The development and validation of a novel LC–MS/MS method for the quantification of cenicriviroc in human plasma and cerebrospinal fluid

A high-performance liquid chromatography tandem mass spectrometric method was developed and validated for cenicriviroc (CVC) quantification in human plasma and cerebrospinal fluid (CSF). The method involved precipitation with acetonitrile and injecting supernatants onto the column. Separation was achieved on an XBridge C₁₈ column with a gradient elution of 0.1% formic acid in water and acetonitrile. Analyte detection was conducted in positive ion mode using selected reaction monitoring. The m/z transitions were: CVC (697.3 → 574.3) and CVC-d7 (704.4 → 574.3). Calibration curve ranged from 5 to 1000 ng/mL for plasma and from 0.241 to 15.0 ng/mL for CSF. The intra- and inter-day precision and accuracy were <15% for both plasma and CSF across four different concentrations. CVC recovery from plasma and artificial CSF was >90%. The method was utilized for the measurement of patients’ plasma and CSF samples taking a dose of 50, 150 and 300 mg q.d.     

Visualizing Microglia with a Fluorescence Turn‐On Ugt1a7c Substrate

Microglia, the brain‐resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure–activity relationships study, we developed CDr20, a high‐performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome‐scale CRISPR‐Cas9 knockout screen, the UDP‐glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.     

Antibacterial alkaloids from Artabotrys crassifolius Hook.f. & Thomson

Chloroform extract of bark of Artabotrys crassifolius Hook.f. & Thomson exhibited antibacterial activities against both American Type Culture Collection and clinical bacterial strains in vitro with zones of inhibition ranging from 7 to 14 mm. Further analysis of this extract yielded artabotrine, liridine, lysicamine and atherospermidine. Artabotrine displayed a broad array of antibacterial activity mostly against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 1.25 μg/mL to 5 μg/mL. Of note, artabotrine, liridine and lysicamine are bactericidal against Gram-negative extended-spectrum beta-lactamase-producing Klebsiella with MIC values equal 2.5, 2.5 and 10 μg/mL, respectively, and minimum bactericidal concentrations values equal to 2.5, 5 and 20 μg/mL.     

Novel Semi-Synthetic Cu (II)–Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)–cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.     

Effusing core at the center of A potential vortex

Experiments were carried out to measure the base pressure distribution of a flow field induced by a potential vortex with its axis normal to a stationary disk. The center base pressure coefficient of the vortex, C₀(0), was found to be proportional to Reynolds number from Re = 2.0 × 10³ to Re > 2.5 × 10⁴, where Re is based on the disk radius and azimuthal velocity at the disk edge. This behavior of C₀(0) is at variance with the experimental results of Phillips (Phys. Fluids, 27, 2215, 1984) and Khoo (M. Eng. Thesis, Natl. Univ. Singapore, 1984), which showed vastly different trends depending on Re. Plausible reasons are suggested for the apparent discrepancies observed. Finally, the extent of the effusing core at the center, r₁ (taken to be the radial position where departure from the outer potential flow took place), was found to be proportional to Re^−1/2 for all Re values considered.     

The structure and evolution of a two-dimensional H2/O2/Ar cellular detonation

This paper reports on two-dimensional numerical simulation of cellular detonation wave in a / / mixture with low initial pressure using a detailed chemical reaction model and high order WENO scheme. Before the final equilibrium structure is produced, a fairly regular but still non-equilibrium mode is observed during the early stage of structure formation process. The numerically tracked detonation cells show that the cell size always adapts to the channel height such that the cell ratio is fairly independent of the grid sizes and initial and boundary conditions. During the structural evolution in a detonation cell, even as the simulated detonation wave characteristics suggest the presence of an ordinary detonation, the evolving instantaneous detonation state indicates a mainly underdriven state. As a considerable region of the gas mixture in a cell is observed to be ignited by the incident wave and transverse wave, it is further suggested that these two said waves play an essential role in the detonation propagation.Received: 16 September 2003, Accepted: 14 June 2004, Published online: 20 August 2004[/PUBLISHED]PACS: 47.40.-x, 82.40.Fp, 82.33.Vx, 83.85.PtX.Y. Hu: Correspondence to Current address: Institut für Strömungsmechanik, Technische Universität Dresden, 01062 Dresden, Deutschland     

Dynamic behaviour of a bubble near an elastic infinite interface

This paper presents a study to describe the behaviour of a non-equilibrium bubble in a fluid (Fluid 1) that is in contact with another fluid (Fluid 2). Fluid 2 is assumed to incorporate some elastic properties, which are modelled through a pressure term at the fluid–fluid interface. The Laplace equation is assumed to be valid in both fluids and the boundary integral method is employed to simulate the dynamics of the bubble and the fluid–fluid interface. Interesting characteristic phenomena concerning bubble oscillations and the deformation of the fluid–fluid interface are studied for a range of parameters (distance from the fluid–fluid interface, density ratios of the two fluids and elastic properties of Fluid 2). Some of the phenomena observed are jet formation in the bubble, bubble splitting, a ring bubble separating from the main bubble, mushroom-shaped bubbles and the dynamic elevation of the elastic interface. Most of these phenomena are only observed when Fluid 2 possesses some elastic properties (besides the usual formation of a high speed liquid jet). Comparisons with experimental observations confirm the validity of our simulations.     

Finite temperature Casimir effect of massive fermionic fields in the presence of compact dimensions

We consider the finite temperature Casimir effect of a massive fermionic field confined between two parallel plates, with MIT bag boundary conditions on the plates. The background spacetime is Mp+1×Tq which has q dimensions compactified to a torus. On the compact dimensions, the field is assumed to satisfy periodicity boundary conditions with arbitrary phases. Both the high temperature and the low temperature expansions of the Casimir free energy and the force are derived explicitly. It is found that the Casimir force acting on the plates is always attractive at any temperature regardless of the boundary conditions assumed on the compact torus. The asymptotic limits of the Casimir force in the small plate separation limit are also obtained.     

Determination of total arsenic in soil and arsenic-resistant bacteria from selected ground water in Kandal Province, Cambodia

Cambodia has geological environments conducive to generation of high-arsenic groundwater and people are at high risk of chronic arsenic exposure. The aims of this study are to investigate the concentration of total arsenic and to isolate and identify arsenic-resistant bacteria from selected locations in Kandal Province, Cambodia. The INAA technique was used to measure the concentration of total arsenic in soils. The arsenic concentrations in soils were above permissible 5 mg/kg, ranging from 5.34 to 27.81 mg/kg. Bacteria resistant to arsenic from two arsenic-contaminated wells in Preak Russey were isolated by enrichment method in nutrient broth (NB). Colonies isolated from NB was then grown on minimal salt media (MSM) added with arsenic at increasing concentrations of 10, 20, 30, 50, 100 and 250 ppm. Two isolates that can tolerate 750 ppm of arsenic were identified as Enterobacter agglomerans and Acinetobacter lwoffii based on a series of biochemical, physiological and morphological analysis. Optimum growth of both isolates ranged from pH 6.6 to 7.0 and 30–35 °C. E. agglomerans and A. lwoffii were able to remove 66.4 and 64.1 % of arsenic, respectively at the initial concentration of 750 ppm, within 72 h of incubation. Using energy dispersive X-ray technique, the percentage of arsenic absorbed by E. agglomerans and A. lwoffii was 0.09 and 0.15 %, respectively. This study suggested that arsenic-resistant E. agglomerans and A. lwoffii removed arsenic from media due to their ability to absorb arsenic.