Concentration effects on the local structures and electronic properties of ErxBaY2-xF8: A first-principles study.

Er3+ doped barium yttrium fluoride (BaY2F8) crystal has gained long-term attention due to its great potential in laser and medical device applications. However, the local structures of Er3+ doped BaY2F8 system (Er:BYF) remain uncertain, and the effect of doping concentration on structures and properties is unknown. Therefore, in this study, the first-principles study of the structural evolution of ErxBaY2-xF8 (x = 0.125, 0.25) crystals was carried out. By means of density functional theory and particle swarm optimization algorithm, the stable structures of Er:BYF crystals with two different concentrations are shown as standard monoclinic structures with P2 symmetry for the first time. The impurity Er3+ ions successfully enter the main lattice, replacing the Y3+ ions, and forming a [ErF8]5- polyhedron with C2 point group symmetry. By calculating the electronic properties, the band gap values of the two structures are significantly reduced compared with that of pure BaY2F8 crystal. However, the conduction band does not break through the Fermi level, and the crystals still maintain the insulation characteristic. According to the calculation of the electron local density function, we conclude that Er-F and Y-F in Er:BYF are connected by ionic bonds. These results fill a theoretical gap in the study of Er:BYF crystals and provide inspiration for structural evolution and material design at different doping concentrations.

LC-MS/MS profiling of colon oxysterols and cholesterol precursors in mouse model of ulcerative colitis.

Oxysterols and cholesterol precursors are being increasingly investigated in humans and laboratory animals as markers for various diseases in addition to their important functions. However, the quantitative analysis of these bioactive molecules is obstructed by high structural similarity, poor ionization efficiency and low abundance. The current assay methods are still cumbersome to be of practical use, and their applicability in different bio-samples needs to be evaluated and optimized as necessary. In the present work, chromatographic separation conditions were carefully studied to achieve baseline separation of difficult-to-isolate compound pairs. On the other hand, an efficient sample purification method was established for colon tissue samples with good recoveries of sterols, demonstrating negligible autoxidation of cholesterol into oxysterols. The developed UPLC-APCI-MS/MS method was thoroughly validated and applied to measure oxysterols and cholesterol precursors in colon tissue of dextran sulfate sodium (DSS)-induced mouse colitis models, and it is expected to be successfully applied to the quantitative determination of such components in other tissue samples.

Highly-efficient heterojunction solar cells based on 2D Janus transition-metal nitride halide (TNH) monolayers with ultrahigh carrier mobility.

Symmetry breaking has a crucial effect on electronic band structure and subsequently affects the light-absorption coefficient of monolayers. We systematically report a family of two-dimensional (2D) Janus transition-metal nitride halides (TNHs, T = Ti, Zr, Hf, Fe, Pd, Pt, Os, and Re; H = Cl and F) with breaking of both in-plane and out-of-plane structural symmetry. The dynamical, thermal and mechanical stabilities are calculated to check the stability of the Janus TNHs. The electric properties of ten TNHs are studied via the HSE06+SOC method and the band gaps range from 0.93 eV (PdNCl) to 4.74 eV (HfNCl). Desirable light adsorption coefficients of up to 105 cm-1 are obtained for the Janus TNHs with no central symmetry. The Janus OsNCl monolayer shows excellent electrical transport properties and ultrahigh carrier mobility (104 cm2 V-1 s-1). Heterojunctions formed by stacking two Janus TNH monolayers are further investigated for solar cell applications. Eight of the heterojunctions have type-II band alignments. Surprisingly, the OsNCl/FeNCl heterojunction has a power conversion efficiency (PCE) of 23.45%, which is a larger value compared to the PCE of GeSe/SnSe heterostructures (21.47%). The optical properties and the built-in electric field of the OsNCl/FeNCl heterojunction are investigated. These results indicate that the stable Janus TNH monolayers have potential applications in photoelectric devices, and the vertical heterojunctions can be used in solar cells.

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment.

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.

Saikosaponins and the deglycosylated metabolites exert liver meridian guiding effect through PXR/CYP3A4 inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri (RB), traditionally used to treat inflammatory disorders and infectious diseases, represents one of the most successful and widely used herbal drugs in Asia over the past 2000 years. Being realized the role in regulating metabolism and controlling Yin/Yang, RB is not only chosen specifically for treating liver meridian and the corresponding organs, but also believed to have liver meridian guiding property and help potentiate the therapeutic effects of liver. However, the ingredients in RB with liver meridian guiding property and the underly mechanism have not been comprehensively investigated. AIM OF STUDY: Considering the important role of CYP3A4 in first-pass metabolism and the liver exposure of drugs, the present study aimed to determine whether saikosaponins (SSs) and the corresponding saikogenins (SGs) have a role in inhibiting the catalytic activity of CYP3A4 in human liver microsomes and HepG2 hepatoma cells and whether they could suppress CYP3A4 expression by PXR-mediated pathways in HepG2 hepatoma cells. MATERIALS AND METHODS: The effect of SSs and SGs on CYP3A4-mediated midazolam1'-hydroxylation activities in pooled human liver microsomes (HLMs) was first studied. Dose-dependent experiments were performed to obtain the half inhibit concentration (IC50) values. HepG2 cells were used to assay catalytic activity of CYP3A4, reporter function, mRNA levels, and protein expression. The inhibitory effects of SSa and SSd on CYP3A4 activity are negligible, while the corresponding SGs (SGF and SGG) have obvious inhibitory effects on CYP3A4 activity, with IC50 values of 0.45 and 1.30 µM. The similar results were obtained from testing CYP3A4 catalytic activity in HepG2 cells, which correlated well with the suppression of the mRNA and protein levels of CYP3A4. Time-dependent testing of CYP3A4 mRNA and protein levels, as well as co-transfection experiments using the CYP3A4 promoter luciferase plasmid, further confirmed that SSs and SGs could inhibit the expression of CYP3A4 at the transcription level. Furthermore, PXR protein expression decreased in a concentration- and time-dependent manner after cells were exposed to SSs and SGs. PXR overexpression and RNA interference experiments further showed that SSs and SGs down-regulate the catalytic activity and expression of CYP3A4 in HepG2 may be mainly through PXR-dependent manner. CONCLUSION: SSs and SGs inhibit the catalytic activity and expression of CYP3A4 in a PXR-dependent manner, which may be highly related to the liver meridian guiding property of RB.