Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), but its clinical effects are still limited. In this study we identify Quiescin sulfhydryl oxidase 1 (QSOX1) acting as a cellular pro-oxidant, specifically in the context of sorafenib treatment of HCC. QSOX1 disrupts redox homoeostasis and sensitizes HCC cells to oxidative stress by inhibiting activation of the master antioxidant transcription factor NRF2. A negative correlation between QSOX1 and NRF2 expression was validated in tumor tissues from 151 HCC patients. Mechanistically, QSOX1 restrains EGF-induced EGFR activation by promoting ubiquitination-mediated degradation of EGFR and accelerating its intracellular endosomal trafficking, leading to suppression of NRF2 activity. Additionally, QSOX1 potentiates sorafenib-induced ferroptosis by suppressing NRF2 in vitro and in vivo . In conclusion, the data presented identify QSOX1 as a novel candidate target for sorafenib-based combination therapeutic strategies in HCC or other EGFR-dependent tumor types.

Field trials were initiated in fall 2011 to determine the potential of pyroxasulfone to control acetolactate synthase (ALS) inhibitor-resistant weeds in field pea. Pyroxasulfone was applied in split-plot trials at five locations in western Canada using fall and PRE spring applications of 0 to 400 g ai ha−1. Trial locations were chosen with a range of soil organic matter content: 2.9, 4.3, 5.5, 10.5, and 10.6% at Scott, Kernen, Kinsella, Melfort, and Ellerslie, respectively. The herbicide dose required to reduce biomass by 50% (ED50) in false cleavers ranged between 53 and 395 g ha−1at Scott and Ellerslie, respectively. Wild oat ED50s varied between 0.54 g ha−1at Scott in the fall and 410 g ai ha−1in the spring at Melfort. ED50s for wild oat and false cleavers varied by 7.4- and 746-fold, respectively, depending primarily on the organic matter content at the trial location. The effect of application timing was not consistent. Significant yield reductions and pea injury occurred at 150 and 100 g ha−1and higher at Kernen and Scott, respectively. Low organic matter and high precipitation levels at these locations indicates increased herbicide activity under these conditions. Pyroxasulfone may allow control of ALS inhibitor-resistant false cleavers and wild oat; however, locations with high soil organic matter will require higher rates than those with low organic matter for similar control levels.

Grassland management aimed at enhancing carbon (C) in soil is an important tool in mitigation of rising atmospheric CO2, yet little is known of how grassland soil C changes with livestock stocking rate (SR). We relate soil organic and inorganic C mass (t ha−1 to 60 cm depth) with cattle stocking over periods of 7–27 year for 32 paddocks distributed across nine community pastures in the mixed‐grass prairie of Saskatchewan, Canada. Initial analysis comparing Akaike information criterion models showed that cattle SR explained a greater proportion of variance in soil C, particularly soil organic C, than rainfall. Soil organic C mass increased with cattle SR (R2 = .293; p = .001), even when the latter was normalized to account for differences in vegetation composition and growing conditions among pastures. Normalized SR varied from 0.49 to 2.30 times recommended levels, over which SOC increased from 24.7 to 57.4 t ha−1. Increases in soil organic C under greater stocking coincided with increased abundance of introduced vegetation, particularly the rhizomatous grass Poa pratensis. Inorganic soil C accounted for 34.6% of total soil C, being particularly large below 30 cm soil depth, but did not vary with stocking rate. These findings indicate that both organic and inorganic C are important pools of C in northern temperate grassland soils, with soil organic C positively associated with long‐term cattle SR. Further studies are recommended to understand more fully the mechanisms regulating grazing impacts on soil C mass in northern temperate grasslands.

Very few annuals produced seed during the season if they emerged after June, but some (< 45%) of these plants successfully overwintered. Summer annuals began dispersing mature seed 7 wk after emergence, but were also capable of persisting in a quiescent state for extended periods (up to 19 wk). Wheat and canola yield loss attributable to field violet was minimal. We compared domestic and European field violet accessions to determine if the study population represented a unique agroecotype. Plants from both cohorts grown in the greenhouse were near-identical, suggesting that differences resulted from phenotypic plasticity, rather than genetic divergence. Field violet appears to be well adapted to growing conditions and farming practices in Alberta, but is a poor competitor and is unlikely to cause serious crop production losses. La plante éclot en nombre variable, avec un pic au début de juin et en septembre. Lorsqu'elles germent après juin, très peu de violettes montent en graines, mais quelques plants survivent à l'hiver (moins de 45 %). Les annuelles alternatives répan-dent les graines matures sept semaines après la germination, mais elles peuvent persister longtemps (jusqu'à 19 semaines) au stade de repos. La violette cause des pertes de rendement minimes au blé et au canola. Les auteurs ont comparé les obtentions canadiennes et européennes afin d'établir si la population à l'étude constituait un écotype agricole particulier. Les plantes des deux cohortes cultivées en serre étaient presque identiques, signe que les variations résultent de la plasticité du phénotype et n'ont pas une origine génétique. La violette des champs semble bien adaptée aux conditions de croissance et aux pratiques agricoles de l'Alberta, mais s'avère une piètre compétitrice et il est peu probable qu'elle entraîne de grandes pertes pour l'agriculture.