[Ecological Risk Assessment and Migration and Accumulation Characteristics of Heavy Metals in Farmland Soil-crop System from Typical Pyrite Mining Area].

To evaluate the ecological risk of heavy metals in the soil-crop system in the superimposed high background and human activities from pyrite mining, the heavy metal contents and chemical speciation in soil and crop samples were analyzed, and these data were used to assess the potential ecological risk and factors affecting the migration ability of heavy metals using bioconcentration factors(BCF), potential ecological risk index(RI), risk assessment code(RAC), and correlation analysis. The results indicate that the average Cd, Cu, Pb, and Zn concentrations exceeded the background values of soils in Zhejiang Province and China. Cd had the greatest potential ecological harm, followed by that of Hg. The bioactive components and potential bioactive components of Cd accounted for 46% and 33%, respectively, indicating relatively high bioavailability. Cu and Pb were mainly in potential bioactive components accounting for 60% and 73%, respectively. The As, Cr, Hg, Ni, and Zn were predominantly residual and accounted for >60%, which indicated low biological activity. The RAC levels were in the following order:Cd>Zn>Cu>Pb>Ni>As>Cr>Hg; soil Cd had the highest ecological risk, mainly with high and extremely high levels, whereas other elements had no risk or low risk. Compared with Cd content in soil, only eight rice samples had Cd contents exceeding the safety limit, and sweet potato samples did not exceed the standard. The migration and enrichment capability of rice in order from strong to weak was s follows:Cd>Zn>Cu>Hg>As>Ni>Cr>Pb; the bioactive component of Cd played a significant role in promoting Cd absorption by rice. Soil OM had a bi-directional effect on Cd bioavailability, whereas soil texture had an indirect effect. This comprehensive study shows that the total amount of heavy metals in soil, chemical speciation, biological activities, absorption, and enrichment of heavy metals by crops should be taken into consideration when assessing the ecological risks in the superimposed areas affected by high background and human activities, such as the pyrite mining area.

[Heavy Metal Concentration Characteristics and Health Risks of Farmland Soils in Typical Pyrite Mining Area of the Central Zhejiang Province, China].

In order to ascertain the impact of pyrite mining on the surrounding farmland soil environment and human health, 42 surface soil samples (from 0-20 cm) were collected around the pyrite mining area in Longyou county. In this study, the concentrations of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and the pH in the topsoil were analyzed, and the concentration characteristics of heavy metals, source analysis, and human health risks assessment were studied using statistical analysis (SA), geo-accumulation index (Igeo), positive matrix factorization (PMF), and the health risk model. The average of ω(Cd), ω(Cu), ω(Pb), and ω(Zn) concentrations exceeded the background values of soils in Zhejiang province and China. According to the agricultural land pollution risk screening values (GB 15618-2018), Cd, Cu, Pb, and Zn were up to 82%, 49%, 42%, and 31%, respectively. The Igeo shows that the major pollutant element in the soils was Cd, followed by Cu, Pb, and Zn. The PMF analysis indicates that nature sources (As, Cr, and Ni), comprehensive pollution sources caused by high geological background and mining of ore-forming geological bodies (Cd, Cu, Pb, and Zn), and anthropogenic sources (Hg) were the three major sources of heavy metals in the study area, with contributions of 32%, 46%, and 22%, respectively. The results of the health risk assessment indicate that the major non-carcinogenic factor triggering risks was the ingestion of Pb; Cr exposure had carcinogenic risk for adults, and Cr and As exposure had carcinogenic risk for children.

Preparation and analysis of photochromic behavior of carboxymethyl chitin derivatives containing spiropyran moieties.

1'-(2-Acryloxyethyl)-3,3'-dimethyl-6-nitrospiro[2 H-1-benzopyran-2,2'-indoline] (SPA) was synthesized and grafted onto a water-soluble carboxymethyl chitin (CMCH) macromolecule to prepare a photochromic copolymer (CMCH-g-SPA). The structure of CMCH-g-SPA was characterized by Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) analysis, X-ray diffraction (XRD) analysis, water-solubility evaluation, and UV-vis spectroscopy. XRD patterns of CMCH-g-SPA revealed that grafting copolymerization disrupts the CMCH semicrystalline structure, thus improving water solubility. UV-vis spectroscopy results supported the negative photochromic behavior of the merocyanine (MC) form of CMCH-g-SPA (CMCH-g-MCA) present in a water solution of the target copolymer. In addition to high solvent polarity, the intermolecular and intramolecular electrostatic attraction between the indolenine cation and the COO- anion were found to be influencing factors, which stabilize these MC form of spiropyran groups grafted onto CMCH. In a water solution, visible light bleaching was completed over a short period (8 minutes) under artificial visible light irradiation and the thermal coloration reaction, whose rate constant at 25 °C was 4.64 × 10-4 s-1, which fit the first-order reaction equation. After ten photochromic cycles in water solution, the relative absorption intensity of CMCH-g-MCA decreased by 7.92%.

Physiologically based pharmacokinetic-pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans.

Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations (fu × C2) in the stomach were simulated and linked to the antisecretory effects of the drug (I) (increases in pH or acid output) using the fomula dI/dt = k × fu × C2 × (Imax - I) - kd × I. The vonoprazan dissociation rate constant kd (0.00246 min-1) and inhibition index KI (35 nM) for H+/K+-ATPase were obtained from literatures. The vonoprazan-H+/K+-ATPase binding rate constant k was 0.07028 min-1· µM-1 using ratio of kd to KI. The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration.

Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp.

HIV infection is often associated with liver failure, which alters the pharmacokinetics of many drugs. In this study we investigated whether acute liver failure (ALF) altered the pharmacokinetics of the first-line anti-HIV agent zidovudine (AZT), a P-gp/BCRP substrate, in rats. ALF was induced in rats by injecting thioacetamide (TAA, 300 mg·kg-1·d-1, ip) for 2 days. On the second day after the last injection of TAA, the pharmacokinetics of AZT was investigated following both oral (20 mg/kg) and intravenous (10 mg/kg) administration. ALF significantly increased the plasma concentrations of AZT after both oral and intravenous doses of AZT, but without affecting the urinary excretion of AZT. AZT metabolism was studied in rat hepatic microsomes in vitro, which revealed that hepatic UGT2B7 was the main enzyme responsible for the formation of AZT O-glucuronide (GAZT); ALF markedly impaired AZT metabolism in hepatic microsomes, which was associated with the significantly decreased hepatic UGT2B7 expression. Intestinal absorption of AZT was further studied in rats via in situ single-pass intestinal perfusion. Intestinal P-gp function and intestinal integrity were assessed with rhodamine 123 and FD-70, respectively. We found that ALF significantly downregulated intestinal P-gp expression, and had a smaller effect on intestinal BCRP. Further studies showed that ALF significantly increased the intestinal absorption of both rhodamine 123 and AZT without altering intestinal integrity, thus confirming an impairment of intestinal P-gp function. In conclusion, ALF significantly increases the oral plasma exposure of AZT in rats, a result partly attributed to the impaired function and expression of hepatic UGT2B7 and intestinal P-gp.

Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal ß-glucuronidase activity.

AIM: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. METHODS: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. ß-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. RESULTS: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, ß-glucuronidase activity in small intestinal content was region-dependent: proximal intestine