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The correlation coefficient between plasma [EPO] and plasma cFGF23 levels was R2 = 0.01 and insignificant. The results demonstrate that cFGF23 is not sensitive to low doses of subcutaneous rhEpo injections in healthy males. © 2020 John Wiley & Sons, Ltd.Cetuximab therapy, which heavily relies on the activation of Ras pathway, has been used in KRAS, NRAS, BRAF and PIK3CA wild-type colorectal cancer (CRC) (Ras-normal). However, the response rate only reached 60%, due to false-negative mutation detection and mutation-like transcriptome features in wild-type patients. Herein, by integrating RNAseq, microarray and mutation data, we developed a Ras pathway signature by characterizing KRAS/NRAS/BRAF/PIK3CA mutations to identify the hidden non-responders from the Ras-normal patients by mutation detection. Using public and in-house data of CRC patients treated with Cetuximab, discovery of the signature could identify cetuximab-resistant samples from the Ras-normal samples. Cetuximab resistance-related genes, such as PTEN, were significantly and frequently mutated in the identified Ras-activated samples, whereas two Cetuximab sensitivity-related genes, APC and TP53, showed co-mutation and significantly higher mutation frequencies in the remaining Ras-normal samples. Futhermore, all the NF1 and BCL2L1 mutated samples were identified as Ras-activated from the Ras-normal samples by the Ras pathway signature with significantly under-regulated expression. Genes co-expressed with the two genes were both involved in Ras signaling pathway, the out-of-control of which could be attributed by the genes' loss-of-function mutations. To improve the treatment of Cetuximab in colorectal cancer, NF1 and BCL2L1 could be used as complementary detection technique to those applied in clinical. In conclusion, the proposed Ras pathway signature could identify the hidden CRC patients resistant to cetuximab therapy and help to reveal resistance mechanisms. https://www.selleckchem.com/products/alkbh5-inhibitor-2.html © 2020 Federation of European Biochemical Societies.The high mobility group box 1 protein (HMGB1) is recognized as a prototypical endogenous danger cytokine in sepsis. We previously reported that a polyacrylonitrile (AN69ST) membrane rapidly adsorbed HMGB1. Herein, an in vitro hemofiltration system was designed to assess the HMGB1 adsorption capacity, adsorption sites, and adsorption mechanism of the AN69ST membrane. HMGB1 was repeatedly added seven times during hemofiltration. A rapid decrease in circulating HMGB1 was observed after every addition with no sign of saturation. Presence of HMGB1 on the filter membrane was observed on both membrane surfaces and within the bulk layer using a high-concentration of HMGB1 by immunoelectron microscopy. We hypothesized that the addition of heparin to the membrane surface or filtration rate would contribute to the adsorption mechanism. We could not measure the influence of heparin and filtration. Although, the membrane was too large to saturate under the μg/mL HMGB1 conditions, our results demonstrate that the AN69ST has a robust absorption capacity that could be used to treat sepsis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Plant based oils are valuable agricultural products, and seed oil content (SOC) is the major yield component in oil crops. Increasing SOC has been successfully targeted through the selection and genetic modification of oil biosynthesis. The SOC in rapeseed declined during the seed maturation and eventually caused the final accumulated seed oil quantity. However, genes involved in oil degradation during seed maturity are not deeply studied so far. We performed a candidate gene association study using a world-wide collection of rapeseed germplasm. We identified SEED FATTY ACID REDUCER (SFAR) genes, which had a significant effect on SOC and fatty acid (FA) composition. SFAR genes belong to the GDSL lipases, and GDSL lipases have a broad range of functions in plants. After quantification of gene expression using RNA-seq and quantitative PCR, we used targeted (CRISPR-Cas mediated) and random (chemical) mutagenesis to modify turnover rates of seed oil in winter rapeseed. For the first time, we demonstrate significant increase of SOC in a crop after knocking out members of the BnSFAR4 and BnSFAR5 gene families without pleiotropic effects on seed germination, vigor, and oil mobilization. Our results offer new perspectives for improving oil yield by targeted mutagenesis. This article is protected by copyright. All rights reserved.BACKGROUND Direct factor Xa (FXa) inhibitors are increasingly prescribed for outpatients, and those transitioning to unfractionated heparin (UFH) for hospital admission are monitored via an anti-FXa assay. Due to assay interference, UFH results would often be critically elevated, confounding dosing. OBJECTIVES An anti-factor IIa (FIIa) UFH assay was evaluated for clinical use. METHODS The BIOPHEN™ ANTI-IIa (Aniara Diagnostica) assay and anti-FXa INNOVANCE® Heparin assay (Siemens Healthcare Diagnostics Products GmbH) were compared on the Siemens BCS XP system. Samples included UFH controls and calibrators and specimens from patients transitioning from apixaban or rivaroxaban to UFH. Method comparison, linearity, recovery, precision, and interference by direct FXa inhibitors were evaluated. The effect of the BIOPHEN™ ANTI-IIa assay on the rate of critically high UFH results was retrospectively reviewed 4 months after implementation. RESULTS Accuracy studies using 0.24 and 0.50 IU/mL UFH yielded means and standard deviations of 0.26 ± 0.01 and 0.58 ± 0.01 IU/mL, respectively. Within-run and between-run coefficients of variation were 4.6% and 15.5% for the low control, and 1.8% and 10.6% for the high control. The method comparison slope was 0.9965 (r2 = 0.9468). The linear range was 0.1 - 1.3 IU/mL. The assay measured UFH in the presence of 192 ng/mL apixaban or 158 ng/mL rivaroxaban. Introduction of the assay for clinical use reduced the monthly percentage of critically high results from 9.4% to 3.8% for admitted heparinized patients who recently discontinued apixaban or rivaroxaban. CONCLUSIONS The BIOPHEN™ ANTI-IIa assay is suitable for patients transitioning off apixaban or rivaroxaban. This article is protected by copyright. All rights reserved.
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