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As dental 5 mol% yttria-stabilized (5Y-) zirconia demand high esthetics, it is necessary to clarify how the optical properties are affected by high-speed sintering, which is not yet fully understood. Our study aimed to investigate the effect of high-speed sintering on the translucency and opalescence parameters (TP and OP, respectively), as well as their related microstructure and phase distribution, using two types of multilayered 5Y-zirconia. Multilayered 5Y-zirconia (Cercon xt ML, Lava Esthetic) were cut layer-by-layer, followed by conventional and high-speed sintering. The TP and OP values were subsequently obtained using a spectrophotometer, and field emission scanning electron microscopy images were used to analyze the average grain size. The phase fractions were analyzed using X-ray diffraction. Regardless of the zirconia type, the TP was slightly lowered by high-speed sintering in all the layers except the dentin layer (DL) for Lava Esthetic (p < 0.05). The OP decreased by high-speed sintering in the DL for Cercon xt ML and in all the layers for Lava Esthetic (p < 0.05). The decrease in translucency after high-speed sintering was attributed to a decrease in the yttria-rich t'-phase with low tetragonality, along with an increase in the yttria-lean t-phase with high tetragonality. [ABSTRACT FROM AUTHOR]

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]

Abstract: Mitochondrial dysfunction is a prominent feature of neurodegenerative diseases and aging. A recent study showed that phosphorylation of dynamin-related protein 1 (Drp1) is increased in Alzheimer''s disease (AD) brains compared to control brains, indicating that mitochondrial fission is increased in AD brains. Here, we showed that Drp1 phosphorylation and mitochondrial fission were also increased in rat cortical neurons treated with okadaic acid (OA), which inhibits protein phosphatase-2A (PP2A) and induces AD-like tau phosphorylation and neuronal death. Concurrent with this abnormal increase in mitochondrial fission, mitochondrial reactive oxygen species (ROS) were also increased, suggesting mitochondrial damage and detrimental effects on cell survival. Parkin, which is necessary for mitophagy of abnormal mitochondria and has been shown to be decreased in AD brains, and K48-linked polyubiquitin were also decreased in OA-treated neurons, suggesting that the mitophagic process required to degrade detrimental ROS-generating mitochondria is disabled. Collectively, our results demonstrate that abnormal mitochondrial fission, ROS generation, and inefficient mitophagy all occur in PP2A-inhibited neurons, as in AD brains, and suggest that this model could be used in developing inhibitors of mitochondrial fission or ROS generation. [Copyright &y& Elsevier]

Glazing is the final heat treatment process in the manufacturing of a monolithic zirconia prosthesis. Herein, the effect of cooling rate during zirconia glazing was investigated. A 3 mol% yttria-stabilized tetragonal zirconia polycrystal was glazed at the general cooling rate suggested by the manufacturer, as well as at higher and lower cooling rates, and the differences in flexural strength, hardness, optical properties, and crystal structure were evaluated. A higher cooling rate did not affect the flexural strength, hardness, grain size, optical properties, or crystal structure; however, the Weibull modulus decreased by 1.3. A lower cooling rate did not affect the flexural strength, optical properties, or crystal structure; however, the Weibull characteristic strength increased by 26.7 MPa and the Weibull modulus increased by 0.9. The decrease in hardness and the increase in grain size were statistically significant; however, the numerical differences were negligible. This study revealed that a lower cooling rate provides more reliable flexural strength. Therefore, glazing can proceed at a general cooling rate, which takes 3–4 min; however, glazing at a lower cooling rate will provide a more consistent flexural strength if desired, despite being time-consuming. [ABSTRACT FROM AUTHOR]

The link between Val232Met variant of phospholipase D3 (PLD3) and late-onset Alzheimer's disease (AD) is still obscure. While it may not affect directly the amyloid precursor protein function, PLD3 could be regulating multiple cellular compartments. Here, we investigated the function of wild-type human PLD3 (PLD3WT) and the Val232Met variant (PLD3VM) in the presence of β-amyloid (Aβ) in a Drosophila melanogaster model of AD. We expressed PLD3WT in CNS of the Aβ-model flies and monitored its effect on the ER stress, cell apoptosis and recovery the Aβ-induced cognitive impairment. The expression reduced ER stress and neuronal apoptosis, which resulted in normalized antioxidative phospholipids levels and brain protection. A specific O-glycosylation at pT271 in PLD3 is essential for its normal trafficking and cellular localization. The V232 M substitution impairs this O-glycosylation, leading to enlarged lysosomes and plausibly aberrant protein recycling. PLD3VM was less neuroprotective, and while, PLD3WT expression enhances the lysosomal functions, V232 M attenuated PLD3's trafficking to the lysosomes. Thus, the V232 M mutation may affect AD pathogenesis. Further understanding of the mechanistic role of PLD3 in AD could lead to developing novel therapeutic agents. • A specific O-glycosylation at pT271 in PLD3 is essential for its normal trafficking and cellular localization. • PLD3WT expression is neuroprotective, while pV232M attenuated PLD3's glycosylation, trafficking and lead to enlarged lysosomal structures. • The mechanistic role of PLD3 in AD could lead to developing novel therapeutic agents. [ABSTRACT FROM AUTHOR]

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.

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.

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.

Obesity-induced insulin resistance and diabetes are significantly associated with infiltrates of inflammatory cells in adipose tissue. Previous studies recognized the involvement of autophagy in the regulation of metabolism in multiple tissues, including β-cells, hepatocytes, myocytes, and adipocytes. However, despite the importance of macrophages in obesity-induced insulin resistance, the role of macrophage autophagy in regulating insulin sensitivity is seldom addressed. In the present study, we show that macrophage autophagy is important for the regulation of systemic insulin sensitivity. We found that macrophage autophagy is downregulated by both acute and chronic inflammatory stimuli, and blockade of autophagy significantly increased accumulation of reactive oxygen species (ROS) in macrophages. Macrophage-specific Atg7 knockout mice displayed a shift in the proportion to pro-inflammatory M1 macrophages and impairment of insulin sensitivity and glucose homeostasis under high-fat diet conditions. Furthermore, inhibition of ROS in macrophages with antioxidant recovered adipocyte insulin sensitivity. Our results provide evidence of the underlying mechanism of how macrophage autophagy regulates inflammation and insulin sensitivity. We anticipate our findings will serve as a basis for development of therapeutics for inflammatory diseases, including diabetes., Competing Interests: The authors declare that there is no conflict of interest associated with this manuscript.

The aim of this study was to determine the hardening effect by controlling the cooling rate during the porcelain firing process and performing an additional post-firing heat treatment in a Pd-Ag-Sn alloy. The most effective cooling rate for alloy hardening was determined by cooling the specimens at various cooling rates after oxidation treatment. A subsequent porcelain firing simulation followed by cooling at the selected cooling rate was performed. A post-firing heat treatment was then done at 600°C in a porcelain furnace. The hardening mechanism was characterized by a hardness test, X-ray diffraction, field emission scanning electron microscopy and energy dispersive X-ray spectroscopy. Alloy softening occurred during the porcelain firing process followed by cooling at a controlled cooling rate. A post-firing heat treatment allowed apparent precipitation hardening. It is advisable to perform a postfiring heat treatment at 600°C in a porcelain furnace by annealing metal substructure after porcelain fusing.

Accumulation of β-amyloid (Aβ) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular Aβ fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in Aβ degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular Aβ fibrils by microglia and in the regulation of the Aβ-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7 knockout mice and cell cultures. We found in microglial cultures that Aβ interacts with MAP1LC3B-II via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for AD.

Determination of structures and functions of pattern recognition proteins are important for understanding pathogen recognition mechanisms in host defense and for elucidating the activation mechanism of innate immune reactions. In this study, a novel 40-kDa protein, named LPS recognition protein (LRP), was purified to homogeneity from the cell-free plasma of larvae of the large beetle, Holotrichia diomphalia. LRP exhibited agglutinating activities on Escherichia coli, but not on Staphylococcus aureus and Candida albicans. This E. coli-agglutinating activity was preferentially inhibited by the rough-type LPS with a complete core oligosaccharide. LRP consists of 317 aa residues and six repeats of an epidermal growth factor-like domain. Recombinant LRP expressed in a baculovirus system also showed E. coli agglutination activity in vitro and was able to neutralize LPS by inhibition of LPS-induced IL-6 production in mouse bone marrow mast cells. Furthermore, E. coli coated with the purified LRP were more rapidly cleared in the Holotrichia larvae than only E. coli, indicating that this protein participates in the clearance of E. coli in vivo. The three amino-terminal epidermal growth factor-like domains of LRP, but not the three carboxyl epidermal growth factor-like domains, are involved in the LPS-binding activity. Taken together, this LRP functions as a pattern recognition protein for LPS and plays a role as an innate immune protein.