Childhood obesity has become a global pandemic in developed countries, leading to a host of medical conditions that contribute to increased morbidity and premature death. The causes of obesity in ...childhood and adolescence are complex and multifaceted, presenting researchers and clinicians with myriad challenges in preventing and managing the problem. This article reviews the state of the science for understanding the etiology of childhood obesity, the preventive interventions and treatment options for overweight and obesity, and the medical complications and co-occurring psychological conditions that result from excess adiposity, such as hypertension, nonalcoholic fatty liver disease, and depression. Interventions across the developmental span, varying risk levels, and service contexts (e.g.,community, school, home, health care systems) are reviewed. Future directions for research are offered with an emphasis on translational issues for taking evidence-based interventions to scale in a manner that will reduce the public health burden of the childhood obesity pandemic.
In high-temperature applications such as hot sections of gas turbines, the sintering rate of the porous microstructure of a ceramic coating, and their mechanical and thermomechanical properties are ...important parameters for thermal barrier coating systems. In the present research, hardness, elastic modulus, thermal expansion, thermal stress and sintering rate of the porous microstructure of yttria-stabilized zirconia (YSZ) and ceria-stabilized zirconia (CSZ) were investigated and compared using the thermal spray technique on IN738LC base metal in thermal cycling to 1100 °C. To determine the structural and phase characteristics of the coatings, scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis were employed. The experimental results showed that the CSZ coatings exhibit a considerably better sintering rate of the porous microstructure resulting in better mechanical, and thermomechanical properties when compared to the YSZ coatings. Moreover, the study of microstructures of coatings showed that the CSZ coating is formed with a laminar and porous structure, with pores being smaller and more uniform than those of the YSZ coating.
•This work aims to investigate and compare the mechanical and thermomechanical properties of CSZ to YSZ coatings.•CSZ coatings showed better mechanical and thermomechanical properties than did YSZ coatings.•Micro structure of CSZ coatings were more uniform with smaller pores than those of YSZ coatings.
We present the quasar luminosity function at z ∼ 5 derived from the optical wide-field survey data obtained as a part of the Subaru strategic program (SSP) with the Hyper Suprime-Cam (HSC). From a ...∼81.8 deg2 area in the Wide layer of the HSC-SSP survey, we selected 224 candidates of low-luminosity quasars at z ∼ 5 by adopting the Lyman-break method down to i = 24.1 mag. Based on our candidates and spectroscopically confirmed quasars from the Sloan Digital Sky Survey (SDSS), we derived the quasar luminosity function at z ∼ 5, covering a wide luminosity range of −28.76 < M1450 < −22.32 mag. We found that the quasar luminosity function is fitted by a double power-law model with a break magnitude of mag. The inferred number density of low-luminosity quasars is lower, and the derived faint-end slope, , is flatter than those of previous studies at z ∼ 5. A compilation of the quasar luminosity function at 4 ≤ z ≤ 6 from the HSC-SSP suggests that there is little redshift evolution in the break magnitude and in the faint-end slope within this redshift range, although previous studies suggest that the faint-end slope becomes steeper at higher redshifts. The number density of low-luminosity quasars decreases more rapidly from z ∼ 5 to z ∼ 6 than from z ∼ 4 to z ∼ 5.
Chronic stress-induced aberrant gene expression in the brain and subsequent dysfunctional neuronal plasticity have been implicated in the etiology and pathophysiology of mood disorders. In this ...study, we examined whether altered expression of small, regulatory, noncoding microRNAs (miRNAs) contributes to the depression-like behaviors and aberrant neuronal plasticity associated with chronic stress. Mice exposed to chronic ultra-mild stress (CUMS) exhibited increased depression-like behaviors and reduced hippocampal expression of the brain-enriched miRNA-124 (miR-124). Aberrant behaviors and dysregulated miR-124 expression were blocked by chronic treatment with an antidepressant drug. The depression-like behaviors are likely not conferred directly by miR-124 downregulation because neither viral-mediated hippocampal overexpression nor intrahippocampal infusion of an miR-124 inhibitor affected depression-like behaviors in nonstressed mice. However, viral-mediated miR-124 overexpression in hippocampal neurons conferred behavioral resilience to CUMS, whereas inhibition of miR-124 led to greater behavioral susceptibility to a milder stress paradigm. Moreover, we identified histone deacetylase 4 (HDAC4), HDAC5, and glycogen synthase kinase 3β (GSK3β) as targets for miR-124 and found that intrahippocampal infusion of a selective HDAC4/5 inhibitor or GSK3 inhibitor had antidepressant-like actions on behavior. We propose that miR-124-mediated posttranscriptional controls of HDAC4/5 and GSK3β expressions in the hippocampus have pivotal roles in susceptibility/resilience to chronic stress.
Depressive disorders are a major public health concern worldwide. Although a clear understanding of the etiology of depression is still lacking, chronic stress-elicited aberrant neuronal plasticity has been implicated in the pathophysiology of depression. We show that the hippocampal expression of microRNA-124 (miR-124), an endogenous small, noncoding RNA that represses gene expression posttranscriptionally, controls resilience/susceptibility to chronic stress-induced depression-like behaviors. These effects on depression-like behaviors may be mediated through regulation of the mRNA or protein expression levels of histone deacetylases HDAC4/5 and glycogen synthase kinase 3β, all highly conserved miR-124 targets. Moreover, miR-124 contributes to stress-induced dendritic hypotrophy and reduced spine density of dentate gyrus granule neurons. Modulation of hippocampal miR-124 pathways may have potential antidepressant effects.
•Gas tunnel plasma spraying produced HA–nanostructure TiO2 coatings with minimum decomposition.•Reinforced nanostructure TiO2 improves the mechanical properties of the HA coating.•Reinforced ...nanostructure TiO2 cannot effect the bioactivity of the HA surface.
Hydroxyapatite (HA) can be coated onto metal implants as a ceramic biocompatible coating to bridge the growth between implants and human tissue. Meanwhile many efforts have been made to improve the mechanical properties of the HA coatings without affecting its bioactivity. In the present study, nanostructure titania (TiO2) was mixed with HA powder and HA–nanostructure TiO2 composite coatings were produced by gas tunnel type plasma spraying torch under optimized spraying conditions. For this purpose, composition of 10wt% TiO2+90wt% HA, 20wt% TiO2+80wt% HA and 30wt% TiO2+70wt% HA were selected as the feedstock materials. The phase, microstructure and mechanical properties of the coatings were characterized. The obtained results validated that the increase in weight percentage of nanostructure TiO2 in HA coating significantly increased the microhardness, adhesive strength and wear resistance of the coatings. Analysis of the in vitro bioactivity and cytocompatibility of the coatings were done using conventional simulated body fluid (c-SBF) solution and cultured green fluorescent protein (GFP) labeled marrow stromal cells (MSCs) respectively. The bioactivity results revealed that the composite coating has bio-active surface with good cytocompatibility.
Notch signaling is often and aberrantly activated by hypoxia during tumor progression; however, the exact pathological role of hypoxia-induced Notch signaling in tumor metastasis is as yet poorly ...understood. In this study, we aimed to define the mechanism of Notch-ligand activation by hypoxia in both primary tumor and bone stromal cells in the metastatic niche and to clarify their roles in tumor progression. We have analyzed the expression profiles of various Notch ligands in 779 breast cancer patients in GEO database and found that the expression of Jagged2 among all five ligands is most significantly correlated with the overall- and metastasis-free survival of breast cancer patients. The results of our immunohistochemical (IHC) analysis for Jagged2 in 61 clinical samples also revealed that both Jagged2 and Notch signaling were strongly upregulated at the hypoxic invasive front. Activation of Jagged2 by hypoxia in tumor cells induced EMT and also promoted cell survival in vitro. Notably, a γ-secretase inhibitor significantly blocked Notch-mediated invasion and survival under hypoxia by promoting expression of E-cadherin and inhibiting Akt phosphorylation. Importantly, Jagged2 was also found to be upregulated in bone marrow stroma under hypoxia and promoted the growth of cancer stem-like cells by activating their Notch signaling. Therefore, hypoxia-induced Jagged2 activation in both tumor invasive front and normal bone stroma has a critical role in tumor progression and metastasis, and Jagged2 is considered to be a valuable prognostic marker and may serve as a novel therapeutic target for metastatic breast cancer.
Abstract
We present a new catalog of 9318 Ly
α
emitter (LAE) candidates at
z
= 2.2, 3.3, 4.9, 5.7, 6.6, and 7.0 that are photometrically selected by the SILVERRUSH program with a machine learning ...technique from large area (up to 25.0 deg
2
) imaging data with six narrowband filters taken by the Subaru Strategic Program with Hyper Suprime-Cam and a Subaru intensive program, Cosmic HydrOgen Reionization Unveiled with Subaru. We construct a convolutional neural network that distinguishes between real LAEs and contaminants with a completeness of 94% and a contamination rate of 1%, enabling us to efficiently remove contaminants from the photometrically selected LAE candidates. We confirm that our LAE catalogs include 177 LAEs that have been spectroscopically identified in our SILVERRUSH programs and previous studies, ensuring the validity of our machine learning selection. In addition, we find that the object-matching rates between our LAE catalogs and our previous results are ≃80%–100% at bright NB magnitudes of ≲24 mag. We also confirm that the surface number densities of our LAE candidates are consistent with previous results. Our LAE catalogs will be made public on our project webpage.
Abstract Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo ...from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5–3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.
Recent observations show that the space density of luminous active galactic nuclei (AGNs) peaks at higher redshifts than that of faint AGNs. This downsizing trend in the AGN evolution seems to be ...contradictory to the hierarchical structure formation scenario. In this study, we present the AGN space density evolution predicted by a semi-analytic model of galaxy and AGN formation based on the hierarchical structure formation scenario. We demonstrate that our model can reproduce the downsizing trend of the AGN space density evolution. The reason for the downsizing trend in our model is a combination of the cold gas depletion as a consequence of star formation, the gas cooling suppression in massive halos, and the AGN lifetime scaling with the dynamical timescale. We assume that a major merger of galaxies causes a starburst, spheroid formation, and cold gas accretion onto a supermassive black hole (SMBH). We also assume that this cold gas accretion triggers AGN activity. Since the cold gas is mainly depleted by star formation and gas cooling is suppressed in massive dark halos, the amount of cold gas accreted onto SMBHs decreases with cosmic time. Moreover, AGN lifetime increases with cosmic time. Thus, at low redshifts, major mergers do not always lead to luminous AGNs. Because the luminosity of AGNs is correlated with the mass of accreted gas onto SMBHs, the space density of luminous AGNs decreases more quickly than that of faint AGNs. We conclude that the anti-hierarchical evolution of the AGN space density is not contradictory to the hierarchical structure formation scenario.
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