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C-arm Drape Perforation Through Principal Anterior Stylish Arthroplasty.
The farnesoid X receptor (FXR) is a bile acid-sensing transcription factor with indispensable roles in regulating metabolic processes. Nowadays, FXR has become a highly promising drug target for severe liver disorders, especially nonalcoholic steatohepatitis (NASH). A recent study showed that imatinib and its analogues were able to allosterically enhance agonist-induced FXR activation and its target gene expression. However, the allosteric modulation mechanism of FXR by these compounds remains unclear. In this work, the most effective imatinib analogue, P16, was used as a probe to explore this issue by computational approaches. Our results identified one potential allosteric site surrounded by residues Ile335, Phe336, Lys338, Glu339, Leu340, and Leu348, which could efficiently accommodate P16. In addition, the long-time molecular dynamics simulations indicated that the binding of P16 could significantly decrease the fluctuation of the co-activator and enhance the communications between the endogenous ligand chenodeoxycholic acid (CDCA) and FXR. By analyzing the residue interaction network, we observed two unique communication pathways connecting P16 and CDCA through three key residues, Arg331, Ser332, and Phe336. The communications of network organization in the P16-bound complex may allow the synergistic effect of the two compounds via robust signal transmission between the binding sites and global network bridges, which coordinate allosteric transitions and modulate the receptor activity. Our study offers insights into the allosteric modulation occurring in FXR and would be helpful for discovery of new allosteric modulators targeting FXR for further clinical research.Gold-silica (Au-SiO2) nanohybrids are of great technological importance, and it is crucial to develop facile synthetic protocols to prepare Au-SiO2 nanohybrids with novel structures. Here we report the bioinspired synthesis of pomegranate-like SiO2@Au nanoparticles (P-SiO2@Au NPs) via one-step aqueous synthesis from chloroauric acid and tetraethyl orthosilicate mediated by a basic amino acid, arginine. Effects of chloroauric acid, tetraethyl orthosilicate, and arginine on the morphology and optical property of the products are investigated in detail. The P-SiO2@Au NPs achieve tunable plasmon resonance depending on the amount of chloroauric acid, which affects the size and shape of the P-SiO2@Au NPs. Finite-difference time-domain simulations are performed, revealing that the plasmon peak red-shifts with increasing particle size. Arginine serves as the reducing and capping agents for Au as well as the catalyst for SiO2 formation and also promotes the combination of Au and SiO2. learn more Formation process of the P-SiO2@Au NPs is clarified through time-course analysis. The P-SiO2@Au NPs show good sensitivity for both colloidal and paper-based surface-enhanced Raman scattering measurements. They achieve enhancement factors of 4.3 × 107-8.5 × 107 and a mass detection limit of ca. 1 ng using thiophenol as the model analyte.Decoding protein C-termini is a challenging task in protein chemistry using conventional chemical and enzymatic approaches. With the rapid development in modern mass spectrometer, many advanced mass spectrometry (MS)-based protein C-termini analysis approaches have been established. Although great progress is being continually achieved, it is still necessary to develop more efficient approaches in order to discover a proteome-scale protein C-termini (C-terminome) and consequently to help understand their biological functions. In this report, we describe the BaSCX method, for basic strong cation exchange chromatography, for C-terminome studies. Taking advantage of carboxylic amidation, LysargiNase digestion, and optimized search parameters, BaSCX enables identification of 1806 and 1812 database-annotated human protein C-termini from HeLa and 293T cells, resepctively, by triplicate experiments using 40 μg proteins each. Combined together, 2151 human protein C-termini, nearly three times the recently reported largest human C-terminome data set, are reported in this study. Similar results were acquired in different organisms, including mice, C. elegans, and tomatoes. Furthermore, we report for the first time the discovery of C-terminal-specific modifications using a proteomic approach, including three methyl-esterified protein C-termini and 16 α-amidated protein C-termini, demonstrating the excellent performance and great potential of BaSCX in C-terminomic studies. Data are available via ProteomeXchange with identifier PXD016317.Here, we show that the turn-on voltage for the hydrogen evolution reaction on a graphene surface can be tuned in a semiconductor-insulator-graphene (SIG) device immersed in a solution. Specifically, it is shown that the hydrogen evolution reaction (HER) onset for the graphene can shift by >0.8 V by application of a voltage across a graphene-Al2O3-silicon junction. We show that this shift occurs due to the creation of a hot electron population in graphene due to tunneling from the Si to graphene. Through control experiments, we show that the presence of the graphene is necessary for this behavior. By analyzing the silicon, graphene, and solution current components individually, we find an increase in the silicon current despite a fixed graphene-silicon voltage, corresponding to an increase in the HER current. This additional silicon current appears to directly drive the electrochemical reaction, without modifying the graphene current. We term this current "direct injection current" and hypothesize that this current occurs due to electrons injected from the silicon into graphene that drives the HER before any electron-electron scattering occurs in the graphene. To further determine whether hot electrons injected at different energies could explain the observed total solution current, the nonequilibrium electron dynamics was studied using a 2D ensemble Monte Carlo Boltzmann transport equation (MCBTE) solver. By rigorously considering the key scattering mechanisms, we show that the injected hot electrons can significantly increase the available electron flux at high energies. These results show that semiconductor-insulator-graphene devices are a platform which can tune the electrochemical reaction rate via multiple mechanisms.
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