Near infrared luminescence properties and mechanism of high bismuth-doped SiO2-Al2O3-La2O3 glass.

This research investigated the wideband near-infrared spectroscopy characteristics of 60SiO2-25Al2O3-10La2O3 glass doped with high levels of bismuth up to 5 mol%. The near-infrared radiation range was explored under excitation wavelengths of 488 nm, 532 nm, 808 nm, and 980 nm, resulting in near-infrared radiation spanning from 1000 nm to 1800nm with Full Width at Half Maximum (FWHM) values of 313.0 nm, 336.3 nm, 296.2 nm, and 262.9 nm, respectively. Notably, the sample exhibited a lifetime of 1.473 ms when pumped at 808 nm, corresponding to a stimulated cross-section of σe=3.35 × 10-21 cm2. Through an in-depth investigation of the luminescence properties, the underlying physical mechanism behind the near-infrared luminescence was revealed. The emissions observed at approximately 1150 nm and 1300 nm were attributed to the aluminum-related bismuth active center (BAC-Al) and the silicon-related bismuth active center (BAC-Si), respectively. Furthermore, it is postulated that the emission at the 1150 nm band originates from the 3P1, 3P2 →3P0 transition of Bi+ and the 2D3/2 → 4S3/2 transition of Bi°, while the emission at the 1300 nm band may be linked to mixed valence states of Bi3+. This work will find potential applications in broadband near-infrared optical devices.

Assessment of the reliability and quality of breast cancer related videos on TikTok and Bilibili: cross-sectional study in China.

Background: As the most common malignant tumor in the world, breast cancer also brings a huge disease burden to China. Ordinary people are increasingly inclined to use the Internet, especially video social platforms, as a source of health information. Educating the public to obtain correct information is important to reduce the incidence of breast cancer and improve the prognosis. However, the quality and reliability of breast cancer-related video content have not been fully studied. Objective: This study aims to evaluate the quality of the information of breast cancer-related videos on TikTok and Bilibili video sharing platforms and factors related to video quality. Methods: We collected the top 100 videos about breast cancer on TikTok and Bilibili, respectively. Categorize videos according to video source and video content. Video quality and reliability were assessed using Global Quality Score (GQS) and modified DISCERN (mDISCERN) tools. We also analyzed the correlation between video quality and video likes, comments, saves, and shares. Results: Although the quality and reliability of Bilibili's breast cancer videos were higher than TikTok (p = 0.002 and p = 0.001, respectively), the video quality of both video sharing platforms was not satisfactory, with a median GQS scores of 2.00 and 3.00 and mDISCERN scores of 1.00 and 2.00, respectively. In general, the quality and reliability of videos released by medical practitioners were higher than those of non-medical practitioners, and the quality and reliability of videos covering disease-related knowledge were higher than those of news reports (all p < 0.001). Among medical practitioners, the quality of videos uploaded by doctors in breast disease was significantly lower than that of doctors in other areas (p < 0.05). There was a significant positive correlation between video quality and duration (r = 0.240, p < 0.001), a weak negative correlation between video quality and likes (r = 0.191, p < 0.01), video quality and comments (r = 0.256, p < 0.001), video reliability and likes (r = 0.198, p < 0.001), video reliability and comments (r = 0.243, p < 0.01). Conclusion: Our study shows that the quality and reliability of breast cancer-related videos on TikTok and Bilibili are poor, and the overall quality is unsatisfactory. But videos uploaded by medical practitioners covering disease knowledge, prevention and treatment are of higher quality. Medical practitioners are encouraged to publish more high-quality videos, while video social platforms should formulate relevant policies to censor and supervise health education videos, so as to enable the public to obtain reliable health information.

Propagation properties of autofocusing off-axis hollow vortex Gaussian beams in free space.

By solving the (2 + 1) dimensional Schrödinger equation in free space, we find that the autofocusing off-axis hollow vortex Gaussian beams (HVGBs) are analytically derived for the first time. The off-axis HVGBs can be adjusted by changing the off-axis coordinate (x0,y0) and topological charge n2. In particular, by increasing the off-axis coordinate (x0,y0), the self-focusing intensity can be increased. Besides, the self-focusing property can be more obvious. Furthermore, by increasing the hollow order n1, we can deepen the depth of focus, make the focus position further away, and increase the self-focusing intensity too. We also discuss other propagation properties that are used to enrich the autofocusing off-axis HVGBs, such as Poynting vector, angular momentum, gradient force, and maximum scattering force during propagation.

Systematic screening for CYP3A4 genetic polymorphisms in a Han Chinese population.

AIM: To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. MATERIALS & METHODS: The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. RESULTS: In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28-*34. CONCLUSION: This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.

Effects of CYP2C19 variants on methadone metabolism in vitro.

CYP2C19 is an important member of the cytochrome P450 (CYP450) enzyme super family and is responsible for clearing approximately 10% of commonly used clinical drugs that undergo phase I metabolism. Genetic polymorphisms of CYP2C19 significantly influence the efficacy and safety of some drugs, which might cause undesirable adverse effects or cure failure at standard dosages. The aim of this study was to clarify the catalytic activities of 31 CYP2C19 alleles on the oxidative in vitro metabolism of methadone. Insect microsomes expressing the CYP2C19 alleles were incubated with 50-2000 µM methadone for 30 min at 37 °C and terminated by cooling to -80 °C immediately. Methadone and its metabolite EDDP were analyzed by an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system. Of the 31 tested CYP2C19 allelies variants, CYP2C19*1 is the wild-type. Compared with CYP2C19*1, two CYP2C19 variants (CYP2C19*3 and *35FS) had no detectable enzyme activity, one variant L16F exhibited slightly increased intrinsic clearance values, and one variant N277K showed no significant difference. In addition, 26 variants exhibited significantly decreased values (from 1.48% to 80.40%). These findings suggest that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2C19 alleles. Copyright © 2016 John Wiley & Sons, Ltd.

An UPLC-MS/MS method for the quantitation of alectinib in rat plasma.

Currently, crizotinib is the first generation drug, which has been used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). However, more and more patients are found in crizotinib-resistance. In the last year, alectinib has been approved for treatment of patients with crizotinib-resistance. In this study, we aim to develop and validate a simple, rapid and sensitive tandem mass spectrometry (UHPLC-MS/MS) method for determination of alectinib in rat plasma. Diazepam was chosen as an internal standard (IS). Protein precipitation by acetonitrile was utilized to prepare plasma samples. Chromatographic separation was achieved on a RRHD Eclipse Plus C18 (2.1×50mm, 1.8µ) column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). The analytes were detected by an electrospray ionization (ESI) source in positive mode. A dynamic multiple reaction monitoring (MRM) method was developed to detect specific precursor and product ions. The target fragment ions were m/z 483.2→396.1 for alectinib and m/z 285.0→192.9 for diazepam (IS). Linear calibration plots were achieved in the range of 1-500ng/ml for alectinib (R2=0.997) in rat plasma. Mean recoveries of alectinib in rat plasma ranged from 84.2% to 92.2%. The intra- and inter-day precision was below 9.3% and accuracy was from -1.4% to 12.1%. No obvious matrix effect was found. This method shows a good performance: accuracy, precision and stability. It has been fully validated and successfully applied to pharmacokinetic study of alectinib.

Functional characterization of 22 novel CYP2D6 variants for the metabolism of Tamoxifen.

OBJECTIVES: This study aimed to assess the catalytic characteristics of 24 CYP2D6 allelic isoforms found in Chinese Han population on the metabolism of tamoxifen in vitro. METHODS: Recombinant CYP2D6 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity towards tamoxifen. About 5-2500 µm tamoxifen was incubated for 30 min at 37 °C. Using high-performance liquid chromatography to detect the products, the kinetic parameters Km , Vmax and intrinsic clearance (Vmax /Km ) of N-desmethyltamoxifen were determined. KEY FINDINGS: Of the 24 tested allelic variants, the differences of intrinsic clearance value were shown as follows: CYP2D6.89 was much higher than wild-type CYP2D6.1, 2 allelic isoforms (CYP2D6.88 and D336N) exhibited similar intrinsic clearance values as the wild-type enzyme, two variants displayed weak or no activity, while the rest 19 variants showed significantly reduced intrinsic clearance values ranging from 7.46 to 81.11%. CONCLUSION: The comprehensive assessment of CYP2D6 variants provides significant insights into allele-specific activity towards tamoxifen in vitro, suggesting that most of the carriers of these alleles might be paid more attention when using CYP2D6-mediated drugs clinically.

Effect of 22 Novel Cytochrome P450 2D6 (CYP2D6) Variants Found in the Chinese Population on Hemangeol Metabolism In Vitro.

BACKGROUND AND OBJECTIVES: Hemangeol, approved for the treatment of proliferative infantile hemangiomas requiring systemic therapy, is metabolized by cytochrome P450 2D6 (CYP2D6), which is a highly polymorphic enzyme that metabolizes a large number of drugs. More than 100 CYP2D6 allelic variants have been reported so far, including 22 novel variants that discovered in our lab in the Chinese population. Our study aimed to probe the enzymatic activity of these variants toward hemangeol in vitro with recombinant microsomes that expressed in sf21 insect cells using a baculovirus-mediated expression system. METHODS: The wild-type CYP2D6.1 and other variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) were incubated with 1-200 µM hemangeol for 50 min at 37 °C. Then the products were extracted, and signal detection was performed by high-performance liquid chromatography with fluorescence detector. RESULTS: All of the variants exhibited changed apparent Michaelis-Menten constant (Km) or maximum velocity of the reaction (V max) values compared with that of wild-type protein. The intrinsic clearances (V max /Km) were significantly decreased by 0.37 to 42.74 %. However, CYP2D6.92 and CYP2D6.96 showed no or minimal enzymatic activity as no concentration of 4'-hydroxypropranolol was detected. CONCLUSIONS: The comprehensive in vitro assessment of CYP2D6 variants provides significant insights into allele-specific activity towards hemangeol in vivo.

Effects of 22 Novel CYP2D6 Variants Found in the Chinese Population on the Bufuralol and Dextromethorphan Metabolisms In Vitro.

Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that metabolizes a large number of therapeutic drugs. To date, more than 100 CYP2D6 allelic variants have been reported. Among these variants, we recently identified 22 novel variants in the Chinese population. The aim of this study was to functionally characterize the enzymatic activity of these variants in vitro. A baculovirus-mediated expression system was used to express wild-type CYP2D6.1 and other variants (CYP2D6.2, CYP2D6.10 and 22 novel CYP2D6 variants) at high levels. Then, the insect microsomes containing expressed CYP2D6 proteins were incubated with bufuralol or dextromethorphan at 37°C for 20 or 25 min., respectively. After termination, the metabolites were extracted and used for the detection with high-performance liquid chromatography. Among the 24 CYP2D6 variants tested, two variants (CYP2D6.92 and CYP2D6.96) were found to be catalytically inactive. The remaining 22 variants exhibited significantly decreased intrinsic clearance values for bufuralol 1'-hydroxylation and 20 variants showed significantly lower intrinsic clearance values for dextromethorphan O-demethylation than those of the wild-type CYP2D6.1. Our in vitro results suggest that most of the variants exhibit significantly reduced catalytic activities compared with the wild-type, and these data provide valuable information for personalized medicine in Chinese and other Asian populations.

Inhibitory effect of ketoconazole and voriconazole on the pharmacokinetics of carvedilol in rats.

The aim of this study was to investigate the effect of orally administered ketoconazole and voriconazole on the pharmacokinetics of carvedilol and its metabolites in rats. Fifteen healthy male Sprague-Dawley (SD) rats were randomly divided into three groups: A group (30 mg/kg ketoconazole), B group (30 mg/kg voriconazole) and C group (control group). A single dose of carvedilol was administered orally 30 min after administration of ketoconazole and voriconazole. Carvedilol and its metabolites plasma levels were measured by ultra-high performance liquid chromatography-mass spectrometry method (UPLC-MS/MS), and pharmacokinetic parameters were calculated by DAS 3.0 software. The co-administrated with ketoconazole could significantly increase the maximal plasma concentration (Cmax) and area under the curve (AUC) of carvedilol (p < 0.01). And the Cmax of its three metabolites 4'-hydroxyphenyl carvedilol (4'-HPC), 5'-hydroxyphenyl carvedilol (5'-HPC) and o-desmethyl carvedilol (o-DMC) decreased drastically by 39.4% (p < 0.01), 45.0% (p < 0.01) and 40.8% (p < 0.05), respectively. Following co-administered with voriconazole, Tmax of carvedilol and o-DMC increased, and the Cmax of 5'-HPC decreased by 27.7% (p < 0.05), while other drugs pharmacokinetic parameters performed no significant differences. Therefore, in clinical, when carvedilol was co-administrated with ketoconazole, dose adjustment of carvedilol should be taken into account.