Novel mesoporous silica surface loaded gold nanocomposites SERS aptasensor for sensitive detection of zearalenone.

Mycotoxin contamination is a severe threat to global food security, thus fast and effective detection of mycotoxins is of great significance. Herein, mesoporous silica surface loaded gold nanocomposites (MSN-Rh6G-AuNPs) were prepared as surface-enhanced Raman scattering (SERS) substrate, and the SERS aptasensor (MSN-Rh6G-AuNPs@apt) was further obtained by aptamer functionalization which can realize the quantitative and sensitive detection of zearalenone (ZEN). The small nanogaps between AuNPs made MSN-Rh6G-AuNPs present strong SERS performance under excitation light irradiation, while the aptamer performed the functions of ZEN recognition and Raman signal masking. The acquired results revealed that the SERS intensity at 1508 cm-1 had a good linear relationship with ZEN concentration of 3-200 ng/mL and the limit of detection (LOD) was calculated to be 0.0064 ng/mL. In addition, the designed SERS aptasensor was successfully applied to the detection of ZEN in corn, indicating great potential in practical implications.

Multi-Label Feature Selection Combining Three Types of Conditional Relevance.

With the rapid growth of the Internet, the curse of dimensionality caused by massive multi-label data has attracted extensive attention. Feature selection plays an indispensable role in dimensionality reduction processing. Many researchers have focused on this subject based on information theory. Here, to evaluate feature relevance, a novel feature relevance term (FR) that employs three incremental information terms to comprehensively consider three key aspects (candidate features, selected features, and label correlations) is designed. A thorough examination of the three key aspects of FR outlined above is more favorable to capturing the optimal features. Moreover, we employ label-related feature redundancy as the label-related feature redundancy term (LR) to reduce unnecessary redundancy. Therefore, a designed multi-label feature selection method that integrates FR with LR is proposed, namely, Feature Selection combining three types of Conditional Relevance (TCRFS). Numerous experiments indicate that TCRFS outperforms the other 6 state-of-the-art multi-label approaches on 13 multi-label benchmark data sets from 4 domains.

Study on the metabolic mechanism of chiral inversion of S-mandelic acid in vitro.

Mandelic acid (MA) is generally used as a biological indicator of occupational exposure to styrene, which is classified as a class of hazardous environmental pollutants. It was found to undergo one-directional chiral inversion (S-MA to R-MA) in Wistar and Sprague-Dawley rats in vivo. This study was aimed to explore the metabolic mechanism of chiral inversion of S-MA in vitro. S-MA was converted to R-MA in rat hepatocytes, whereas MA enantiomers remained unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora. In addition, the synthesized S-MA-CoA thioester was rapidly racemized and hydrolyzed to R-MA by rat liver homogenate and S9, cytosolic and mitochondrial fractions. The data suggest that chiral inversion of S-MA may involve the hydrolysis of S-MA-CoA, and its metabolic mechanism could be the same as that of 2-arylpropionic acid (2-APA) drugs.

Detection of phenolic metabolites of styrene in mouse liver and lung microsomal incubations.

Metabolic activation is considered to be a critical step for styrene-induced pulmonary toxicity. Styrene-7,8-oxide is a primary oxidative metabolite generated by vinyl epoxidation of styrene. In addition, urinary 4-vinylphenol (4-VP), a phenolic metabolite formed by aromatic hydroxylation, has been detected in workers and experimental animals after exposure to styrene. In the present study, new oxidative metabolites of styrene, including 2-vinylphenol (2-VP), 3-vinylphenol (3-VP), vinyl-1,4-hydroquinone, and 2-hydroxystyrene glycol were detected in mouse liver microsomal incubations. The production rates of 2-VP, 3-VP, 4-VP, and styrene glycol were 0.0527 ± 0.0045, 0.0019 ± 0.0006, 0.0053 ± 0.0002, and 4.42 ± 0.33 nmol/(min · mg protein) in mouse liver microsomes, respectively. Both disulfiram (100 µM) and 5-phenyl-1-pentyne (5 µM) significantly inhibited the formation of the VPs and styrene glycol. 2-VP, 3-VP, and 4-VP were metabolized in mouse liver microsomes at rates of 2.50 ± 0.30, 2.63 ± 0.13, and 3.45 ± 0.11 nmol/(min · mg protein), respectively. The three VPs were further metabolized to vinylcatechols and/or vinyl-1,4-hydroquinone and the corresponding glycols. Pulmonary toxicity of 2-VP, 3-VP, and 4-VP was evaluated in CD-1 mice, and 4-VP was found to be more toxic than 2-VP and 3-VP.

[Cloning, expression and the application of human, rat alcohol dehydrogenase and aldo-keto reductase].

This study is aimed to clone and express human, rat alcohol dehydrogenase (ADH) and aldo-keto reductase. Then the enantioselective metabolism of mandelic acid (MA) was studied. Human alcohol dehydrogenase 2, rat alcohol dehydrogenase 1, human and rat aldo-keto reductase 1A1 were amplified using RT-PCR from human and rat liver samples. Then subcloned into pET-28a (+) and expressed in E. coli BL21 (DE3) stably. The protein was induced with IPTG and purified by affinity chromatography. Then the enzyme activities were measured. MA enantiomers were incubated with rat, human ADH and phenylglyoxylic acid (PGA) with AKR1A1, respectively. The metabolism was analyzed with HPLC. The proper genes were cloned and purified and proteins were obtained. All of the proteins obtained showed good activity. Stereoselective-metabolism of MA was observed in human ADH2, which favors for S-MA metabolism. The expression plasmids are constructed and the recombinant proteins are expressed successfully. The recombinant alcohol dehydrogenase and aldo-keto reductase have been employed to study MA metabolism.

Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp.

This study was designed to understand the transport profiles of astilbin and taxifolin in Caco-2 cell model and their effects on the function and expression of P-glycoprotein. The transport studies were examined using Caco-2 cells cultured on Transwell inserts. Their effects on the function and expression of P-glycoprotein were detected using Western Blot and RT-PCR. The transport was concentration and temperature dependent. The apparent permeability (P(app)) of these two compounds in the secretory direction was larger than that in the absorptive direction in the concentration range of 10-1000 microM. Those compounds had no effects on the P-glycoprotein-mediated transport of Rhodamine 123. Caco-2 cells exposed to astilbin or taxifolin for 36 h exhibited higher P-glycoprotein activity through up-regulating P-glycoprotein expression at protein and mRNA levels. These results indicated that P-glycoprotein and Multidrug Resistance Protein 2 might play important roles in limiting the bioavailability of those compounds. Drugs which are the inhibitors of P-glycoprotein or Multidrug Resistance Protein 2 may increase the oral bioavailability of astilbin or taxifolin and the possibility of unwanted drug-food interactions. The increased expression of P-glycoprotein in Caco-2 cells may serve as an adaptation and defense mechanism in limiting the entry of xenobiotics into the body.

PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA.

Danshen (Radix Salvia miltiorrhiza) is a famous Traditional Chinese Medicine used widely for the treatment of coronary heart disease and cerebrovascular disease. Diterpenoid tanshinones including tanshinone I, tanshinone IIA and cryptotanshinone are the major bioactive components from Danshen herb. Previous reports have demonstrated that Danshen extracts could induce the expression of CYP3A in rodents, however, the constituents responsible for Danshen-mediated CYP3A induction and the underlying molecular mechanisms remain unknown. The discovery of a family of nuclear receptors such as pregnane X receptor (PXR), constitutive androstane receptor (CAR) and glucocorticoid receptor (GR) gives insight into the molecular explanation of CYP3A induction by xenobiotics. In the present study, interactions between Danshen constituents and human PXR were evaluated using a reporter gene assay. Our observations showed that Danshen ethanol extract could activate human PXR and induce the CYP3A4 reporter construct in HepG2 cells. Tanshinone IIA and cryptotanshinone were identified as efficacious PXR agonists, and cryptotanshinone activated the CYP3A4 promoter more strongly than tanshinone IIA. Furthermore, CAR and GR were also involved in the induction of CYP3A4 expression by tanshinones, though their roles seemed not as important as PXR. Treatment of LS174T cells with cryptotanshinone or tanshinone IIA resulted in a significant increase of CYP3A4 mRNA, which was consistent with the results from the reporter gene assay. Collectively, activation of PXR and the resultant CYP3A4 induction mediated by cryptotanshinone and tanshinone IIA provide a molecular mechanism for previously observed CYP3A induction by Danshen extracts, and our findings also suggest that caution should be taken when Danshen products are used in combination with therapeutic drugs metabolized by CYP3A4.