Metabolic profile, bioavailability and toxicokinetics of zearalenone-14-glucoside in rats after oral and intravenous administration by liquid chromatography high-resolution mass spectrometry and tandem mass spectrometry

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V-Z), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V-Z, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G

Photoflexoelectric effect in halide perovskites

Harvesting environmental energy to generate electricity is a key scientific and technological endeavour of our time. Photovoltaic conversion and electromechanical transduction are two common energy-harvesting mechanisms based on, respectively, semiconducting junctions and piezoelectric insulators. However, the different material families on which these transduction phenomena are based complicate their integration into single devices. Here we demonstrate that halide perovskites, a family of highly efficient photovoltaic materials, display a photoflexoelectric effect whereby, under a combination of illumination and oscillation driven by a piezoelectric actuator, they generate orders of magnitude higher flexoelectricity than in the dark. We also show that photoflexoelectricity is not exclusive to halides but a general property of semiconductors that potentially enables simultaneous electromechanical and photovoltaic transduction and harvesting in unison from multiple energy inputs

In-orbit background simulation of a type-B CATCH satellite

The Chasing All Transients Constellation Hunters (CATCH) space mission plans to launch three types of micro-satellites (A, B, and C). The type-B CATCH satellites are dedicated to locating transients and detecting their time-dependent energy spectra. A type-B satellite is equipped with lightweight Wolter-I X-ray optics and an array of position-sensitive multi-pixel Silicon Drift Detectors. To optimize the scientific payloads for operating properly in orbit and performing the observations with high sensitivities, this work performs an in-orbit background simulation of a type-B CATCH satellite using the Geant4 toolkit. It shows that the persistent background is dominated by the cosmic X-ray diffuse background and the cosmic-ray protons. The dynamic background is also estimated considering trapped charged particles in the radiation belts and low-energy charged particles near the geomagnetic equator, which is dominated by the incident electrons outside the aperture. The simulated persistent background within the focal spot is used to estimate the observation sensitivity, i.e. 4.22$\times$10$^{-13}$ erg cm$^{-2}$ s$^{-1}$ with an exposure of 10$^{4}$ s and a Crab-like source spectrum, which can be utilized further to optimize the shielding design. The simulated in-orbit background also suggests that the magnetic diverter just underneath the optics may be unnecessary in this kind of micro-satellites, because the dynamic background induced by charged particles outside the aperture is around 3 orders of magnitude larger than that inside the aperture.Comment: 24 pages, 13 figures, 7 tables, accepted for publication in Experimental Astronom

Genome-Wide Profiling Identified a Set of miRNAs that Are Differentially Expressed in Glioblastoma Stem Cells and Normal Neural Stem Cells

A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells

The serious games ecosystem: Interdisciplinary and intercontextual praxis

This chapter will situate academia in relation to serious games commercial production and contextual adoption, and vice-versa. As a researcher it is critical to recognize that academic research of serious games does not occur in a vaccum. Direct partnerships between universities and commercial organizations are increasingly common, as well as between research institutes and the contexts that their serious games are deployed in. Commercial production of serious games and their increased adoption in non-commercial contexts will influence academic research through emerging impact pathways and funding opportunities. Adding further complexity is the emergence of commercial organizations that undertake their own research, and research institutes that have inhouse commercial arms. To conclude, we explore how these issues affect the individual researcher, and offer considerations for future academic and industry serious games projects

The Efficacy and Safety of Different Kinds of Laparoscopic Cholecystectomy: A Network Meta Analysis of 43 Randomized Controlled Trials

<div><p>Background and Objective</p><p>We conducted a network meta analysis (NMA) to compare different kinds of laparoscopic cholecystectomy [LC] (single port [SPLC], two ports [2PLC], three ports [3PLC], and four ports laparoscopic cholecystectomy [4PLC], and four ports mini-laparoscopic cholecystectomy [mini-4PLC]).</p><p>Methods</p><p>PubMed, the Cochrane library, EMBASE, and ISI Web of Knowledge were searched to find randomized controlled trials [RCTs]. Direct pair-wise meta analysis (DMA), indirect treatment comparison meta analysis (ITC) and NMA were conducted to compare different kinds of LC.</p><p>Results</p><p>We included 43 RCTs. The risk of bias of included studies was high. DMA showed that SPLC was associated with more postoperative complications, longer operative time, and higher cosmetic score than 4PLC, longer operative time and higher cosmetic score than 3PLC, more postoperative complications than mini-4PLC. Mini-4PLC was associated with longer operative time than 4PLC. ITC showed that 3PLC was associated with shorter operative time than mini-4PLC, and lower postoperative pain level than 2PLC. 2PLC was associated with fewer postoperative complications and longer hospital stay than SPLC. NMA showed that SPLC was associated with more postoperative complications than mini-4PLC, and longer operative time than 4PLC.</p><p>Conclusion</p><p>The rank probability plot suggested 4PLC might be the worst due to the highest level of postoperative pain, longest hospital stay, and lowest level of cosmetic score. The best one might be mini-4PLC because of highest level of cosmetic score, and fewest postoperative complications, or SPLC because of lowest level of postoperative pain and shortest hospital stay. But more studies are needed to determine which will be better between mini-4PLC and SPLC.</p></div

Characteristics of included studies.

<p>I: intervention group; C: control group; F: female; M: male.</p

The flow chart.

<p>The flow chart.</p