Axitinib targets cardiac fibrosis in pressure overload-induced heart failure through VEGFA-KDR pathway

BackgroundThere are no specific clinical medications that target cardiac fibrosis in heart failure (HF). Recent studies have shown that tyrosine kinase inhibitors (TKIs) may benefit fibrosis in various organs. However, there is limited research on their application in cardiac fibrosis. Axitinib, an FDA-approved tyrosine kinase inhibitor, was used to evaluate its effects on cardiac fibrosis and function in pressure overload-induced heart failure.MethodsTo build a pharmacological network, the pharmacological targets of axitinib were first retrieved from databases and coupled with key heart failure gene molecules for analysis and prediction. To validate the results outlined above, 8-week-old male C57BL/6 J mice were orally administrated of axitinib (30 mg/kg) daily for 8 weeks after Transverse Aortic Constriction (TAC) surgery. Mouse cardiomyocytes and cardiac fibroblasts were used as cell lines to test the function and mechanism of axitinib.ResultsWe found that the pharmacological targets of axitinib could form a pharmacological network with key genes involved in heart failure. The VEGFA-KDR pathway was found to be closely related to the differential gene expression of human heart-derived primary cardiomyocyte cell lines treated with axitinib, based on analysis of the publicly available dataset. The outcomes of animal experiments demonstrated that axitinib therapy greatly reduced cardiac fibrosis and improved TAC-induced cardiac dysfunction. Further research has shown that the expression of transforming growth factor-β(TGF-β) and other fibrosis genes was significantly reduced in vivo and in vitro.ConclusionOur study provides evidence for the repurposing of axitinib to combat cardiac fibrosis, and offers new insights into the treatment of patients with HF

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A Task Scheduling Algorithm Based on Classification Mining in Fog Computing Environment

Fog computing (FC) is an emerging paradigm that extends computation, communication, and storage facilities towards the edge of a network. In this heterogeneous and distributed environment, resource allocation is very important. Hence, scheduling will be a challenge to increase productivity and allocate resources appropriately to the tasks. We schedule tasks in fog computing devices based on classification data mining technique. A key contribution is that a novel classification mining algorithm I-Apriori is proposed based on the Apriori algorithm. Another contribution is that we propose a novel task scheduling model and a TSFC (Task Scheduling in Fog Computing) algorithm based on the I-Apriori algorithm. Association rules generated by the I-Apriori algorithm are combined with the minimum completion time of every task in the task set. Furthermore, the task with the minimum completion time is selected to be executed at the fog node with the minimum completion time. We finally evaluate the performance of I-Apriori and TSFC algorithm through experimental simulations. The experimental results show that TSFC algorithm has better performance on reducing the total execution time of tasks and average waiting time

OPTIMIZING SULFITE PRRETREATMENT FOR SACCHARIFICATION OF WHEAT STRAW USING ORTHOGONAL DESIGN

An orthogonal designed experiment was used to investigate the effects of sulfite pretreatment on the components separation and saccharification of wheat straw. The process involved sulfite pretreatment of wheat straw under acidic conditions followed by mechanical size reduction using a high consistency refiner. Reaction temperature, retention time, and charges of sodium bisulfite and sulphuric acid were considered as key factors. The results showed the four factors had impact on saccharification of wheat straw. Raising the temperature, increasing the charge of sodium bisulfite or sulphuric acid, or extending the retention time would improve the dissolution of pentosan, lignin, and saccharification efficiency, while causing further conversion of pentose. The separation of lignin and pentosan from wheat straw was the main cause of improvements in saccharification. With an enzyme loading of 5 FPU cellulase plus 4 CBU β-glucosidase per gram of o.d. substrate, a glucose yield 72.45% was achieved using the substrate pretreated under the conditions of temperature 180 oC, sodium bisulfite charge 3%, sulfuric acid charge 1.48%, and retention time 20 min

Building an ensemble learning model for gastric cancer cell line classification via rapid raman spectroscopy

Cell misuse and cross-contamination can affect the accuracy of cell research results and result in wasted time, manpower and material resources. Thus, cell line identification is important and necessary. At present, the commonly used cell line identification methods need cell staining and culturing. There is therefore a need to develop a new method for the rapid and automated identification of cell lines. Raman spectroscopy has become one of the emerging techniques in the field of microbial identification, with the advantages of being rapid and noninvasive and providing molecular information for biological samples, which is beneficial in the identification of cell lines. In this study, we built a library of Raman spectra for gastric mucosal epithelial cell lines GES-1 and gastric cancer cell lines, such as AGS, BGC-823, HGC-27, MKN-45, MKN-74 and SNU-16. Five spectral datasets were constructed using spectral data and included the full spectrum, fingerprint region, high-wavelength number region and Raman background of Raman spectra. A stacking ensemble learning model, SL-Raman, was built for different datasets, and gastric cancer cell identification was achieved. For the gastric cancer cells we studied, the differentiation accuracy of SL-Raman was 100% for one of the gastric cancer cells and 100% for six of the gastric cancer cells. Additionally, the separation accuracy for two gastric cancer cells with different degrees of differentiation was 100%. These results demonstrate that Raman spectroscopy combined with SL-Raman may be a new method for the rapid and accurate identification of gastric cancer. In addition, the accuracy of 94.38% for classifying Raman spectral background data using machine learning demonstrates that the Raman spectral background contains some useful spectral features. These data have been overlooked in previous studies