Root vacuolar Na+ sequestration but not exclusion from uptake correlates with barley salt tolerance.

SummarySoil salinity is a major constraint for the global agricultural production. For many decades, Na+ exclusion from uptake has been the key trait targeted in breeding programs; yet, no major breakthrough in creating salt‐tolerant germplasm was achieved. In this work, we have combined the microelectrode ion flux estimation (MIFE) technique for non‐invasive ion flux measurements with confocal fluorescence dye imaging technique to screen 45 accessions of barley to reveal the relative contribution of Na+ exclusion from the cytosol to the apoplast and its vacuolar sequestration in the root apex, for the overall salinity stress tolerance. We show that Na+/H+ antiporter‐mediated Na+ extrusion from the root plays a minor role in the overall salt tolerance in barley. At the same time, a strong and positive correlation was found between root vacuolar Na+ sequestration ability and the overall salt tolerance. The inability of salt‐sensitive genotypes to sequester Na+ in root vacuoles was in contrast to significantly higher expression levels of both HvNHX1 tonoplast Na+/H+ antiporters and HvVP1 H+‐pumps compared with tolerant genotypes. These data are interpreted as a failure of sensitive varieties to prevent Na+ back‐leak into the cytosol and existence of a futile Na+ cycle at the tonoplast. Taken together, our results demonstrated that root vacuolar Na+ sequestration but not exclusion from uptake played the main role in barley salinity tolerance, and suggested that the focus of the breeding programs should be shifted from targeting genes mediating Na+ exclusion from uptake by roots to more efficient root vacuolar Na+ sequestration

Are Proselfs More Deceptive and Hypocritical? Social Image Concerns in Appearing Fair

Deception varies across individuals and social contexts. The present research explored how individual difference measured by social value orientations, and situations, affect deception in moral hypocrisy. In two experiments, participants made allocations between themselves and recipients with an opportunity to deceive recipients where recipients cannot reject their allocations. Experiment 1 demonstrated that proselfs were more deceptive and hypocritical than prosocials by lying to be apparently fair, especially when deception was unrevealed. Experiment 2 showed that proselfs were more concerned about social image in deception in moral hypocrisy than prosocials were. They decreased apparent fairness when deception was revealed and evaluated by a third-party reviewer and increased it when deception was evaluated but unrevealed. These results show that prosocials and proselfs differed in pursuing deception and moral hypocrisy social goals and provide implications for decreasing deception and moral hypocrisy

C5aR1 shapes a non-inflammatory tumor microenvironment and mediates immune evasion in gastric cancer

C5a receptor 1 (C5aR1) is associated with various inflammatory processes, the pathogenesis of immune diseases, and tumor growth. However, its role in the tumor microenvironment of gastric cancer (GC) remains unclear. In this study, the expression of C5aR1 in GC and normal gastric mucosa tissues was compared using data retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and the results were validated by in vitro qRT-PCR and immunohistochemical analyses. The relationship between C5aR1 expression and the overall survival of patients with GC was analyzed using the Kaplan–Meier method. Subsequently, enrichment analysis was performed, and the signaling pathways were screened. C5aR1 expression was also correlated with genes related to the immune checkpoint and immune cell infiltration. The results revealed that C5aR1 expression was enhanced in GC tissues compared to normal gastric tissues, and that patients with high expression of C5aR1 had a worse 10-year overall survival compared to those showing low expression of C5aR1. Functional analysis revealed that C5aR1 is a gene related to theimmune system and may play a crucial role in inflammatory and tumor immune responses. Additionally, C5aR1 showed a positive correlation with most immune checkpoint-related genes and a negative correlation with natural killer cells, dendritic cells, and CD8+ T cells. Immune evasion risk was observed to be significantly greater in patients with higher expression of C5aR1 than in those with lower expression. The results of this study reveal that C5aR1 shapes a non-inflammatory tumor microenvironment in GC and mediates immune evasion

Study on the fermentation effect of Rhodotorula glutinis utilizing tofu whey wastewater and the influence of Rhodotorula glutinis on laying hens

BackgroundTofu whey wastewater (TWW) is the wastewater of tofu processing, which is rich in a variety of nutrients. Rhodotorula glutinis can make full use of TWW to ferment and reproduce yeast cells, produce carotenoids and other nutrients, improve the utilization value of TWW, and reduce environmental pollution and resource waste.MethodsIn this study, the nutrient composition changes of TWW treated by Rhodotorula glutinis were analyzed to reformulate TWW medium, and the optimal composition and proportion of TWW medium that can improve the biomass and carotenoids production of Rhodotorula glutinis were explored. Meanwhile, the Rhodotorula glutinis liquid obtained under these conditions was used to prepare biological feed for laying hens, and the effect of Rhodotorula glutinis growing on TWW as substrate on laying performance and egg quality of laying hens were verified.ResultsThe results showed that the zinc content of TWW after Rhodotorula glutinis fermentation increased by 62.30%, the phosphorus content decreased by 42.31%, and the contents of vitamin B1, B2 and B6 increased to varying degrees. The optimal fermentation conditions of Rhodotorula glutinis in the TWW medium were as follow: the initial pH was 6.40, the amount of soybean oil, glucose and zinc ions was 0.80 ml/L, 16.32 g/L, and 20.52 mg/L, respectively. Under this condition, the biomass of Rhodotorula glutinis reached 2.23 g/L, the carotenoids production was 832.86 μg/g, and the number of effective viable yeast count was 7.08 × 107 cfu/ml. In addition, the laying performance and egg quality of laying hens fed Rhodotorula glutinis biological feed were improved.DiscussionIn this study, we analyzed the composition changes of TWW, optimized the fermentation conditions of Rhodotorula glutinis in TWW medium, explored the influence of Rhodotorula glutinis utilizing TWW on laying layers, and provided a new idea for the efficient utilization of TWW

Morphine Induces Expression of Platelet-Derived Growth Factor in Human Brain Microvascular Endothelial Cells: Implication for Vascular Permeability

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF) has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling) and loss-of-function (Egr-1) approaches demonstrated the role of mitogen-activated protein kinases (MAPKs), PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation

Activating Transcription Factor 4 Confers a Multidrug Resistance Phenotype to Gastric Cancer Cells through Transactivation of SIRT1 Expression

BACKGROUND: Multidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression confered the MDR phenotype to gastric cancer cells, while knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we also showed that the NAD(+)-dependent histone deacetylase SIRT1 was required for ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4 facilitated MDR in gastric cancer cells through direct binding to the SIRT1 promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by small interfering RNA (siRNA) or a specific inhibitor (EX-527) reintroduced therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells in response to chemotherapy and these findings suggest that targeting ATF4 could relieve therapeutic resistance in gastric cancer