Transcriptional up-regulation of relaxin-3 by Nur77 attenuates β-adrenergic agonist-induced apoptosis in cardiomyocytes.

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 (RLN1), in neonatal rat ventricular cardiomyocytes (NRVMs). Furthermore, we found that the -adrenergic agonist isoproterenol (ISO) markedly stimulated RLN3 expression, and this stimulation was significantly attenuated in Nur77 knockdown cardiomyocytes and Nur77 knockout hearts. We showed that Nur77 significantly increased RLN3 promoter activity via specific binding to the RLN3 promoter, as demonstrated by electrophoretic mobility shift assay (EMSA) and chromatin immuno-precipitation (ChIP) assays. Furthermore, we found that Nur77 overexpression potently inhibited ISO-induced cardiomyocyte apoptosis, whereas this protective effect was significantly attenuated in RLN3 knockdown cardiomyocytes, suggesting that Nur77-induced RLN3 expression is an important mediator for the suppression of cardiomyocyte apoptosis. These findings show that Nur77 regulates RLN3 expression, therefore suppressing apoptosis in the heart, and suggest that activation of Nur77 may represent a useful therapeutic strategy for inhibition of cardiac fibrosis and heart failure. © 2018 You et al

Protective effect of maternal exposure to α-lipoic acid during pregnancy and lactation on susceptibility to OVAinduced neonatal asthma

Purpose: To investigate the beneficial effect of alpha-lipoic acid (ALA) during pregnancy and lactation on susceptibility to ovalbumin (OVA)-induced neonatal asthma, and the mechanism of involved.Methods: Pregnant BALB/c mice were administered ALA (1 % mixed with mouse chow) or standard mouse chow from 6th day of gestation to 21st day of lactation (postnatal). The offspring (neonatal pups) from the OVA and ALA+OVA groups were sensitized on 1st, 7th and 14th postnatal days (PNDs) via intraperitoneal (i.p.) injection of OVA (0.5 μg). Control mice pups were not exposed to OVA. On PND 21, all pubs were again exposed to 1 % OVA aerosol using a nebulizer.Results: Neonatal mice exposed to ALA showed a significant decline (p < 0.05) in the number of inflammatory cells (eosinophils), levels of inflammatory markers (IL-4, IL-13, IL-5 and TNF-α) as well as OVA-specific IgE and total IgE, when compared to neonatal mice from pregnant mice that did not receive ALA (control). Moreover, the antioxidant profiles of ALA-treated mice offspring were significantly improved (p < 0.05). Marked downregulation (p < 0.05) of the protein expressions of NF-κB p-p65 subunit and TNF-α were observed in ALA-treated mice pups.Conclusion: ALA exposure during pregnancy (maternal exposure) markedly decreases OVA-induced asthmatic airway inflammatory response in pups. Thus, ALA might be beneficial for use along with standard anti-asthmatic drugs in the management of pediatric asthmatic patient

Investigating mechanism of inclined CPT in granular ground using DEM

Abstract. This paper presents an investigation on mechanism of the inclined 1 cone penetration test (CPT) using the numerical discrete element method (DEM). 2 A series of penetration tests with the penetrometer inclined at different angles 3 (i.e., 0°,15°, 30°, 45° and 60°) were numerically performed under µ=0.0 and 4 µ=0.5, where µ is the frictional coefficient between the penetrometer and the soil. 5 The deformation patterns, displacements of soil particles adjacent to the cone tip, 6 velocity fields, rotations of the principal stresses and the averaged pure rotation 7 rate (APR) were analyzed. Special focus was placed on the effect of friction. The 8 DEM results showed that soils around the cone tip experienced complex 9 displacement paths at different positions as the inclined penetration proceeded, 10 and the friction only had significant effects on the soils adjacent to the 11 penetrometer side and tip. Soils exhibited characteristic velocity fields 12 corresponding to three different failure mechanisms and the right side was easier 13 to be disturbed by friction. Friction started to play its role when the tip approached 14 the observation points, while it had little influence on rotation rate. The 15 normalized tip resistance (q c = f /σ v0 ) increased with friction as well as inclination 16 angle. The relationship between q c and relative depth (y/R) can be described as q c 17 =a×(y/R) -b , with parameters a and b dependent on penetration direction. The 18 normalized resistance perpendicular to the penetrometer axis q p increases with the 19 inclination angle, thus the inclination angle should be carefully selected to ensure 20 the penetrometer not to deviate from its original direction or even be broken in 21 real tests. 2

Synergistic Computational–Experimental Discovery of Highly Selective PtCu Nanocluster Catalysts for Acetylene Semihydrogenation

Semihydrogenation of acetylene (SHA) in an ethylene-rich stream is an important process for polymer industries. Presently, Pd-based catalysts have demonstrated good acetylene conversion (XC2H2), however, at the expense of ethylene selectivity (SC2H4). In this study, we have employed a systematic approach using density functional theory (DFT) to identify the best catalyst in a Cu–Pt system. The DFT results showed that with a 55 atom system at ∼1.1 Pt/Cu ratio for Pt28Cu27/Al2O3, the d-band center shifted −2.2 eV relative to the Fermi level leading to electron-saturated Pt, which allows only adsorption of ethylene via a π-bond, resulting in theoretical 99.7% SC2H4 at nearly complete XC2H2. Based on the DFT results, Pt–Cu/Al2O3 (PtCu) and Pt/Al2O3 (Pt) nanocatalysts were synthesized via cluster beam deposition (CBD), and their properties and activities were correlated with the computational predictions. For bimetallic PtCu, the electron microscopy results show the formation of alloys. The bimetallic PtCu catalyst closely mimics the DFT predictions in terms of both electronic structure, as confirmed by X-ray photoelectron spectroscopy, and catalytic activity. The alloying of Pt with Cu was responsible for the high C2H4 specific yield resulting from electron transfer between Cu and Pt, thus making PtCu a promising catalyst for SHA

The Orbitofrontal Cortex Gray Matter Is Associated With the Interaction Between Insomnia and Depression

Insomnia and depression are highly comorbid symptoms in both primary insomnia (PI) and major depressive disorder (MDD). In the current study, we aimed at exploring both the homogeneous and heterogeneous brain structure alteration in PI and MDD patients. Sixty-five MDD patients and 67 matched PI patients were recruited and underwent a structural MRI scan. The subjects were sub-divided into four groups, namely MDD patients with higher or lower insomnia, and PI patients with higher or lower severe depression. A general linear model was employed to explore the changes in cortical thickness and volume as a result of depression or insomnia, and their interaction. In addition, partial correlation analysis was conducted to detect the clinical significance of the altered brain structural regions. A main effect of depression on cortical thickness was seen in the superior parietal lobe, middle cingulate cortex, and parahippocampal gyrus, while a main effect of insomnia on cortical thickness was found in the posterior cingulate cortex. Importantly, the interaction between depression and insomnia was associated with decreased gray matter volume in the right orbitofrontal cortex, i.e., patients with co-occurring depression and insomnia showed smaller brain volume in the right orbitofrontal cortex when compared to patients with lower insomnia/depression. These findings highlighted the role of the orbitofrontal cortex in the neuropathology of the comorbidity of insomnia and depression. Our findings provide new insights into the understanding of the brain mechanism underlying comorbidity of insomnia and depression

Atomically dispersed Fe in a C2N based catalyst as a sulfur host for efficient lithium–sulfur batteries

Lithium–sulfur batteries (LSBs) are considered to be one of the most promising next generation energy storage systems due to their high energy density and low material cost. However, there are still some challenges for the commercialization of LSBs, such as the sluggish redox reaction kinetics and the shuttle effect of lithium polysulfides (LiPS). Here a 2D layered organic material, C2N, loaded with atomically dispersed iron as an effective sulfur host in LSBs is reported. X-ray absorption fine spectroscopy and density functional theory calculations prove the structure of the atomically dispersed Fe/C2N catalyst. As a result, Fe/C2N-based cathodes demonstrate significantly improved rate performance and long-term cycling stability. Fe/C2N-based cathodes display initial capacities up to 1540 mAh g-1 at 0.1 C and 678.7 mAh g-1 at 5 C, while retaining 496.5 mAh g-1 after 2600 cycles at 3 C with a decay rate as low as 0.013% per cycle. Even at a high sulfur loading of 3 mg cm-2, they deliver remarkable specific capacity retention of 587 mAh g-1 after 500 cycles at 1 C. This work provides a rational structural design strategy for the development of high-performance cathodes based on atomically dispersed catalysts for LSBs.Peer ReviewedPostprint (author's final draft

NbSe2 meets C2N: a 2D-2D heterostructure catalysts as multifunctional polysulfide mediator in ultra-long-life lithium–sulfur batteries

The shuttle effect and sluggish conversion kinetics of lithium polysulfides (LiPS) hamper the practical application of lithium–sulfur batteries (LSBs). Toward overcoming these limitations, herein an in situ grown C2N@NbSe2 heterostructure is presented with remarkable specific surface area, as a Li–S catalyst and LiPS absorber. Density functional theory (DFT) calculations and experimental results comprehensively demonstrate that C2N@NbSe2 is characterized by a suitable electronic structure and charge rearrangement that strongly accelerates the LiPS electrocatalytic conversion. In addition, heterostructured C2N@NbSe2 strongly interacts with LiPS species, confining them at the cathode. As a result, LSBs cathodes based on C2N@NbSe2/S exhibit a high initial capacity of 1545 mAh g-1 at 0.1 C. Even more excitingly, C2N@NbSe2/S cathodes are characterized by impressive cycling stability with only 0.012% capacity decay per cycle after 2000 cycles at 3 C. Even at a sulfur loading of 5.6 mg cm-2, a high areal capacity of 5.65 mAh cm-2 is delivered. These results demonstrate that C2N@NbSe2 heterostructures can act as multifunctional polysulfide mediators to chemically adsorb LiPS, accelerate Li-ion diffusion, chemically catalyze LiPS conversion, and lower the energy barrier for Li2S precipitation/decomposition, realizing the “adsorption-diffusion-conversion” of polysulfides.Award-winningPostprint (author's final draft

Electrochemical reforming of ethanol with acetate Co-Production on nickel cobalt selenide nanoparticles

The energy efficiency of water electrolysis is limited by the sluggish reaction kinetics of the anodic oxygen evolution reaction (OER). To overcome this limitation, OER can be replaced by a less demanding oxidation reaction, which in the ideal scenario could be even used to generate additional valuable chemicals. Herein, we focus on the electrochemical reforming of ethanol in alkaline media to generate hydrogen at a Pt cathode and acetate as a co-product at a NiCoSe anode. We first detail the solution synthesis of a series of NiCoSe electrocatalysts. By adjusting the Ni/Co ratio, the electrocatalytic activity and selectivity for the production of acetate from ethanol are optimized. Best performances are obtained at low substitutions of Ni by Co in the cubic NiSe phase. Density function theory reveals that the Co substitution can effectively enhance the ethanol adsorption and decrease the energy barrier for its first step dehydrogenation during its conversion to acetate. However, we experimentally observe that too large amounts of Co decrease the ethanol-to-acetate Faradaic efficiency from values above 90% to just 50 %. At the optimized composition, the NiCoSe electrode delivers a stable chronoamperometry current density of up to 45 mA cm, corresponding to 1.2 A g, in a 1 M KOH + 1 M ethanol solution, with a high ethanol-to-acetate Faradaic efficiency of 82.2% at a relatively low potential, 1.50 V vs. RHE, and with an acetate production rate of 0.34 mmol cm h.This work was supported by the start-up funding at Chengdu University. It was also supported by the European Regional Development Funds and by the Spanish Ministerio de Economía y Competitividad through the project SEHTOP (ENE2016-77798-C4-3-R), MCIN/ AEI/10.13039/501100011033/ project, and NANOGEN (PID2020-116093RB-C43). X. Wang, C. Xing, X. Han, R. He, Z. Liang, and Y. Zhang are grateful for the scholarship from China Scholarship Council (CSC). X. Han and J. Arbiol acknowledge funding from Generalitat de Catalunya 2017 SGR 327. ICN2 acknowledges support from the Severo Ochoa Programme (MINECO, Grant no. SEV-2013-0295). IREC and ICN2 are funded by the CERCA Programme / Generalitat de Catalunya

Molecular engineering to tune the ligand environment of atomically dispersed nickel for efficient alcohol electrochemical oxidation

Altres ajuts: ICN2 is funded by the CERCA Programme /Generalitat de Catalunya. Part of the present work has been performed in the framework of Universitat Autònoma de Barcelona Materials Science Ph.D. program. J.L. is a Serra Húnter Fellow and is grateful to ICREA Academia program.Atomically dispersed metals maximize the number of catalytic sites and enhance their activity. However, their challenging synthesis and characterization strongly complicates their optimization. Here, the aim is to demonstrate that tuning the electronic environment of atomically dispersed metal catalysts through the modification of their edge coordination is an effective strategy to maximize their performance. This article focuses on optimizing nickel-based electrocatalysts toward alcohol electrooxidation in alkaline solution. A new organic framework with atomically dispersed nickel is first developed. The coordination environment of nickel within this framework is modified through the addition of carbonyl (CO) groups. The authors then demonstrate that such nickel-based organic frameworks, combined with carbon nanotubes, exhibit outstanding catalytic activity and durability toward the oxidation of methanol (CHOH), ethanol (CHCHOH), and benzyl alcohol (CHCHOH); the smaller molecule exhibits higher catalytic performance. These outstanding electrocatalytic activities for alcohol electrooxidation are attributed to the presence of the carbonyl group in the ligand chemical environment, which enhances the adsorption for alcohol, as revealed by density functional theory calculations. The work not only introduces a new atomically dispersed Ni-based catalyst, but also demonstrates a new strategy for designing and engineering high-performance catalysts through the tuning of their chemical environment