Perfluorooctanoic acid (PFOA) is a typical persistent organic pollutant commonly detected in ecosystem. Insights into the risks of PFOA in crops, from the perspectives of food nutritional compositions, are sparse. In this study, the physiological responses to PFOA induced oxidative stress were investigated in lettuce (Lactuca sativa) leaves hydroponically exposed to 5 and 50 μg/L PFOA. The effects on photosynthesis and nutritional compositions were characterized. 35.1 and 316.7 ng/g dry weight PFOA were bio-accumulated in lettuce leaves under exposure to 5 and 50 μg/L PFOA, respectively. PFOA led to exposure-dependent over-generation of reactive oxidative species (ROS; H2O2, 8.1%-38.7%; OH, 11.3%-26.4%; O2-, 3.1%-22.8%) in leaves. Both non-enzymatic and enzymatic antioxidants were activated to scavenge ROS. Nevertheless, metabolomics results indicated some nutritional compositions in lettuce leaves were elevated by environmentally relevant concentrations of PFOA. Both primary metabolites, such as carbohydrates in the tricarboxylic acid cycle and amino acids, and secondary metabolites, such as bioactive (poly)phenol and alkaloid compounds, were significantly up-regulated. Leaf net photosynthetic rates were stimulated and intercellular CO2 concentration was decreased. A thorough scheme on the interaction between PFOA and lettuce leaves was proposed as well, to enhance the understanding of PFOA risks in crops.Zearalenone (ZEN), a mycotoxin with endocrine disruptive activity and oxidative stress generating ability, has been a worldwide environmental concern for its prevalence and persistency. However, the long-term effect of ZEN on aging process is not fully elucidated. Thus, the present study applied the Caenorhabditis elegans model to investigate the aging-related toxic effect and possible underlying mechanisms under prolonged and chronic ZEN exposure. Our results showed that locomotive behaviors significantly decreased in ZEN (0.3, 1.25, 5, 10, 50 μM) treated C. elegans. In addition, lifespan and aging markers including pharyngeal pumping and lipofuscin were also adversely affected by ZEN (50 μM). Furthermore, ZEN (50 μM) increased ROS level and downregulated antioxidant genes resulted from inhibition of nuclear DAF-16 translocation in aged C. elegans, which was further confirmed by more significant aging-related defects observed in ZEN treated daf-16 mutant. In conclusion, our findings suggest that the aging process and aging-related decline were induced by long-term exposure of ZEN in C. elegans, which is associated with oxidative stress, inhibition of antioxidant defense, and transcription factor DAF-16/FOXO.Groundwater quality monitoring typically employs testing for the presence of E. coli as a fecal indicator of recent ingress of human or animal fecal material. The efficacy of fecal indicator organisms is based on the primary criteria that the organism does not reproduce in the aquatic environment. However, recent studies have reported that E. coli may proliferate (i.e., has adapted to) in the external environment, including soil and surface water. To date, the presence of environmentally-adapted E. coli in groundwater has not been examined. The current study employed Clermont phylotyping and the presence of six accessory genes to identify the likely presence of adapted E. coli in private groundwater sources. E. coli isolates (n = 325) from 76 contaminated private water wells located in a southeastern Ontario watershed were compared with geographically analogous human and animal fecal E. coli isolates (n = 234). Cryptic clades III-V, a well-described environmentally-adapted Escherichia population, were identified in three separate groundwater wells, one of which exclusively comprised this adapted population. Dimensionality reduction (via Principal Component Analysis) was used to develop an „E. coli adaptation model“, comprising three distinct components (groundwater, animal feces, human feces) and suggests adaptation occurs frequently in the groundwater environment. Model findings indicate that 23/76 (30.3%) wells had an entirely adapted community. Accordingly, the use of E. coli as a FIO returned a false positive result in these instances, while an additional 23/76 (30.3%) wells exhibited some evidence of adaptation (i.e., not all isolates were adapted) representing an over-estimate of the magnitude (concentration) of contamination. Study findings highlight the need to further characterize environmentally-adapted E. coli in the groundwater environment and the potential implications with respect to water quality policy, legislation and determinants of human health risk both regionally and internationally.Remdesivir has demonstrated clinical benefits in randomized placebo-controlled trials (RCTs) in patients with coronavirus disease 2019 (COVID-19)1-4 and was first approved for COVID-19 patients.5 However, whether remdesivir causes gastrointestinal adverse drug reaction (GI-ADRs) including hepatotoxicity is less clear.1-4,6 Therefore, we aimed to detect a diverse spectrum of GI-ADRs associated with remdesivir using VigiBase, the World Health Organization’s international pharmacovigilance database of individual case safety reports.Skeletal development and bone formation are regulated by epigenetic mechanisms that either repress or enhance osteogenic commitment of mesenchymal stromal/stem cells and osteoblasts. The transcriptional suppressive trimethylation of histone 3 lysine 27 (H3K27me3) hinders differentiation of pre-committed osteoblasts. Osteoblast maturation can be stimulated by genetic loss of the H3K27 methyltransferase Ezh2 which can also be mimicked pharmacologically using the classical Ezh2 inhibitor GSK126. Identification of other Ezh2 inhibitors (iEzh2) that enhance osteogenic potential would increase chemical options for developing new bone stimulatory compounds. In this study, we examined a panel of iEzh2s and show that all eight inhibitors we tested are capable of accelerating osteoblast differentiation to different degrees at concentrations that are well below cytotoxic concentrations. Inhibition of Ezh2 is commensurate with loss of cellular H3K27me3 levels while forced expression of Ezh2 reverses the effect of Ezh2 suppression. Reduced Ezh2 function by siRNA depletion of Ezh2 mRNA and protein levels also stimulates osteoblastogenesis, consistent with the specificity of iEzh2 to target the active site of Ezh2. Diminished Ezh2 levels preempt the effects of iEzh2s on H3K27me3. GSK126, EPZ-6438 and siRNA depletion of Ezh2 each are effective in reducing H3K27me3 levels. However, EPZ-6438 is more potent than GSK126 in stimulating osteoblastogenesis, as reflected by increased extracellular matrix mineralization. Collectively, our data indicate that Ezh2 inhibitors properly target Ezh2 consistent with their biochemical affinities. The range of compounds capable of promoting osteogenesis presented in this study offers the opportunity to develop diverse bone anabolic strategies for distinct clinical scenarios, including spine fusion, non-union of bone and dental implant enhancement.Osteoporosis is defined as a decrease of bone mass and strength, as well as an increase in fracture risk. It is conventionally treated with antiresorptive drugs, such as bisphosphonates (BPs) and selective estrogen receptor modulators (SERMs). Although both drug types successfully decrease the risk of bone fractures, their effect on bone mass and strength is different. For instance, BP treatment causes an increase of bone mass, stiffness and strength of whole bones, whereas SERM treatment causes only small (4%) increases of bone mass, but increased bone toughness. Such improved mechanical behavior of whole bones can be potentially related to the bone mass, bone structure or material changes. While bone mass and architecture have already been investigated previously, little is known about the mechanical behavior at the tissue/material level, especially of trabecular bone. As such, the goal of the work presented here was to fill this gap by performing cyclic tensile tests in a wet, close to physiologic environmerization of trabecular bone at the level of individual trabeculae for better understanding of clinically relevant mechanical behavior of bone.The current study investigated whether impaired emotional response inhibition to self-harm stimuli is a risk factor for real-time nonsuicidal self-injury (NSSI) urges. Participants were 60 university students with a history of repetitive NSSI. At baseline, participants completed an emotional stop-signal task assessing response inhibition to self-harm stimuli. Participants subsequently completed an ecological momentary assessment protocol in which they reported negative affect, urgency, and NSSI urge intensity three times daily over a ten-day period. Impaired emotional response inhibition to self-harm stimuli did not evidence a main effect on the strength of momentary NSSI urges. However, emotional response inhibition to self-harm images interacted with momentary negative affect to predict the strength of real-time NSSI urges, after adjusting for emotional response inhibition to neutral images. Our findings suggest that emotional response inhibition deficits specifically to self-harm stimuli may pose vulnerability for increased NSSI urge intensity during real-time, state-level negative affect.

Nourishment of gut microbiota via consumption of fermentable fiber promotes gut health and guards against metabolic syndrome. In contrast, how dietary fiber impacts type 1 diabetes is less clear.

To examine impact of dietary fibers on development of type 1 diabetes in the streptozotocin (STZ)-induced and spontaneous non-obese diabetes (NOD) models, mice were fed grain-based chow (GBC) or compositionally defined diets enriched with a fermentable fiber (inulin) or an insoluble fiber (cellulose). Spontaneous (NOD mice) or STZ-induced (wild-type mice) diabetes was monitored.

Relative to GBC, low-fiber diets exacerbated STZ-induced diabetes, whereas diets enriched with inulin, but not cellulose, strongly protected against or treated it. Inulin’s restoration of glycemic control prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin’s beneficial impact on glycemic control, indicating a role for short-chain fatty acids (SCFA). Furthermore, inulin’s microbiota-dependent anti-diabetic effect associated with SCFA-independent restoration of interleukin 22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Inulin-enriched diets significantly delayed diabetes in NOD mice.

Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes.

Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes.

Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD.

C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed.

Mice fed with High-Na

/HFD showed a lower MR expression in liver (p=0.01) and less steatosis on histology (p=0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p=0.028) and lower hepatic triglyceride content (p=0.008). Phycocyanobilin order This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p<0.