1D Chiral Enantiomer Lead-Free Perovskites Induced Chiralopical Activity and Photoelectric Response.

Chirality is a fascinating geometrical concept with widespread applications in biology, chemistry, and materials. Incorporating chirality into hybrid perovskite materials can induce novel physical properties (chiral optical activity, nonlinear optics, etc.). Hybrid lead-free or lead-substituted perovskite materials, as representatives of perovskites, have been widely used in fields such as photovoltaics, sensors, catalysis, and detectors. However, the successful introduction of chirality into hybrid lead-free perovskites, which can enable their potential applications in areas such as circularly polarized light photodetectors, memories, and spin transistors, remains a challenging research topic. Here, we synthesized two new chiral lead-free perovskites, [(R)-2-methylpiperazine][BiI5] and [(S)-2-methylpiperazine][BiI5]. The material possesses a perovskite structure with a one-dimensional (1D) arrangement, denoted as ABX5. This structure is composed of chiral cations, specifically methylpiperazine, and endless chains of [BiI3] along the a-axis. These chains are assembled from distorted coplanar [BiI5]2- octahedra. The testing results revealed that (R)-1 and (S)-1 have narrow band gaps (Eg-R = 2.016 eV, Eg-S = 1.964 eV), high photoelectric response, and long carrier lifetime [R = 4.94 µs (τ), S = 7.85 µs (τ)]. It is worth noting that 1D chiral lead-free perovskites (R)-1 and (S)-1, which are synthesized in this study with narrow band gaps, high photoelectric response, and long carrier lifetime, have the potential to serve as alternative materials for the perovskite layer in future iterations of lead-free perovskite solar cells. Moreover, this research will inspire the preparation of multifunctional, lead-free perovskites.

UPLC-MS/MS-ESI assay for simultaneous determination of magnolol and honokiol in rat plasma: application to pharmacokinetic study after administration emulsion of the isomer.

ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis is one of the commonly used in traditional Chinese medicine for the treatment of fever, chronic bronchitis and stomach ailments. Magnolol and honokiol are isomers with hydroxylated biphenol compound in the extract of Magnolia officinalis. This study aims to determine the isomers in rat plasma and evaluate their pharmacokinetic pattern after administration emulsion. MATERIALS AND METHODS: Sprague Dawley male rats received either an intravenous (i.v.25, mg/kg) or oral (50mg/kg) dose of the emulsion of the isomer. A sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for the investigation of the pharmacokinetics of magnolol and honokiol in rats. Kaempferol was employed as an internal standard. RESULTS: The plasma samples were deproteinized with acetonitrile, the post-treatment samples were analyzed on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Acetonitrile and 5 mmol/L ammonium acetate buffer solution (65: 35, v/v) was used as the mobile phase at a flow rate of 0.2 mL/min. Following oral administration of emulsion to rats, magnolol attained mean peak plasma concentrations of 426.4 ± 273.8 ng/mL at 1.20 h, whereas honokiol reached peak plasma concentrations of 40.3 ± 30.8 ng/mL at 0.45 h. The absolute bioavailability of magnolol and honokiol is 17.5 ± 9.7% and 5.3 ± 11.7%. By comparison, the AUC0-∞ of magnolol was 5.4 times higher than that of honokiol after intravenous administration, but AUC0-∞ of magnolol was about 18-fold higher than honokiol after oral administration.

Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol: preparation and evaluation.

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3ß;12ß;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

Simultaneous determination by LC-MS/MS of 25-methoxydammarane-3ß,12ß,20-triol epimers and active metabolites in rat plasma after intravenous administration.

1. The pharmacokinetics of the 25-OCH3-PPD epimers and active metabolites in rat plasma after a single intravenous (i.v.) administration were studied by a rapid, selective and sensitive UPLC-MS/MS method. 2. Chromatographic separation was performed on an Acquity UPLC with Agela C18 column, and the solvents of 5 mM ammonium acetate (pH 7.8) - acetonitrile (65: 35, v/v) were used as mobile phase for elution. The quantification was performed with the transitions of m/z 493.5 → 475.5 for 20(R,S)-25-OCH3-PPD, m/z 479.5 → 461.5 for 20(R,S)-25-OH-PPD. The Lower Limit Of Quantitation (LLOQ) was 20.0 ng mL(-1) for 20(R,S)-25-OCH3-PPD, 2.0 ng mL(-1) for 20(R,S)-25-OH-PPD in the plasma samples assay. 3. The pharmacokinetic parameters of AUC, t1/2 and MRT had no difference between 20(R)- and (S)-25-OCH3-PPD, but S-epimer has a lower plasma clearance compared to the R-isomer. The active metabolite 20(S)-25-OH-PPD showed significantly higher AUC, MRT and a longer half-life than that of 20(R)-25-OH-PPD. These assay results are necessary for the evaluation of the pharmacokinetic behavior of 25-methoxydammarane-3ß,12ß,20-triol in vivo.

Cardiac fibroblast-derived extracellular matrix produced in vitro stimulates growth and metabolism of cultured ventricular cells.

Cardiac fibroblasts (CFs) produce extracellular matrix (ECM) which is a potent regulator of heart cell function and growth, and provides a supportive microenvironment for heart cells. Therefore, CF-derived ECM produced in vitro is very suitable for heart-cell culturing and cardiac tissue engineering. The aim of this study was to investigate the effect of CF-derived ECM produced in vitro on the growth and metabolism of cultured ventricular cells. CF-derived ECM-coated cell culture dishes were prepared by culturing rat CFs and then decellularizing the cultures. Isolated neonatal rat ventricular cells were seeded on ECM-coated, collagen I-coated or uncoated dishes, and the growth of cells after 1-5 days of culture was assayed with MTT reagent. In addition, cellular metabolic activity was analyzed by spectrophotometric methods and protein levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase type 2a (SERCA2a) by Western blotting. The relative growth of ventricular cells was better on ECM-coated than on uncoated or collagen I-coated dishes. Furthermore, the glucose consumption ratio, lactic acid production ratio, Na(+)/K(+)-ATPase activity, SERCA activity and protein levels of SERCA2a were all higher in cells on the ECM-coated dishes. In conclusion, cardiac fi broblast-derived ECM produced in vitro stimulates the growth and metabolism of cultured ventricular cells. This study indicates that the bioactivity of the ECM supports heart cell growth in vitro, and this might be useful for cardiac tissue engineering.

In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets.

The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.

Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential.

BACKGROUND: The extracellular matrix (ECM) provides a supportive microenvironment for cells, which is suitable as a tissue engineering scaffold. Mechanical stimulus plays a significant role in the fate of osteoblast, suggesting that it regulates ECM formation. Therefore, we investigated the influence of mechanical stimulus on ECM formation and bioactivity. METHODS: Mouse osteoblastic MC3T3-E1 cells were cultured in cell culture dishes and stimulated with mechanical tensile strain. After removing the cells, the ECMs coated on dishes were prepared. The ECM protein and calcium were assayed and MC3T3-E1 cells were re-seeded on the ECM-coated dishes to assess osteoinductive potential of the ECM. RESULTS: The cyclic tensile strain increased collagen, bone morphogenetic protein 2 (BMP-2), BMP-4, and calcium levels in the ECM. Compared with the ECM produced by unstrained osteoblasts, those of mechanically stimulated osteoblasts promoted alkaline phosphatase activity, elevated BMP-2 and osteopontin levels and mRNA levels of runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and increased secreted calcium of the re-seeded MC3T3-E1 cells. CONCLUSION: Mechanical strain promoted ECM production of osteoblasts in vitro, increased BMP-2/4 levels, and improved osteoinductive potential of the ECM. This study provided a novel method to enhance bioactivity of bone ECM in vitro via mechanical strain to osteoblasts.

Analysis of the diagnostic value of plasma endothelin for diabetic retinopathy using the receiver operating characteristic curve.

AIM: To investigate the diagnostic efficacy and clinical application value of plasma endothelin-1 for diabetic retinopathy using receiver operating characteristic (ROC) curve analysis. METHODS: This was a prospective investigational study. Funduscopy and fundus fluorescein angiography were used as gold standards for the diagnosis of diabetic retinopathy. Plasma endothelin-1 was measured in 96 diabetic patients with retinopathy (the case group) and 144 diabetic patients without retinopathy (the control group). Enumerative data were listed in a fourfold table. The measurement data were analyzed by Student's t test and evaluated by cross-table analysis and ROC curve analysis. RESULTS: (1) The plasma endothelin-1 concentration was higher in the case group than the control group (p = 0.002 < 0.01). (2) If the plasma endothelin-1 level of 162 pg/ml was adopted as the threshold for clinical diagnosis of diabetic retinopathy, the diagnostic sensitivity was 71.2%, diagnostic specificity 58% and diagnostic accuracy 66%. The positive predictive value was 69.81% and the negative predictive value 59.46%, and the positive likelihood ratio was 1.69 and the negative likelihood ratio 0.50. (3) When plasma endothelin-1 was used as a diagnostic criterion for diabetic retinopathy, the area under the ROC curve was 0.737. CONCLUSIONS: Plasma endothelin-1 plays an important role in the development and progression of diabetic retinopathy. When 162 pg/ml of plasma endothelin-1 was adopted as the diagnostic threshold, the diagnostic accuracy was medium; hence, the plasma endothelin-1 level can be used as the first step for diabetic retinopathy screening.

[Changes of plasma endothelin-1 and vascular endothelial growth factor in diabetic retinopathy and the clinical application value thereof].

OBJECTIVE: To investigate the levels of plasma endothelin (ET)-1 and vascular endothelial growth factor (VEGT) in type 2 diabetes mellitus patients, evaluate their clinical application values in different clinical types of diabetic retinopathy (DR), and to investigate the correlation between the levels of plasma ET-1, serum VEGF and the types of DR. METHODS: Peripheral blood samples were collected from 240 patients with type 2 diabetes mellitus, 96 with retinopathy and 144 without retinopathy as controls, diagnosed by ophthalmoscopy and fundus fluorescein angiography. The level of plasma ET-1 was detected with radioimmunoassay, and the serum VEGF was measured by ELISA. Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted. RESULTS: The expression plasma ET-1 levels of the DM patients with mild non-proliferative retinopathy (NPDR), moderate and severe NPDR and proliferative diabetic retinopathy (PDR), were (178+/-24), (197+/-51), and (231+/-77) ng/L respectively (F=12.186, P<0.01).; and all significantly higher than that of those without DR [(155+/-26) ng/L, all P<0.01]. There was no difference in the expression of VEGF in different courses of DR [(31+/-10), (31+/-8), and (32+/-10) ng/L respectively, F=1.329, P>0.05]. The plasma ET-1 was positively correlated with the type of DR (r=0.504, P<0.01) and the courses of DR (r=0.291, P<0.01). There was a negative correlation between the VEGF level and the type of DR (r=-0.252, P>0.01). ROC curve analysis showed that the plasma ET-1 curve lied in the top left corner, and the curve of VEGF lied under the chance diagonal in all the three different types of DR. The under-curve area of plasma ET-1 were 0.742 at the level of mild retinopathy, 0.723 at the level of moderate and severe NPDR, and 0.857 at the level of PDR. The under-curve areas of VEGF were 0.296, 0.297, and 0.293 respectively. The cut-off points in different types of DR were 173, 197, and 180 ng/L respectively. CONCLUSION: Plasma ET-1 is superior to VEGF in diagnosing different types of DR. The expression of VEGF in the blood may not accord with that in the retina. The pathogenetic condition of DR in type 2 diabetes mellitus is aggravated with the course of DR.