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.     

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.     

Mechanical properties and morphology of polymer blends of poly(ethylene terephthalate) and semiflexible thermotropic liquid crystalline polyesters

Two thermotropic liquid crystalline polyesters (TLCPs) with long flexible spacer groups in the main chain were prepared by melt polymerization: one was a homopolymer with only decane groups (LCPHO) and the other was a copolymer with hexane or decane groups (LCPCO) between mesogen units. These polyesters were blended with a matrix polymer of poly(ethylene terephthalate) (PET). Scanning electron microscopy (SEM) revealed the excellent interfacial adhesion between polyester and PET, and the large aspect ratio of polyester microfibrils in the blend fiber made by extruding and drawing the blend through a die. The aspect ratio was estimated by using the modified Halpin-Tsai equation. The fiber with LCPHO showed more extensive fibril formation than that with LCPCO.     

New Process for the Preparation of Monodispersed, Spherical Silica Particles

A new method is presented for preparing highly monodispersed silica particles using a two-stage semibatch/batch hydrolysis reaction of Si(OC₂H₅)₄. The slower rate of hydrolysis of the tetraethylorthosilicate (TEOS) that occurred during the semibatch process resulted in larger silica particles with a higher yield and narrower size distribution. This was in direct contrast to the batch process. In addition, the ability of four different mixed processes to produce silica particles with good packing density, narrower particle-size distribution, and higher yield were evaluated. These were batch/batch (B-B), batch/semibatch (B-S), semibatch/batch (S-B), and semibatch/semibatch (S-S) processes. The S-S system produced the largest particles with the highest yields. The size of the silica particles obtained by the S-B method decreased with increasing reaction time, while the particles obtained by the B-S process had the best particle-size distribution and packing density. In conclusion, a mixed batch/semibatch system was the best way to produce an extremely narrow particle-size distribution and a good packing density.     

Biodegradability and mechanical properties of agro‐flour–filled polybutylene succinate biocomposites

The objective of this study was the production of rice husk flour (RHF) and wood flour (WF) filled polybutylene succinate (PBS) biocomposites as alternatives to cellulosic material filled conventional plastic (polyolefins) composites. PBS is one of the biodegradable polymers, made from the condensation reaction of 1,4‐butanediol and succinic acid that can be naturally degraded in the natural environment. We compared the mechanical properties between conventional plastics and agro‐flour–filled PBS biocomposites. We evaluated the biodegradability and mechanical properties of agro‐flour–filled PBS biocomposites according to the content and filler particle size of agro‐flour. As the agro‐flour loading was increased, the tensile and impact strength of the biocomposites decreased. As the filler particle size decreased, the tensile strength of the biocomposites increased but the impact strength decreased. The addition of agro‐flour to PBS produced a more rapid decrease in the tensile strength, notched Izod impact strength, and percentage weight loss of the biocomposites during the natural soil burial test. These results support the application of biocomposites as environmentally friendly materials. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1513–1521, 2005