melt

Owing to its well-known high complexing power toward Al³⁺ ion, fluoride ion is able to increase the solubility of alumina in alkali chloride melts. To determine the extent of this effect, the formation of aluminium(III) fluoro-complexes was studied potentiometrically in LiCl-KCl eutectic at 470°. But the sodium fluoride addition appeared to produce not only the complexation effect but also a mineralization effect on alumina. So, the thermodynamical stability of alumina formed in this melt by precipitation from aluminium chloride with carbonate ion (oxide anion donor) depends on the fluoride ion concentration. These two effects explain the solubility variation of alumina in the LiCl-KCl eutectic + NaF mixtures. A pF^? - pO^2? diagram, which represents the stability area of the various aluminium (III) species is established, and leads to some conclusions concerning the electrowinning of aluminium from molten chloride melts.The cumulative formation constants of the aluminium(lII) fluoro-complexes (AlF^3?i_i) have been obtained, whose values are the following: 2.5 ± 0.4, 4.7 ± 0.6, 5.7 ± 0.5, 7.5 ± 0.4, 8.0 ± 0.5, 9.0 ± 0.6, respectively for i = 1, 2, 3, 4, 5 and 6. It has been shown that oxyfluoride species such as AlOF^1?j_i does not exist. The solubility products of gamma and alpha-alumina have been determined and are equal to 10^?42.9 and 10^?44.0 respectively (all the constants are given in the molality scale). They differ widely from the solubility product of the alumina obtained in the absence of fluoride ion, ie 10^?27.4.     

Curing behavior and structure of an epoxy/clay nanocomposite system

The curing behavior of an epoxy/clay nanocomposite system composed of a bifunctional epoxy resin with an aromatic amine curing agent and an organically modified clay was investigated. Differential scanning calorimetry (DSC) was used to investigate the curing behavior of the epoxy/clay nanocomposite system. The curing rate of the nanocomposite system increased with increasing clay content. A kinetic equation, considering an autocatalytic reaction mechanism, could describe fairly well the curing behavior of the epoxy/clay nanocomposite system. The reaction kinetic parameters of the kinetic equation were determined by fitting DSC conversion data to the kinetic equation, using a nonlinear numerical method. Dynamic mechanical analysis was used to investigate the thermomechanical properties of the epoxy/clay nanocomposite system. The glass transition temperature of the epoxy/clay nanocomposite system increased slightly with increasing clay content. The structure of the nanocomposite system was characterized by X‐ray diffraction analysis and transmission electron microscope imaging. The formation of intercalated structures was observed dominantly in the epoxy/clay nanocomposites, together with some exfoliated structures. POLYM. ENG. SCI., 46:1318–1325, 2006. © 2006 Society of Plastics Engineers     

An experimental investigation of mixing of carbon nanotube/polymer composite in a batch-type screw mixer

We develop a miniaturized batch-type screw mixer (BSM) for uniform mixing of polymer resin and nanoparticles, based on the stretching of material elements. This stretching is induced by the combination of recirculating cross-sectional flows in deep channels of the screw and high shear stress developed at flight regions. The BSM is used to produce a polymer nano-composite composed of multi-walled carbon nanotubes and polydimethylsiloxane resin. The mixing performance of the BSM is characterized quantitatively by estimating two different types of mixing efficiencies (i.e., dispersive mixing and distributive mixing) via transmitted light microscope images. The developed BSM highly improves the mixing performance rather than that of a conventional ultrasonic mixing device.     

Water sorption of poly(vinyl alcohol)/ poly(diallyldimethylammonium chloride) interpenetrating polymer network hydrogels

Temperature‐responsive interpenetrating polymer network (IPN) hydrogels constructed with poly(vinyl alcohol) and poly(diallyldimethylammonium chloride) using the sequential IPN method were studied. The characteristics of IPN hydrogels were investigated using the dynamic vapor sorption system. IPN hydrogels exhibited a relatively high sorption ratio, 180–360% at room temperature. The sorption ratio of hydrogels depended on temperature. Diffusion coefficients were calculated according to the Fickian Law at several temperatures. The apparent activation energy was 5.43 kJ mol^?1, which corresponds to typical diffusion processes. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1389–1392, 2003