Особенности структуры живого напочвенного покрова и биологической активности лесных почв в условиях урбанизации

Branched octahydro-indenes were first synthesized with methyl isobutyl ketone (MIBK) and methyl benzaldehyde, which can be obtained from lignocellulose. Initially, C-14 oxygenates were prepared by the aldol condensation reaction of MIBK with methyl benzaldehydes. K2CO3/Al2O3 exhibited the highest activity among the studied solid base catalysts. On the basis of the characterizations, the outstanding activity of K2CO3/Al2O3 was comprehended, because this material has a relatively higher surface area and a larger base site concentration. Subsequently, the aldol condensation products were converted to branched octahydro-indene by hydrodeoxygenation over a Pt/C catalyst. This method is also applicable for the manufacture of C-11-C-13 polycycloalkanes with methyl benzaldehyde and other lignocellulosic ketones. According to our measurements, the polycycloalkanes obtained in this work have low freezing points (227.7 similar to 240.0 K) and high densities (0.857 similar to 0.944 g mL(-1)). Consequently, they may potentially be utilized to raise the volumetric heat values and/or the thermal stability of jet fuels

The effect of iodide on the synthesis of gold nanoprisms

<div><p>It has been known that the iodide (I⁻) anions are necessary for the production of high-quality Au nanoprisms. Based on a previously reported seed-mediated synthesis of triangular gold nanoprisms, herein, we further optimised the synthesis process by varying the concentration of added NaI and seeds, respectively, to get high-quality (size-monodisperse, tip-sharp and purity-high) Au nanoprisms. The results show that the ratio between the concentration of I⁻ and seeds is a very sensitive parameter to control the quality (size-monodispersity, tip-sharpness and purity) of Au nanoprisms.</p></div

Discovery of Novel Androgen Receptor Ligands by Structure-based Virtual Screening and Bioassays

Androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling pathway. Therefore, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening (VS) on the basis of the crystal structure of the AR ligand binding domain (LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them (HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC50 values of HBP1-51 and HBP1-58 are 3.96 µM and 4.92 µM, respectively, which are even lower than that of enzalutamide (Enz, IC50 = 13.87 µM), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics (MD) simulations and principal components analysis (PCA) were carried out to reveal the binding principle of the newly-identified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary, the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases. Keywords: Androgen receptor, AR ligand, Virtual screening, AR agonist, AR antagonis

Molecular Dynamics Simulations Revealed the Regulation of Ligands to the Interactions between Androgen Receptor and Its Coactivator

The androgen receptor (AR) plays important roles in gene expression regulation, sexual phenotype maintenance, and prostate cancer (PCa) development. The communications between the AR ligand-binding domain (LBD) and its coactivator are critical to the activation of AR. It is still unclear how the ligand binding would affect the AR–coactivator interactions. In this work, the effects of the ligand binding on the AR–coactivator communications were explored by molecular dynamics (MD) simulations. The results showed that the ligand binding regulates the residue interactions in the function site AF-2. The ligand-to-coactivator allosteric pathway, which involves the coactivator, helix 3 (H3), helix 4 (H4), the loop between H3 and H4 (L3), and helix 12 (H12), and ligands, was characterized. In addition, the interactions of residues on the function site BF-3, especially on the boundary of AF-2 and BF-3, are also affected by the ligands. The MM/GBSA free energy calculations demonstrated that the binding affinity between the coactivator and apo-AR is roughly weaker than those between the coactivator and antagonistic ARs but stronger than those between the coactivator and agonistic ARs. The results indicated that the long-range electrostatic interactions and the conformational entropies are the main factors affecting the binding free energies. In addition, the F876L mutation on AR-LBD affects the ligand-to-coactivator allosteric pathway, which could be the reason for point mutation induced tolerance for the antagonistic drugs such as enzalutamide. Our study would help to develop novel drug candidates against PCa