Prevotella histicola ameliorates DSS-induced colitis by inhibiting IRE1α-JNK pathway of ER stress and NF-κB signaling.

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.

Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported by the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression is associated with reduced BDNF signaling. We found that peptidomimetic compounds that bind to PSD-95 promoted signaling by the BDNF receptor TrkB in the hippocampus and reduced depression-like behaviors in mice. The compounds CN2097 and Syn3 both bind to the PDZ3 domain of PSD-95, and Syn3 also binds to an α-helical region of the protein. Syn3 reduced depression-like behaviors in two mouse models of stress-induced depression; CN2097 had similar but less potent effects. In hippocampal neurons, application of Syn3 enhanced the formation of TrkB-Gαi1/3-PSD-95 complexes and potentiated downstream PI3K-Akt-mTOR signaling. In mice subjected to chronic mild stress (CMS), systemic administration of Syn3 reversed the CMS-induced, depression-associated changes in PI3K-Akt-mTOR signaling, dendrite complexity, spine density, and autophagy in the hippocampus and reduced depression-like behaviors. Knocking out Gαi1/3 in hippocampal neurons prevented the therapeutic effects of Syn3, indicating dependence of these effects on the TrkB pathway. The findings suggest that compounds that induce the formation of PSD-95-TrkB complexes have therapeutic potential to alleviate depression.

Heightened neural reward responsiveness functions as a plasticity factor moderating the association between childhood emotional abuse and young adult depressive symptoms: Evidence of differential susceptibility.

As a neural indicator of reward responsiveness (RR), reward positivity (RewP) has been demonstrated to moderate the association between stress exposure and depressive symptoms. However, extant research has primarily (a) focused on life stress rather than early maltreatment, (b) ignored the time-frequency components, and (c) has been based on a traditional perspective of diathesis stress. The present study aimed to comprehensively examine whether and how neurophysiological (RewP and its time-frequency decomposition components) and self-reported measures of RR interact with childhood emotional abuse on young adult depressive symptoms. The sample of 192 Chinese university students aged 18-25 (Mage = 21.08 ± 1.91 years; 59.4% girls) completed self-reported questionnaires of emotional abuse, depressive symptoms and RR. The RewP and its time-frequency components delta and theta were elicited via a monetary reward task. The results demonstrated that RewP significantly moderated the association between emotional abuse and young adult depressive symptoms in a differential susceptibility but not diathesis-stress manner. However, gain-related delta, loss-related theta, or self-reported RR did not drive such moderation effects. These findings were robust and survived a series of rigorous sensitivity analyses. The current findings provide preliminary evidence that heightened RewP may function as a plasticity factor moderating the association between early maltreatment exposure and depression, and highlight the effect specific to emotional abuse. However, caution should be paid to the generalizability of these findings in high-risk clinical samples, in light of the current high-functioning sample features and low rates of high symptom and abuse levels. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

GABPB1 plays a cancer-promoting role in non-small cell lung cancer.

BACKGROUND: GABPB1, the gene that encodes two isoforms of the beta subunit of GABP, has been identified as an oncogene in multiple malignant tumors. However, the role and mode of action of GABPB1 in malignant tumors, especially in lung cancer, are not well understood and need further research. METHODS: Our research focused on examining the biological function of GABPB1 in NSCLC (Non-Small Cell Lung Cancer). We analysed tumor data from public databases to assess the expression of GABPB1 in NSCLC  and its correlation with patient prognosis and investigated GABPB1 expression and methylation patterns in relation to the tumor microenvironment. In parallel, experiments were conducted using short hairpin RNA (shRNA) to suppress the GABPB1 gene in human lung cancer cells to evaluate the effects on cell proliferation, viability, and apoptosis. RESULTS: GABPB1 was widely expressed in various tissues of the human body. Compared to that in normal tissues, the expression of this gene was different in multiple tumor tissues. GABPB1 was highly expressed in lung cancer tissues and cell lines. Its expression was associated with molecular subtype and cellular signalling pathways, and a high level of GABPB1 expression was related to a poor prognosis in lung adenocarcinoma patients. The expression and methylation of GABPB1 affect the tumor microenvironment. After suppressing the expression of GABPB1 in both A549 and H1299 cells, we found a decrease in cell growth and expression, the formation of clones and an increase in the apoptosis rate. CONCLUSIONS: Our research verified that GABPB1 promotes the tumorigenesis of NSCLC and has an inhibitory effect on tumor immunity. The specific role of GABPB1 may vary among different pathological types of NSCLC. This molecule can serve as a prognostic indicator for lung adenocarcinoma, and its methylation may represent a potential breakthrough in treatment by altering the tumor immune microenvironment in lung squamous cell carcinoma. The role and mechanism of action of GABPB1 in NSCLC should be further explored.

Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP-Activated Exchange Protein-1.

Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH-induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood-induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single-cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP-activated exchange protein-1 (EPAC-1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC-1) to inhibit its interaction with voltage-dependent anion-selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron-specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC-1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC-1 with celastrol can be a promising therapeutic approach for treating ICH-induced SBI.

G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.

The role of SUMO specific peptidase 3 in secondary inflammation of ischemic stroke in mice.

Ischemic stroke is the main cause of death and disability, and microglia play a crucial role in the pathophysiology of hypoxic ischemic brain injury. We found that SENP3 is highly expressed in the early stages of ischemic stroke in both in vivo and in vitro mouse models, and may be related to the deSUMOylation of the key kinase MKK7 in the TLR4/p-JNK signaling pathway. Knocking down SENP3 can inhibit the deSUMOylation of MKK7, thereby inhibiting the activation of the TLR4/p-JNK signaling pathway in an in vitro stroke model. Proteomic analysis showed that SENP3 undergoes phosphorylation at the T429 site after ischemic stroke. Computer simulation predictions show a significant enhancement of the interaction between pT429-SENP3 and MKK7, which has been confirmed through experiments on the interaction of biological macromolecules (SPR). The mitochondrial metabolic abnormalities caused by energy abnormalities in the early stages of stroke provide a good explanation for the phosphorylation of SENP3. Therefore, we used the mitochondrial complex inhibitor TTFA to reverse demonstrate that the phosphorylation of SENP3 comes from the large amount of adenosine triphosphate produced by mitochondrial abnormal metabolism caused by early oxygen glucose deficiency. Finally, proteomic analysis indicates that a significant amount of oxidative phosphorylation does occur in the early stages of stroke. In summary, targeted regulation of SENP3 phosphorylation to affect the deSUMOylation of MKK7 may inhibit secondary inflammation in ischemic stroke.

Childhood maltreatment, multilocus HPA-axis genetic variation and adolescent comorbidity profiles of depressive and anxiety symptoms.

BACKGROUND: Despite a growing body of evidence showing both genetic and environmental influences on adolescent depression and anxiety, the involved comorbid mechanisms regarding gene-by-environment (G × E) interaction remain unclear. OBJECTIVE: The current study was the first to investigate the extent to which multilocus hypothalamic-pituitary-adrenal (HPA)-axis genetic variants moderated the association between childhood maltreatment and adolescent comorbid depression and anxiety. METHODS: The participants were 827 Chinese Han adolescents (Mage = 16.45 ± 1.37 years; 50.2 % girls). A theory-driven multilocus genetic profile score (MGPS) was computed by calculating alleles of core HPA-axis genes (CRHR1, NR3C1, NR3C2, and FKBP5) associated with heightened stress reactivity. Childhood maltreatment was retrospectively collected using Childhood Trauma Questionnaire. Comorbidity profiles of self-reported adolescent depressive and anxiety symptoms were constructed via person-centered latent profile analysis. RESULTS: Three heterogeneous comorbidity profiles of depressive and anxiety symptoms were identified: comorbid severe symptoms (9.7 %), comorbid moderate symptoms (46.4 %) and comorbid mild symptoms (43.9 %). The HPA-axis related MGPS significantly interacted with childhood maltreatment, especially emotional maltreatment (emotional abuse: OR = 1.14, 95 % CI [1.03, 1.26], p < .01; emotional neglect: OR = 1.07, 95 % CI [1.01, 1.13], p < .05), to distinguish the comorbid severe symptoms profile from the comorbid mild symptoms profile (OR = 1.03, 95 % CI [1.01, 1.06], p < .05). CONCLUSION: The HPA-axis related genes showed an additive polygenic sensitivity toward childhood maltreatment, which might be one of the polygenic G × E mechanisms underlying adolescent comorbid depression and anxiety.

The effects of childhood maltreatment, recent interpersonal and noninterpersonal stress, and HPA-axis multilocus genetic variation on prospective changes in adolescent depressive symptoms: A multiwave longitudinal study.

Based on a multiwave, two-year prospective design, this study is the first to examine the extent to which multilocus hypothalamic-pituitary-adrenal axis (HPA axis)-related genetic variants, childhood maltreatment, and recent stress jointly predicted prospective changes in adolescent depressive symptoms. A theory-driven multilocus genetic profile score (MGPS) was calculated to combine the effects of six common polymorphisms within HPA-axis related genes (CRHR1, NR3C1, NR3C2, FKBP5, COMT, and HTR1A) in a sample of Chinese Han adolescents (N = 827; 50.2% boys; Mage = 16.45 ± 1.36 years). The results showed that the three-way interaction of HPA-axis related MGPS, childhood maltreatment and recent interpersonal, but not noninterpersonal, stress significantly predicted prospective changes in adolescent depressive symptoms. For adolescents with high but not low HPA-axis related MGPS, exposure to severe childhood maltreatment predisposed individuals more vulnerable to recent interpersonal stress, exhibiting greater prospective changes in adolescent depressive symptoms. The findings provide preliminary evidence for the cumulative risk mechanism regarding gene-by-environment-by-environment (G × E1 × E2) interactions that underlie the longitudinal development of adolescent depressive symptoms and show effects specific to interpersonal stress.

Controllable nonreciprocal phonon laser in a hybrid photonic molecule based on directional quantum squeezing.

Here, a scheme for a controllable nonreciprocal phonon laser is proposed in a hybrid photonic molecule system consisting of a whispering-gallery mode (WGM) optomechanical resonator and a χ(2)-nonlinear WGM resonator, by directionally quantum squeezing one of two coupled resonator modes. The directional quantum squeezing results in a chiral photon interaction between the resonators and a frequency shift of the squeezed resonator mode with respect to the unsqueezed bare mode. We show that the directional quantum squeezing can modify the effective optomechanical coupling in the optomechanical resonator, and analyze the impacts of driving direction and squeezing extent on the phonon laser action in detail. Our analytical and numerical results indicate that the controllable nonreciprocal phonon laser action can be effectively realized in this system. The proposed scheme uses an all-optical and chip-compatible approach without spinning resonators, which may be more beneficial for integrating and packaging of the system on a chip. Our proposal may provide a new route to realize integratable phonon devices for on-chip nonreciprocal phonon manipulations, which may be used in chiral quantum acoustics, topological phononics, and acoustical information processing.

Pyruvate maintains and enhances the pro-inflammatory response of microglia caused by glucose deficiency in early stroke.

Pro-inflammatory microglia mainly rely on glycolysis to maintain cytokine production during ischemia, accompanied by an increase in inducible nitric oxide synthase (iNOS) and monocarboxylate transporter 1 (MCT1). The role of energy metabolism in the pro-inflammatory response of microglia is currently unclear. In this study, we tested the response of microglia in mice after cerebral ischemia and simulated an energy environment in vitro using low glucose culture medium. The research results indicate that the expression levels of iNOS and arginase 1 (ARG1) increase in the ischemic mouse brain, but the upregulation of MCT1 expression is mainly present in iNOS positive microglia. In microglia exposed to low glucose conditions, iNOS and MCT1 levels increased, while ARG1 levels decreased. Under the same conditions, knocking down MCT1 in microglia leads to a decrease in iNOS levels, while overexpression of MCT1 leads to the opposite result. The use of NF-κB inhibitors reduced the expression levels of iNOS and MCT1 in microglia. In summary, our data indicate that pyruvate maintains and enhances the NF-κB regulated pro-inflammatory response of microglia induced by low glucose.

Effects of Brown Fishmeal on Growth Performance, Digestibility, and Lipid Metabolism of the Chinese Soft-Shelled Turtle (Pelodiscus sinensis).

The aim of this study was to evaluate the effect of brown fishmeal in replacement of white fishmeal in the diet of Chinese soft-shelled turtles and to find the optimal amount of brown fishmeal to add. Five experimental groups were set up and fed to animals, and they were composed by different proportions of white and brown fishmeal: G1 (30% white and 25% brown fishmeal), G2 (25% white and 30% brown fishmeal), G3 (20% white and 35% brown fishmeal), G4 (15% white and 40% brown fishmeal), G5 (10% white and 45% brown fishmeal). G1 is regarded as the control group. Turtles were randomly divided into five experimental groups with four replicates each. The experiment lasted 72 days. The results showed that the WGR, SGR, FCR, and HSI of the G3 group were not significantly different from those of the control group (P > 0.05). In addition, brown fishmeal can increase the crude protein content in the muscles of them. Among the serum biochemical indices, there was no significant difference between the G3 group and the G1 group, except for the level of TG (P > 0.05). Meanwhile, the activities of AST, ALT, and CAT in the liver of the G3 group did not differ significantly from those of the G1 group (P > 0.05). However, the activities of ACP, AKP, and T-AOC were significantly decreased in the G3 group (P < 0.05). In addition, the alteration of fishmeal did not affect the digestive enzyme activities in the stomach, liver, and intestine, and there is no significant difference (P > 0.05). Importantly, with increasing brown fishmeal addition, the expression of Fas, Pparγ, Scd, and Stat3 showed a significant increase, while the expression of Bmp4 decreased significantly (P < 0.05). In this study, the addition of 20% white fishmeal and 35% brown fishmeal to the diet of Chinese soft-shelled turtles did not adversely affect growth performance. Therefore, 20% white fishmeal and 35% brown fishmeal are the most practical feed formulations for Chinese soft-shelled turtles in this study.

The mediation effect of glucocorticoid receptor gene (NR3C1) methylation between childhood maltreatment and depressive symptoms in Chinese adolescents: A 2-year longitudinal study.

This three-wave longitudinal study examined whether methylation alterations in promoter exon 1F of a stress-related gene-NR3C1 (NR3C1-1F)-explained the longitudinal associations between childhood maltreatment and adolescent depressive symptoms. A total of 370 Han Chinese adolescents (Mage = 16.31 ± 1.28 years; 51.4% girls) recruited from Shandong, China were tracked from 2018 to 2020. The results showed that the severity of childhood maltreatment, especially that of emotional abuse and physical neglect, conferred risk for adolescent depressive symptoms via reducing NR3C1-1F methylation levels. These mediation effects of NR3C1-1F methylation did not vary between adolescent sex or NR3C1 BclI and Tth111I polymorphisms. The findings highlight how childhood maltreatment contributes to psychopathology development at a biological level.

Distinct dyadic quality of life profiles among patient-caregiver dyads with advanced lung cancer: a latent profile analysis.

PURPOSE: This study aimed to identify the heterogeneity of dyadic quality of life (QoL) profiles, determine whether these profiles differ in terms of demographic and medical factors, neuroticism, resilience, and family functioning, and explore the combined effect of patient and caregiver neuroticism, resilience, and family functioning on dyadic QoL profiles. METHODS: A cross-sectional study was conducted with 304 advanced lung cancer patient-caregiver dyads. Self-report questionnaires were administered to patient-caregiver dyads to assess demographic and medical characteristics, neuroticism, resilience, family functioning, and QoL. RESULTS: The latent profile analysis identified four subgroups of dyadic QoL: patient-low-caregiver-high profile (38.82%), patient-high-caregiver-high profile (22.37%), patient-high-caregiver-low profile (19.74%), and patient-low-caregiver-low profile (19.08%). Additionally, when both patients and their caregivers had a high level of neuroticism or low level of resilience and low family functioning, compared with only member having them, there was a higher risk of poorer dyadic QoL. CONCLUSIONS: Our study identified the four heterogeneities of dyadic QoL profiles among advanced lung cancer patient-caregiver dyads. Future dyadic interventions should consider the heterogeneity of dyadic QoL in this population and prioritize patient-caregiver dyads at risk of poor dyadic QoL. Furthermore, when high neuroticism, low resilience, or family functioning coexist between patients and their caregivers, both parties exhibit much lower dyadic QoL.

A Digital Mask-Voiceprint System for Postpandemic Surveillance and Tracing Based on the STRONG Strategy.

Lockdowns and border closures due to COVID-19 imposed mental, social, and financial hardships in many societies. Living with the virus and resuming normal life are increasingly being advocated due to decreasing virus severity and widespread vaccine coverage. However, current trends indicate a continued absence of effective contingency plans to stop the next more virulent variant of the pandemic. The COVID-19-related mask waste crisis has also caused serious environmental problems and virus spreads. It is timely and important to consider how to precisely implement surveillance for the dynamic clearance of COVID-19 and how to efficiently manage discarded masks to minimize disease transmission and environmental hazards. In this viewpoint, we sought to address this issue by proposing an appropriate strategy for intelligent surveillance of infected cases and centralized management of mask waste. Such an intelligent strategy against COVID-19, consisting of wearable mask sample collectors (masklect) and voiceprints and based on the STRONG (Spatiotemporal Reporting Over Network and GPS) strategy, could enable the resumption of social activities and economic recovery and ensure a safe public health environment sustainably.

Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.

The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and ß-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

Morphologic Analysis of Zirconia Ceramics: Effect of Different Surface Treatments.

PURPOSE: To investigate the effects of airborne-particle abrasion and nanosilica (nano-Si) infiltration treatment on the surface characteristics of dental zirconia. MATERIALS AND METHODS: A total of 15 unsintered zirconia ceramic green bodies (10 × 10 × 3 mm) were divided into three groups (n = 5): Group C, no treatment after sintering; Group S, airborne-particle abrasion with 50-µm aluminum oxide particles after sintering; and Group N, infiltration of nano-Si followed by sintering and hydrofluoric acid (HF) etching. The zirconia disks' surface roughness was analyzed by atomic force microscopy (AFM). The surface morphology of the specimens was analyzed using scanning electron microscopy (SEM), and the chemical composition was analyzed by energy-dispersive x-ray (EDX). Data were statistically analyzed by the Kruskal-Wallis test (P < .05). RESULTS: Zirconia surface treatments by infiltration of nano-Si, sintering, and HF etching showed multiple changes in the surface features. The surface roughness of Groups C, S, and N were 0.88 ± 0.07 µm, 1.26 ± 0.10 µm, and 1.69 ± 0.15 µm, respectively. The surface roughness of Group N was significantly higher than that of Groups C and S (P < .05). EDX analysis showed peaks that corresponded to silica (Si) after infiltration with colloidal Si that disappeared following acid etching. CONCLUSIONS: Infiltrating nano-Si increases the surface roughness of zirconia. The formation of retentive nanopores on the surface potentially improves the zirconia-resin cement bonding strengths.

Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.

We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.