Dideriksenhougaard3437

In summary, our study provides evidence that upregulated TRIM2 in pancreatic cancer predicts short survival for pancreatic cancer patients. TRIM2 accelerates pancreatic cancer progression via the ROS-related NRF2/ITGB7/FAK axis.A major clinical challenge of ovarian cancer is the development of malignant ascites accompanied by widespread peritoneal metastasis. In ovarian clear cell carcinoma (OCCC), a challenging subtype of ovarian cancer, this problem is compounded by near-universal primary chemoresistance; patients with advanced stage OCCC thus lack effective therapies and face extremely poor survival rates. Here we show that tumor-cell-expressed serine protease inhibitor Kazal type 1 (SPINK1) is a key driver of OCCC progression and metastasis. Using cell culture models of human OCCC, we find that shRNA silencing of SPINK1 sensitizes tumor cells to anoikis and inhibits proliferation. Knockdown of SPINK1 in OCCC cells also profoundly suppresses peritoneal metastasis in mouse implantation models of human OCCC. We next identify a novel autocrine signaling axis in OCCC cells whereby tumor-cell-produced interleukin-6 (IL-6) regulates SPINK1 expression to stimulate a common protumorigenic gene expression pattern leading to anoikis resistance and proliferation of OCCC cells. We further demonstrate that this signaling pathway can be successfully interrupted with the IL-6Rα inhibitor tocilizumab, sensitizing cells to anoikis in vitro and reducing metastasis in vivo. These results suggest that clinical trials of IL-6 pathway inhibitors in OCCC may be warranted, and that SPINK1 might offer a candidate predictive biomarker in this population.Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.The SW Japan arc built by subduction of the Philippine Sea (PHS) plate exhibits uneven distribution of volcanoes thirteen Quaternary composite volcanoes form in the western half of this arc, Kyushu Island, while only two in the eastern half, Chugoku district. Reconstruction of the PHS plate back to 14 Ma, together with examinations based on thermal structure models constrained by high-density heat flow data and a petrological model for dehydration reactions suggest that fluids are discharged actively at depths of 90-100 km in the hydrous layer at the top of the old (> 50 Ma), hence, cold lithosphere sinking beneath Kyushu Island. In contrast, the young (15-25 Ma) oceanic crust downgoing beneath Chugoku district releases fluids largely at shallower depths, i.e. beneath the non-volcanic forearc, to cause characteristic tectonic tremors and low-frequency earthquakes (LFEs) and be the source of specific brine springs. Much larger amounts of fluids supplied to the magma source region in the western SW Japan arc could build more densely-distributed volcanoes.The overuse or abuse of antibiotics as veterinary medicine and growth promoters accelerates antibiotic resistance, creating a serious threat to public health in the world. Swine liquid manure as an important reservoir of antibiotic resistance genes (ARGs) has received much attention, but little information is known regarding the occurrence, persistence and fate of ARGs-associated mobile genetic elements (MGEs) in swine farms, especially their change patterns and removal in full-scale piggery wastewater treatment systems (PWWTSs). In this study, we searched the presence and distribution of MGEs and associated ARGs in swine farms, and addressed their fate and seasonal variation in full-scale PWWTSs by real-time quantitative PCR (qPCR). Our results revealed class 1 integrons, class 2 integrons and conjugative plasmids were prevalent in pig feces and piggery wastewater. A clear pattern of these MGE levels in swine liquid manure was also observed, i.e., intI1 > intI2 > traA (p  less then  0.01), and their absolute abundances in winter were all higher than that in summer with 0.07-2.23 logs. Notably, MGEs and ARGs prevailed through various treatment units of PWWTSs, and considerable levels of them were present in the treated effluent discharged from swine farms (up to 101-107 copies/mL for MGEs and 103-108 copies/mL for ARGs). Decitabine in vivo There were significant correlations between most ARG abundance and MGE levels (p  less then  0.05), such as tetQ and traA (r = 0.775), sul1 and intI1 (r = 0.847), qnrS and inI2 (r = 0.859), suggesting the potential of ARGs-horizontal transfer. Thus the high prevalence and enrichment of MGEs and ARGs occurred in pig feces and piggery wastewater, also implicating that swine liquid manure could be a hotspot for horizontal transfer of ARGs.Newly developed millennial δ13C larch tree-ring chronology from Siberia allows reconstruction of summer (July) vapor pressure deficit (VPD) changes in a temperature-limited environment. VPD increased recently, but does not yet exceed the maximum values reconstructed during the Medieval Warm Anomaly. The most humid conditions in the Siberian North were recorded in the Early Medieval Period and during the Little Ice Age. Increasing VPD under elevated air temperature affects the hydrology of these sensitive ecosystems by greater evapotranspiration rates. Further VPD increases will significantly affect Siberian forests most likely leading to drought and forest mortality even under additional access of thawed permafrost water. Adaptation strategies are needed for Siberian forest ecosystems to protect them in a warming world.