Stereoselective degradation of fungicide benalaxyl in soils and cucumber plants

The enantioselective degradation of benalaxyl has been investigated to elucidate its behavior in several agricultural soils and plants (cucumber). Racemic benalaxyl was fortified into five types of agricultural soils and sprayed leaves of cucumber plants, respectively. The degradation kinetics and the enantiomer fraction (EF) were determined by normal-phase high-performance liquid chromatography (HPLC) with diode array detection (DAD) on the chiral column filled cellulose-tri-(3,5-dimethylphenylcarbamate)-based chiral stationary phase (CDMPC-CSP). The process of the degradation of benalaxyl enantiomers followed pseudo-first-order kinetics in cucumber plant. However, the dissipation phases of benalaxyl enantiomers in soils were biphasic ("slow-fast-slow" process). It has been shown that the degradation of benalaxyl was stereoselective. The results indicated that the (+)-S-benalaxyl showed a faster degradation in plants, while the (-)-R-benalaxyl showed a faster degradation in Soils 3, 4, and 5. No stereoselective degradation was observed in other soils.     

Trace Metal Mixture Toxicity in Aquatic Organism Reviewed from a Biotoxicity Perspective

Biotoxicity of individual metals is well investigated but that of metal mixture, an environmental reality, in the developing metal mixture, is relatively obscure. Experimental evidences had shown that this mixture could give rise to combined effects that were different from the effect of metals one by one. This review provides an overview of recent research on metal mixture toxicity and the methods employed to predict their toxic combined effects. The two established reference models, the concentration-addition model and the independent-addition model, were used for evaluating the combined effect from the biological activities of the metal mixtures. While the reference models had provided reasonable tools for analyzing the combined effects, the actual predictions for binary metal mixtures showed often somewhat less than additive combined effects compared to what has been observed. As the metal bioavailability is oriented by several environmental factors as well as the toxicodynamics of metals is highly compound-specific, the non-interactive combined effects may be confused with different processes of the interactions. Thus, for improving the predictability of combined effects in metal mixture toxicity, numerous qualitative and quantitative analysis are required for the processes governing the toxicokinetics and dynamics of metals in aquatic organisms.     

Inhibition of integrin β3, a binding partner of kallistatin,leads to reduced viability,invasion and proliferation in NCI-H446 cells

Background

Kallistatin is a serine proteinase inhibitor and heparin-binding protein. It is considered an endogenous angiogenic inhibitor. In addition, multiple studies demonstrated that kallistatin directly inhibits cancer cell growth. However, the molecular mechanisms underlying these effects remain unclear.

Methods

Pull-down, immunoprecipitation, and immunoblotting were used for binding experiments. To elucidate the mechanisms, integrin β3 knockdown (siRNA) or blockage (antibody treatment) on the cell surface of small the cell lung cancer NCI-H446 cell line was used.

Results

Interestingly, kallistatin was capable of binding integrin β3 on the cell surface of NCI-H446 cells. Meanwhile, integrin β3 knockdown or blockage resulted in loss of antitumor activities induced by kallistatin. Furthermore, kallistatin suppressed tyrosine phosphorylation of integrin β3 and its downstream signaling pathways, including FAK/-Src, AKT and Erk/MAPK. Viability, proliferation and migration of NCI-H446 cells were inhibited by kallistatin, with Bcl-2 and Grb2 downregulation, and Bax, cleaved caspase-9 and caspase 3 upregulation.

Conclusions

These findings reveal a novel role for kallistatin in preventing small cell lung cancer growth and mobility, by direct interaction with integrin β3, leading to blockade of the related signaling pathway.

     

Stereoselective degradation of Diclofop-methyl during alcohol fermentation process

Stereoselective degradation of Diclofop-methyl (DM) has been found in alcohol fermentation of grape must and sucrose solution with dry yeast. A method was developed for separation and determination the two enantiomers of DM during the fermentation process by high-performance liquid chromatography based on cellulose tri-(3,5-dimethylphenyl-carbamate) chiral stationary phase. The results showed that the enantiomers of DM degraded following the first-order kinetics in the sucrose solution and the degradation of DM enantiomers in grape must were biphasic (slow-fast-slow process). In the sucrose solution, half lives of (+)-(R)-DM and (-)-(S)-DM were calculated to be 8.5 h and 3.1 h, respectively. In the grape must, half life of (+)-(R)-DM was calculated to be 41.7 h while (-)-(S)-DM was 16.0 h. The result was that (-)-(S)-enantiomer degraded faster than the (+)-(R)-enantiomer in both alcohol fermentation. The results also showed that the differences of the enantioselective degradation of DM depended on the fermentation matrix. DM was configurationally stable in fermentation, showing no interconversion of (-)-(S)- to (+)-(R)- enantiomer, and vice-versa.     

重组腺相关病毒载体相关性杂质

可以稳定表达治疗基因而无明显不良反应的重组腺相关病毒(rAAV)载体被认为是最有发展前景的基因治疗载体。但如何建立可以有效去除rAAV载体内具有潜在致病危害的杂质、产品质量符合临床使用要求的纯化工艺是研究人员面临的巨大挑战。其中针对载体相关性杂质的纯化工艺尤为关键,因为该类杂质的性质与真正的rAAV载体极其相似,一旦存在便难以去除,且会引起严重不良反应。以下总结了该类杂质形成的过程及有别于rAAV载体的特点,并对可以防止其生成或将其与rAAV载体有效分离的技术手段进行了评价。