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Morphine may be administered in pregnant women as an analgesic agent. The transplacental pharmacokinetics (PK) of morphine varies during pregnancy because of physiological and metabolic changes. In this work, we use a multi-compartment model to simulate ex vivo human placental transfer studies of morphine. The computational model is based on a recently published model for metformin with both passive and active transport kinetics. Modifications were made to incorporate morphine-specific transfer parameters. Parameters for the PK models were determined via the nonlinear regression method. In addition, the Latin hypercube sampling (LHS) method was used for the global parameter analysis of the model. Simulation results show good agreement between the model and observed fetal and maternal morphine concentrations. In addition, the lower efflux of morphine from fetal to maternal plasma reflects reduced P-glycoprotein (P-gp) transport as pregnancy progresses, which leads to slower clearance of morphine in the maternal plasma. The LHS analysis also indicates the more significant roles played by the passive diffusion parameters than the active transport parameter on the fetal/maternal morphine concentrations. In conclusion, we used an in silico model to investigate the transplacental properties of morphine and to predict the in vivo transplacental properties of morphine when PK parameters change.

The KTK 4A-related Thermoplasmata thrives in the sediment of saline lakes; however, systematic research on its taxonomy, environmental adaptation and metabolism is lacking. Here, we detected this abundant lineage in the sediment of five artificially separated ponds (salinity 7.0%-33.0%) within a Chinese soda-saline lake using culture-independent metagenomics and archaeal 16S rRNA gene amplicons. The phylogenies based on the 16S rRNA gene, and 122 archaeal ubiquitous single-copy proteins and genome-level identity analyses among the metagenome-assembled genomes demonstrate this lineage forming a novel order, Candidatus Haloplasmatales, comprising four genera affiliated with the identical family. Isoelectric point profiles of predicted proteomes suggest that most members adopt the energetically favourable 'salt-in' strategy. Functional prediction indicates the lithoheterotrophic nature with the versatile metabolic potentials for carbohydrate and organic acids as well as carbon monoxide and hydrogen utilization. Additionally, hydrogenase genes hdrABC-mvhADG are linked with incomplete reductive citrate cycle genes in the genomes, suggesting their functional connection. Comparison with the coupling of HdrABC-MvhADG and methanogenesis pathway provides new insights into the compatibility of laterally acquired methanogenesis with energy metabolism in the related order Methanomassiliicoccales. Globally, our research sheds light on the taxonomy, environmental adaptative mechanisms, metabolic potentials and evolutional significance of Ca. Haloplasmatales.

Previous studies have found microRNA-1 (miR-1) and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) may be involved in the pathogenesis of thyroid hormone (TH) induced cardiac hypertrophy. However, little is known about the role of miR-1 and HCN2 in thyroid stimulation hormone (TSH)-induced cardiac dysfunction. In order to investigate the molecular mechanisms of TSH induced cardiac dysfunction and the role of miR-1/HCN2 in that process, we evaluated the expression of miR-1a/HCN2 in the ventricular myocardium of hypothyroid mice and in TSH-stimulated H9c2 cardiomyocytes. Our data revealed that hypothyroidism mice had smaller hearts, ventricular muscle atrophy, and cardiac contractile dysfunction compared with euthyroid controls. The upregulation of miR-1a and downregulation of HCN2 were found in ventricular myocardium of hypothyroid mice and TSH-stimulated H9c2 cardiomyocytes, indicating that miR-1a and HCN2 may be involved in TSH-induced cardiac dysfunction. We also found that the regulation of miR-1a and HCN2 expression and HCN2 channel activity by TSH requires TSHR, while the regulation of HCN2 expression and HCN2 channel function by TSH requires miR-1a. Thus, our data revealed the potential mechanism of TSH-induced cardiac dysfunction and might shed new light on the pathological role of miR-1a/HCN2 in hypothyroid heart disease.

OBJECTIVE To report perioperative outcomes in robot-assisted radical cystectomy and laparoscopic radical cystectomy. PATIENTS AND METHODS Between January 2010 and July 2019, 298 patients with bladder cancer underwent robotic-assisted radical cystectomy (RARC) (n = 172) and laparoscopic radical cystectomy (LRC) (n = 126) at our institution were enrolled in the retrospective study. The demographic, perioperative, and complication data were collected and analyzed. RESULTS The RARC group had less operative duration (P

Understanding hot carrier dynamics between plasmonic nanomaterials and its adsorbate is of great importance for plasmon‐enhanced photoelectronic processes such as photocatalysis, optical sensing and spectroscopic analysis. However, it is often challenging to identify specific dominant mechanisms for a given process because of the complex pathways and ultrafast interactive dynamics of the photoelectrons. Here, using CO2 reduction as an example, the underlying mechanisms of plasmon‐driven catalysis at the single‐molecule level using time‐dependent density functional theory calculations is clearly probed. The CO2 molecule adsorbed on two typical nanoclusters, Ag20 and Ag147, is photoreduced by optically excited plasmon, accompanied by the excitation of asymmetric stretching and bending modes of CO2. A nonlinear relationship has been identified between laser intensity and reaction rate, demonstrating a synergic interplay and transition from indirect hot‐electron transfer to direct charge transfer, enacted by strong localized surface plasmons. These findings offer new insights for CO2 photoreduction and for the design of effective pathways toward highly efficient plasmon‐mediated photocatalysis.

Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38α plays a regulatory role in the tissue repair following d-galactosamine (GalN)/tumor necrosis factor-α (TNF-α)-induced acute liver injury. We found that macrophage p38α-deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon-γ treatment but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38α induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38α signaling is involved in the pathogenesis of liver injury induced by GalN/TNF-α, and inhibition of p38α signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype.

We report high-energy-resolution X-ray absorption spectroscopy detection of ethylene and CO ligands adsorbed on catalytically active iridium centers isolated on zeolite HY and on MgO supports. The data are supported by density functional theory and FEFF X-ray absorption near-edge modelling, together with infrared (IR) spectra. The results demonstrate that high-energy-resolution X-ray absorption spectra near the iridium LIII (2p3/2 ) edge provide clearly ascribable, distinctive signatures of the ethylene and CO ligands and illustrate effects of supports and other ligands. This X-ray absorption technique is markedly more sensitive than conventional IR spectroscopy for characterizing surface intermediates, and it is applicable to samples having low metal loadings and in reactive atmospheres and is expected to have an increasing role in catalysis research by facilitating the determination of mechanisms of solid-catalyzed reactions through identification of reaction intermediates in working catalysts.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim MgO-supported osmium dioxo species, described as Os(=O)2{−Osupport}1 or 2(the brackets denote O atoms of the MgO surface), formed from Os3(CO)12via supported Os(CO)2, and characterized by spectroscopy, microscopy, and theory, react with ethylene at 298 K to form osmium glycol species or with CO to give osmium mono- and di-carbonyls. Os(=O)2{−Osupport}1 or 2is the precursor of a CO oxidation catalyst characterized by a turnover frequency of 4.0×10−3(molecules of CO)/(Os atom×s) at 473 K; the active species are inferred to be osmium monocarbonyls. The structures and frequencies calculated at the level of density functional theory with the B3LYP functional bolster the experimental results and facilitate structural assignments. The lowest-energy structures have various osmium oxidation and spin states. The results demonstrate not only new chemistry of the supported single-site catalysts but also their complexity and the value of complementary techniques used in concert to unravel the chemistry.