A small synthetic molecule functions as a chloride–bicarbonate dual-transporter and induces chloride secretion in cells

A C2 symmetric small molecule composed of L-phenylalanine and isophthalamide was found to function as a Cl−/HCO3− dual transporter and self-assemble into chloride channels. In Ussing-chamber based short-circuit current measurements, this molecule elicited chloride-dependent short-circuit current (Isc) increase in both Calu-3 cell and CFBE41o-cell (with F508del mutant CFTR) monolayers.postprin

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

The sudden change phenomenon of quantum discord

Even if the parameters determining a system's state are varied smoothly, the behavior of quantum correlations alike to quantum discord, and of its classical counterparts, can be very peculiar, with the appearance of non-analyticities in its rate of change. Here we review this sudden change phenomenon (SCP) discussing some important points related to it: Its uncovering, interpretations, and experimental verifications, its use in the context of the emergence of the pointer basis in a quantum measurement process, its appearance and universality under Markovian and non-Markovian dynamics, its theoretical and experimental investigation in some other physical scenarios, and the related phenomenon of double sudden change of trace distance discord. Several open questions are identified, and we envisage that in answering them we will gain significant further insight about the relation between the SCP and the symmetry-geometric aspects of the quantum state space.Comment: Lectures on General Quantum Correlations and their Applications, F. F. Fanchini, D. O. Soares Pinto, and G. Adesso (Eds.), Springer (2017), pp 309-33

Additive Contributions of Two Manganese-Cored Superoxide Dismutases (MnSODs) to Antioxidation, UV Tolerance and Virulence of Beauveria bassiana

The biocontrol potential of entomopathogenic fungi against arthropod pests depends on not only their virulence to target pests but tolerance to outdoor high temperature and solar UV irradiation. Two Beauveria bassiana superoxide dismutases (SODs), BbSod2 and BbSod3, were characterized as cytosolic and mitochondrial manganese-cored isoenzymes (MnSODs) dominating the total SOD activity of the fungal entomopathogen under normal growth conditions. To probe their effects on the biocontrol potential of B. bassiana, ΔBbSod2, ΔBbSod3, and three hairpin RNA-interfered (RNAi) mutants with the transcripts of both BbSod2 and BbSod3 being suppressed by 91–97% were constructed and assayed for various phenotypic parameters in conjunction with ΔBbSod2/BbSod2, ΔBbSod3/BbSod3 and wild-type (control strains). In normal cultures, the knockout and RNAi mutants showed significant phenotypic alterations, including delayed sporulation, reduced conidial yields, and impaired conidial quality, but little change in colony morphology. Their mycelia or conidia became much more sensitive to menadione or H2O2-induced oxidative stress but had little change in sensitivity to the hyperosmolarity of NaCl and the high temperature of 45°C. Accompanied with the decreased antioxidative capability, conidial tolerances to UV-A and UV-B irradiations were reduced by 16.8% and 45.4% for ΔBbSod2, 18.7% and 44.7% for ΔBbSod3, and ∼33.7% and ∼63.8% for the RNAi mutants, respectively. Their median lethal times (LT50s) against Myzus persicae apterae, which were topically inoculated under a standardized spray, were delayed by 18.8%, 14.5% and 37.1%, respectively. Remarkably, the effects of cytosolic BbSod2 and mitochondrial BbSod3 on the phenotypic parameters important for the fungal bioncontrol potential were additive, well in accordance with the decreased SOD activities and the increased superoxide levels in the knockout and RNAi mutants. Our findings highlight for the first time that the two MnSODs co-contribute to the biocontrol potential of B. bassiana by mediating cellular antioxidative response

Identification and classification of high risk groups for Coal Workers' Pneumoconiosis using an artificial neural network based on occupational histories: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Coal workers' pneumoconiosis (CWP) is a preventable, but not fully curable occupational lung disease. More and more coal miners are likely to be at risk of developing CWP owing to an increase in coal production and utilization, especially in developing countries. Coal miners with different occupational categories and durations of dust exposure may be at different levels of risk for CWP. It is necessary to identify and classify different levels of risk for CWP in coal miners with different work histories. In this way, we can recommend different intervals for medical examinations according to different levels of risk for CWP. Our findings may provide a basis for further emending the measures of CWP prevention and control.</p> <p>Methods</p> <p>The study was performed using longitudinal retrospective data in the Tiefa Colliery in China. A three-layer artificial neural network with 6 input variables, 15 neurons in the hidden layer, and 1 output neuron was developed in conjunction with coal miners' occupational exposure data. Sensitivity and ROC analyses were adapted to explain the importance of input variables and the performance of the neural network. The occupational characteristics and the probability values predicted were used to categorize coal miners for their levels of risk for CWP.</p> <p>Results</p> <p>The sensitivity analysis showed that influence of the duration of dust exposure and occupational category on CWP was 65% and 67%, respectively. The area under the ROC in 3 sets was 0.981, 0.969, and 0.992. There were 7959 coal miners with a probability value < 0.001. The average duration of dust exposure was 15.35 years. The average duration of ex-dust exposure was 0.69 years. Of the coal miners, 79.27% worked in helping and mining. Most of the coal miners were born after 1950 and were first exposed to dust after 1970. One hundred forty-four coal miners had a probability value ≥0.1. The average durations of dust exposure and ex-dust exposure were 25.70 and 16.30 years, respectively. Most of the coal miners were born before 1950 and began to be exposed to dust before 1980. Of the coal miners, 90.28% worked in tunneling.</p> <p>Conclusion</p> <p>The duration of dust exposure and occupational category were the two most important factors for CWP. Coal miners at different levels of risk for CWP could be classified by the three-layer neural network analysis based on occupational history.</p

Identification of the risk for liver fibrosis on CHB patients using an artificial neural network based on routine and serum markers

<p>Abstract</p> <p>Background</p> <p>Liver fibrosis progression is commonly found in patients with CHB. Liver biopsy is a gold standard for identifying the extent of liver fibrosis, but has many draw-backs. It is essential to construct a noninvasive model to predict the levels of risk for liver fibrosis. It would provide very useful information to help reduce the number of liver biopsies of CHB patients.</p> <p>Methods</p> <p>339 chronic hepatitis B patients with HBsAg-positive were investigated retrospectively, and divided at random into 2 subsets with twice as many patients in the training set as in the validation set; 116 additional patients were consequently enrolled in the study as the testing set. A three-layer artificial neural network was developed using a Bayesian learning algorithm. Sensitivity and ROC analysis were performed to explain the importance of input variables and the performance of the neural network.</p> <p>Results</p> <p>There were 329 patients without significant fibrosis and 126 with significant fibrosis in the study. All markers except gender, HB, ALP and TP were found to be statistically significant factors associated with significant fibrosis. The sensitivity analysis showed that the most important factors in the predictive model were age, AST, platelet, and GGT, and the influence on the output variable among coal miners were 22.3-24.6%. The AUROC in 3 sets was 0.883, 0.884, and 0.920. In the testing set, for a decision threshold of 0.33, sensitivity and negative predictive values were 100% and all CHB patients with significant fibrosis would be identified.</p> <p>Conclusions</p> <p>The artificial neural network model based on routine and serum markers would predict the risk for liver fibrosis with a high accuracy. 47.4% of CHB patients at a decision threshold of 0.33 would be free of liver biopsy and wouldn't be missed.</p

Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression

BACKGROUND: Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the formation of prostaglandins. The inducible isoform of COX (COX-2) is highly expressed in aggressive metastatic breast cancers and may play a critical role in cancer progression (i.e. growth and metastasis). However, the exact mechanism(s) for COX-2-enhanced metastasis has yet to be clearly defined. It is well established that one of the direct results of COX-2 action is increased prostaglandin production, especially prostaglandin E(2 )(PGE(2)). Here, we correlate the inhibition of COX-2 activity with decreased breast cancer cell proliferation, migration, invasion and matrix metalloproteinase (MMP) expression. METHODS: Breast cancer cells (Hs578T, MDA-MB-231 and MCF-7) were treated with selective COX-2 inhibitors (NS-398 and Niflumic acid, NA). Cell proliferation was measured by staining with erythrosin B and counting the viable cells using a hemacytometer. Cell migration and invasion were measured using migration and invasion chamber systems. MMP expression was determined by enzyme immunoassay (secreted protein) and real-time quantitative polymerase chain reaction (mRNA). RESULTS: Our results show that there is a decline in proliferation, migration and invasion by the Hs578T and MDA-MB-231 breast cancer cell lines in the presence of either low concentrations (1 μM or lower) NA or NS-398. We also report that MMP mRNA and protein expression by Hs578T cells is inhibited by NS-398; there was a 50% decrease by 100 μM NS-398. PGE(2 )completely reversed the inhibitory effect of NS-398 on MMP mRNA expression. CONCLUSION: Our data suggests that COX-2-dependent activity is a necessary component for cellular and molecular mechanisms of breast cancer cell motility and invasion. COX-2 activity also modulates the expression of MMPs, which may be a part of the molecular mechanism by which COX-2 promotes cell invasion and migration. The studies suggest that COX-2 assists in determining and defining the metastatic signaling pathways that promote the breast cancer progression to metastasis

Astragalus Polysaccharides Attenuate Postburn Sepsis via Inhibiting Negative Immunoregulation of CD4+CD25high T Cells

BACKGROUND: Astragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. However, it is not yet clear whether APS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of APS on the immune function of peripheral blood Tregs in postburn sepsis. METHODOLOGY/PRINCIPAL FINDINGS: BALB/C mice were randomly divided into six groups as follows: sham burn group, burn control (burn without infection animals) group, burn plus P. aeruginosa group, burn plus P. aeruginosa with APS (50 mg/kg) treatment group, burn plus P. aeruginosa with APS (100 mg/kg) treatment group, and burn plus P. aeruginosa with APS (200 mg/kg) treatment group, and they were sacrificed on postburn day 1, 3, 5, and 7, respectively, with seven animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4(+) T cells. Phenotypes were analyzed by flow cytometry, and cytokine levels were determined with ELISA. In the burn plus P. aeruginosa group, forkhead/winged helix transcription factor p3 (Foxp3) expression on CD4(+)CD25(+)Tregs were strongly enhanced in comparison to the sham group, and the capacity of CD4(+)CD25(+)Tregs to produce interleukin (IL)-10 was markedly increased. Administration of APS to inhibit CD4(+)CD25(+)Tregs could significantly decrease expression of Foxp3 on CD4(+)CD25(+)Tregs, and IL-10 production in burned mice with P. aeruginosa infection. At the same time, proliferative activity and expression of IL-2 and IL-2Rα on CD4(+) T cells were restored. In contrast, anti-Toll-like receptor 4 (TLR4) antibody could block the effect of APS on Tregs immune function. CONCLUSION: APS might suppress CD4(+)CD25(+)Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1 with activation of CD4(+) T cells in burned mice with P. aeruginosa infection

Differential Regulation and Recovery of Intracellular Ca2+ in Cerebral and Small Mesenteric Arterial Smooth Muscle Cells of Simulated Microgravity Rat

BACKGROUND: The differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca(2+) determined by the alterations in the functions of plasma membrane Ca(L) channels and ryanodine-sensitive Ca(2+) releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity. In addition, tail-suspended rats were submitted to a recovery period of 3 or 7 days after removal of suspension. The function of Ca(L) channels was evaluated by patch clamp and Western blotting. The function of ryanodine-sensitive Ca(2+) releases in response to caffeine were assessed by a laser confocal microscope. Our results indicated that simulated microgravity increased the functions of Ca(L) channels and ryanodine-sensitive Ca(2+) releases in cerebral VSMCs, whereas, simulated microgravity decreased the functions of Ca(L) channels and ryanodine-sensitive Ca(2+) releases in small mesenteric VSMCs. In addition, 3- or 7-day recovery after removal of suspension could restore the functions of Ca(L) channels and ryanodine-sensitive Ca(2+) releases to their control levels in cerebral and small mesenteric VSMCs, respectively. CONCLUSIONS: The differential regulation of Ca(L) channels and ryanodine-sensitive Ca(2+) releases in cerebral and small mesenteric VSMCs may be responsible for the differential regulation of intracellular Ca(2+), which leads to the altered autoregulation of cerebral vasculature and the inability to adequately elevate peripheral vascular resistance in postspaceflight orthostatic intolerance