Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes

Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics. In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s. In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes. CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s. Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2. The values of inhibition kinetic parameters (Ki) were 21.15 μM and 2.22 μM for CYP1A2 and CYP3A4, respectively. The metabolism of xanthotoxol obeyed the typical monophasic Michaelis-Menten kinetics and Vmax, Km, and CLint values were calculated as 0.55 nmol·min−1·mg−1, 8.46 μM, and 0.06 mL·min−1·mg−1. In addition, the results of molecular docking showed that xanthotoxol was bound to CYP1A2 with hydrophobic and π-π bond and CYP3A4 with hydrogen and hydrophobic bond. We predicted the hepatic clearance (CLh) and the CLh value was 15.91 mL·min−1·kg−1 body weight. These data were significant for the application of xanthotoxol and xanthotoxol-containing herbs

The tonoplast-localized transporter OsHMA3 plays an important role in maintaining Zn homeostasis in rice

In order to respond to fluctuating zinc (Zn) in the environment, plants must have a system to control Zn homeostasis. However, how plants maintain an appropriate level of Zn during their growth and development is still poorly understood. In this study, we found that OsHMA3, a tonoplast-localized transporter for Zn/Cd, plays an important role in Zn homeostasis in rice. Accessions with the functional allele of OsHMA3 showed greater tolerance to high Zn than those with the non-functional allele based on root elongation test. A 67Zn-labeling experiment showed that accessions with loss of function of OsHMA3 had lower Zn accumulation in the roots but similar concentrations in the shoots compared with functional OsHMA3 accessions. When exposed to Zn-free growing medium, the concentration in the root cell sap was rapidly decreased in accessions with functional OsHMA3, but less dramatic changes were observed in non-functional accessions. A mobility experiment showed that more Zn in the roots was translocated to the shoots in accessions with functional OsHMA3. Higher expression levels of OsZIP4, OsZIP5, OsZIP8, and OsZIP10 were found in the roots of accessions with functional OsHMA3 in response to Zn deficiency. Taken together, our results indicate that OsHMA3 plays an important role in rice roots in both Zn detoxification and storage by sequestration into the vacuoles, depending on Zn concentration in the environment

Dark Energy Perturbations Revisited

In this paper we study the evolution of cosmological perturbations in the presence of dynamical dark energy, and revisit the issue of dark energy perturbations. For a generally parameterized equation of state (EoS) such as w_D(z) = w_0+w_1\frac{z}{1+z}, (for a single fluid or a single scalar field ) the dark energy perturbation diverges when its EoS crosses the cosmological constant boundary w_D=-1. In this paper we present a method of treating the dark energy perturbations during the crossing of the $w_D=-1$ surface by imposing matching conditions which require the induced 3-metric on the hypersurface of w_D=-1 and its extrinsic curvature to be continuous. These matching conditions have been used widely in the literature to study perturbations in various models of early universe physics, such as Inflation, the Pre-Big-Bang and Ekpyrotic scenarios, and bouncing cosmologies. In all of these cases the EoS undergoes a sudden change. Through a detailed analysis of the matching conditions, we show that \delta_D and \theta_D are continuous on the matching hypersurface. This justifies the method used[1-4] in the numerical calculation and data fitting for the determination of cosmological parameters. We discuss the conditions under which our analysis is applicable.Comment: 10 pages and 1 figure

A data-driven model to quantify the impact of river discharge on tide-river dynamics in the Yangtze River estuary

Understanding the role of river discharge on tide-river dynamics is of essential importance for sustainable water management (flood control, salt intrusion, and navigation) in estuarine environments. It is well known that river discharge impacts fundamental tide-river dynamics, especially in terms of subtidal (residual water levels) and tidal properties (amplitudes and phases for different tidal constituents). However, the quantification of the impact of river discharge on tide-river dynamics is challenging due to the complex interactions of barotropic tides with channel geometry, bottom friction, and river discharge. In this study, we propose a data-driven model to quantify the impact of river discharge on tide-river dynamics, using water level time series data collected through long-term observations along an estuary with substantial variations in river discharge. The proposed model has a physically-based structure representing the tide-river interaction, and can be used to predict water level using river discharge as the sole predictor. The satisfactory correspondence of the model outputs with measurements at six gauging stations along the Yangtze River estuary suggest that the proposed model can serve as a powerful instrument to quantify the impacts of river discharge on tide-river dynamics (including time-varying tidal properties and tidal distortion), and separate the contribution made by riverine and tidal forcing on water level. The proposed approach is very efficient and can be applied to other estuaries showing considerable impacts of river discharge on tide-river dynamics.info:eu-repo/semantics/publishedVersio

Global behavior of cosmological dynamics with interacting Veneziano ghost

In this paper, we shall study the dynamical behavior of the universe accelerated by the so called Veneziano ghost dark energy component locally and globally by using the linearization and nullcline method developed in this paper. The energy density is generalized to be proportional to the Hawking temperature defined on the trapping horizon instead of Hubble horizon of the Friedmann-Robertson-Walker (FRW) universe. We also give a prediction of the fate of the universe and present the bifurcation phenomenon of the dynamical system of the universe. It seems that the universe could be dominated by dark energy at present in some region of the parameter space.Comment: 8 pages, 7 figures, accepted for publication in JHE