Scottcole1311

Primary sclerosing cholangitis (PSC) is characterized by chronic liver inflammation and cholestasis due to intrahepatic and extrahepatic bile duct inflammation and fibrosis. Cholestasis results in accumulation of bile acids in the liver with a concomitant deficit in the intestines. Accumulation of bile acids could be causal for inflammation of the liver, whereas deficiency of bile acids in the intestines could result in insufficient deoxycholic acid (DCA) in both the intestines and the liver, leading to decreased activation of intestinal farnesoid X receptor (FXR). This article is protected by copyright. All rights reserved.PURPOSE Detection and accurate localization of renal masses (RM) are important steps towards future potential classification of benign versus malignant RM. A fully automated algorithm for detection and localization of RM may eliminate the observer variability in the clinical workflow. METHOD In this paper, we describe a fully automated methodology for accurate detection and segmentation of RM from contrast-enhanced computed tomography (CECT) images. We first determine the boundaries of the kidneys on the CECT images utilizing a convolutional neural network-based method to be used as a region of interest to search for RM. We then employ a homogenous U-Net-based ensemble learning model to identify and delineate RM. We used an institutional dataset comprised of CECT images in 315 patients to train and evaluate the proposed method. We compared results of our method to those of 3D U-Net for RM localization and further evaluated our algorithm using the kidney tumor segmentation (KiTS19) challenge dataset. RESULTS Tis article is protected by copyright. All rights reserved.Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC-MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated by using acetonitrile and then separated on an ACQUITY BEH C18 column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 mL/min. Ziritaxestat and internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range of 0.5-2000 ng/mL, with correlation coefficient greater than 0.9987. The extraction recovery was more than 82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD%) were below 11.20% and accuracies were in the range of -8.50-7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed short half-life (~3 h) and low bioavailability (20.52%). This article is protected by copyright. All rights reserved.BACKGROUND As a non-destructive testing technology, electrochemical impedance spectroscopy (EIS) has been applied to evaluate food quality because of its rapid, low-cost, non-destructive and portability. However, fish freshness evaluation based on existing EIS technology is affected by the difference of biological individual. In this study, the difference of electrical property between the two orthogonal directions was extracted to develop a new freshness indicator. A real part orthogonal direction difference parameter set (RODDS) was used to establish a prediction model for total volatile base-Nitrogen (TVB-N). RESULTS Compared with the traditional parameter of EIS, coefficient of determination between RODDS and TVB-N increased from 0.55 to 0.71 for calibration group, and root mean squared error (RMSE) between predicted and measured values of TVB-N decreased from 5.46 to 3.81 for test group. CONCLUSION The results implied that RODDS could effectively offset individual difference in basic electrical property and improve the TVB-N prediction accuracy in practical application scenario with samples from multiple origins. The proposed method may provide a new idea for the development and improvement of EIS-based portable testing device for fish and meat. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Compound marker consists of two different types of genetic markers like deletion/insertion polymorphism (DIP) and single nucleotide polymorphism (SNP) in the genomic region of 200 bp, and microhaplotype consists of a series of closely linked SNPs in a small DNA segment (0.5). Cumulative power of discrimination (0.999 999 999 99 4835) of the 18 loci revealed that the multiplex panel could also be utilized for human identifications in the studied Shaanxi Han population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.PREMISE Although polyploidy has been studied since the early 1900s, fundamental aspects of polyploid ecology and evolution remain unexplored. In particular, surprisingly little is known about how newly formed polyploids (neopolyploids) become demographically established. Models predict that most polyploids should go extinct within the first few generations as a result of reproductive disadvantages associated with being the minority in a primarily diploid population (i.e., the minority cytotype principle), yet polyploidy is extremely common. Therefore, a key goal in the study of polyploidy is to determine the mechanisms that promote polyploid establishment in nature. Because premating isolation is critical in order for neopolylpoids to avoid minority cytotype exclusion and thus facilitate establishment, we examined floral morphology and three common premating barriers to determine their importance in generating reproductive isolation of neopolyploids from diploids. METHODS We induced neopolyploidy in Trifolium pratense and compared their floral traits to the diploid progenitors. In addition to shifts in floral morphology, we examined three premating barriers isolation by self-fertilization, flowering-time asynchrony, and pollinator-mediated isolation. RESULTS We found significant differences in the morphology of diploid and neopolyploid flowers, but these changes did not facilitate premating barriers that would generate reproductive isolation of neopolyploids from diploids. There was no difference in flowering phenology, pollinator visitation, or selfing between the cytotypes. CONCLUSIONS Our results indicate that barriers other than the ones tested in this study-such as geographic isolation, vegetative reproduction, and pistil-stigma incompatibilities-may be more important in facilitating isolation and establishment of neopolyploid T. pratense. © 2020 Botanical Society of America.Epigenetic factors play a critical role in carcinogenesis by imparting a distinct feature to the chromatin architecture. The present study aimed to develop a novel epigenetic signature for evaluating the relapse-free survival of colon cancer patients. Public microarray datasets were acquired from the Gene Expression Omnibus databases GSE39582, GSE17538, GSE33113, and GSE37892 set. Patients from GSE39582 set were randomized 11 into training and internal validation series. Patients were divided into high-risk and low-risk groups in training series based on a set of 11 epigenetic factors (p  less then  .001). The good reproducibility for the prognostic value of the epigenetic signature was confirmed in the internal validation series (p  less then  .001), external validation series (a combination of GSE17538 set, GSE33113 set, and GSE37892 set; p = .018), and entire series (p  less then  .001). Furthermore, a nomogram, which integrated the epigenetic signature, pathological stage, and postoperative chemotherapy, was developed based on the GSE39582 set. The time-dependent receiver operating characteristic curve at 1 year demonstrated that the comprehensive signature presented superior prognostic value than the pathological stage. In conclusion, an epigenetic signature, which could be utilized to divide colon cancer patients into two groups with significantly different risk of relapse, was established. This biomarker would aid in identifying patients who require an intensive follow-up and aggressive therapeutic intervention. © 2020 Wiley Periodicals, Inc.Ferroptosis, an autophagy-dependent cell death, is characterized by lipid peroxidation and iron accumulation, closely associated with pathogenesis of gestational diabetes mellitus (GDM). Sirtuin 3 (SIRT3) has positive regulation on phosphorylation of activated protein kinase (AMPK), related to maintenance of cellular redox homeostasis. However, whether SIRT3 can confer autophagy by activating the AMPK-mTOR pathway and consequently promote induction of ferroptosis is unknown. We used human trophoblastic cell line HTR8/SVneo and porcine trophoblastic cell line pTr2 to deterimine the mechanism of SIRT3 on autophagy and ferroptosis. The expression of SIRT3 protein was significantly elevated in trophoblastic cells exposed to high concentrations of glucose and ferroptosis-inducing compounds. Increased SIRT3 expression contributed to classical ferroptotic events and autophagy activation, whereas SIRT3 silencing led to resistance against both ferroptosis and autophagy. In addition, autophagy inhibition impaired SIRT3-enhanced ferroptosis. On the contrary, autophagy induction had a synergistic effect with SIRT3. Based on mechanistic investigations, SIRT3 depletion inhibited activation of the AMPK-mTOR pathway and enhanced glutathione peroxidase 4 (GPX4) level, thereby suppressing autophagy and ferroptosis. Selleckchem Taselisib Furthermore, depletion of AMPK blocked induction of ferroptosis in trophoblasts. We concluded that upregulated SIRT3-enhanced autophagy activation by promoting AMPK-mTOR pathway and decreasing GPX4 level to induce ferroptosis in trophoblastic cells. SIRT3 deficiency was resistant to high glucose- and erastin-induced autophagy-dependent ferroptosis and is, therefore, a potential therapeutic approach for treating GDM. © 2020 Wiley Periodicals, Inc.BACKGROUND The nutrients in human milk, particularly amino acids and minerals, are important for infant growth and development. Since there are fewer reports of amino acids and minerals of Chinese breast milk, we conducted this study to establish representative preliminary database of breast milk nutrients in China. In this study, we collected breast milk from healthy mothers in seven cities in western, southern and central China. The composition, content and proportion of total amino acids and ten elements (potassium, sodium, calcium, magnesium, iron, zinc, manganese, copper, selenium and phosphorus) in human milk in different lactation stages were investigated. RESULTS In this study, it was found that the content of total essential amino acids (671.47 mg/100mL) in Chinese breast milk was higher compared with ESPGHAN (574 mg/100mL), but the content of LEU (129.01 mg/100mL) and CYS (20.31 mg/100mL) was much lower than that recommended by ESPGHAN. Moreover, it was found that the content of most of these ten elements decreased during lactation, and the content of calcium in Chinese breast milk was lower compared with ESPGHAN.