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1. Xanthotoxol is a furanocoumarin that possesses many pharmacological activities and in this study itsin vitroglucuronidation was studied. 2. Xanthotoxol can be rapidly metabolized to a mono-glucuronide in both human intestine microsomes (HIM) and human liver microsomes (HLM); the structure of the metabolite was confirmed by NMR spectroscopy. 3. Reaction phenotyping with 12 commercial recombinant human UGTs, as well as with the Helsinki laboratory UGT1A10 that carry a C-terminal His-tag (UGT1A10-H), revealed that UGT1A10-H catalyzes xanthotoxol glucuronidation at the highest rate, followed by UGT1A8. The other enzymes, namely UGT1A3, UGT1A1, UGT1A6, UGT1A10 (commercial), and UGT2B7 displayed moderate-to-low reaction rates. 4. In kinetic analyses, HIM exhibited much higher affinity for xanthotoxol, along with highVmaxand mild substrate inhibition, whereas the kinetics in HLM was biphasic. UGT1A1 (highKmvalue), UGT1A10-H (lowKmvalue), and UGT1A8 exhibited mild substrate inhibition. 5. Considering the above findings and the current knowledge on UGTs expression in HIM, it is likely that UGT1A10 is mainly responsible for xanthotoxol glucuronidation in the human small intestine, with some contribution from UGT1A1. In the liver, this reaction is mainly catalyzed by UGT1A1 and UGT2B7. 6. Glucuronidation appears to be the major metabolic pathway of xanthotoxol in human. [ABSTRACT FROM PUBLISHER]

1. The exposed level of vitamin A in plasma might be exceeded due to the both inadvertent and clinical utilization. The adverse effects of vitamin A have been frequently reported, however, the mechanism remains unclear. The inhibition of vitamin A on the activity of UDP-glucuronosyltransferases (UGTs) was determined usingin vitroincubation system to explain the adverse effects of vitamin A from a new perspective. 2. UGT supersomes catalyzed glucuronidation of 4-methylumbelliferone (4-MU), trifluoperazine (TFP), and cotinine was used as the probe reaction to evaluate the inhibition of vitamin A toward UGT isoforms, and 100 μM of vitamin A significantly inhibited the activity of all the tested UGT isoforms. Vitamin A exerted competitive inhibition on the activity of UGT1A1, 2B4, 2B7, and 2B15, and the inhibition kinetic parameters (Ki) were calculated to be 31.1, 16.8, 2.2, and 11.6 μM for UGT1A1, 2B4, 2B7, and 2B15.In silicodocking method was used to try to elucidate the inhibition mechanism of vitamin A toward UGT2B7. The results showed the significant contribution of hydrogen bonds and hydrophobic interaction on the UGT2B7 inhibition by vitamin A. 3. The present study provides a new perspective for the adverse effects of vitamin A through reporting the inhibition of vitamin A on the activity of important phase II drug-metabolizing enzymes UGTs, which benefits our deep understanding of mechanism of vitamin A's adverse effects when high exposure of vitamin A occurs. [ABSTRACT FROM PUBLISHER]

To study the influence of isolated coal face mining on rock burst or strong tremor, the structure characteristics of thick-hard strata above 10305 isolated face were analyzed in this paper, and the seismic activity and burst risk were also monitored and analyzed. The results show that the strata structure above 10305 isolated face is an unsymmetrical isolated "T" structure, with the main key strata fractured on the short-arm side and non-fractured on the long-arm side, that is, the long-arm main key strata will fractrure and move in large-scale after face mining, and the risk of strong tremor or rock burst is relatively high. In addition, the inferior key strata can only form "O" fracturing structures, and the super-thick main key strata will form layered "O-X" structures, while the fracturing and movement of main and inferior key strata are the main sources of seismic activities. According to seismic monitoring, seismic events manily located on the long-arm side of "T" structure, especially the strong tremors occurred almost within the super-thick main key strata above 10305 and 10306. Moreover, the stong tremors present high ratios of S-wave to P-wave energy, which means they are mainly the results of shear fracturing or slip movement of main and inferior key strata. The burst risks caused by unsymmetrical "T" structure were evaluated by volocity gradient inversion, and the evaluation results are satisfactory. The big-diameter pressure-relief boreholes in coal seam and pre-blastings in main roof were implemented respectively in advance, and the burst effects of strong tremors were greatly reduced. [ABSTRACT FROM AUTHOR]

Thienorphine has been demonstrated to be a potent, long-acting partial opioid agonist. It is being developed as a good candidate to treat opioid dependence. The thienorphine's glucuronide was detected after thienorphine was incubated with human liver microsomes (HLMs). Recombinant UGT isoforms screening experiment and enzyme kinetic study showed that UGT1A1 completely contributed to the glucuronidation of thienorphine. Among the tested UGT isoforms, UGT1A3 and UGT2B7 were inhibited by thienorphine, with other UGT isoforms negligibly influenced. The inhibition type is competitive, and inhibition kinetic parameters (Ki) were 1.65 and 5.27 μM for UGT1A3 and UGT2B7, respectively. However, due to low plasma concentration of thienorphine, in vivo drug–drug interaction might not occur. [ABSTRACT FROM AUTHOR]

The Lower Cambrian shale cores in southeast Chongqing were systematically collected, observed and described. Using total organic carbon content, XRD analyses, methane isothermal adsorption and nitrogen adsorption method, the nanoscale pore structure types, characteristics and influenced factors were analyzed and its impact on gas content was discussed. The results show that the nanoscale pore structures in the shale are complex, and are divided into three structure types based on the nitrogen adsorption-desorption curves and pore diameter distribution. The nanoscale pores mainly consist of cylinder pores with two open ends, slit type pores with parallel plates, and wedge shape pores with all sides open, which are related to the organic matter. The pore diameters are generally less than 60 nm, and have 2-5, 8-12 and 24-34 nm peak distributions. Total volume percentage of macropore (>50 nm) is 8. 5%,the BET surface area percentage is 0. 3%. Total volume percentage of mesopore (2-50 nm) is 82.1%, the BET surface area percentage is 79.0%. Total volume percentage of micropore (<2 nm) is 9.4%, and the BET surface area percentage is 20.7%. TOC is the main controlling factor of nanoscale pore structure characteristics and the organic matter is the material basis of total pore volume and BET surface area. There is an obvious linear correlation between total pore volume, BET surface area and gas adsorption capacity. [ABSTRACT FROM AUTHOR]

In order to explore the migration and transformation characteristics of soil heavy metals in rice in an area of ground source cadmium anomaly and to evaluate the safe planting of rice, a total of 91 pairs of soil and rice samples were collected from paddy fields in the typical area of Liuzhou city, Guangxi province, and the contents of heavy metals such as Cd, soil pH, and organic matter were tested. The results showed that:① Cd, Cu, Ni, and Zn in the paddy field exceeded the background values of 92.31%, 34.07%, 36.26%, and 90.11%, respectively. Compared with the screening values in the Soil Environmental Quality Agricultural Land Soil Pollution Risk Control Standard, Cd and Zn exceeded 30.53% and 25.26%, respectively. Super standard points were mainly distributed in Fushi Town. ② Cd and Ni exceeded 35.16% and 3.30%, respectively, and Daliang town had the highest Cd enrichment coefficient and Cd exceeded rate. ③ Correlation analysis showed that soil pH was the main influencing factor of heavy metals in rice, and Cd and Ni had similar pollution sources in rice. ④ The results of rice health risk assessment showed that the THQ value of rice Cd in Daliang town was greater than 1.0, indicating the potential health risk of rice Cd in this area. The TTHQ values were all greater than 1.0, indicating that the risks to children were higher than those to adult women, which were higher than those of adult men, showing that reasonable dietary structure is crucial to prevent heavy metal intake in different ages and genders. Therefore, there are certain risks in rice planting in the Liuzhou area of ground source cadmium anomaly, which need to be controlled using different safety utilization measures.

Carvacrol and thymol are phenolic compounds with similar structures isolated from many aromatic plants, and have been demonstrated to exert multiple pharmacological effects. The metabolic and pharmacokinetic behaviour of thymol and carvacrol has received much attention. Carvacrol and thymol have been demonstrated to undergo phase I metabolism such as hydroxylation reaction. However, drug-metabolizing enzymes involved in this process remain unclear. Given that cytochrome P450s (CYPs) are involved in most phase I metabolism, the aim of the present study was to investigate the role of CYPs in the metabolism of thymol and carvacrol. After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. A combination of chemical inhibition studies and assays with recombinant CYP isoforms demonstrated that CYP2A6 was the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol. All these results remind the researchers that special attention should be paid on pharmacokinetic and clinical outcomes when thymol or carvacrol was co-administrated with other compounds mainly undergoing CYP2A6-mediated metabolism.

Background: Task-based measurement (TBM) is a method to assess the eight-hour A-weighted equivalent noise exposure level (L(Aeq.8h)) besides dosimeter. TBM can be better used in factories by non-professional workers and staffs. However, it is still not clear if TBM is equal or similar with dosimeter for L(Aeq.8h) measurement in general. This study considered the measurement with dosimeter as real personal noise exposure level (PNEL) and assessed the accuracy of TBM by comparing the consistencies of TBM and dosimeter in L(Aeq.8h) measurement., Methods: The study was conducted in one automobile firm among 387 workers who are exposed to unstable noise. Dosimeters and TBM were used to compare the two strategies and assess the degree of agreement and causes of disagreement. Worker's PNEL was measured via TBM for noise; the real PNEL was also recorded. The TBM for noise was computed with task/position noise levels measured via sound level meter and workers' exposure information collected via working diary forms (WDF) filled by participants themselves. Full-shift noise exposure measurement via personal noise dosimeters were taken as the real PNEL. General linear model (GLM) was built to analyze the accuracy of TBM for noise and the source of difference between TBM for noise and real PNEL., Results: The L(Aeq.8h) with TBM were slightly higher than the real PNELs, except the electricians. Differences of the two values had statistical significance in stamping workers (P < 0.001), assembly workers (P = 0.015) and welding workers (P = 0.001). The correlation coefficient of L(Aeq.8h) with TBM and real PNELs was 0.841. Differences of the two results were mainly affected by real PNEL (F = 11.27, P = 0.001); and work groups (F = 3.11, P < 0.001) divided by jobs and workshops were also independent factors. PNEL of workers with fixed task/position ((86.53 ± 8.82) dB(A)) was higher than those without ((75.76 ± 9.92) dB(A)) (t = 8.84, P < 0.01). Whether workers had fixed task/position was another factor on the accuracy of TBM for noise (F = 4.36, P = 0.038)., Conclusion: TBM for noise has acceptable accuracy on workers' PNEL measurement. The accuracy is affected by job categories, workshops and variability of task/position. TBM for noise can yield a relatively conservative result of worker's PNEL in most cases, so it can be used to measure and assess workers' real PNEL.

Diethylstilbestrol (DES), a synthetic estrogen clinically used to treat threatened abortion between the 1940s and the 1970s, has been restricted to treat certain cases of prostatic and breast cancer due to its adverse drug responses such as teratogenicity and carcinogenicity. Some reports have demonstrated that the addition of DES to docetaxel could modify tubulin composition and improve response of prostate cancer to chemotherapy. Given that DES might be co-administered with other drugs such as docetaxel, the present study focused on CYP-based drug-drug interaction (DDI). In vitro inhibitory effects of DES on CYP isoforms were investigated, and the results showed that DES could competitively inhibit CYP3A4, CYP2C8, CYP2C9 and CYP2E1. The inhibition constants (Ki) were calculated to be 4.4 microM, 3.0 microM, 5.0 microM and 8.0 microM for CYP3A4, CYP2C9, CYP2E1 and CYP2C8, respectively. Based on peak serum DES level after drip influsion of 500 mg of fosfestrol (DES diphosphate) in patients, [I]/Ki was calculated to be 4.3, 6.2, 3.7 and 2.3 for CYP3A4, CYP2C9, CYP2E1 and CYP2C8, which suggested that DES was likely to induce in vivo DDI through inhibition of these four major CYP isoforms. These results collectively demonstrate that adverse drug responses might exist when DES is co-administered with other drugs.

Chlormadinone acetate (CMA), a derivative of 17-a-hydroxyprogesterone, has been widely used as an orally effective progestogen in hormone replacement therapy (HRT). Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the major steps responsible for the metabolism of many drugs, environmental chemicals and endogenous compounds. Pharmacokinetic behaviours of drugs could be altered by inhibition of these UGT isoforms, and the search for drugs that potentially inhibit these UGT isoforms is very significant from a clinical point of view. In the present study, inhibition of five important UGT isoforms in human liver (UGT1A1, 1A3, 1A6, 1A9 and 2B7) by CMA was investigated using 4-MU as nonspecific substrate and recombinant UGT isoforms as enzyme sources. The results showed that CMA exhibited inhibitory effects on UGT1A3 (IC50 = 8.6 +/- 1.4 microM) and UGT2B7 (IC50 = 14.2 +/- 3.8 microM), with other UGT isoforms negligibly influenced. Lineweaver-Burk and Dixon plots showed that CMA noncompetitively inhibited UGT1A3 and UGT2B7. The Ki value was calculated to be 36.9 microM and 4.1 microM for UGT1A3 and UGT2B7, respectively. Considering that UGT1A3 and UGT2B7 are involved in the metabolism of many drugs, special attentions should be paid when CMA was co-administered with the drugs which mainly underwent UGT1A3, 2B7-mediated metabolism.

Objective: To measure the concentration of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (sRANKL) in peripheral blood among normal healthy people and investigate the relationship pf the concentration with age and sex., Methods: The peripheral blood samples of 220 normal healthy people (included 108 males and 112 females, aged from 35 to 70) were collected in the morning. The OPG and sRANKL concentration of blood serum were measured by ELISA., Results: The concentrations in female peripheral blood were: OPG 21.95 to 315.47 pg/ml, sRANKL 10.25 to 370.20 pmol/L; while in male were: OPG 14.78 to 192.55 pg/ml, sRANKL 9.22 to 300.32 pmol/L. There was positive correlation between the OPG concentration and age in the females older than 46 years. And for female older than 57, the sRANKL concentration of peripheral blood increases obviously., Conclusion: Age and sex are the elements that affect the OPG and sRANKL concentration in peripheral blood. For female older than 46, the OPG concentration of peripheral blood increases with age, while the sRANKL concentration of peripheral blood increases for females older than 57.