Boosting the High Performance of BiFeO3-BaTiO3 Lead-Free Piezoelectric Ceramics: One-Step Preparation and Reaction Mechanisms.

One of the notorious problems in BiFeO3-based piezoelectric ceramics is how to limit the formation of Bi25FeO39 and Bi2Fe4O9 impurities to achieve excellent piezoelectric performance. In this study, a one-step preparation technology, namely, excluding PVA, calcining, and sintering are completed in one step, instead of three steps in the ordinary sintering method, is developed to prepare BiFeO3-xBaTiO3 (BF-xBT) ceramics. The significance of this one-step method is that the thermodynamically unstable region of BiFeO3 is successfully avoided based on the Gibbs free energy of BiFeO3, Bi25FeO39, and Bi2Fe4O9. Benefiting from preventing the formation of Bi25FeO39 and Bi2Fe4O9 impurities, the resultant ceramics show dense structures, macroscopic stripe domains, and a small number of island domains and display saturated P-E curves, sharp I-V characteristics, butterfly-shape S-E loops, and good piezoelectric properties (d33 = 174-199 pC/N; TC = 494-513 °C). By analyzing X-ray diffraction patterns of BF-xBT (0 ≤ x ≤ 1) powders at different calcination temperatures (Tcal), the different reaction mechanisms between 750 °C ≤ Tcal ≤ 900 °C and 950 °C ≤ Tcal ≤ 1000 °C are revealed. When 750 °C ≤ Tcal ≤ 900 °C, Bi3+ diffuses into Fe2O3 particles to form BiFeO3 and Bi25FeO39 and then reacts with BaTiO3; in this temperature range, the formed Bi25FeO39 is hard to eliminate. At 950 °C ≤ Tcal ≤ 1000 °C, Bi3+ and Fe ions simultaneously diffuse into BaTiO3 to form BF-xBT, which is beneficial to preventing the formation of Bi25FeO39 and the improvement of performance.

Identification of novel selective TRPV3 antagonists based on virtual screening, molecular docking and bioassay / 药学学报

Transient receptor potential vanilloid member 3 (TRPV3) is a temperature-sensitive cation channel protein, which contributes to nociception, itch, hair growth, emotional control and the pathophysiology of migraine. However, research progress on TRPV3 fundamental molecular biology is rather slow, compared to other TRP channels due to the lack of its selective antagonists. It's necessary to identify TRPV3 selective antagonists for the study on TRPV3 physiological functions. In this study, several selective TRPV3 antagonists were identified by ligand-based virtual screening of shape-based similarity and electrostatic matching. The most potent one (V-39) blocked 2-APB-activated currents in a stable human TRPV3 expressed HEK293T cell line with IC50=18.0 ±1.1 μmol·L-1 (n=4). Besides, the interaction pattern between TRPV3 and its antagonists were studied through docking the antagonists into a homology model (TRPV3_HM4) generated from the crystal structure of TPRV1. The docking results show that the binding site of TRPV3 locates between linker domain (of N-terminus and TM1) and TRP Box. There are a π-π stacking interaction and hydrogen bonding interactions between compound V-39 and residues His-310, His-314 and Arg-577 of the pocket. Identification of these antagonists provides new probes for understanding the pharmacological function of TRPV3 channel.

Treatment of triple negative breast cancer cells with combination of mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901 / 药学学报

MEK inhibition activates PI3K/AKT/mTOR pathway in triple negative breast cancer (TNBC) cell lines. Combination of PI3K inhibitor and MEK1/2 inhibitor is not appropriate for PI3K inhibitor insensitive TNBC cell lines. This study was designed to investigate the effects of dual treatments with mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901 in MDA-MB-435 cell line. MEK1/2 inhibition led to activation of AKT, which is the downstream signaling protein of PI3K pathway. The combination inhibited the phosphorylation of AKT and therefore abolished the feedback interaction of two pathways. Cell proliferation assay and DNA replication assay demonstrated that the dual treatments led to a significant synergistic inhibition of cell cycle progression and cell proliferation.

Design and synthesis of photoaffinity biotin labelled 2'-O-propargyl-guanosine / 药学学报

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.

The synthesis of purine derivatives and its inhibitory activity on CD38 NADase / 药学学报

CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.

Design, synthesis and biological assay of novel tripeptidic tetrazoles as inhibitors of 20S proteasome / 药学学报

Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place. Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with 1H NMR, MS and elemental analysis. Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome.

A method for detecting and preventing negative RNA interference in preparation of lentiviral vectors for siRNA delivery.

The lentiviral vector is a useful tool for delivery of hairpin siRNA (shRNA) into mammalian cells. However, the efficiency of this system for carrying double-stranded siRNA (dsRNA) has not been explored. In this study we cloned the two forms of siRNA-coding sequence, a palindromic DNA with a spacer loop for shRNA and a double-stranded DNA with opposing Pol III promoters for dsRNA, into lentiviral DNA vectors, and compared their viral vector production yields. Our results indicate that sharply lower titer vector was obtained for dsRNA while much higher titer vector was produced for shRNA, posing a fundamental concern whether siRNA-carrying viral RNA itself is an inherent target of RNAi. Further experimental analyses using packaging cells that either allow or do not allow siRNA transcription indicate that the shRNA-carrying viral RNA is resistant to RNAi but the viral RNA carrier for dsRNA is not, offering a linker of RNAi bias-target secondary structure that causes shRNA vector to evade RNAi degradation. More importantly, the poor yield of dsRNA vector production was restored when a novel packaging cell line was used that blocks the antisense strand from dsRNA duplexes. This method has important implications for the RNAi field, especially for those who are using lentiviral dsRNA and dsRNA libraries for various biological discovery and therapeutic interventions.