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Comprehensive Summary: Optical controlling of solid‐sate electric properties is emerging as a non‐contact and nondestructive avenue to optimize the physical properties of electronic and optoelectronic devices. In term of strong light‐material coupling, two‐dimensional (2D) double perovskites hold great prospects to create photo‐dielectric activities for high‐performance device applications. Here, we have achieved the photo‐excited switching and enhancement of dielectric properties in the orientational thin films of a 2D double perovskite, (C4H12N)4AgBiI8 (1, where C4H9NH3+ is isobutylammonium). It undergoes a structural phase transition at 384 K (Tc), triggered by the dynamic ordering of organic cations and tilting motion of isometallic perovskite sheets. Most notably, the orientational thin films of 1 are extremely sensitive to light illumination, of which the dielectric constants can be facilely photo‐switched between the low‐ and high‐states. During this photo‐switching process, the dielectric constants are enhanced with a magnitude up to ~350% under 405 nm, far beyond most of the inorganic phase transition counterparts. In addition, this photo‐excited switching and enhancement of dielectric response exhibits an operational stability with superior anti‐fatigue characteristics. Our work opens up a potential avenue for assembling high‐performance optoelectronic devices with the controllable physical properties. [ABSTRACT FROM AUTHOR]

What is known and objective: Linezolid is an alternative first‐line agent for MRSA pneumonia. This study assessed whether dose adjustments of linezolid against methicillin‐resistant Staphylococcus aureus (MRSA) infections were needed based on renal function in populations with different body weight. Methods: Monte Carlo simulations were conducted to evaluate renal function in relation to the probability of target attainment (PTA) in three population groups with different body weight. Area under the concentration time curve (AUC)/ minimum inhibitory concentration (MIC) ratio and percentage of time above the MIC (%T > MIC) were regarded as pharmacokinetic/pharmacodynamic targets. The PTA and cumulative fractions of response (CFR) were calculated to assess the efficacy. Regarding safety, trough plasma concentration (Cmin) > 8 mg/L was used as target for toxicity. Results and discussion: Using AUC/MIC >100 as the target pharmacodynamic (PD) index, the CFR of linezolid at the standard dose (600 mg every 12 h [q12h]) were 57.01%, 93.22%, and 99.93% in patients with normal renal function, patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. Using 100%T > MIC as the target PD index, all the CFR of three population groups were more than 90% at the standard dose. The percentages of Cmin > 8 mg/L at the standard dose of linezolid were 24.16%, 53.24%, and 90.10% in three population groups on day 7. What is new and conclusion: The risk of thrombocytopenia of linezolid was extremely higher in low body weight patients with renal impairment when receiving standard linezolid dose compared with patients with normal renal function. 450 mg q12h and 300 mg q12h might be effective and safe against MRSA infection in patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. [ABSTRACT FROM AUTHOR]

Raltitrexed (RTX) has shown clinical activity in a variety of advanced solid tumours. Its oral bioavailability is low and its intestinal absorption mechanism is not clear. In the present study, the absorption mechanism of RTX in the small intestine was investigated, and the effects of absorption enhancers and efflux transporter inhibitors were evaluated by in vitro transport studies using the Caco-2 cell model and in situ perfusion experiments in rats. Oral bioavailability of RTX in rats in the presence or absence of enhancers were also investigated. The results of in vitro and in situ experiments indicated that the kinetic model of combined mechanism (active and passive transport) fitted the concentration-time data of RTX best with the highest R2 and lowest SSE (Sum of Squares for Error). The apparent or effective permeability coefficient (P(app) or P(eff)) of RTX remained statistically constant in a certain concentration range, then decreased when the concentration increased. But the decrease trend did not continue with further increase in concentration. And folic acid could competitively inhibit RTX absorption. These results suggested that a combined absorption mechanism for RTX existed. Furthermore, within certain concentration ranges, Carbomer 934P and sodium caprate (Cap-Na) exhibited significant absorption enhancement effects with low toxicity, whereas the enhancement effects of sodium deoxycholate (Deo-Na) were accompanied with acute toxicities. Moreover, probenecid and pantoprazole obviously enhanced RTX absorption, demonstrating that RTX is a substrate of the multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP). A secretion experiment indicated that RTX could be effluxed into the intestines both with bile and by active efflux action. Oral bioavailability of RTX was significantly improved by the investigated absorption enhancers and transporter inhibitors, which is consistent with the in vitro and in situ experiments.