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Carbon-supported noble-metal-free single-atom catalysts (SACs) have aroused widespread interest due to their green chemistry aspects and excellent performances. Herein, we propose a "ligand regulation strategy" and achieve the successful fabrication of bifunctional SAC/MOF (MOF = metal–organic framework) nanocomposite (abbreviated NiSA/ZIF-300; ZIF = ZIF-8) with exceptional catalytic performance and robustness. The designed NiSA/ZIF-300 has a planar interfacial structure with the Ni atom, involving one S and three N atoms bonded to Ni(II), fabricated by controllable pyrolysis of volatile Ni-S fragments. For CO2 cycloaddition to styrene epoxide, NiSA/ZIF-300 exhibits ultrahigh activity (turnover number (TON) = 1.18 × 105; turnover frequency (TOF) = 9830 molSC·molNi−1·h−1; SC = styrene carbonate) and durability at 70 °C under 1 atm CO2 pressure, which is much superior to Ni complex/ZIF, NiNP/ZIF-300, and most reported catalysts. This study offers a simple method of bifunctional SAC/MOF nanocomposite fabrication and usage, and provides guidance for the precise design of additional original SACs with unique catalytic properties. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction (MGD) is a group of disorders linked by functional abnormalities of the meibomian glands. Current studies on MGD pathogenesis focus on meibomian gland cells, providing information on a single cell's response to experimental manipulation, and do not maintain the architecture of an intact meibomian gland acinus and the acinar epithelial cells' secretion state in vivo. In this study, rat meibomian gland explants were cultured by a Transwell chamber-assisted method under an air-liquid interface (airlift) in vitro for 96 h. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and TUNEL assays, hematoxylin and eosin (H&E) staining, immunofluorescence, Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), transmission electron microscopy (TEM), and western blotting (WB). MTT, TUNEL, and H&E staining indicated better tissue viability and morphology than the submerged conditions used in previous studies. Levels of MGD biomarkers, including keratin 1 (KRT1) and 14 (KRT14) and peroxisome proliferator-activated receptor-gamma (PPAR-γ), along with oxidative stress markers, including reactive oxygen species, malondialdehyde, and 4-hydroxy-2-nonenal, gradually increased over culture time. The MGD pathophysiological changes and biomarker expression of meibomian gland explants cultured under airlift conditions were similar to those reported by previous studies, indicating that abnormal acinar cell differentiation and glandular epithelial cell hyperkeratosis may contribute to obstructive MGD occurrence. [ABSTRACT FROM AUTHOR]

Electrostrictive materials have wide applications in modern high‐precision electronic devices. Driven by growing environmental concerns, there is demand for lead‐free materials with superior electrostriction behaviors. In this study, we demonstrate a record‐high electrostrictive coefficient of ~0.0712 m4 C−2 in perovskite ferroelectric ceramics, along with hysteresis‐free strain as well as excellent frequency and thermal stabilities, in lead‐free BaTiO3‐based ceramics through a polarization nanocluster design. By appropriately introducing Li+ and Bi3+ into the BaTiO3 lattice matrix, the long‐range ferroelectric ordering can be broken, and polarization nanoclusters can be formed, resulting in a relaxor state with concurrently suppressed polarization and maintained electro‐strain. A three‐dimensional atomic model constructed using advanced neutron total‐scattering data combined with the reverse Monte Carlo method indicates the existence of Bi and Li segregations at the subnanometer scale, which confirms the prediction made by density functional theory calculations. Such a short‐range chemical order destroys the long‐range ferroelectric order of the off‐centered Ti polar displacements and leads to the embedding of Li+/Bi3+‐rich polar nanoregions in the Ba2+‐rich polarization disorder matrix. Further, a completely reversible electric‐field‐induced lattice strain is observed, giving rise to pure electrostriction without hysteresis behavior. This work provides a novel strategy for developing lead‐free relaxor ferroelectrics with high electrostriction performance. [ABSTRACT FROM AUTHOR]

Regulatory T-cells (Tregs) play pivotal roles during infection, cancer, and autoimmunity. In our previous study, we demonstrated a role for the PD-1:PD-L1 pathway in controlling cytolytic responses of CD8+ T lymphocytes against microglial cells presenting viral peptides. In this study, we investigated the role of Tregs in suppressing CD8+ T-cell-mediated cytotoxicity against primary microglial cells. Using in vitro cytotoxicity assays and flow cytometry, we demonstrated a role for Tregs in suppressing antigen-specific cytotoxic T-lymphocyte (CTL) responses against microglia loaded with a model peptide (SIINFEKL). We went on to show a significant decrease in the frequency of IFN-γ- and TNF-producing CD8+ T-cells when cultured with Tregs. Interestingly, a significant increase in the frequency of granzyme B- and Ki67-producing CTLs was observed. We also observed a significant decrease in the production of interleukin (IL)-6 by microglia. On further investigation, we found that Tregs significantly reduced MHC class 1 (MHC-1) expression on IFN-γ-treated microglial cells. Taken together, these studies demonstrate an immunosuppressive role for Tregs on CTL responses generated against primary microglia. Hence, modulation of Treg cell activity in combination with negative immune checkpoint blockade may stimulate anti-viral T-cell responses to more efficiently clear viral infection from microglial cell reservoirs. [ABSTRACT FROM AUTHOR]

Highly active and multifunctional non‐precious metal‐based hydrogen evolution reaction (HER) eletcrocatalysts have aroused great interest in the large‐scale conversion of sustainable electrical energy to fuels and feedstocks in different application scenarios. Here, a metal sulfide‐based super hybrid nanoarray composed of a metallic Co3S4 nanosheet, P doped WS2 nanosheet, and Co9S8 nanoparticles (Super‐Co3S4/P‐WS2/Co9S8) for all‐pH HER is reported. The Super‐Co3S4/P‐WS2/Co9S8 only requires 58, 70, and 129 mV in alkaline, acid, and neutral media, respectively, to reach 10 mA cm‐2, which also presents fast reaction kinetics and high long‐term stability. The experimental and density functional theory (DFT) results verify that the abundant active heterostructure in Super‐Co3S4/P‐WS2/Co9S8 can not only provide Pt‐like H*‐adsorption Gibbs free energy (ΔGH*) but also promote the H2O adsorption and dissociation kinetics for all‐pH HER. Moreover, the collaboration of favorable metallic components and special nanoarray morphology can also strengthen the electric conductivity for electron transfer and promote the maximum exposure of active heterointerfaces for mass transport in electrocatalysis. The interesting strategy herein is expected to inspire the future design of advanced metal sulfide‐based heterostructures for energy storage and conversion. [ABSTRACT FROM AUTHOR]

Electrocatalytic hydrogen production in alkaline media is extensively adopted in industry. Unfortunately, further performance improvement is severely impeded by the retarded kinetics, which requires the fine regulation of water dissociation, hydrogen recombination, and hydroxyl desorption. Herein, we develop a multi-interface engineering strategy to make an elaborate balance for the alkaline hydrogen evolution reaction (HER) kinetics. The graphene cross-linked three-phase nickel sulfide (NiS-NiS2-Ni3S4) polymorph foam (G-NNNF) was constructed through hydrothermal sulfidation of graphene wrapped nickel foam as a three-dimensional (3D) scaffold template. The G-NNNF exhibits superior catalytic activity toward HER in alkaline electrolyte, which only requires an overpotential of 68 mV to drive 10 mA·cm−2 and is better than most of the recently reported metal sulfides catalysts. Density functional theory (DFT) calculations verify the interfaces between nickel sulfides (NiS/NiS2/Ni3S4) and cross-linked graphene can endow the electrocatalyst with preferable hydrogen adsorption as well as metallic nature. In addition, the electron transfer from Ni3S4/NiS2 to NiS results in the electron accumulation on NiS and the hole accumulation on Ni3S4/NiS2, respectively. The electron accumulation on NiS favors the optimization of the H* adsorption, whereas the hole accumulation on Ni3S4 is beneficial for the adsorption of H2O. The work about multi-interface collaboration pushes forward the frontier of excellent polymorph catalysts design. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is a chronic disease that places a heavy burden on caregivers. Previous studies have shown that caregivers of epilepsy patients often experience anxiety and depression; however, few comprehensive studies have assessed their sleep quality and family function. Based on the current understanding of the anxiety and depression state of caregivers in children with epilepsy, we further explored the caregivers' sleep and family function and evaluated the predictors of the depression state of caregivers. Methods: In this cross-sectional online anonymous survey, we sent an online questionnaire to the caregivers of children with epilepsy who visited our hospital. The QR code of the questionnaire was scanned at the follow-up course to conduct an online survey. The questionnaire contained questions about sociodemographic and clinical information, the Self-rating Anxiety Scale, Self-rating Depression Scale, Pittsburgh Sleep Quality Index, and the Family Assessment Device. Results: A total of 308 caregivers of children with epilepsy aged 0–12 years were included in this study. The mean age of children with epilepsy was 4.8 ± 3.18 years, and the average illness duration was 34.2 ± 29.18 months. Further, 47.1% of the children took three or more anti-seizure medications, and 43.2% were on ketogenic diet therapy. We found that in 77.9% of the cases, the subjects were the mothers, in 89% there was more than one co-caregiver, and in 51.9%, financial help was required. Further, 63.6% of the caregivers thought they could not get enough access to disease knowledge education, and 83.7% perceived epilepsy was a terrible disease. Our results also showed that 65.6% of the caregivers were in depression status, 41.9% were in anxiety status, and 49.0% had poor sleep quality. The proportion of unhealthy family functioning in each subscale was 45.1–96.1%, and the unhealthy behavior control function accounted for 96.1%. Binary logistic regression analysis of the data showed that without co-caregivers [odds ratio (OR), 5.193], free of anxiety status (OR, 0.063), good sleep quality (OR, 0.446), healthy family role dimension (OR, 0.344), and healthy family general functional dimension (OR, 0.259) were predictors of depression status in caregivers of children with epilepsy. Conclusion: Anxiety and depression status are common in caregivers of children with epilepsy, with depression status being more prominent. Moreover, a considerable proportion of caregivers had poor sleep quality and unhealthy family function. The caregivers' anxiety status, sleep quality, family role dimension, family general function dimension, and the number of co-caregivers were predictors of depression status in caregivers. In clinical practice, caregivers' anxiety and depression status, poor sleep quality, and unhealthy family functioning should be addressed along with the treatment of children with epilepsy. [ABSTRACT FROM AUTHOR]

Upon reactivation of quiescent neurotropic viruses antigen (Ag)-specific brain resident-memory CD8+ T-cells (bTRM) may respond to de novo -produced viral Ag through the rapid release of IFN-γ, which drives subsequent interferon-stimulated gene expression in surrounding microglia. Through this mechanism, a small number of adaptive bTRM may amplify responses to viral reactivation leading to an organ-wide innate protective state. Over time, this brain-wide innate immune activation likely has cumulative neurotoxic and neurocognitive consequences. We have previously shown that HIV-1 p24 Ag-specific bTRM persist within the murine brain using a heterologous prime-CNS boost strategy. In response to Ag restimulation, these bTRM display rapid and robust recall responses, which subsequently activate glial cells. In this study, we hypothesized that repeated challenges to viral antigen (Ag) (modeling repeated episodes of viral reactivation) culminate in prolonged reactive gliosis and exacerbated neurotoxicity. To address this question, mice were first immunized with adenovirus vectors expressing the HIV p24 capsid protein, followed by a CNS-boost using Pr55Gag/Env virus-like particles (HIV-VLPs). Following the establishment of the bTRM population [>30 days (d)], prime-CNS boost animals were then subjected to in vivo challenge, as well as re-challenge (at 14 d post-challenge), using the immunodominant HIV-1 AI9 CD8+ T-cell epitope peptide. In these studies, Ag re-challenge resulted in prolonged expression of microglial activation markers and an increased proliferative response, longer than the challenge group. This continued expression of MHCII and PD-L1 (activation markers), as well as Ki67 (proliferative marker), was observed at 7, 14, and 30 days post-AI9 re-challenge. Additionally, in vivo re-challenge resulted in continued production of inducible nitric oxide synthase (iNOS) with elevated levels observed at 7, 14 and 30 days post re-challenge. Interestingly, iNOS expression was significantly lower among challenged animals when compared to re-challenged groups. Furthermore, in vivo specific Ag re-challenge produced lower levels of arginase (Arg)-1 when compared with the challenged group. Taken together, these results indicate that repeated Ag-specific stimulation of adaptive immune responses leads to cumulative dysregulated microglial cell activation. [ABSTRACT FROM AUTHOR]

Defects in metal oxides can significantly improve their physical and chemical properties. However, the conventional methods to generate defects often require complex procedures and harsh conditions. In this study, we design a simple and room-temperature preparation route to prepare defective metal oxide nanoparticles with high yield. The formation of defects is attributed to the generation of oxygen vacancies (VO) and hydrogenation caused by charge transfer at a Mg–metal oxide junction structure. Defective TiO2 exhibits excellent performance toward wastewater cleaning and water splitting. The proposed route is promising in terms of convenience, low cost, and large-scale production. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Previous work from our laboratory has demonstrated in vivo persistence of CD103+CD69+ brain resident memory CD8+ T‐cells (bTRM) following viral infection, and that the PD‐1: PD‐L1 pathway promotes development of these TRM cells within the brain. Although glial cells express low basal levels of PD‐L1, its expression is upregulated upon IFN‐γ‐treatment, and they have been shown to modulate antiviral T‐cell effector responses through the PD‐1: PD‐L1 pathway. Methods: We performed flow cytometric analysis of cells from co‐cultures of mixed glia and CD8+ T‐cells obtained from wild type mice to investigate the role of glial cells in the development of bTRM. Results: In this study, we show that interactions between reactive glia and anti‐CD3 Ab‐stimulated CD8+ T‐cells promote development of CD103+CD69+ CD8+ T‐cells through engagement of the PD‐1: PD‐L1 pathway. These studies used co‐cultures of primary murine glial cells obtained from WT animals along with CD8+ T‐cells obtained from either WT or PD‐1 KO mice. We found that αCD3 Ab‐stimulated CD8+ T‐cells from WT animals increased expression of CD103 and CD69 when co‐cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8+ T‐cells from PD‐1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69+ CD8+ T‐cells, which promotes development of TRM cells. Interestingly, results obtained using T‐cells from PD‐1 KO animals showed significantly reduced expression of CD127 on CD69+ CD8+ cells. Additionally, blocking of glial PD‐L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69+ CD8+ T‐cells. Conclusions: Taken together, these results demonstrate a role for activated glia in promoting development of bTRM through the PD‐1: PD‐L1 pathway. [ABSTRACT FROM AUTHOR]