The TBIL in patients and CYP3A5*3 genetic polymorphism in both donors and recipients contribute to the inter-individual variability of oral tacrolimus apparent clearance in Chinese adult liver transplant patients.

We study the oxygen doping dependence of the equilibrium first-order melting and second-order glass transitions of vortices in Bi2Sr2CaCu2O 8+delta. Doping affects both anisotropy and disorder. Anisotropy scaling is shown to collapse the melting lines only where thermal fluctuations are dominant. Yet, in the region where disorder breaks that scaling, the glass lines are still collapsed. A quantitative fit to melting and replica symmetry-breaking lines of a 2D Ginzburg-Landau model further reveals that disorder amplitude weakens with doping, but to a lesser degree than thermal fluctuations, enhancing the relative role of disorder.

We describe quantitatively the combined effects of both the thermal fluctuations and of the quenched disorder via the replica trick applied to the Ginzburg-Landau (GL) theory. We show that the vortex state can appear in either of the three disordered phases: (i) unpinned vortex liquid, (ii) amorphous vortex glass (pinned), and (iii) the crystalline (pinned but not containing topological defects) Bragg glass. The formation of the vortex glass is associated with the continuous replica symmetry breaking (RSB) reflecting the hierarchial structure of the potential barriers in a vortex glass state. An earlier analysis in the framework of London approximation have established that activation barriers controlling vortex dynamics obey the extreme value statistics within roughly the same domain of the phase diagram. We show that the disordered GL model in which only the coefficient at the quadratic term |ψ| 2 is random, first considered by Dorsey et al., exhibits, in the gaussian approximation, an additional nonhierarchical state possessing certain glassy properties like nonzero Edwards-Anderson order parameter. We associate this state with the "marginal glass phase" predicted in the earlier work of one of the authors; the marginal glass state being characterized by the marginally glassy dynamics. We show further that when the random component of the coefficient of the quartic term |ψ| 4 in GL free energy is taken into account, RSB effects appear. Application of the obtained results to description of various disorder-generated phenomena in vortex matter are briefly considered. The location of the glass transition line is determined and compared to experiments. This line is clearly different from both the melting line and the second peak line describing the translational and rotational symmetry breaking at high and low temperatures respectively. The phase diagram is separated by these two lines into the four phases described above.

Human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) are multipotent progenitor cells with osteogenic differentiation potential. The relationship between adiponectin (APN) and the metabolism of h-JBMMSCs has not been fully elucidated, and the underlying mechanism remains unclear. The aim of the study was to investigate the effect and mechanism of APN on h-JBMMSC metabolism. h-JBMMSCs were obtained from the primary culture of human jaw bones and treated with or without APN (1 µg/mL). Osteogenesis-related gene expression was evaluated by real-time polymerase chain reaction (PCR), alkaline phosphatase (ALP) activity assay, and enzyme-linked immunosorbent assay (ELISA). To further investigate the signaling pathway, mechanistic studies were performed using Western blotting, immunofluorescence, lentiviral transduction, and SB202190 (a specific p38 inhibitor). Alizarin Red staining showed that APN promoted h-JBMMSC osteogenesis. Real-time PCR, ALP assay, and ELISA showed that ALP, osteocalcin (OCN), osteopontin, and integrin-binding sialoprotein were up-regulated in APN-treated cells compared to untreated controls. Immunofluorescence revealed that adaptor protein containing a pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL1) translocated from the nucleus to the cytoplasm with APN treatment. Additionally, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) increased over time with APN treatment. Moreover, knockdown of APPL1 or p38 MAPK inhibition blocked the expression of APN-induced calcification-related genes including ALP, Runt-related transcription factor 2 (RUNX2), and OCN. Furthermore, Alizarin Red staining of calcium nodes was not increased by the knockdown of APPL1 or p38 inhibition. Our data suggest that this regulation is mediated through the APPL1-p38 MAPK signaling pathway. These findings collectively provide evidence that APN induces the osteogenesis of h-JBMMSCs through APPL1-mediated p38 MAPK activation.