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Ketamine is a psychotropic drug that can cause significant neurological symptoms and is closely linked to the activity of the CYP3A4 enzyme. This study aimed to examine the diversity of CYP3A4 activity affects the metabolism of ketamine, focusing on genetic variation and drug-induced inhibition. We used a baculovirus-insect cell expression system to prepare recombinant human CYP3A4 microsomes. Then, in vitro enzyme incubation systems were established and used UPLC-MS/MS to detect ketamine metabolite. In rats, we investigated the metabolism of ketamine and its metabolite in the presence of the CYP3A4 inhibitor voriconazole. Molecular docking was used to explore the molecular mechanism of inhibition. The results showed that the catalytic activity of CYP3A4.5, .17, .23, .28, and .29 significantly decreased compared to CYP3A4.1, with a minimum decrease of 3.13%. Meanwhile, the clearance rate of CYP3A4.2, .32, and .34 enhanced remarkably, ranging from 40.63% to 87.50%. Additionally, hepatic microsome incubation experiments revealed that the half-maximal inhibitory concentration (IC 50 ) of voriconazole for ketamine in rat and human liver microsomes were 18.01 ± 1.20 µM and 14.34 ± 1.70 µM, respectively. When voriconazole and ketamine were co-administered, the blood exposure of ketamine and norketamine significantly increased in rats, as indicated by the area under the concentration-time curve (AUC) and maximum concentration (C max ). The elimination half-life (t 1/2Z ) of these substances was also prolonged. Moreover, the clearance (CL z/F ) of ketamine decreased, while the apparent volume of distribution (V z/F ) increased significantly. This might be attributed to the competition between voriconazole and ketamine for binding sites on the CYP3A4 enzyme. In conclusion, variations in CYP3A4 activity would result in the stratification of ketamine blood exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although there is no direct major riverine input, a large quantity of waste produced in mainland China and Korea is transported continuously to the Yellow Sea (YS) through atmospheric deposition, currents and tides; therefore, the environment is distinctly influenced by man-made pollution. This study focuses on the associated pollutant transport mechanisms and fluxes by sampling polychlorinated biphenyls (PCBs). PCBs (Σ24PCB) in YS sediments ranged between 99 pg/g and 3.13 ng/g of dry sediment (with a mean value of 715 pg/g). PCBs produced unintentionally by industrial and other processes appeared to be the major source of PCBs in the sediments, accounting for 60.5%. Industrially synthesized PCBs with 3Cl and 5Cl accounted for 15.5% and 24.0%, respectively. PCBs were mainly from atmospheric deposition (84.5%), followed by continental runoff (15.5%). The average atmospheric deposition flux of technical PCBs was 789 ng/(m(2)a) and flux of surface runoff was 2.27 ng/L., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The Yangtze River estuary (YRE) and the adjacent East China Sea (ECS) inner shelf is an important sink of pollutants originated from mainland China. In this work, we studied the spatial and temporal variations and sources of polychlorinated biphenyls (PCBs) in sediments from the YRE and the ECS inner shelf. Total concentration of 23 PCBs (Σ23PCB) ranged between 24.3 and 343.3 pg/g (with a mean value of 126.7 pg/g), and higher values occurred in the estuarine region. The homolog profile was dominated by 3-5Cl CBs, accounting for 76.1% of Σ23PCB. The Cl proportion ranged from 45.1% to 58.8% (with a mean value of 49.9%); the lowest level appeared in the estuarine region, and it increased with distance from the YRE. Lower chlorinated congeners were carried mainly by the YR into the ocean, to be finally buried in sediments of the estuary region and vicinity. However, higher chlorinated ones were imported mainly via direct emission from local sources, to be finally buried in sediments farther away from the estuary. Of the PCBs in surface sediments, 40.1% came from the YR, 37.9% from the local sources and the rest 22.0% from atmospheric deposition. In a sediment core, we found that 81% of PCBs were technically produced and 19% unintentionally produced in the last century. Before the 1970s, PCB levels were influenced predominantly by the production and consumption of technical PCBs. While in recent decades, the effect of human activities on PCB levels has been increasing continuously., (© 2013.)