Association of Mu-Opioid Receptor(MOR) Expression and Opioids Requirement With Survival in Patients With Stage I-III Pancreatic Ductal Adenocarcinoma

BackgroundThe use of opioids in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is associated with shorter survival and not dependent on the expression of the mu-opioid receptor (MOR). The role of opioid use and MOR expression in stage I-III PDAC has not been investigated.MethodsWe conducted retrospective study in patients with stage I-III PDAC. MOR expression and OPRM1 gene expression in tumour tissue and non-tumour tissue was measured. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints included perineural invasion, intraoperative sufentanil consumption, and length of stay. We performed a subgroup group analysis to evaluate the interaction between levels of MOR expression, amount of opioids use (high versus low) and its association with survival.ResultsA total of 236 patients were enrolled in this study.There were no significantly difference in OS rates in patients with high versus low levels of MOR (1-year OS: 65.2% versus 70.6%, P=0.064; 3-year: 31.4% versus 35.8%, P=0.071; 5-year: 19.4% versus. 16.2%, P=0.153, respectively) in the tumours. The DFS rates between the groups were no significantly difference. Of note, a high expression of MOR combined with high opioid consumption was associated with poor prognosis in stage I-III PDAC patients. Tumor expressing high levels of MOR show higher rates of perineural invasion.ConclusionMOR is not an independent predictor of poor survival in stage I-III PDAC but associated with perineural invasion. Patients requiring high amounts of opioids intraoperatively show worse outcome if they are expressing high levels of MOR

Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro

Purpose: This study was conducted to determine whether paeoniflorin (PF) could prevent H(2)O(2)-induced oxidative stress in ARPE-19 cells and to elucidate the molecular pathways involved in this protection. Methods: Cultured ARPE-19 cells were subjected to oxidative stress with H(2)O(2) in the presence and absence of PF. The preventive effective of PF on reactive oxygen species (ROS) production and retinal pigment epithelium (RPE) cell death induced by H(2)O(2) was determined by 2', 7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) fluorescence and 3-(4, 5dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) assay. The ability of PF to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and 4', 6-diamidino-2-phenylindole (DAPI) staining. Furthermore, the protective effect of PF via the mitogen-activated protein kinase (MAPK) pathway was determined by western blot analysis. Results: PF protected ARPE-19 cells from H(2)O(2)-induced cell death with low toxicity. H(2)O(2)-induced oxidative stress increased ROS production and caspase-3 activity, which was significantly inhibited by PF in a dose-dependent manner. Pretreatment with PF attenuated H(2)O(2)-induced p38MAPK and extracellular signal regulated kinase (ERK) phosphorylation in human RPE cells, which contributed to cell viability in ARPE-19 cells. Conclusions: This is the first report to show that PF can protect ARPE-19 cells from the cellular apoptosis induced by oxidative stress. The results of this study open new avenues for the use of PF in treatment of ocular diseases, such as age-related macular degeneration (AMD), where oxidative stress plays a major role in disease pathogenesis.Biochemistry & Molecular BiologyOphthalmologySCI(E)PubMed1ARTICLE373-783512-35221

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis

International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1) : Study design, statistical analysis plan and study protocol

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.Peer reviewedPublisher PD

A multi-terrain feature-based deep convolutional neural network for constructing super-resolution DEMs

Scale conversion between DEMs is an important issue in geomorphometry. There are many mature studies on the generation of low-resolution(LR) DEMs from high-resolution(HR) DEMs. However, as an important and convenient means of obtaining HR DEMs, traditional super resolution (SR) methods have shown insufficient consideration of the terrain features embedded in DEMs. Therefore, this article investigates the combination of terrain features and the use of convolutional neural networks (CNN) to reconstruct HR DEMs, and proposes a multi-terrain feature-based deep CNN for super-resolution(SR) DEMs (MTF-SR). In the experiments, from the perspective of vector and raster terrain features, we fuse raster terrain features in the input and loss functions, and fuse vector terrain features in the optimization of the output of the model. The results show that the MTF-SR model has a 30–50 % reduction in mean absolute error (MAE) compared with interpolation methods, has the lowest slope and aspect error and has a 10 to 30 % improvement in streamline matching rate (SMR). These results point to the advantages of the method in overall elevation accuracy and the preservation of terrain features

Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1‐mediated lipid metabolism

Abstract Metastasis is responsible for at least 90% of colon cancer (CC)‐related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further investigation. Herein, through the utilisation of single‐cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1‐ konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1‐KO. Notably, we revealed that lovastatin can block the SULT2B1‐induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis

Resources and extraction of gallium: A review

Gallium (Ga) is extensively employed in integrated circuits and advanced electronic devices as it provides the benefits of low energy consumption and high computation speeds. However, the Ga-bearing host minerals are scarce in nature. Ga occurs in combination with several minerals, mainly including aluminum, zinc, iron ores and coals, of which bauxite, zinc ores and coals are the primary original sources of Ga currently. Mining minerals for the sole extraction of Ga is not economical due to the low concentration of Ga. Accordingly, Ga is mainly recovered as a by-product from the processing of minerals. The current main commercial resources of Ga are Bayer liquor and zinc residue, which contribute to nearly all of the worldwide Ga production. The production of low-grade (99.99% pure) Ga has been increasing at an average rate of 7.4% p.a. for the past four decades and amounted to 375 tons in 2016. It is estimated to increase by 20-fold by the year 2030 compared to the yield of 275 tons in 2012. The mounting worldwide demand for Ga necessitates the search for additional resources and recovery technologies for this particular element. Apart from the Bayer liquor and the zinc residue, there are several other Ga-resources, which include red mud, coal fly ash, Ga-bearing electronics industrial waste, and flue dust from electric furnaces at phosphorus factories. Based on the chemical properties of Ga, it is evident that both strong acidic/basic conditions and high temperatures favor the efficient extraction of Ga from its corresponding minerals. Several hydrometallurgical processes based mainly on acid/alkaline leaching along with solution purification and recovery (e.g. ion exchange, solvent extraction and precipitation) have been proposed for Ga extraction from these resources. In this paper, the current status of Ga recovery was reviewed and specific examples were utilized for each resource to discuss the extraction methods, the recoveries and the optimum Ga-recovery conditions for each resource. Additional research appears to be necessary to establish a highly efficient and environmentally friendly process to recover Ga from these resources

Additional file 5 of Microbiota and metabolites alterations in proximal and distal gastric cancer patients

Additional file 5: Figure S4. Metabolite composition and difference between Proximal N and Distal N. A, B OPLS-DA showed that Proximal N and Distal N were not separated into two clusters. Test for OPLS-DA model showed that the OPLS-DA model for this study was valid

Additional file 1 of Microbiota and metabolites alterations in proximal and distal gastric cancer patients

Additional file 1: Table S1. Clinicopathological characteristics of patients with gastric cancer in this study. Table S2. Different microorganisms in Proximal T and Distal T compared to their respective non tumor samples. Table S3. Significant differences in metabolites between Distal T and Distal N. Table S4. Significant differences in metabolites between Proximal T and Proximal N. Table S5. Metabolic pathway enrichment of differential metabolites between Distal T and Distal N. Table S6. Metabolic pathway enrichment of differential metabolites between Proximal T and Proximal N