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Comprehensive Summary: The conversion of CF3‐alkenes to gem‐difluoroalkenes using reductive cross‐coupling strategy has received much attention in recent years, however, the use of green and readily available reducing salt to mediate these reactions remains to be explored. In this work, a concise construction of gem‐difluoroalkenes, which requires neither a catalyst nor a metal reducing agent, was established. Rongalite, a safe and inexpensive industrial product, was employed as both a radical initiator and reductant. This procedure was compatible with both linear and cyclic diaryliodonium salts, enabling a wide variety of substrates (>70 examples). The utility of this approach was demonstrated through gram‐scale synthesis and efficient late‐stage functionalizations of anti‐inflammatory drugs. [ABSTRACT FROM AUTHOR]

In the trend of multi‐energy integration development and the intellectualisation for demand‐side, the application of integrated energy system (IES) contained demand response is of great significance to the economic operation of energy systems. The energy hubs are widely studied as effective tools for integrating regional energy in the IES. With the expansion of schedulable devices, the mode of multiple energy hubs (MEHs) cooperative operation is proposed in this study. Moreover, in order to adjust the periodic loads, the authors further study the responsiveness of electric vehicles, air‐conditioning and energy storages according to time‐of‐use price incentive mechanisms, and the total operation cost is minimised. Meanwhile, the eco‐friendly target is achieved by the pollutant trading market. Furthermore, due to the complementary characteristic of MEHs, the economics allocation issues are also carefully considered where the cost and benefit of each participant are allocated by cooperative game theory to make them satisfied with the profit brought by cooperation. The simulation takes three hubs cooperation as an example to verify the effectiveness of the proposed methods. The results show that the total profit increased by 53.54% and the peak load is reduced by 27.06% after optimal operation, and the modified propensity to disrupt verifies the fairness of allocation. [ABSTRACT FROM AUTHOR]

1. Quercetin, one of the most abundant natural flavonoids, has been reported to modulate the activity of several drug-metabolising enzymes. The aim of the present study was to investigate the effects of quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase (NAT2) and xanthine oxidase (XO) activity in healthy volunteers using caffeine as a probe drug. 2. Twelve unrelated, healthy volunteers were recruited to the study. There were two phases to the study; in the first phase, each subject was given a single oral dose of caffeine (one 100 mg capsule) with 150 mL water; in the second phase, each subject was give a 500 mg quercetin capsule once daily for 13 continuous days and was coadministered a 100 mg caffeine capsule on the 13th day. Urinary caffeine metabolite ratios were used as indicators of the activity of CYP1A2, CYP2A6, NAT2 and XO. The pharmacokinetics of caffeine and its metabolites were determined by HPLC. 3. In the quercetin-treated group, CYP1A2 activity was decreased by 10.4% (95% confidence interval (CI), 1.1–29.8%; P = 0.039), whereas increases were observed in CYP2A6 (by 25.3%; 95% CI, 6.2–34.5%; P = 0.002), NAT2 (by 88.7%; 95% CI, 7.1–160.2%; P = 0.010) and XO activity (by 15.0%; 95% CI, 1.6–21.6%; P = 0.007). Plasma Cmax and the AUC(0–24 h) of 1,7-dimethylxanthine were decreased by 17.2% (95% CI, 6.4–28.0%; P = 0.024) and 16.2% (95% CI, 3.9–28.5%; P = 0.032), respectively. The urinary excretion of 1,7-dimethylxanthine and 1-methylxanthine was significantly decreased by 32.4% (95% CI, 2.5–62.1%; P = 0.036) and 156.1% (95% CI, 53.3–258.9%; P = 0.004), respectively. The urinary excretion of 1,7-dimethylurate and 1-methylurate was increased by 82.9% (95% CI, 56.0–165.4%; P = 0.030) and 97.8% (95% CI, 12.1–183.5%; P = 0.029), respectively. No changes were observed in the urinary excretion of caffeine and 5-acetylamino-6-formylamino-3-methyluracil between the two study phases. 4. The results of the present study indicate that quercetin inhibits CYP1A2 function, but enhances CYP2A6, NAT2 and XO activity. Simultaneously, some pharmacokinetic parameters relating to 1,7-dimethylxanthine were affected by quercetin. Thus, we conclude that quercetin affects CYP1A2, CYP2A6, NAT2 and XO activity in vivo. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD), a liver function disorder caused by excessive alcohol intake, is a serious threat to global public health and social development. Toxic metabolites and reactive oxygen species produced during the metabolism of alcohol can alter the epigenetic state including DNA methylation, histone modifications, and expression of microRNAs. Epigenetic alterations can conversely involve various signaling pathways, which could contribute to the initiation and progression of ALD. To elucidate the relationship between epigenetic alterations and alcohol damage not only reinforces our understanding on pathogenesis of ALD, but also provides novel targets for clinical diagnosis, treatment, and drug research of ALD. In this review, we have summarized the research progress of epigenetic alterations and related mechanisms caused by alcohol in the pathogenesis of ALD. Considering the invertibility of epigenetic alterations, treatment of ALD through epigenetic modification with common less harmful compounds is also related. [ABSTRACT FROM AUTHOR]

Aims To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. Methods Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1′-hydroxymidazolam:midazolam (1′-OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1′-OH-MDZ and MDZ in plasma were measured by HPLC Results A 13-fold variation of CYP3A activity (log1′-OH-MDZ:MDZ: range -0.949–0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the Kolmogorov–Smirnov test (P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases (P < 0.05). Conclusions A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle. [ABSTRACT FROM AUTHOR]

Aims The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. Methods A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5–7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. Results Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0,∞), P < 0.001), 113% increase in terminal elimination half-life (t½) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean ± (s.d) norfluoxetine AUC(0,192 h) was significantly lower in PMs than that in EMs (1343 ± 277 vs 2935 ± 311, P < 0.001). Mean fluoxetine Cmax and AUC(0,∞) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 ± 3.9 vs 36.7 ± 8.9, P < 0.001; 732 ± 42 vs 2152 ± 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 ± 3.4 vs 36.0 ± 8.7, P < 0.01; 54.7 ± 3.4 vs 20.6 ± 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0,192 h) in PMs was significantly lower than that in wild type homozygotes (1343 ± 277 vs 3163 ± 121, P < 0.05) and that in heterozygotes (1343 ± 277 vs 2706 ± 273, P < 0.001), respectively. Conclusions The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects. [ABSTRACT FROM AUTHOR]