The intercalated nanocomposite of gelatin/montmorillonite-chitosan (Gel/MMT-CS) was prepared via the solution intercalation process. In vitro degradation tests showed that the nanocomposite had a lower degradation rate than Gel-CS composite. And the introduced intercalation structure endowed Gel/MMT-CS nanocomposite with a controllable degradation rate when changing the MMT content. Cells attachment, spread and proliferation on the Gel/MMT-CS membranes were investigated by scanning electron microscopy (SEM) and mitochondrial activity assay. The results provided evidences of good adhesion, proliferation and morphology of rat stromal stem cells on Gel/MMT-CS membranes compared to the tissue culture plates (TCPs), making the Gel/MMT-CS nanocomposite a promising candidate towards tissue engineering.

A general method for determining bacterial uptake of compounds independent of antibacterial activity would be a valuable tool in antibacterial drug discovery. LC-MS/MS assays have been described, but it has not been shown whether the data can be used directly to inform medicinal chemistry. We describe the evaluation of an LC-MS/MS assay measuring association of compounds with bacteria, using a set of over a hundred compounds (inhibitors of NAD-dependent DNA ligase, LigA) for which in vitro potency and antibacterial activity had been determined. All compounds were active against an efflux-deficient strain of Escherichia coli with reduced LigA activity ( E. coli ligA251 Δ tolC). Testing a single compound concentration and incubation time, we found that, for equipotent compounds, LC-MS/MS values were not predictive of antibacterial activity. This indicates that measured bacteria-associated compound was not necessarily exposed to the target enzyme. Our data suggest that, while exclusion from bacteria is a major reason for poor antibacterial activity of potent compounds, the distribution of compound within the bacterial cell may also be a problem. The relative importance of these factors is likely to vary from one chemical series to another. Our observations provide directions for further study of this difficult issue.

A ZrO 2 nanoparticle strengthened lead-free Sn-3.5Ag-ZrO 2 solder was prepared by mechanically stirring ZrO 2 nanoparticles into the molten melt of eutectic Sn-3.5Ag alloy. The influence of ZrO 2 nanoparticles on the eutectic solidification process, in particular, the formation of Ag 3 Sn intermetallic compounds (IMCs) and the associated microstructure that forms and microhardness of Sn-3.5Ag solder, was systematically investigated. The addition of ZrO 2 nanoparticles significantly refined the size of Ag 3 Sn IMCs due to the strong adsorption effect of the ZrO 2 nanoparticles. The refined Ag 3 Sn IMCs increase the Vicker's microhardness of the prepared Sn-3.5Ag-ZrO 2 solder, which corresponds well with the prediction of the classic theory of dispersion strengthening.

Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound 1 analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than 1 did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD(50) of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.

Distribution of drugs into tissues is an important determinant of the overall PK and PD profile. Thus, bioanalysis of drugs and their metabolites in tissues can play an important role in understanding the pharmacological and toxicological properties of new drug candidates. Unlike liquid matrices, bioanalysis in tissues offers unique challenges such as proper tissue sampling, appropriate tissue sample preparation, efficient extraction of the analytes from the tissue homogenates, and demonstration of stability and recovery of analytes in intact tissues. This article provides a systematic review of tissue sample analysis for small molecules using LC-MS/MS. The authors provide rationale for tissue sample analysis, and discuss strategies for method development, method qualification or validation, and sample analysis. Unique aspects of method development and qualification/validation are highlighted based on authors' direct experiences and literature summary. Analysis using intact tissue samples such as MALDI imaging is also briefly discussed.