Untargeted metabolomics in doping control : detection of new markers of testosterone misuse by ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry

The use of untargeted metabolomics for the discovery of markers is a promising and virtually unexplored tool in the doping control field. Hybrid quadrupole time-of-flight (QTOF) and hybrid quadrupole Orbitrap (Q Exactive) mass spectrometers, coupled to ultrahigh pressure liquid chromatography, are excellent tools for this purpose. In the present work, QTOF and Q Exactive have been used to look for markers for testosterone cypionate misuse by means of untargeted metabolomics. Two different groups of mine samples were analyzed, collected before and after the intramuscular administration of testosterone cypionate. In order to avoid analyte losses in the sample treatment, samples were just 2-fold diluted with water and directly injected into the chromatographic system. Samples were analyzed in both positive and negative ionization modes. Data from both systems were treated under untargeted metabolomic strategies using XCMS application and multivariate analysis. Results from the two mass spectrometers differed in the number of detected features, but both led to the same potential marker for the particular testosterone ester misuse. The in-depth study of the MS and MS/MS behavior of this marker allowed for the establishment of 1-cydopentenoylglycine as a feasible structure. The putative structure was confirmed by comparison with synthesized material. This potential marker seems to come from the metabolism of the cypionic acid release after hydrolysis of the administered ester. Its suitability for doping control has been evaluated

The effect of Er3+ concentration on the kinetics of multiband upconversion in NaYF4:Yb/Er microcrystals

In Yb-Er co-doped upconversion (UC) nanomaterials, upconversion luminescence (UCL) can be modulated to generate multiband UCL emissions by changing the concentration of activator Er3+. Nonetheless, the effect of the Er3+ concentrations on the kinetics of these emissions is still unknown. We here study the single β-NaYF4:Yb3+/Er3+ microcrystal (MC) doped with different Er3+ concentrations by nanosecond time-resolved spectroscopy. Interestingly, different Er3+ doping concentrations exhibit different UCL emission bands and UCL response rates. At low Er3+ doping concentrations (1 mol%), multiband emission in β-NaYF4:Yb3+/Er3+ (20/1 mol%) MCs could not be observed and the response rate of UCL was slow (5–10 μs) in β-NaYF4:Yb3+/Er3+. Increasing the Er3+ doping concentration to 10 mol% can shorten the distance between Yb3+ ions and Er3+ ions, which promotes the energy transfer between them. β-NaYF4:Yb3+/Er3+ (20/10 mol%) can achieve obvious multiband UCL and a quick response rate (0.3 µs). However, a further increase in the Er doping concentration (80 mol%) makes MCs limited by the CR process and cannot achieve the four-photon UC process (4F5/2 → 2K13/2 and 2H9/2 → 2D5/2). Therefore, the result shows that changing the Er3+ doping concentration could control the energy flow between the different energy levels in Er3+, which could affect the response time and UCL emission of the Yb/Er doped rare earth materials. Our work can facilitate the development of fast-response optoelectronics, optical-sensing, and display industries

Landau Quantization of Massless Dirac Fermions in Topological Insulator

The recent theoretical prediction and experimental realization of topological insulators (TI) has generated intense interest in this new state of quantum matter. The surface states of a three-dimensional (3D) TI such as Bi_2Te_3, Bi_2Se_3 and Sb_2Te_3 consist of a single massless Dirac cones. Crossing of the two surface state branches with opposite spins in the materials is fully protected by the time reversal (TR) symmetry at the Dirac points, which cannot be destroyed by any TR invariant perturbation. Recent advances in thin-film growth have permitted this unique two-dimensional electron system (2DES) to be probed by scanning tunneling microscopy (STM) and spectroscopy (STS). The intriguing TR symmetry protected topological states were revealed in STM experiments where the backscattering induced by non-magnetic impurities was forbidden. Here we report the Landau quantization of the topological surface states in Bi_2Se_3 in magnetic field by using STM/STS. The direct observation of the discrete Landau levels (LLs) strongly supports the 2D nature of the topological states and gives direct proof of the nondegenerate structure of LLs in TI. We demonstrate the linear dispersion of the massless Dirac fermions by the square-root dependence of LLs on magnetic field. The formation of LLs implies the high mobility of the 2DES, which has been predicted to lead to topological magneto-electric effect of the TI.Comment: 15 pages, 4 figure

An Improved Deadbeat Plus Plug-In Repetitive Controller for Three-Phase Four-Leg Inverters

An improved deadbeat plus plug-in repetitive control scheme is proposed for grid-connected three-phase four-leg inverters to achieve fast and accurate feed-in grid current tracking. Discrete-time mathematical model of the three-phase four-leg grid-connected inverter is developed. An improved deadbeat (DB) plus plug-in repetitive control (RC) scheme is proposed to reject periodic disturbances while keeping good dynamic response. Simulation results are provided to validate the effectiveness and advantages of the proposed method

The Role of Hemicellulose in Cadmium Tolerance in Ramie (Boehmeria nivea (L.) Gaud.)

Ramie cell walls play an important role in cadmium (Cd) detoxification. However, the Cd binding capacity of the cell wall components and the cell wall compositions among ramie species remains unclear. Therefore, this study compared two ramie populations (‘Dazhuhuangbaima’ (low-Cd-accumulating population) and ‘Zhongzhu 1’ (high-Cd-accumulating population)) with different Cd enrichment characteristics. The two ramie populations were treated with 0, 25, and 75 mg kg−1 Cd for 30 days; then, their root length, plant height, biomass, Cd enrichment in the organs, subcellular Cd distribution, Cd content in the cell wall polysaccharides, and hemicellulose content were determined. The root length, plant height, biomass, and Cd enrichment in all organs were significantly higher (p ≤ 0.05) in ‘Zhongzhu 1’ than in ‘Dazhuhuangbaima’ under Cd stress. In addition, the subcellular Cd distribution analysis revealed that Cd was mainly found in the cell wall in both ramie populations. Among the cell wall fractions, Cd was mainly bound to the hemicelluloses, with 60.38–73.10% and 50.05–64.45% Cd accumulating in the ‘Zhongzhu 1’ and ‘Dazhuhuangbaima’ cell wall hemicelluloses, respectively. However, the Cd concentration in the ‘Zhongzhu 1’ hemicellulose was significantly higher (p ≤ 0.05) than that in the ‘Dazhuhuangbaima’ hemicellulose. Hemicellulose content analysis further revealed that the hemicellulose concentration increased with the Cd concentration in both populations, but it was significantly higher (p ≤ 0.05) in ‘Zhongzhu 1’ than in ‘Dazhuhuangbaima’ across all Cd treatments. Thus, ramie copes under Cd stress by increasing the hemicellulose content in the cell wall. The findings in this study confirm that hemicellulose is the main enrichment site for Cd in ramie. It also provides a theoretical basis for Cd enrichment breeding in ramie

A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation

A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC50 < 5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC50 > 20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed