17alpha-Ethinylestradiol (EE) is widely used as the estrogenic component of oral contraceptives (OC). In vitro and in vivo metabolism studies indicate that EE is extensively metabolised, primarily via intestinal sulfation and hepatic oxidation, glucuronidation and sulfation. Cytochrome P450 (CYP)3A4-mediated EE 2-hydroxylation is the major pathway of oxidative metabolism of EE. For some time it has been known that inducers of drug-metabolising enzymes (such as the CYP3A4 inducer rifampicin [rifampin]) can lead to breakthrough bleeding and contraceptive failure. Conversely, inhibitors of drug-metabolising enzymes can give rise to elevated EE plasma concentrations and increased risks of vascular disease and hypertension. In vitro studies have also shown that EE inhibits a number of human CYP enzymes, such as CYP2C19, CYP3A4 and CYP2B6. Consequently, there are numerous reports in the literature describing EE-containing OC formulations as perpetrators of pharmacokinetic drug interactions. Because EE may participate in multiple pharmacokinetic drug interactions as either a victim or perpetrator, pharmaceutical companies routinely conduct clinical drug interaction studies with EE-containing OCs when evaluating new chemical entities in development. It is therefore critical to understand the mechanisms underlying these drug interactions. Such an understanding can enable the interpretation of clinical data and lead to a greater appreciation of the profile of the drug by physicians, clinicians and regulators. This article summarises what is known of the drug-metabolising enzymes and transporters governing the metabolism, disposition and excretion of EE. An effort is made to relate this information to known clinical drug-drug interactions. The inhibition and induction of drug-metabolising enzymes by EE is also reviewed.

As a member of the lead-halide perovskite family, inorganic perovskite CsPbBr3 exhibits excellent optical and electrical properties with higher stability to the environment. However, former efforts to obtain large-size CsPbBr3 single crystals with satisfactory quality using low temperature solution methods reached limited results. In this work, we have studied the growth of CsPbBr3 crystals using the antisolvent vapor-assisted crystallization (AVC) method. By adjusting the mole ratio of PbBr2 and CsBr, the phase diagram of the final products is acquired. Five regions are identified, including the Cs4PbBr6 single phase region, Cs4PbBr6 and CsPbBr3 two phases region, CsPbBr3 single phase region, CsPbBr3 and PbBr2­·2­[(CH3)2SO] metastable two phases region, and CsPbBr3 and PbBr2­·2­[(CH3)2SO] two phases region. Three methods are adopted to improve the size and crystalline quality of CsPbBr3. The growth rate is effectively tailored by diluting the antisolvent MeOH solution using DMSO to reduce the MeOH vapor pressure. Centimeter-size bright CsPbBr3 crystals have been obtained. The room temperature bandgap of CsPbBr3 is estimated at ∼2.29 eV by the transmission spectra. The photoluminescence spectra show two strong emission peaks, located at 530 and 555 nm, respectively, which are related to the free and bond excitons. The resistivity is as large as 2.1 × 109 Ω·cm. Hall effect measurements demonstrate the CsPbBr3 is p-type conductivity with a hole carrier concentration of 4.55 × 107 cm–3 and the mobility of 143 cm2 V–1 s–1. The resulting Au/CsPbBr3/Au device exhibits strong photoresponse to optical light, with an on–off ratio of two orders under a light emitting diode (∼1 mW/cm2) with a wavelength of 365–420 nm. Our research would shed more light on the growth and the photoresponse properties of CsPbBr3 crystals.

High-sensitivity X-ray detectors made of solution grown CsPbBr3 single crystals with high crystalline quality was reported in this work. The device with asymmetric electrodes configuration shows high sensitivity of 1256 μC Gy−1 cm−2.

The revolutionary and pioneering advancements of flexible electronics provide the boundless potential to become one of the leading trends in the exploitation of wearable devices and electronic skin. Working as substantial intermediates for the collection of external mechanical signals, flexible strain sensors that get intensive attention are regarded as indispensable components in flexible integrated electronic systems. Compared with conventional preparation methods including complicated lithography and transfer printing, 3D printing technology is utilized to manufacture various flexible strain sensors owing to the low processing cost, superior fabrication accuracy, and satisfactory production efficiency. Herein, up-to-date flexible strain sensors fabricated via 3D printing are highlighted, focusing on different printing methods based on photocuring and materials extrusion, including Digital Light Processing (DLP), fused deposition modeling (FDM), and direct ink writing (DIW). Sensing mechanisms of 3D printed strain sensors are also discussed. Furthermore, the existing bottlenecks and future prospects are provided for further progressing research.

Cs3Bi2I9 single crystals with significant anisotropies show a capability of detecting 241Am@5.49 MeV α particles ((FWHM) of ∼32%).

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40%, v/v) and saline mixture with and without Tween 80 (1 or 10%, v/v). Digoxin oral AUC increased 30 and 61% when dosed in 1% and 10% Tween 80, respectively, compared to control (P < 0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10% v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

Abstract. It is widely accepted that today's practice of polypharmacy inevitably increases the incidence of drug-drug interactions (DDIs). Serious DDI is a major liability for any new chemical entity (NCE) entering the pharmaceutical market. As such, pharmaceutical companies employ various strategies to avoid problematic compounds for clinical development. A key cause for DDIs is the inhibition of cytochrome P450 enzymes (CYPs) that are responsible for metabolic clearance of many drugs. Screening for inhibition potency of CYPs by NCEs has therefore become a routine practice during the drug discovery stage. However, in order to make proper use of DDI data, an understanding of the strengths and weaknesses of the various experimental systems in current use is required. An illustrated review of experimental practices is presented with discussion of likely future developments. The combination of high quality in vitro data generation and the application of in vivo CYP inhibition modelling approaches should allow more informed decisions to be made in the search for drug molecules with acceptable DDI characteristics.

An important factor for the high performance of lightharvesting devices is the presence of surface trappings. Therefore, understanding and controlling the carrier recombination of the organic−inorganic hybrid perovskite surface is critical for the device design and optimization. Here, we report the use of aluminum zinc oxide (AZO) as the anode to construct a p−n junction structure MAPbBr 3 nuclear radiation detector. The AZO/MAPbBr 3 /Au detector can tolerate an electrical field of 500 V•cm −1 and exhibit a very low leakage current of ∼9 nA, which is 1 order of magnitude lower than that of the standard ohmic contact device. The interface state density of AZO/MAPbBr 3 contact was reduced from 2.17 × 10 10 to 8.7 × 10 8 cm −2 by annealing at 100°C under an Ar atmosphere. Consequently, a photocurrent to dark current ratio of 190 was realized when exposed to a green light-emitting diode with a wavelength of 520 nm (∼200 mW•cm −2). Simultaneously, a high X-ray sensitivity of ∼529 μC•Gy air −1 cm −2 was achieved under 80 kVp X-ray at an electric field of 50 V•cm −1. These results demonstrate the use of surface engineering to further optimize the performance of MAPbBr 3 detectors, which have many potential applications in medical and security detection with low radiation dose brought to the human body.