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

Interrupted time series analysis to evaluate the performance of drug overdose morbidity indicators shows discontinuities across the ICD-9-CM to ICD-10-CM transition

Introduction: On 1 October 2015, the USA transitioned from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, 10th Revision (ICD-10-CM). Considering the major changes to drug overdose coding, we examined how using different approaches to define all-drug overdose and opioid overdose morbidity indicators in ICD-9-CM impacts longitudinal analyses that span the transition, using emergency department (ED) and hospitalisation data from six states’ hospital discharge data systems. Methods: We calculated monthly all-drug and opioid overdose ED visit rates and hospitalisation rates (per 100 000 population) by state, starting in January 2010. We applied three ICD-9-CM indicator definitions that included identical all-drug or opioid-related codes but restricted the number of fields searched to varying degrees. Under ICD-10-CM, all fields were searched for relevant codes. Adjusting for seasonality and autocorrelation, we used interrupted time series models with level and slope change parameters in October 2015 to compare trend continuity when employing different ICD-9-CM definitions. Results: Most states observed consistent or increased capture of all-drug and opioid overdose cases in ICD10-CM coded hospital discharge data compared with ICD-9-CM. More inclusive ICD-9-CM indicator definitions reduced the magnitude of significant level changes, but the effect of the transition was not eliminated. Discussion: The coding change appears to have introduced systematic differences in measurement of drug overdoses before and after 1 October 2015. When using hospital discharge data for drug overdose surveillance, researchers and decision makers should be aware that trends spanning the transition may not reflect actual changes in drug overdose rates

Natural antibiotic alternatives to boost animal immunity and disease resistance

Antibiotics have been used in the feed of livestock and poultry for growth promotion and disease prevention for many decades; however, in recent years, there has been an outcry for elimination of antibiotics in order to reduce the emergence and increase in drug-resistant bacteria. The Food and Drug Administration (FDA) has implemented a new guideline to phase out the use of medically important antibiotics in poultry, cattle, and swine as of January 2017. Therefore, new antibiotic alternative strategies are needed to ensure animal health and productivity. Modulating the synthesis of endogenous host defense peptides (HDPs) is being explored as a novel antibiotic-alternative approach to disease control and prevention. My study will focus on the evaluation of two natural dietary compounds, named butyrate and lactose, and if they will have a synergy in enhancing chicken HDP synthesis and barrier function genes far greater than when each compound is used individually. Butyrate was found to synergize with lactose to enhance the expressions of AvBD9 and the barrier function genes in chicken HD11 cells at the highest levels. The results also suggest that there is a beneficial role of using a combination of butyrate and lactose in enhancing gut health and possibly animal performance. The outcome of this research will help pave the way for the development of natural antibiotic alternatives to boost animal immunity and disease resistance for livestock and poultry use.Lew Wentz FoundationAnimal Scienc

Dopamine and cAMP‐regulated phosphoprotein 32kDa (DARPP‐32), protein phosphatase‐1 and cyclin‐dependent kinase 5 expression in ovarian cancer

Dopamine and cyclic‐AMP activated phosphoprotein Mr32kDa (DARPP‐32) is a central signalling protein in neurotransmission. Following DARPP‐32 phosphorylation by protein kinase A (PKA), DARPP‐32 becomes a potent protein phosphatase 1 (PP1) inhibitor. DARPP‐32 can itself inhibit PKA following DARPP‐32 phosphorylation by cyclin‐dependent kinase 5 (Cdk5). Increasing evidence indicates a role for DARPP‐32 and its associated signalling pathways in cancer; however, its role in ovarian cancer remains unclear. Using immunohistochemistry, expression of DARPP‐32, PP1 and Cdk5 was determined in a large cohort of primary tumours from ovarian cancer patients (n = 428, 445 and 434 respectively) to evaluate associations between clinical outcome and clinicopathological criteria. Low cytoplasmic and nuclear DARPP‐32 expression was associated with shorter patient overall survival and progression‐free survival (P = .001, .001, .004 and .037 respectively). Low nuclear and cytoplasmic DARPP‐32 expression remained significantly associated with overall survival in multivariate Cox regression (P = .045, hazard ratio (HR) = 0.734, 95% confidence interval (CI) = 0.542‐0.993 and P = .001, HR = 0.494, 95% CI = 0.325‐0.749, respectively). High cytoplasmic and nuclear PP1 expression was associated with shorter patient overall survival and high cytoplasmic PP1 expression with shorter progression‐free survival (P = .005, .033, and .037, respectively). High Cdk5 expression was associated with shorter progression‐free survival (P = .006). These data suggest a role for DARPP‐32 and associated signalling kinases as prognostic markers with clinical utility in ovarian cancer

Numerical modelling of additive manufacturing process for stainless steel tension testing samples

Nowadays additive manufacturing (AM) technologies including 3D printing grow rapidly and they are expected to replace conventional subtractive manufacturing technologies to some extents. During a selective laser melting (SLM) process as one of popular AM technologies for metals, large amount of heats is required to melt metal powders, and this leads to distortions and/or shrinkages of additively manufactured parts. It is useful to predict the 3D printed parts to control unwanted distortions and shrinkages before their 3D printing. This study develops a two-phase numerical modelling and simulation process of AM process for 17-4PH stainless steel and it considers the importance of post-processing and the need for calibration to achieve a high-quality printing at the end. By using this proposed AM modelling and simulation process, optimal process parameters, material properties, and topology can be obtained to ensure a part 3D printed successfully

Probing the Galactic halo with RR Lyrae stars -- IV. On the Oosterhoff dichotomy of RR Lyrae stars

We use 3653 (2661 RRab, 992 RRc) RR Lyrae stars (RRLs) with 7D (3D position, 3D velocity, and metallicity) information selected from SDSS, LAMOST, and Gaia EDR3, and divide the sample into two Oosterhoff groups (Oo I and Oo II) according to their amplitude-period behaviour in the Bailey Diagram. We present a comparative study of these two groups based on chemistry, kinematics, and dynamics. We find that Oo I RRLs are relatively more metal rich, with predominately radially dominated orbits and large eccentricities, while Oo II RRLs are relatively more metal poor, and have mildly radially dominated orbits. The Oosterhoff dichotomy of the Milky Way's halo is more apparent for the inner-halo region than for the outer-halo region. Additionally, we also search for this phenomenon in the halos of the two largest satellite galaxies, the Large and Small Magellanic clouds (LMC, SMC), and compare over different bins in metallicity. We find that the Oosterhoff dichotomy is not immutable, and varies based on position in the Galaxy and from galaxy-to-galaxy. We conclude that the Oosterhoff dichotomy is the result of a combination of stellar and galactic evolution, and that it is much more complex than the dichotomy originally identified in Galactic globular clusters

The draft genome of a socially polymorphic halictid bee, Lasioglossum albipes

Background: Taxa that harbor natural phenotypic variation are ideal for ecological genomic approaches aimed at understanding how the interplay between genetic and environmental factors can lead to the evolution of complex traits. Lasioglossum albipes is a polymorphic halictid bee that expresses variation in social behavior among populations, and common-garden experiments have suggested that this variation is likely to have a genetic component. Results: We present the L. albipes genome assembly to characterize the genetic and ecological factors associated with the evolution of social behavior. The de novo assembly is comparable to other published social insect genomes, with an N50 scaffold length of 602 kb. Gene families unique to L. albipes are associated with integrin-mediated signaling and DNA-binding domains, and several appear to be expanded in this species, including the glutathione-s-transferases and the inositol monophosphatases. L. albipes has an intact DNA methylation system, and in silico analyses suggest that methylation occurs primarily in exons. Comparisons to other insect genomes indicate that genes associated with metabolism and nucleotide binding undergo accelerated evolution in the halictid lineage. Whole-genome resequencing data from one solitary and one social L. albipes female identify six genes that appear to be rapidly diverging between social forms, including a putative odorant receptor and a cuticular protein. Conclusions: L. albipes represents a novel genetic model system for understanding the evolution of social behavior. It represents the first published genome sequence of a primitively social insect, thereby facilitating comparative genomic studies across the Hymenoptera as a whole

The propensity of the bacterial rodlin protein RdlB to form amyloid fibrils determines its function in Streptomyces coelicolor.

Streptomyces bacteria form reproductive aerial hyphae that are covered with a pattern of pairwise aligned fibrils called rodlets. The presence of the rodlet layer requires two homologous rodlin proteins, RdlA and RdlB, and the functional amyloid chaplin proteins, ChpA-H. In contrast to the redundancy shared among the eight chaplins, both RdlA and RdlB are indispensable for the establishment of this rodlet structure. By using a comprehensive biophysical approach combined with in vivo characterization we found that RdlB, but not RdlA, readily assembles into amyloid fibrils. The marked difference in amyloid propensity between these highly similar proteins could be largely attributed to a difference in amino acid sequence at just three sites. Further, an engineered RdlA protein in which these three key amino acids were replaced with the corresponding residues from RdlB could compensate for loss of RdlB and restore formation of the surface-exposed amyloid layer in bacteria. Our data reveal that RdlB is a new functional amyloid and provide a biophysical basis for the functional differences between the two rodlin proteins. This study enhances our understanding of how rodlin proteins contribute to formation of an outer fibrillar layer during spore morphogenesis in streptomycetes

Volcanically-induced floral changes across the Triassic-Jurassic (T-J) transition

The End-Triassic Mass Extinction (ETME) saw the catastrophic loss of ca. 50% of marine genera temporally associated with emplacement of the Central Atlantic Magmatic Province (CAMP). However, the effects of the ETME on land is a controversial topic. Evaluation of the disparate cause(s) and effects of the extinction requires additional, detailed terrestrial records of these events. Here, we present a multidisciplinary record of volcanism and environmental change from an expanded Triassic-Jurassic (T-J) transition preserved in lacustrine sediments from the Jiyuan Basin, North China. High-resolution chemostratigraphy, palynological, kerogen, and sedimentological data reveal that terrestrial conditions responded to and were defined by large-scale volcanism. The record of sedimentary mercury reveals two discrete CAMP eruptive phases during the T-J transition. Each of these can be correlated with large, negative C isotope excursions (CIE-I of -4.7 ‰; CIE-II of -2.9 ‰), significantly reduced plant diversity (with ca. 45% and 44% generic losses respectively), enhanced wildfire (marked by increased fusinite or charcoal content), and major climatic shifts towards drier and hotter conditions (indicated by the occurrence of calcareous nodules, increased Classopollis pollen content, and PCA analysis). Our results show that CAMP eruptions may have followed a bimodal eruptive model and demonstrate the powerful ability of large-scale volcanism to alter the global C cycle and profoundly affect the climate, in turn leading to enhanced wildfires and a collapse in land plant diversity during the T-J transition