In-situ Electric Field-Induced Modulation of Photoluminescence in Pr-doped Ba0.85Ca0.15Ti0.90Zr0.10O3 Lead-Free Ceramics.

Luminescent materials with dynamic photoluminescence activity have aroused special interest because of their potential widespread applications. One proposed approach of directly and reversibly modulating the photoluminescence emissions is by means of introducing an external electric field in an in-situ and real-time way, which has only been focused on thin films. In this work, we demonstrate that real-time electric field-induced photoluminescence modulation can be realized in a bulk Ba0.85Ca0.15Ti0.90Zr0.10O3 ferroelectric ceramic doped with 0.2 mol% Pr(3+), owing to its remarkable polarization reversal and phase evolution near the morphotropic phase boundary. Along with in-situ X-ray diffraction analysis, our results reveal that an applied electric field induces not only typical polarization switching and minor crystal deformation, but also tetragonal-to-rhombohedral phase transformation of the ceramic. The electric field-induced phase transformation is irreversible and engenders dominant effect on photoluminescence emissions as a result of an increase in structural symmetry. After it is completed in a few cycles of electric field, the photoluminescence emissions become governed mainly by the polarization switching, and thus vary reversibly with the modulating electric field. Our results open a promising avenue towards the realization of bulk ceramic-based tunable photoluminescence activity with high repeatability, flexible controllability, and environmental-friendly chemical process.

[Treatment of type 2 diabetic peripheral neuropathy patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome by internal application of qigui mixture and external application of qigui huoxue lotion: a clinical study].

OBJECTIVE: To evaluate the efficacy of internal application of Qigui Mixture (QM) and external application of Qigui Huoxue Lotion (QHL) in treating type 2 diabetic peripheral neuropathy (DNP) patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome (QYD-PDBCS), and to primarily discuss its mechanism. METHODS: Totally 62 DPN patients of QYD-PDBCS were randomly assigned to the treatment group (31 cases) and the control group (31 cases). All patients received routine comprehensive therapy. Patients in the control group took Mecobalamine Tablet, 500 microg each time, 3 times per day. Patients in the treatment group additionally took QM, 200 mL per day, twice daily. Besides, they had foot bath in QHL 10 - 15 min every evening for 3 months. The efficacy was assessed by Chinese medical symptom integrals and Toronto clinical scoring system (TCSS) before treatment, 2 and 3 months after treatment. The nerve conduction velocity was determined; the serum levels of total antioxidant capacity (T- AOC), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected 2 and 3 months after treatment. RESULTS: The total effective rates of Chinese medical symptom integrals and TCSS score were obviously higher in the treatment group than in the control group (P < 0.05). The nerve conduction velocity was significantly improved in the treatment group, when compared with before treatment (P < 0.01). There was statistical difference in the nerve conduction velocity difference of right median nerve motor branch, bilateral tibial nerve motor branches, bilateral common peroneal nerve motor branches, bilateral ulnar nerve sensory branches, and left tibial nerve sensory branch (P < 0.05). Compared with before treatment, serum levels of T-AOC and SOD significantly increased, and the level of MDA decreased significantly in the treatment group after 2 and 3 months of treatment (P < 0.01). But only the SOD level increased significantly in the control group (P < 0.01). There was no statistical difference in increased T-AOC level between the two groups after 2 months of treatment (P > 0.05), but there was statistical difference in increased SOD level and decreased MDA level (P < 0.05). There was statistical difference in increased T-AOC and SOD levels and decreased MDA level between the two groups after 3 months of treatment (P < 0.05). No adverse reaction occurred during the therapeutic course. CONCLUSIONS: The internal application of QM and external application of QHL combined with Mecobalamine in treating DPN was safe and effective, with more significant efficacy than using Mecobalamine alone. Its mechanism might be associated with resistance to oxidative stress.

Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.

Synthesis, chiral resolution, and determination of novel furan lignan derivatives with potent anti-tumor activity.

A kind of racemic furan lignans were synthesized via a novel route, and two optical isomers were obtained through a selective hydrolization. The absolute configurations were determined by circular dichroism spectroscopy after separated through a preparative column. The different activities of isomers and the racemates were evaluated on QGY-7701 and HeLa cell lines, and compound 2c showed the best activity on QGY-7701 and HeLa cell lines with IC(50) 12 microM and 13 microM, respectively.

Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist.

Effects of caffeine on regadenoson-induced coronary vasodilation and changes in hemodynamics were examined in conscious dogs. Sixteen dogs were chronically instrumented for measurements of coronary blood flow (CBF), mean arterial pressure (MAP), and heart rate (HR). Regadenoson (5 microg/kg, IV) increased CBF from 34 +/- 2 to 191 +/- 7 mL/min. The duration of the 2-fold increase in CBF was 515 +/- 71 seconds. Regadenoson decreased MAP by 15 +/- 2% and increased HR by 114 +/- 14%. Regadenoson-induced maximum increases in CBF were not significantly lower in the presence of caffeine at 1, 2, 4, and 10 mg/kg (2 +/- 3, 0.7 +/- 3, 16 +/- 5, and 13 +/- 8%, respectively; all P > 0.05). Caffeine at 1, 2, 4, and 10 mg/kg significantly decreased the duration of the 2-fold increase in CBF induced by regadenoson by 17% +/- 4%, 48% +/- 8%, 62% +/- 5%, and 82% +/- 5%, respectively (all P < 0.05). Caffeine at 4 and 10 mg/kg significantly attenuated the effects of regadenoson on MAP and HR. The results indicate that 1 to 10 mg/kg caffeine dose-dependently reduced the duration, but not the peak increase of CBF caused by 5 microg/kg regadenoson.

A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers.

OBJECTIVES: The aims of this study were to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of regadenoson (CVT-3146) in healthy, male volunteers. METHODS: Thirty-six healthy, male volunteers aged 18-50 years were included in this randomised, double-blind, crossover, placebo-controlled study to evaluate single intravenous bolus doses of regadenoson that ranged from 0.1 to 30.0 micro g/kg. Subjects received one dose of regadenoson or placebo on successive days while supine, then the same dose of regadenoson or placebo on successive days while standing. As part of the safety evaluation, vital signs and adverse events were monitored and recorded throughout the course of the study in all subjects. Up to 20 plasma samples were collected for regadenoson concentration determination within the 24 hours after each supine dosage. All urine was collected during the 24-hour time period post-dose and an aliquot was used for the determination of the regadenoson concentration. Heart rate and blood pressure were recorded at many of the same timepoints that the samples for the pharmacokinetic analysis were taken. A non linear mixed-effect modelling approach, using the software NONMEM, was utilised in modelling the plasma and urine concentration-time profiles and temporal changes in heart rate after regadenoson administration in the supine position. The influences of several covariates, including bodyweight, body mass index and age, on pharmacokinetic model parameters were investigated. RESULTS: Adverse events were more prevalent at regadenoson doses above 3 micro g/kg, and the increase in the occurrence of adverse events was dose-related. Most of the adverse events were related to vasodilation and an increase in heart rate and were generally of mild to moderate severity. Based on the severity and frequency of adverse events, the maximum tolerated doses of regadenoson were deemed to be 10 micro g/kg in the standing position and 20 micro g/kg in the supine position. The pharmacokinetics of regadenoson were successfully described by a three-compartment model with linear clearance. Following intravenous bolus dose administration, regadenoson was rapidly distributed throughout the body, followed by relatively slower elimination (terminal elimination half-life of approximately 2 hours). The clearance was estimated to be 37.8 L/h, with renal excretion accounting for approximately 58% of the total elimination. The volume of distribution of the central compartment and the volume of distribution at steady state were estimated to be 11.5L and 78.7L, respectively. Individual pharmacokinetic parameter estimates were fixed in the pharmacodynamic model, where changes in heart rate were related to plasma drug concentrations using a Michaelis-Menten model. The maximum heart rate increase (Emax) and plasma regadenoson concentration causing a 50% increase in the maximum heart rate (EC50) were estimated to be 76 beats per minute and 12.3 ng/mL, respectively. None of the tested covariates was found to be correlated with any of the pharmacokinetic model parameters. CONCLUSIONS: The pharmacokinetics and the effects of regadenoson on heart rate were successfully described using pharmacokinetic/pharmacodynamic modelling. The lack of a correlation between the model estimates and various baseline patient demographics supports unit-based dose administration of regadenoson.