A broad-spectrum substrate for the human UDP-glucuronosyltransferases and its use for investigating glucuronidation inhibitors

Strong inhibition of the human UDP-glucuronosyltransferase enzymes (UGTs) may lead to undesirable effects, including hyperbilirubinaemia and drugiherb-drug interactions. Currently, there is no good way to examine the inhibitory effects and specificities of compounds toward all the important human UGTs, side-by-side and under identical conditions. Herein, we report a new, broad-spectrum substrate for human UGTs and its uses in screening and characterizing of UGT inhibitors. Following screening a variety of phenolic compound(s), we have found that methylophiopogonanone A (MOA) can be readily O-glucuronidated by all tested human UGTs, including the typical N-glucuronidating enzymes UGT1A4 and UGT2B10. MOA-O-glucuronidation yielded a single mono-O-glucuronide that was biosynthesized and purified for structural characterization and for constructing an LC-UV based MOA-O-glucuronidation activity assay, which was then used for investigating MOA-O-glucuronidation kinetics in recombinant human UGTs. The derived K-m values were crucial for selecting the most suitable assay conditions for assessing inhibitory potentials and specificity of test compound(s). Furthermore, the inhibitory effects and specificities of four known UGT inhibitors were reinvestigated by using MOA as the substrate for all tested UGTs. Collectively, MOA is a broad-spectrum substrate for the human UGTs, which offers a new and practical tool for assessing inhibitory effects and specificities of UGT inhibitors. (C) 2021 Elsevier B.V. All rights reserved.Peer reviewe

BOAT: Basic Oligonucleotide Alignment Tool

<p>Abstract</p> <p>Background</p> <p>Next-generation DNA sequencing technologies generate tens of millions of sequencing reads in one run. These technologies are now widely used in biology research such as in genome-wide identification of polymorphisms, transcription factor binding sites, methylation states, and transcript expression profiles. Mapping the sequencing reads to reference genomes efficiently and effectively is one of the most critical analysis tasks. Although several tools have been developed, their performance suffers when both multiple substitutions and insertions/deletions (indels) occur together.</p> <p>Results</p> <p>We report a new algorithm, Basic Oligonucleotide Alignment Tool (BOAT) that can accurately and efficiently map sequencing reads back to the reference genome. BOAT can handle several substitutions and indels simultaneously, a useful feature for identifying SNPs and other genomic structural variations in functional genomic studies. For better handling of low-quality reads, BOAT supports a "3'-end Trimming Mode" to build local optimized alignment for sequencing reads, further improving sensitivity. BOAT calculates an E-value for each hit as a quality assessment and provides customizable post-mapping filters for further mapping quality control.</p> <p>Conclusion</p> <p>Evaluations on both real and simulation datasets suggest that BOAT is capable of mapping large volumes of short reads to reference sequences with better sensitivity and lower memory requirement than other currently existing algorithms. The source code and pre-compiled binary packages of BOAT are publicly available for download at <url>http://boat.cbi.pku.edu.cn</url> under GNU Public License (GPL). BOAT can be a useful new tool for functional genomics studies.</p

Effects of spray angle variation on mixing in a cold supersonic combustor with kerosene fuel

Abstract: Effective fuel injection and mixing is of particular importance for scramjet engines to be operated reliably because the fuel must be injected into high-speed crossflow and mixed with the supersonic air at an extremely short time-scale. This study numerically characterizes an injection jet under different spray angles in a cold kerosene-fueled supersonic flow and thus assesses the effects of the spray angle on the mixing between incident shock wave and transverse cavity injection. A detailed computational fluid dynamics model is developed in accordance with the real scramjet combustor. Next, the spray angles are designated as 45º, 90º, and 135º respectively with the other constant operational conditions (such as the injection diameter, velocity and pressure). Next, a combination of a three dimensional Couple Level Set & Volume of Fluids with an improved Kelvin-Helmholtz & Rayleigh-Taylor model is used to investigate the interaction between kerosene and supersonic air. The numerical predictions are focused on penetration depth, span expansion area, angle of shock wave and sauter mean diameter distribution of the kerosene droplets with or without evaporation. Finally, validation has been implemented by comparing the calculated to the measured in literature with good qualitative agreement. Results show that no matter whether the evaporation is considered, the penetration depth, span-wise angle and expansion area of the kerosene droplets are all increased with the spray angle, and most especially, that the size of the kerosene droplets is surely reduced with the spray angle increase. These calculations are beneficial to better understand the underlying atomization mechanism in the cold kerosene-fueled supersonic flow and hence provide insights into scramjet design improvement

An Ultrasonic-Based Radiomics Nomogram for Distinguishing Between Benign and Malignant Solid Renal Masses

ObjectivesThis study was conducted in order to develop and validate an ultrasonic-based radiomics nomogram for diagnosing solid renal masses.MethodsSix hundred renal solid masses with benign renal lesions (n = 204) and malignant renal tumors (n = 396) were divided into a training set (n = 480) and a validation set (n = 120). Radiomics features were extracted from ultrasound (US) images preoperatively and then a radiomics score (RadScore) was calculated. By integrating the RadScore and independent clinical factors, a radiomics nomogram was constructed. The diagnostic performance of junior physician, senior physician, RadScore, and radiomics nomogram in identifying benign from malignant solid renal masses was evaluated based on the area under the receiver operating characteristic curve (ROC) in both the training and validation sets. The clinical usefulness of the nomogram was assessed using decision curve analysis (DCA).ResultsThe radiomics signature model showed satisfactory discrimination in the training set [area under the ROC (AUC), 0.887; 95% confidence interval (CI), 0.860–0.915] and the validation set (AUC, 0.874; 95% CI, 0.816–0.932). The radiomics nomogram also demonstrated good calibration and discrimination in the training set (AUC, 0.911; 95% CI, 0.886–0.936) and the validation set (AUC, 0.861; 95% CI, 0.802–0.921). In addition, the radiomics nomogram model showed higher accuracy in discriminating benign and malignant renal masses compared with the evaluations by junior physician (DeLong p = 0.004), and the model also showed significantly higher specificity than the senior and junior physicians (0.93 vs. 0.57 vs. 0.46).ConclusionsThe ultrasonic-based radiomics nomogram shows favorable predictive efficacy in differentiating solid renal masses

A data analysis method for isochronous mass spectrometry using two time-of-flight detectors at CSRe

The concept of isochronous mass spectrometry (IMS) applying two time-of-flight (TOF) detectors originated many years ago at GSI. However, the corresponding method for data analysis has never been discussed in detail. Recently, two TOF detectors have been installed at CSRe and the new working mode of the ring is under test. In this paper, a data analysis method for this mode is introduced and tested with a series of simulations. The results show that the new IMS method can significantly improve mass resolving power via the additional velocity information of stored ions. This improvement is especially important for nuclides with Lorentz factor $\gamma$-value far away from the transition point $\gamma _t$ of the storage ring CSRe.Comment: published in Chinese Physics C Vol. 39, No. 10 (2015) 10620