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The differences in the optical properties of multi-layered zirconia with and without yttria-gradient are not fully understood. This study aimed to evaluate and compare the optical properties, related microstructures, and phase fractions of multi-layered zirconia with and without yttria-gradient. For this, multi-layered zirconia of 5 mol% yttria (5Y) stabilized (Katana STML) and 4Y/5Y stabilized (e.max MT Multi) were cut layerwise, sintered, and analyzed using the opalescence parameter (OP), average transmittance (AT%), translucency parameter (TP), and contrast ratio (CR). The average grain size and phase fractions were obtained from field-emission scanning electron micrographs and X-ray diffraction patterns, respectively. Although the TP values of Katana STML and e.max MT Multi did not show a significant difference (except for transition layer 1), the results of AT and CR showed that the translucency of e.max MT Multi was slightly higher than that of Katana STML (p < 0.05). The opalescence gradient was higher in Katana STML than in the e.max MT Multi. In both zirconia types, translucency increased from the dentin to enamel layer based on the AT, TP, and CR results, while OP decreased (p < 0.05). The higher translucency from the dentin to enamel layer in Katana STML was caused by the pigmentation gradient, while in e.max MT Multi, it was caused by the difference in phase fraction and the pigmentation gradient. [ABSTRACT FROM AUTHOR]

Background: Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer's disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce.Objective: To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions.Methods: BV2 cells were treated with orexin and Aβ for various durations and phagocytic and autophagic processes for degradation of extracellular Aβ were examined.Results: After treatment with orexin, the formation of actin filaments around Aβ fibrils, which is needed for phagocytosis, was impaired, and phagocytosis regulating molecules such as PI3K, Akt, and p38-MAPK were downregulated in BV2 cells. Orexin also suppressed autophagic flux, through disruption of the autophagosome-lysosome fusion process, resulting in impaired Aβ degradation in BV2 cells.Conclusions: Our results demonstrate that orexin can hinder clearance of Aβ through the suppression of phagocytosis and autophagic flux in microglia. This is a novel mechanism linking AD and sleep, and suggests that attenuated microglial function, due to sleep deprivation, may increase Aβ accumulation in the brain. [ABSTRACT FROM AUTHOR]

Background: Amyloid precursor protein (APP) is cleaved by β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) to produce β-amyloid (Aβ), a critical pathogenic peptide in Alzheimer's disease (AD). Aβ generation can be affected by the intracellular trafficking of APP or its related secretases, which is thus important to understanding its pathological alterations. Although sorting nexin (SNX) family proteins regulate this trafficking, the relevance and role of sorting nexin-4 (SNX4) regarding AD has not been studied yet., Methods: In this study, human brain tissue and APP/PS1 mouse brain tissue were used to check the disease relevance of SNX4. To investigate the role of SNX4 in AD pathogenesis, several experiments were done, such as coimmunoprecipitation, Western blotting, immunohistochemistry, and gradient fractionation., Results: We found that SNX4 protein levels changed in the brains of patients with AD and of AD model mice. Overexpression of SNX4 significantly increased the levels of BACE1 and Aβ. Downregulation of SNX4 had the opposite effect. SNX4 interacts with BACE1 and prevents BACE1 trafficking to the lysosomal degradation system, resulting in an increased half-life of BACE1 and increased production of Aβ., Conclusions: We show that SNX4 regulates BACE1 trafficking. Our findings suggest novel therapeutic implications of modulating SNX4 to regulate BACE1-mediated β-processing of APP and subsequent Aβ generation.