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β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by β-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the β-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of β-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates β-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway.

Improving the storage capacities of electrode materials is one of the most critical points for ion batteries. Two-dimensional (2D) topological semimetals with high carrier mobility are naturally suitable as electrode materials. Herein, using the first-principle calculations, 2D BP monolayer with Dirac-type band structure is predicted to be a superior anode material with ultrahigh capacity for both Li/Na-ion batteries. The BP monolayer remains metallic after the adsorption of Li/Na ions, ensuring a good conductivity. Furthermore, BP owns low diffusion barriers (0.35 eV for Li ions and 0.16 eV for Na ions) and a moderate lattice change (3%) during the process of charging and discharging. Remarkably, the storage capacity of monolayer BP is enhanced to 1924 mAh/g by multilayer adsorption of both Li/Na ions, much higher than those of most previous 2D anode materials. All these characteristics strongly suggest that BP has great potential as a superior anode material in Li/Na-ion batteries.

Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes1–5. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life)6–8. Here we present a comparative analysis of 162 complete or nearly complete genomes of Asgard archaea, including 75 metagenome-assembled genomes that—to our knowledge—have not previously been reported. Our results substantially expand the phylogenetic diversity of Asgard and lead us to propose six additional phyla that include a deep branch that we have provisionally named Wukongarchaeota. Our phylogenomic analysis does not resolve unequivocally the evolutionary relationship between eukaryotes and Asgard archaea, but instead—depending on the choice of species and conserved genes used to build the phylogeny—supports either the origin of eukaryotes from within Asgard (as a sister group to the expanded Heimdallarchaeota–Wukongarchaeota branch) or a deeper branch for the eukaryote ancestor within archaea. Our comprehensive protein domain analysis using the 162 Asgard genomes results in a major expansion of the set of eukaryotic signature proteins. The Asgard eukaryotic signature proteins show variable phyletic distributions and domain architectures, which is suggestive of dynamic evolution through horizontal gene transfer, gene loss, gene duplication and domain shuffling. The phylogenomics of the Asgard archaea points to the accumulation of the components of the mobile archaeal ‘eukaryome’ in the archaeal ancestor of eukaryotes (within or outside Asgard) through extensive horizontal gene transfer. Comparative analysis of 162 genomes of Asgard archaea results in six newly proposed phyla, including a deep branch that is provisionally named Wukongarchaeota, and sheds light on the evolutionary history of this clade.

Differentiation therapies with all-trans retinoic acid (ATRA) have been successful in treating acute promyelocytic leukemia, a rare subtype of acute myeloid leukemia (AML). However, their efficacy is limited in the case of other AML subtypes. Here, we show that the combination of ATRA with salt-inducible kinase (SIK) inhibition significantly enhances ATRA-mediated AML differentiation. SIK inhibition augmented the ability of ATRA to induce growth inhibition and G1 cell cycle arrest of AML cells. Moreover, combining ATRA and SIK inhibition synergistically activated the Akt signaling pathway but not the MAPK pathway. Pharmacological blockade of Akt activity suppressed the combination-induced differentiation, indicating an essential role for Akt in the action of the combination treatment. Taken together, our study reveals a novel role for SIK in the regulation of ATRA-mediated AML differentiation, implicating the combination of ATRA and SIK inhibition as a promising approach for future differentiation therapy.

Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer’s disease. In this paper, the combined bioassay model of acetylcholinesterase (AChE) inhibition, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and Artemia larval lethality was used to evaluate the activity and toxicity of 35 marine fungal strains from seas around China. Their bioactive constituents were revealed by thin layer chromatography (TLC) autography, bioactivity coupled LC–MS/MS and Global Natural Products Social Molecular Networking (GNPS). The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound, ‘tacrine’, for which the ratio was 89.8% at 200 μg/ml. Six strains displayed both AChE inhibition (inhibition ratios > 20% at 200 μg/ml) and DPPH scavenging activity (scavenging ratios > 30% at 200 μg/ml) together with low Artemia larval toxicity (lethal rates Talaromyces sp. C21-1, Aspergillus terreus C23-3, Trichoderma harzianum DLEN2008005, and Penicillium corylophilum TBG1-17. From the most potent sample F-11-1-b (derived from Aspergillus terreus C23-3), five AChE inhibitors and seven antioxidants were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC–MS/MS, and LC–MS/MS coupled with DPPH incubation. Furthermore, with the aid of GNPS, the AChE inhibitors were plausibly annotated as territrem analogues including territrems A–C/D, arisugacin A and an unknown compound 4, and the seven antioxidants were assigned as butyrolactone Ι, aspernolide E, a phenolic derivative and possibly unknown compounds 8–10 and 12.

To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia. Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively. All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI–symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p

Adolescence is a developmental phase marked by a high risk of depressive symptoms. The Diathesis-Stress Model of Depression proposed that different types of coping strategy can determine depression level in individuals differently. It was found that low self-esteem is linked with greater depressive symptoms among adolescents. Although past studies have discovered the effects of problem-focused coping on depression, there are limited studies examining the underlying mechanism among Malaysian adolescents. Thus, the present study investigated the intervening role of self-esteem on the association between problem-focused coping and depression among adolescents. A total of 852 secondary school students in Kuala Lumpur, Malaysia were recruited through multi-stage cluster sampling. Participants filled out self-reported questionnaires on depression, self-esteem, and problem-focused coping. SPSS macro was used to analyze the mediation model. The findings showed both self-esteem and problem-focused coping negatively correlated with adolescents’ depression. Self-esteem in turn partially mediated the association between problem-focused coping and adolescents’ depression. Thus, it is recommended that intervention on reducing depressive symptoms should focus on providing adolescents with the skills to use problem-focused coping. Workshops could be conducted to heighten adolescents’ self-esteem through the help of teachers, parents and school counselors in reducing depressive symptoms among adolescents.

Objective The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). Methods A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. Results The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. Conclusion The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by β-adrenergic receptors (β-ARs). However, α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

The renormalization group (RNG) turbulent model is used to investigate the fluid resonance in a moonpool formed by two identical rectangular hulls under synchronous heaving excitation (e.g., a catamaran or dual pontoon). The numerical model is validated against the available experimental data, and accurate numerical solutions are obtained. The present study focuses on the amplitude of the moving hulls and the edge configuration of the moonpool entrance, as well as their influences on the piston-modal resonant wave in the moonpool. The dependence of the resonant wave amplitude in the moonpool on the heaving amplitude, the characteristic moonpool dimensions and the local velocity magnitude is derived based on a theoretical analysis, and the results are in good agreement with the RNG turbulent solutions. Five different edge profiles are considered, including two convex edges, two concave edges (both with various dimensions), and a sharp edge. Numerical examinations show that the edge configuration has a significant influence on the piston-modal resonant responses, a larger opening size leading to a higher resonant frequency and a larger resonant wave amplitude in the moonpool. Various flow patterns of the piston-modal resonance in the vicinity of the moonpool entrance are also identified, mainly depending on the edge profile. More intensive turbulent and vortical flows give rise to more significant dissipation, accounting for the smaller relative wave amplitude in the moonpool. With the increase of the heaving amplitude, the relative piston-modal resonant amplitude is decreased in an approximate power function. Within the scope of this work, the numerical investigations show that the piston-modal resonant frequency is hardly affected by the heaving amplitude.

Acute sympathetic stress quickly induces cardiac inflammation and injury, suggesting that pathogenic signals rapidly spread among cardiac cells and that cell-to-cell communication may play an important role in the subsequent cardiac injury. However, the underlying mechanism of this response is unknown. Our previous study demonstrated that acute β-adrenergic receptor (β-AR) signaling activates inflammasomes in the heart, which triggers the inflammatory cascade. In the present study, β-AR overactivation induced inflammasome activation in both the cardiomyocytes and cardiac fibroblasts (CFs) of mice hearts following a subcutaneous injection of isoproterenol (ISO, 5 mg/kg body weight), a selective agonist of β-AR. In isolated cardiac cells, ISO treatment only activated the inflammasomes in the cardiomyocytes but not the CFs. These results demonstrated that inflammasome activation was propagated from cardiomyocytes to CFs in the mice hearts. Further investigation revealed that the inflammasomes were activated in the cocultured CFs that connected with cardiomyocytes via membrane nanotubes (MNTs), a novel membrane structure that mediates distant intercellular connections and communication. Disruption of the MNTs with the microfilament polymerization inhibitor cytochalasin D (Cyto D) attenuated the inflammasome activation in the cocultured CFs. In addition, the MNT-mediated inflammasome activation in the CFs was blocked by deficiency of the inflammasome component NOD-like receptor protein 3 (NLRP3) in the cardiomyocytes, but not NLRP3 deficiency in the CFs. Moreover, ISO induced pyroptosis in the CFs cocultured with cardiomyocytes, and this process was inhibited by disruption of the MNTs with Cyto D or by the NLRP3 inhibitor MCC950 and the caspase-1 inhibitor Z-YVAD-FMK (FMK). Our study revealed that MNTs facilitate the rapid propagation of inflammasome activation among cardiac cells to promote pyroptosis in the early phase of β-adrenergic insult. Therefore, preventing inflammasome transfer is a potential therapeutic strategy to alleviate acute β-AR overactivation-induced cardiac injury.

In order to describe the characteristics of dynamic traffic flow and improve the robustness of its multiple applications, a dynamic traffic temporal-spatial model (DTTS) is established. With consideration of the temporal correlation, spatial correlation and historical correlation, a basic DTTS model is built. And a three-stage approach is put forward for the simplification and calibration of the basic DTTS model. Through critical sections pre-selection and critical time pre-selection, the first stage reduces the variable number of the basic DTTS model. In the second stage, variable coefficient calibration is implemented based on basic model simplification and stepwise regression analysis. Aimed at dynamic noise estimation, the characteristics of noise are summarized and an extreme learning machine is presented in the third stage. A case study based on a real-world road network in Beijing, China, is carried out to test the efficiency and applicability of proposed DTTS model and the three-stage approach.

In order to balance the temporal-spatial distribution of urban traffic flow, a model is established for combined urban traffic signal control and traffic flow guidance. With consideration of the wide use of fixed signal control at intersections, traffic assignment under traffic flow guidance, and dynamic characteristics of urban traffic management, a tri-level programming model is presented. To reflect the impact of intersection delay on traffic assignment, the lower level model is set as a modified user equilibrium model. The middle level model, which contains several definitional constraints for different phase modes, is built for the traffic signal control optimization. To solve the problem of tide lane management, the upper level model is built up based on nonlinear 0-1 integer programming. A heuristic iterative optimization algorithm (HIOA) is set up to solve the tri-level programming model. The lower level model is solved by method of successive averages (MSA), the middle level model is solved by non-dominated sorting genetic algorithm II (NSGA II), and the upper level model is solved by genetic algorithm (GA). A case study is raised to show the efficiency and applicability of the proposed modelling and computing method.

Considering the quantum effects of diffraction and the collective screening effects, the potential of test charge in semiclassical plasmas is derived. It is generalized exponential screened Coulomb potential. Using the Ritz variational method incorporating this potential, the effects of semiclassical plasma on the energy levels and radiative transitions are investigated systematically, taking highly charged H-like ion as an example. The Debye plasma model is also employed for comparison purposes. Comparisons and analysis are made between these two sets of results and the differences are discussed.

Effects of gas temperature on the conversion of benzene and the selectivity of CO and CO2 are analyzed and compared in dielectric barrier discharges. Gas temperature is determined by the method of the optical emission spectroscopy. The result is found that the conversion of benzene increases linearly with gas temperature. The selectivity of CO and CO2 and carbon balance are also investigated.

The support vector classification (SVC) was employed to make a model for classification of antifungal activities of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanols triazole derivatives. The compounds with high antifungal activities and those with low antifungal activities were compared on the basis of the following molecular descriptors: net atomic charge on the atom N connecting with R, dipole moment and heat of formation. By using the SVC, a mathematical model was constructed, which can predict the antifungal activities of the triazole derivatives, with an accuracy of 91% on the basis of the leave-one-out cross-validation (LOOCV) test. The results indicate that the performance of the SVC model can exceed that of the principal component analysis (PCA) and K-Nearest Neighbor (KNN) models for this real world data set.