Nutrient Availability and Phage Exposure Alter the Quorum-Sensing and CRISPR-Cas-Controlled Population Dynamics of Pseudomonas aeruginosa

Quorum sensing (QS) coordinates bacterial communication and cooperation essential for virulence and dominance in polymicrobial settings. QS also regulates the CRISPR-Cas system for targeted defense against parasitic genomes from phages and horizontal gene transfer. Although the QS and CRISPR-Cas systems are vital for bacterial survival, they undergo frequent selection in response to biotic and abiotic factors. Using the opportunistic Pseudomonas aeruginosa with well-established QS and CRISPR-Cas systems, we show how the social interactions between the acyl-homoserine lactone (AHL)-QS signal-blind mutants (ΔlasRrhlR) and the CRISPR-Cas mutants are affected by phage exposure and nutrient availability. We demonstrate that media conditions and phage exposure alter the resistance and relative fitness of ΔlasRrhlR and CRISPR-Cas mutants while tipping the fitness advantage in favor of the QS signal-blind mutants under nutrient-limiting conditions. We also show that the AHL signal-blind mutants are less selected by phages under QS-inducing conditions than the CRISPR-Cas mutants, whereas the mixed population of the CRISPR-Cas and AHL signal-blind mutants reduce phage infectivity, which can improve survival during phage exposure. Our data reveal that phage exposure and nutrient availability reshape the population dynamics between the ΔlasRrhlR QS mutants and CRISPR-Cas mutants, with key indications for cooperation and conflict between the strains

Dietary linoleic acid and the ratio of unsaturated to saturated fatty acids are inversely associated with significant liver fibrosis risk: A nationwide survey

Since no pharmaceuticals have been proven to effectively reduce liver fibrosis, dietary fatty acids may be beneficial as one of the non-pharmaceutical interventions due to their important roles in liver metabolism. In this cross-sectional study, we analyzed the data from the 2017–2018 cycle of National Health and Nutrition Examination Survey to examine the associations between the proportion and composition of dietary fatty acid intakes with significant liver fibrosis among US population. The dietary fatty acid consumptions were calculated based on two 24-h dietary recalls. Significant liver fibrosis was diagnosed based on liver stiffness measurement value derived from the vibration controlled transient elastography. Multivariate logistic regression analysis and sensitivity analysis were performed to assess the association between dietary fatty acid consumption and significant liver fibrosis risk. Finally, restricted cubic spline analysis was carried out to explore the dose–response between polyunsaturated fatty acids (PUFA) or linoleic acid intakes and the risk of significant liver fibrosis. The results showed that the multivariate adjusted odds ratios (95% confidence intervals) of significant liver fibrosis were 0.34 (0.14–0.84), 0.68 (0.50–0.91), and 0.64 (0.47–0.87) for the highest level of unsaturated to saturated fatty acid ratio, dietary PUFA, and linoleic acid intakes compared to the lowest reference, respectively. The sensitivity analysis and restricted cubic spline analysis produced similar results, reinforcing the inverse association of unsaturated to saturated fatty acid ratio, PUFA, and linoleic acid consumptions with significant liver fibrosis risk. However, other dietary fatty acids did not show the statistically significant association with significant liver fibrosis. In conclusion, dietary linoleic acid may play a key role in the inverse association between the unsaturated to saturated fatty acid ratio and the risk of significant liver fibrosis. Further studies are needed to confirm these findings

Dietary fatty acids and risk of non-alcoholic steatohepatitis: A national study in the United States

BackgroundNon-alcoholic steatohepatitis (NASH), the early invertible stage of non-alcoholic fatty liver disease, has become a public health challenge due to the great burden and lack of effective treatment. Dietary nutrients are one of the modifiable factors to prevent and slow down disease progression. However, evidence linking dietary fatty acids intake and risk of NASH is lacking.ObjectivesThis study aimed to examine the association between dietary total saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), their subtypes, the ratio of unsaturated (UFAs) to SFAs, and the risk of NASH among a nationwide population in the United States.MethodsThis cross-sectional study was conducted among 4,161 adults in the national health and nutrition examination survey in 2017–2018 cycle. Moreover, NASH was defined by transient elastography. Dietary fatty acids were assessed using a validated 24-h food recall method. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 2,089 (50.2%) participants with NASH were identified. Compared with participants in the bottom tercile of dietary intakes of total PUFAs, those in the highest tercile had lower risk of NASH, with an adjusted OR of 0.67 (95% CI: 0.46–0.97). Similar associations were found between the subtype of PUFA 18:3 and NASH, while the fully adjusted OR in the highest tercile was 0.67 (95% CI: 0.47–0.96). Interactions of dietary PUFAs and body mass index (BMI) could be found influencing NASH risk. Stronger associations of dietary total PUFAs intakes with NASH risk were found in obese participants (OR, 95% CI: 0.41, 0.22–0.75) than in the non-obese participants (OR, 95% CI: 1.00, 0.70–1.43; p-interaction = 0.006). Similar effects on risk of NASH were also observed between BMI and dietary intakes of PUFA 18:3. However, no significant associations were observed between NASH risk and dietary total SFAs, MUFAs, their subtypes as well as the ratio of UFAs to SFAs.ConclusionDietary intakes of total PUFAs, as well as its subtype of PUFA 18:3, were inversely associated with risk of NASH. The further large prospective studies need to be conducted to confirm the findings of this study

Correlation between preconception maternal non-occupational exposure to interior decoration or oil paint odour and average birth weight of neonates: findings from a nationwide cohort study in China\u27s rural areas

BACKGROUND: Birth weight is a critical indicator of neonatal health and foretells people\u27s health in adolescence and even adulthood. Some researchers have warned against the adverse effects on babies\u27 birth weight of exposure to pollutants in interior decoration or oil paint by odour intake. This study evaluated the effects of maternal exposure to such factors before conception on the birth weights of neonates. METHODS: Data on 213 461 cases in this study were from the database of the free National Pre-pregnancy Checkups Project. Defined as \u27exposed\u27 were those women exposed to oil paint odour or interior decoration at home or in the workplace within 6 months before their pregnancy. The study focused on revealing the correlation between such exposure and the birth weight of the neonates of these women, especially the incidence of macrosomia and low birth weight (LBW). Statistical analysis was conducted using the Kruskal-Wallis H test, the Mann-Whitney U test and logistic regression. RESULTS: The birth weight of babies from mothers non-occupationally exposed to such settings averaged 3465 g (range 3150-3650 g), whereas the birth weight of those from mothers free of such exposure averaged 3300 g (range 3000-3600g). Maternal exposure preconception to interior decoration or oil paint odour reduced the incidence of LBW in their babies (p=0.003, OR 0.749, 95% CI 0.617 to 0.909). Such exposure may also augment the probability of macrosomia (p \u3c 0.001, OR 1.297, 95% CI 1.133 to 1.484). CONCLUSION: Maternal exposure to interior decoration or oil paint odour preconception may increase the average birth weight of neonates, as well as the incidence of macrosomia

Alterations in brain structure and function associated with pediatric growth hormone deficiency: A multi-modal magnetic resonance imaging study

IntroductionPediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children’s cognitive function, brain structure and brain function were not yet fully illustrated.MethodsFull Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls.Results(1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index.ConclusionMultiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index

Dedifferentiation process driven by radiotherapy-induced HMGB1/TLR2/YAP/HIF-1α signaling enhances pancreatic cancer stemness

Differentiated cancer cells reacquiring stem cell traits following radiotherapy may enrich cancer stem cells and accelerate tumor recurrence and metastasis. We are interested in the mechanistic role of dying cells-derived HMGB1 in CD133− pancreatic cancer cells dedifferentiation following radiotherapy. We firstly confirmed that X-ray irradiation induced differentiation of CD133− pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells (iCSCs). Using an in vitro coculture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133− pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. Inhibiting the expression and activity of HMGB1 attenuated the dedifferentiation stimulating effect of irradiated, dying cells on C133− pancreatic cancer cells in vitro and in PDX models. Mechanistically, HMGB1 binding with TLR2 receptor functions in a paracrine manner to affect CD133− pancreatic cancer cells dedifferentiation via activating Hippo-YAP pathway and HIF-1α expression in oxygen independent manner in vitro and in vivo. We conclude that X-ray irradiation induces CD133− pancreatic cancer cell dedifferentiation into a CSC phenotype, and inhibiting HMGB1 may be a strategy to prevent CSC enrichment and further pancreatic carcinoma relapse.</p

LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers

Background: Layilin (LAYN) is a critical gene that regulates T cell function. However, the correlations of LAYN to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear.Methods: LAYN expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of LAYN on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between LAYN and cancer immune infiltrates was investigated via TIMER. In addition, correlations between LAYN expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.Results: A cohort (GSE17536) of colorectal cancer patients showed that high LAYN expression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, high LAYN expression was significantly correlated with poor OS and progression-free survival (PFS) in gastric cancers (OS HR = 1.97, P = 3.6e-10; PFS HR = 2.12, P = 2.3e-10). Moreover, LAYN significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). Specifically, high LAYN expression was correlated with worse OS and PFS in stage 2 to 4 but not stage 1 and stage N0 gastric cancer patients (P = 0.28, 0.34; P = 0.073, 0.092). LAYN expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD) and stomach adenocarcinoma (STAD). LAYN expression showed strong correlations with diverse immune marker sets in COAD and STAD.Conclusions: These findings suggest that LAYN is correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition, LAYN expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that LAYN can be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric and colon cancers

Mechanistic aspects of photo-induced formation of peroxide ions on the surface of cubic Ln(2)O(3) (Ln = Nd, Sm, Gd) under oxygen

National Basic Research Program of China [2010CB732303]; National Natural Science Foundation of China [21173173, 21033006, 20923004]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1036]The photo-induced formation of peroxide ions on the surface of cubic Ln(2)O(3) (Ln = Nd, Sm, Gd) was studied by in situ microprobe Raman spectroscopy using a 325 nm laser as excitation source. It was found that the Raman bands of peroxide ions at 833-843 cm(-1) began to grow at the expense of the Ln(3+)-O-2 bands at 333-359 cm(-1) when the Ln(2)O(3) samples under O-2 were continuously irradiated with a focused 325 nm laser beam at temperatures between 25-150 degrees C. The intensity of the peroxide Raman band was found to increase with increasing O-2 partial pressure, whereas no peroxide band was detected on the Ln(2)O(3) under N-2 as well as on the samples first irradiated with laser under Ar or N-2 followed by exposure to O-2 in the dark. The experiments using O-18 as a tracer further confirmed that the peroxide ions are generated by a photo-induced reaction between O-2 and the lattice oxygen (O2-) species in Ln(2)O(3). Under the excitation of 325 nm UV light, the transformation of O-2 to peroxide ions on the surface of the above lanthanide sesquioxides can even take place at room temperature. Basicity of the lattice oxygen species on Ln(2)O(3) also has an impact on the peroxide formation. Higher temperature or laser irradiation power is required to initiate the reaction between O-2 and O2- species of weaker basicity

Intravenous Injections of Human Mesenchymal Stromal Cells Modulated the Redox State in a Rat Model of Radiation Myelopathy

The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. UC-MSCs were isolated from Wharton’s jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 30 Gy of radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irradiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of radiation myelopathy could significantly improve the antioxidative microenvironment in vivo