A UPLC-MS/MS method for simultaneous determination of tiamulin and its metabolites in Crucian carp (Carassius carassius): an in vivo metabolism and tissue distribution study

Tiamulin (TML) has been studied and analyzed in pigs, cattle, chickens, ducks, and other domestic animals, however, its metabolic state in fish has not been well explored. This study investigated TML metabolism in Crucian carp (Carassius carassius). After intraperitoneal injection of TML into Crucian carp, ultra-high performance liquid chromatography with quadrupole and time-of-flight mass spectrometry (UPLC/Q-TOF MS) analysis, was conducted to identify TML metabolites. The UPLC/Q-TOF MS analysis and the relative molecular mass of the metabolites obtained from related literature identified five metabolites in Crucian carp. These metabolites were M1 (510.2908, C28H48NO5S+), M2 (510.2908, C28H48NO5S+), M3 (466.2750, C26H44NO4S+), M4 (482.2663, C26H44NO5S+), and M5 (482.2663, C26H44NO5S+). The enrichment and metabolism of TML and its metabolites in Crucian carp were investigated using the drug bath method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). TML exhibited an overall trend of an initial increase followed by a decrease. Moreover, the drug enrichment rate was fast and reached saturation after two days. The bioconcentration factor of TML in Crucian carp was 3.01. However, the drug had a slow elimination rate, with its complete metabolism occurring after 20 days

Patterns of Immune Infiltration in Endometriosis and Their Relationship to r-AFS Stages

Background: Endometriosis (EMS) is an estrogen-dependent disease in which endometrial glands and stroma arise outside the uterus. Current studies have suggested that the number and function of immune cells are abnormal in the abdominal fluid and ectopic lesion tissues of patients with EMS. The developed CIBERSORT method allows immune cell profiling by the deconvolution of gene expression microarray data.Methods: By applying CIBERSORT, we assessed the relative proportions of immune cells in 68 normal endometrial tissues (NO), 112 eutopic endometrial tissues (EU) and 24 ectopic endometrial tissues (EC). The obtained immune cell profiles provided enumeration and activation status of 22 immune cell subtypes. We obtained associations between the immune cell environment and EMS r-AFS stages. Macrophages were evaluated by immunohistochemistry (IHC) in 60 patients with ovarian endometriomas.Results: Total natural killer (NK) cells were significantly decreased in EC, while plasma cells and resting CD4 memory T cells were increased in EC. Total macrophages in EC were significantly increased compared to those of EU and NO, and M2 macrophages were the primary macrophages in EC. Compared to those of EC from patients with r-AFS stage I ~ II, M2 macrophages in EC from patients with stage III ~ IV were significantly increased. IHC experiments showed that total macrophages were increased in EC, with M2 macrophages being the primary subtype.Conclusions: Our data demonstrate that deconvolution of gene expression data by CIBERSORT provides valuable information about immune cell composition in EMS

CXCL13/CXCR5 Axis Predicts Poor Prognosis and Promotes Progression Through PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

The chemokine ligands and their receptors play critical roles in cancer progression and patients outcomes. We found that CXCL13 was significantly upregulated in ccRCC tissues compared with normal tissues in both The Cancer Genome Atlas (TCGA) cohort and a validated cohort of 90 pairs ccRCC tissues. Statistical analysis showed that high CXCL13 expression related to advanced disease stage and poor prognosis in ccRCC. We also revealed that serum CXCL13 levels in ccRCC patients (n = 50) were significantly higher than in healthy controls (n = 40). Receiver operating characteristic (ROC) curve revealed that tissue and serum CXCL13 expression might be a diagnostic biomarker for ccRCC with an area under curve (AUC) of 0.809 and 0.704, respectively. CXCL13 was significantly associated with its receptor, CXCR5, in ccRCC tissues, and ccRCC patients in high CXCL13 high CXCR5 expression group have a worst prognosis. Functional and mechanistic study revealed that CXCL13 promoted the proliferation and migration of ccRCC cells by binding to CXCR5 and activated PI3K/AKT/mTOR signaling pathway. These results suggested that CXCL13/CXCR5 axis played a significant role in ccRCC and might be a therapeutic target and prognostic biomarker

Experimental study on the fine-scale characteristics of a geogrid-gravelly soil reinforcement influence zone

Based on a specially designed visualization pullout system and digital photographic measurement technology, geogrid pullout tests were conducted by varying the top load, geogrid type, coarse grain content, and particle shape. The evolution and distribution of the reinforcement influence zone and the soil particle displacement field were analyzed, and the effects of various factors on the formation speed of the reinforcement influence zone, gradient layer thickness, and fine-scale particle displacement characteristics were discussed. The study shows that the reinforcement influence zone’s basic form and particle displacement direction do not change with pullout displacement after it is fully developed. The displacement layers in the influence zone are centered at the reinforced soil interface and are distributed in a diffusion gradient. The thickness of each gradient layer in the upper influence zone is greater than that in the lower influence zone. The greater the normal load is, the smaller the particle displacement and thickness of each gradient layer, and the slower the formation of the reinforcement influence zone. Using high-strength geogrids and geogrids with nodes can increase the upper interface thickness and improve the reinforcement influence zone’s formation speed. Horizontal ribs play a major role in forming the reinforcement influence zone, while longitudinal ribs mainly affect the formation speed. The indirect reinforcement effect of the geogrid on angular gravel soil is better than that on pebble soil. As the coarse grain content in the fill increases from 20% to 30%, the reinforcement influence zone forms faster, and the particle displacement of each gradient layer is smaller. When the coarse grain content increases from 30% to 35%, there is no significant change in the forming rate of the reinforcement influence zone

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Maslov-Type Index in Dimension 2

In this article, we define an index of the Maslov type for paths of 2×2 orthogonal symplectic matrices. The starting point is an arbitrary 2×2 orthogonal symplectic matrix rather than the identity matrix. We use this index to explain the geometric intersection number of a pair of Lagrangian paths and compare it with the Cappell–Lee–Miller index

Hepatorenal Toxicity after 7-Day Oral Administration of Low-Dose Tetrodotoxin and Its Distribution in the Main Tissues in Mice

Tetrodotoxin (TTX) is a highly toxic compound detected in various edible marine animals even in European waters. To characterize the hazard by oral exposure to TTX, its tissue distribution was evaluated after single (75 μg/kg) or 7-day (25–125 μg/kg) oral administration in mice. Moreover, TTX liver and renal toxicity was evaluated after 7-day oral administration. The elimination cycle of a single oral dose of TTX (75 µg/kg) was found to be approximately 168 h (7 days). Daily oral administration of TTX at doses of 25, 75, and 125 µg/kg for 7 consecutive days revealed dose-dependent toxic effects on the liver and kidney. Histopathological examination showed increased inflammatory cell infiltration in the liver and kidney with higher TTX doses, along with disorganization of the hepatic cord and renal tubular cell arrangement. The study results indicated that TTX had more hepatotoxicity than nephrotoxicity in mice. These findings provide insights into the unintentional ingestion of a low dose of TTX in mammals, including humans, and emphasize the importance of food safety

Fas Signaling Promotes Gastric Cancer Metastasis through STAT3-Dependent Upregulation of Fascin.

Fas signaling-activated signal transducers and activators of transcription 3 (STAT3) is required for Fascin upregulation. As an actin-bundling protein, Fascin can mediate gastric cancer (GC) cell migration.Gastric cancer AGS cells were treated with anti-Fas (5 μg/ml) for 2 h, in order to stimulate the activation of the Fas signaling. The in vitro migration of Fas signaling-activated AGS cells was assessed using Transwell chambers. The levels of Fascin and phosphorylated STAT3 were detected by Western blotting analyses. Nude mice were injected intravenously with AGS cells treated with anti-Fas or treated with STAT3 inhibitor without anti-Fas; tumor pulmonary metastases were measured. Fascin protein expression in tumor tissues was detected by immunohistochemistry. The Fas and Fascin mRNA levels in tumor tissues from patients with GC were measured by real-time PCR and their correlation was analyzed.The activation of Fas signaling promoted cell migration and resulted in STAT3-dependent Fascin upregulation in AGS cells. STAT3 enhanced Fascin levels in vivo. Fascin was the mediator of Fas signaling-induced AGS cell migration in vitro and in vivo. Furthermore, there was a positive correlation between Fas and Fascin mRNA levels in tumor tissues from GC patients.Fas signaling promotes GC metastasis through the STAT3/Fascin pathway, which may provide a new target for GC therapy