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

Formation of new stellar populations from gas accreted by massive young star clusters

Stars in star clusters are thought to form in a single burst from a common progenitor cloud of molecular gas. However, massive, old globular clusters -- with ages greater than 10 billion years and masses of several hundred thousand solar masses -- often harbour multiple stellar populations, indicating that more than one star-forming event occurred during their lifetimes. Colliding stellar winds from late-stage, asymptotic-giant-branch stars are often invoked as second-generation star-formation trigger. The initial cluster masses should be at least 10 times more massive than they are today for this to work. However, large populations of clusters with masses greater than a few million solar masses are not found in the local Universe. Here we report on three 1-2 billion-year-old, massive star clusters in the Magellanic Clouds, which show clear evidence of burst-like star formation that occurred a few hundred million years after their initial formation era. We show that such clusters could accrete sufficient gas reservoirs to form new stars if the clusters orbited in their host galaxies' gaseous discs throughout the period between their initial formation and the more recent bursts of star formation. This may eventually give rise to the ubiquitous multiple stellar populations in globular clusters.Comment: 10 pages, 11 figures, Authors' version of a letter published in Nature (27 January 2016), including Methods and Extended Dat

Treating Simple Tibia Fractures with Poly-DL-Lactic Acid Screw as a Locked Intramedullary Nail

Purpose: To investigate the curative effect of poly-DL-lactic acid (PDLLA) absorbable screw as a locked intramedullary nail for simple tibia fractures.Methods: In this study, 35 patients treated with the PDLLA screw were observed, and another 35 patients treated with a traditional locking intramedullary nail were treated as controls. Intraoperative blood loss, postoperative complications, fracture-healing time, and Johner-Wruh grade at the last followup time point of the two treatment groups were compared.Results: No patients experienced neurovascular injury during the operation, and no significant difference was observed in the operation and intraoperative blood loss of both two groups (p > 0.05). Postoperative x-ray results showed that the counterpoint and alignment of the fractures were favorable and that no rotational displacement had occurred. The follow-up period for all patients was 6 - 24 months, with a mean of 15.6 ± 6.7 months. All patients treated with PDLLA screw were observed to have well-healed tibia fractures, while three patients in the traditional treatment group appeared to have undesirable fracture healing. No infection, breakage of the internal fixator, or rotational displacement was found in either of the two groups, and no significant difference was observed in complication incidence between the two groups (p > 0.05). Additionally, Johner-Wruh grading showed no statistically significant difference between the two groups (p > 0.05). Interestingly, the fracture-healing time of the PDLLA screw-treated patients was significantly shortened compared with that of traditional treatment patients (p < 0.05).Conclusion: PDLLA screw, as a locked intramedullary nail, is a promising treatment for simple tibia fracture

Loop Formulas for Description Logic Programs

Description Logic Programs (dl-programs) proposed by Eiter et al. constitute an elegant yet powerful formalism for the integration of answer set programming with description logics, for the Semantic Web. In this paper, we generalize the notions of completion and loop formulas of logic programs to description logic programs and show that the answer sets of a dl-program can be precisely captured by the models of its completion and loop formulas. Furthermore, we propose a new, alternative semantics for dl-programs, called the {\em canonical answer set semantics}, which is defined by the models of completion that satisfy what are called canonical loop formulas. A desirable property of canonical answer sets is that they are free of circular justifications. Some properties of canonical answer sets are also explored.Comment: 29 pages, 1 figures (in pdf), a short version appeared in ICLP'1

Controlled unidirectional reflectionlessness by coupling strength in a non-Hermitian waveguide quantum electrodynamics system

Unidirectional reflectionlessness is investigated in a waveguide quantum electrodynamics system that consists of a cavity and a $\Lambda$-type three-level quantum dot coupled to a one-dimensional plasmonic waveguide. Analytical expressions of transmission and reflection coefficients are derived and discussed for both resonant and off-resonant couplings. By appropriately modulating the coupling strength, phase shift and Rabi frequency, unidirectional reflectionlessness is observed at the exceptional points. And unidirectional coherent perfect absorption is exhibited at the vicinity of exceptional point. These results might find applications in designing quantum devices of photons, such as optical switches and single-photon transistors.Comment: 11 pages, 7 figure

Electrophysiological Correlates of Reading the Single- and Interactive-Mind

Understanding minds is the cognitive basis of successful social interaction. In everyday life, human mental activity often happens at the moment of social interaction among two or multiple persons instead of only one-person. Understanding the interactive mind of two- or multi-person is more complex and higher than understanding the single-person mind in the hierarchical structure of theory of mind. Understanding the interactive mind maybe differentiate from understanding the single mind. In order to examine the dissociative electrophysiological correlates of reading the single mind and reading the interactive mind, the 64 channels event-related potentials were recorded while 16 normal adults were observing three kinds of Chinese idioms depicted physical scenes, one-person with mental activity, and two- or multi-person with mental interaction. After the equivalent N400, in the 500- to 700-ms epoch, the mean amplitudes of late positive component (LPC) over frontal for reading the single mind and reading the interactive mind were significantly more positive than for physical representation, while there was no difference between the former two. In the 700- to 800-ms epoch, the mean amplitudes of LPC over frontal–central for reading the interactive mind were more positive than for reading the single mind and physical representation, while there was no difference between the latter two. The present study provides electrophysiological signature of the dissociations between reading the single mind and reading the interactive mind

MMP7 expression regulated by endocrine therapy in ERβ-positive colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Many studies have shown that colon cancer is an estrogen-dependent carcinoma. This study explored the efficacy of endocrine therapy in colon cancer cells with high metastatic potential (HT29). We investigated the proliferation of HT29 cells after exposure to endocrine therapy (tamoxifen) and 5-FU.</p> <p>Methods</p> <p>Apoptosis was evaluated using flow cytometry. The expression of matrix metalloproteinases 7 (MMP-7) and estrogen receptor beta (ERβ) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The migration capability of treated cells was determined with wound scratch assay.</p> <p>Results</p> <p>Tamoxifen alone, 5-FU alone, and the combination of the two drugs can significantly inhibit HT29 cell proliferation and migration, block the cells in G₂/M phase and induce cell apoptosis. These drugs also can down-regulate MMP7 and ERβ expression.</p> <p>Conclusion</p> <p>Our findings suggest that endocrine therapy is an efficient therapy for inhibiting ERβ-positive colon cancer cell proliferation and migration via down-regulation of MMP7.</p

Curcumin Blocks Small Cell Lung Cancer Cells Migration, Invasion, Angiogenesis, Cell Cycle and Neoplasia through Janus Kinase-STAT3 Signalling Pathway

Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-XL and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1).Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and providenovel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC