chain AHLs enhances current knowledge regarding the variety of AHLs produced by this enzyme. These structural data are expected to serve as a molecular rationale for AHL synthesis by AhyI.Farnesoid X receptor (FXR) agonists can reverse dysregulated bile acid metabolism, and thus, they are potential therapeutics to prevent and treat nonalcoholic fatty liver disease. The low success rate of FXR agonists' R&D and the side effects of clinical candidates such as obeticholic acid make it urgent to discover new chemotypes. Unfortunately, structure-based virtual screening (SBVS) that can speed up drug discovery has rarely been reported with success for FXR, which was likely hindered by the failure in addressing protein flexibility. To address this issue, we devised human FXR (hFXR)-specific ensemble learning models based on pose filters from 24 agonist-bound hFXR crystal structures and coupled them to traditional SBVS approaches of the FRED docking plus Chemgauss4 scoring function. It turned out that the hFXR-specific pose filter ensemble (PFE) was able to improve ligand enrichment significantly, which rendered 3RUT-based SBVS with its PFE the ideal approach for FXR agonist discovery. By screening of the Specs chemical library and in vitro FXR transactivation bioassay, we identified a new class of FXR agonists with compound XJ034 as the representative, which would have been missed if the PFE was not coupled. Following that, we performed in-depth biological studies which demonstrated that XJ034 resulted in a downtrend of intracellular triglyceride in vitro, significantly decreased the serum/liver TG in high fat diet-induced C57BL/6J obese mice, and more importantly, showed metabolic stabilities in both plasma and liver microsomes. To provide insight into further structure-based lead optimization, we solved the crystal structure of hFXR complexed with compound XJ034, uncovering a unique hydrogen bond between compound XJ034 and residue Y375. The current work highlights the power of our pose filter-based ensemble learning approach in terms of scaffold hopping and provides a promising lead compound for further development.Phosphorylation is one of the most abundant types of post-translational modifications of intrinsically disordered proteins (IDPs). This study examines the conformational changes in the 15-residue-long N-terminal fragment of the IDP statherin upon phosphorylation, using computer simulations with two different force fields AMBER ff99SB-ILDN and CHARMM36m.  https://www.selleckchem.com/products/mlt-748.html  The results from the simulations are compared with experimental small-angle X-ray scattering (SAXS) and circular dichroism data. In the unphosphorylated state, the two force fields are in excellent agreement regarding global structural properties such as size and shape. However, they exhibit some differences in the extent and type of the secondary structure. In the phosphorylated state, neither of the force fields performs well compared to the experimental data. Both force fields show a compaction of the peptide upon phosphorylation, greater than what is seen in SAXS experiments, although they differ in the local structure. While the CHARMM force field increases the fraction of bends in the peptide as a response to strong interactions between the phosphorylated residues and arginines, the AMBER force field shows an increase of the helical content in the N-terminal part of the peptide, where the phosphorylated residues reside, in better agreement with circular dichroism results.Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.One of the main challenges for analytical laboratories and food safety authorities is the control of food contaminants hazardous to human health. For the first time, a simple, fast, and cost-effective sample preparation method is proposed as an extraction technique to determine 12 brominated flame retardants (BFRs) (seven polybrominated diphenyl ether (PBDE) congeners and five novel BFRs) in Capsicum cultivars. Different QuEChERS and dispersive solid-phase extract (d-SPE) sorbent compositions were evaluated in terms of recovery and matrix effects. The best results were obtained with citrate-buffered version QuEChERS and a cleanup step, with 150 mg of MgSO4, 50 mg of primary secondary amine (PSA), 50 mg of C18, and 5 mg of carbon. The limit of detection (LOD) was between 1.4 and 9.3 μg/kg and R2 > 0.99. Recoveries and matrix effects were between 66 and 104% and 0.58 and 2.18, respectively. The relative standard deviations from repeatability and reproducibility studies and estimation of measurement uncertainty were lower than 20%. Gas chromatography coupled with a mass spectrometer was used to confirm the presence of BFRs in the samples. Novel BFRs were detected lower than the LOD.Heterogeneous catalysts with precise surface and interface structures are of great interest to decipher the structure-property relationships and maintain remarkable stability while achieving high activity. Here, we report the design and fabrication of the new sandwich composites ZIF-8@Au25@ZIF-67[tkn] and ZIF-8@Au25@ZIF-8[tkn] [tkn = thickness of shell] by coordination-assisted self-assembly with well-defined structures and interfaces. The composites ZIF-8@Au25@ZIF-67 efficiently catalyzed both 4-nitrophenol reduction and terminal alkyne carboxylation with CO2 under ambient conditions with remarkably improved activity and stability, compared to the simple components Au25/ZIF-8 and Au25@ZIF-8, highlighting the highly useful function of the ultrathin shell. In addition, the performances of these composite sandwich catalysts are conveniently regulated by the shell thickness. This concept and achievements should open a new avenue to the targeted design of well-defined nanocatalysts with enhanced activities and stabilities for challenging reactions.