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

Topological Susceptibility under Gradient Flow

We study the impact of the Gradient Flow on the topology in various models of lattice field theory. The topological susceptibility $\chi_{\rm t}$ is measured directly, and by the slab method, which is based on the topological content of sub-volumes ("slabs") and estimates $\chi_{\rm t}$ even when the system remains trapped in a fixed topological sector. The results obtained by both methods are essentially consistent, but the impact of the Gradient Flow on the characteristic quantity of the slab method seems to be different in 2-flavour QCD and in the 2d O(3) model. In the latter model, we further address the question whether or not the Gradient Flow leads to a finite continuum limit of the topological susceptibility (rescaled by the correlation length squared, $\xi^{2}$). This ongoing study is based on direct measurements of $\chi_{\rm t}$ in $L \times L$ lattices, at $L/\xi \simeq 6$.Comment: 8 pages, LaTex, 5 figures, talk presented at the 35th International Symposium on Lattice Field Theory, June 18-24, 2017, Granada, Spai

A Semi-Analytical Model for the Formation and Evolution of Radio Relics in Galaxy Clusters

Radio relics are Mpc-sized synchrotron sources located in the peripheral regions of galaxy clusters. Models based on the diffuse shock acceleration (DSA) scenario have been widely accepted to explain the formation of radio relics. However, a critical challenge to these models is that most observed shocks seem too weak to generate detectable emission, unless fossil electrons, a population of mildly energetic electrons that have been accelerated previously, are included in the models. To address this issue, we present a new semi-analytical model to describe the formation and evolution of radio relics by incorporating fossil relativistic electrons into DSA theory, which is constrained by a sample of 14 observed relics, and employ the Press-Schechter formalism to simulate the relics in a $20^{\circ} \times 20^{\circ}$ sky field at 50, 158, and 1400 MHz, respectively. Results show that fossil electrons contribute significantly to the radio emission, which can generate radiation four orders of magnitude brighter than that solely produced by thermal electrons at 158 MHz, and the power distribution of our simulated radio relic catalog can reconcile the observed $P_{1400}-M_{\mathrm{vir}}$ relation. We predict that $7.1\%$ clusters with $M_{\mathrm{vir}} > 1.2\times 10^{14}\,\mathrm{M}_{\odot}$ would host relics at 158 MHz, which is consistent with the result of $10 \pm 6\%$ given by the LoTSS DR2. It is also found that radio relics are expected to cause severe foreground contamination in future EoR experiments, similar to that of radio halos. The possibility of AGN providing seed fossil relativistic electrons is evaluated by calculating the number of radio-loud AGNs that a shock is expected to encounter during its propagation.Comment: 15 pages, 20 figures. Accepted for publication in MNRAS. Comments welcom

HyFish: hydrological factor fusion for prediction of fishing effort distribution with VMS dataset

Predicting fishing effort distribution is crucial for guiding fisheries management in developing effective strategies and protecting marine ecosystems. This task requires a deep understanding of how various hydrological factors, such as water temperature, surface height, salinity, and currents influence fishing activities. However, there are significant challenges in designing the prediction model. Firstly, how hydrological factors affect fishing effort distributions remains unquantified. Secondly, the prediction model must effectively integrate the spatial and temporal dynamics of fishing behaviors, a task that shows analytical difficulties. In this study, we first quantify the correlation between hydrological factor fields and fishing effort distributions through spatiotemporal analysis. Building on the insights from this analysis, we develop a deep-learning model designed to forecast the daily distribution of fishing effort for the upcoming week. The proposed model incorporates residual networks to extract features from both the fishing effort distribution and the hydrological factor fields, thus addressing the spatial limits of fishing activity. It also employs Long Short-Term Memory (LSTM) networks to manage the temporal dynamics of fishing activity. Furthermore, an attention mechanism is included to capture the importance of various hydrological factors. We apply the approach to the VMS dataset from 1,899 trawling fishing vessels in the East China Sea from September 2015 to May 2017. The dataset from September 2015 to May 2016 is used for correlation analysis and training the prediction model, while the dataset from September 2016 to May 2017 is employed to evaluate the prediction accuracy. The prediction error ratio for each day of the upcoming week range is only 5.6% across all weeks from September 2016 to May 2017. HyFish, notable for its low prediction error ratio, will serve as a versatile tool in fisheries management for developing sustainable practices and in fisheries research for providing quantitative insights into fishing resource dynamics and assessing ecological risks related to fishing activities

Peripheral arterial occlusive disease: Global gene expression analyses suggest a major role for immune and inflammatory responses

<p>Abstract</p> <p>Background</p> <p>Peripheral arterial disease (PAD), a major manifestation of atherosclerosis, is associated with significant cardiovascular morbidity, limb loss and death. However, mechanisms underlying the genesis and progression of the disease are far from clear. Genome-wide gene expression profiling of clinical samples may represent an effective approach to gain relevant information.</p> <p>Results</p> <p>After histological classification, a total of 30 femoral artery samples, including 11 intermediate lesions, 14 advanced lesions and 5 normal femoral arteries, were profiled using Affymetrix microarray platform. Following real-time RT-PCR validation, different algorithms of gene selection and clustering were applied to identify differentially expressed genes. Under a stringent cutoff, i.e., a false discovery rate (FDR) <0.5%, we found 366 genes were differentially regulated in intermediate lesions and 447 in advanced lesions. Of these, 116 genes were overlapped between intermediate and advanced lesions, including 68 up-regulated genes and 48 down-regulated ones. In these differentially regulated genes, immune/inflammatory genes were significantly up-regulated in different stages of PAD, (85/230 in intermediate lesions, 37/172 in advanced lesions). Through literature mining and pathway analysis using different databases such as Gene Ontology (GO), and the Kyoto Encyclopedia of Gene and Genomics (KEGG), genes involved in immune/inflammatory responses were significantly enriched in up-regulated genes at different stages of PAD(p < 0.05), revealing a significant correlation between immune/inflammatory responses and disease progression. Moreover, immune-related pathways such as Toll-like receptor signaling and natural killer cell mediated cytotoxicity were particularly enriched in intermediate and advanced lesions (P < 0.05), highlighting their pathogenic significance during disease progression.</p> <p>Conclusion</p> <p>Lines of evidence revealed in this study not only support previous hypotheses, primarily based on studies of animal models and other types of arterial disease, that inflammatory responses may influence the development of PAD, but also permit the recognition of a wide spectrum of immune/inflammatory genes that can serve as signatures for disease progression in PAD. Further studies of these signature molecules may eventually allow us to develop more sophisticated protocols for pharmaceutical interventions.</p

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Reconsidering the Barefoot Doctor Programme

This paper examines the widely acclaimed Barefoot Doctor campaign in China. The Barefoot Doctor Campaign has come to symbolize the success of Chinese health care to the extent that it has become a model for WHO public health strategy. Yet little has been done to understand how or whether it worked on the ground and what difficulties and contradictions emerged in its implementation. Using previously unexplored party archives as well as newly collected oral interviews, this paper moves away from a narrow focus on party politics and policy formulation by examining the reality of health care at the local level and the challenges faced by local authorities and individuals as the campaigns evolved

Wind Structure of a Subtropical Squall Line in China: Results from Dual-Doppler Radar Data

A subtropical squall line moved from Guangxi to Guangdong province in South China on 23-24 April 2007, which resulted in gale and heavy precipitation. The three-dimensional (3D) wind field of the squall line in its mature period was retrieved by Guangzhou-Shenzhen dual-Doppler data. The 3D conceptual model of this squall line was proposed. On the horizontal plane, the storm-relative front-to-rear inflow prevailed at the lower altitudes of the leading edge. The rear-to-front cold inflow in the stratiform region was observed below 3 km height, which enhanced the convergence in the convective region. At the middle altitudes of the squall line, the front-to-rear horizontal flow prevailed. Strong updrafts were observed at the lower and middle altitudes of the leading edge. Some convergence centers were located at the lower altitudes of the convective region. Furthermore, the storm-relative flow in the vertical cross-section perpendicular to the squall line was revealed. The front-to-rear warm flow extended from the surface to 7.5 km altitude at the leading edge. Above it, part of the front-to-rear inflow blew upward and then forward, and the other part of the inflow blew backward. The descending rear-to-front cold flow was only seen below 3 km height in the stratiform region