Abstract
Two-dimensional (2D) topological insulators (TIs) are promising platforms for low-dissipation spintronic devices based on the quantum-spin-Hall (QSH) effect, but experimental realization of ...such systems with a large band gap suitable for room-temperature applications has proven difficult. Here, we report the successful growth on bilayer graphene of a quasi-freestanding WSe
2
single layer with the 1
T
′ structure that does not exist in the bulk form of WSe
2
. Using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we observe a gap of 129 meV in the 1
T
′ layer and an in-gap edge state located near the layer boundary. The system′s 2D TI characters are confirmed by first-principles calculations. The observed gap diminishes with doping by Rb adsorption, ultimately leading to an insulator–semimetal transition. The discovery of this large-gap 2D TI with a tunable band gap opens up opportunities for developing advanced nanoscale systems and quantum devices.
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Aims
The study aimed to investigate the inactivation efficacy and mechanisms of plasma activated water (PAW) on selected bacteria in planktonic state.
Methods and Results
Plasma activated water was ...generated using an atmospheric cold plasma jet at 15, 22 and 30 kV for 5 min. Escherichia coli, Listeria innocua, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas fluorescens and Shewanella putrefaciens were selected as the representative bacterial species. Each bacterial suspension was inoculated into PAW immediately after generation, and the viable counts at different exposure times of 0·5, 1, 3, 5 and 24 h during 4°C storage were measured to determine the inactivation efficacy. Scanning electron microscopy images of the bacteria were conducted to examine the structural changes. Physicochemical properties of PAW, including pH, conductivity, oxidation reduction potential (ORP), and reactive species of H2O2, NO2− and NO3− were measured. The results demonstrated that inactivation efficacy was in positive correlation with voltage and exposure time. Gram‐negative bacteria were more susceptible to PAW than Gram‐positive bacteria. Morphology damage was observed for all the bacterial species. PAW was significantly acidified, conductivity and ORP were significantly increased, and reactive species were detectable after 48 h.
Conclusions
This study offered a better understanding of the inactivation mechanisms of PAW, and the inactivation efficacy can be affected by voltage, exposure time and bacterial species.
Significance and Impact of the Study
This study demonstrated the potential usage of PAW as an alternative disinfectant.
Airway epithelial cells are the first cells to be challenged upon contact with the conidia of
Aspergillus
. In response, they express pattern-recognition receptors that play fundamental roles as ...sentinels and mediators of pulmonary innate immunity. The C-type lectin Dectin-1 is expressed predominantly on the surface of myeloid lineage cells. We examined the induction, regulation, and functions of Dectin-1 in pulmonary epithelial cells by challenging human bronchial epithelial (HBE) cells with
A. fumigatus
. Inflammatory, antimicrobial peptide genes and reactive oxygen species (ROS) were quantified, with and without knockdown of Dectin-1. We found that
A. fumigatus
induced the expression of Dectin-1 mRNA and protein in HBE cells in a toll-like receptor (TLR) 2-dependent manner. In addition,
A. fumigatus
-mediated generation of ROS was dependent on the upregulation of Dectin-1. Moreover,
A. fumigatus
actively induced the expression of TNFα, GM-CSF, IL8, HBD2, and HBD9. Knockdown of Dectin-1 inhibited TNFα, IL8, HBD2, and HBD9 expression. Hence, Dectin-1 was required for the upregulation of pro-inflammatory cytokines and antimicrobial peptides. Finally, knockdown of TLR2 significantly inhibited Dectin-1 upregulation. Our results demonstrate the novel induction of Dectin-1 in human bronchial epithelial cells and its critical role in the innate immune response against
A. fumigatus
in non-phagocytic cells.
MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) measurements taken during passes over Mercury's dayside hemisphere indicate that on four occasions the spacecraft remained in ...the magnetosheath even though it reached altitudes below 300 km. During these disappearing dayside magnetosphere (DDM) events, the spacecraft did not encounter the magnetopause until it was at very high magnetic latitudes, ~66 to 80°. These DDM events stand out with respect to their extremely high solar wind dynamic pressures, Psw ~140 to 290 nPa, and intense southward magnetic fields, Bz ~ −100 to −400 nT, measured in the magnetosheath. In addition, the bow shock was observed very close to the surface during these events with a subsolar altitude of ~1,200 km. It is suggested that DDM events, which are closely associated with coronal mass ejections, are due to solar wind compression and/or reconnection‐driven erosion of the dayside magnetosphere. The very low altitude of the bow shock during these events strongly suggests that the solar wind impacts much of Mercury's sunlit hemisphere during these events. More study of these disappearing dayside events is required, but it is likely that solar wind sputtering of neutrals from the surface into the exosphere maximizes during these intervals.
Key Points
The dayside magnetosphere of Mercury is observed to disappear at MESSENGER's orbit during some coronal mass ejection impacts
The cause appears to be extreme solar wind compression and/or reconnection‐driven erosion of Mercury's dayside magnetic field
The low altitude of the bow shock during these events strongly suggests that Mercury's dayside surface experiences direct solar wind impact
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
Using a sample of nearly 140,000 primary red-clump stars selected from the LAMOST and Gaia surveys, we have identified a large sample of "young" /Fe-enhanced stars with stellar ages younger than 6.0 ...Gyr and /Fe ratios greater than 0.15 dex. The stellar ages and /Fe ratios are measured from LAMOST spectra, using a machine-learning method trained with common stars in the LAMOST-APOGEE fields (for /Fe) and in the LAMOST-Kepler fields (for stellar age). The existence of these "young" /Fe-enhanced stars is not expected from the classical Galactic chemical evolution models. To explore their possible origins, we have analyzed the spatial distribution, and the chemical and kinematic properties of those stars and compared the results with those of the chemically thin and thick disk populations. We find that those "young" /Fe-enhanced stars have distributions in number density, metallicity, C/N abundance ratio, velocity dispersion, and orbital eccentricity that are essentially the same as those of the chemically thick disk population. Our results clearly show those so-called "young" /Fe-enhanced stars are not really young but genuinely old. Although other alternative explanations can not be fully ruled out, our results suggest that the most possible origin of these old stars is the result of stellar mergers or mass transfer.
We present a three-dimensional (3D) extinction map of the southern sky. The map covers the SkyMapper Southern Survey (SMSS) area of ∼14,000 deg2 and has spatial resolutions between 6 9 and 27′. Based ...on the multi-band photometry of SMSS, the Two Micron All Sky Survey, the Wide-Field Infrared Survey Explorer Survey, and the Gaia mission, we have estimated values of the r-band extinction for ∼19 million stars with the spectral energy distribution analysis. Together with the distances calculated from the Gaia data release 2 (DR2) parallaxes, we have constructed a 3D extinction map of the southern sky. By combining our 3D extinction map with those from the literature, we present an all-sky 3D extinction map, and use it to explore the 3D distribution of the Galactic dust grains. We use two different models, one consisting of a single disk and another of two disks, to fit the 3D distribution of the Galactic dust grains. The data is better fitted by a two-disk model, yielding smaller values of the Bayesian Information Criterion. The best-fit model has scale heights of 73 and 225 pc for the "thin" and "thick" dust disks, respectively.
There is a need for improved understanding on the effects of friction stir welding (FSW) on the metallurgical and mechanical properties of aluminium matrix composite (AMC). In this study, ...AA6092/SiC/17.5p-T6 AMC joints were produced by using FSW with varying tool rotation and traverse speeds. The microstructural characterisation by scanning electron microscopy equipped with electron backscattered diffraction (EBSD) system revealed a substantial grain refinement and a homogeneous distribution of reinforcement particles in the nugget zone. The grain size of the nugget zone was greatly influenced by weld pitch, as a key indicator to control the amount of heat input, exposure time and cooling rate. Vickers microhardness profile across the welding zone revealed a significant difference in microhardness among the base metal, heat affected zone, thermo-mechanically affected zone and nugget zone. The tensile strength of the cross-weld specimens showed a high joint efficiency of about 75% of the base metal combined with relatively high ductility. Low-cycle fatigue properties were investigated in the axial total strain-amplitude control mode (from 0.3% to 0.5%) with R=εmin/εmax=−1. The results indicate that the fatigue life of the cross-welded joints varies with grain size in the nugget zone and it is lower than that of the base metal. A significant improvement of fatigue life is found to be related to the finer equiaxed grains dominated by high angle grain boundaries in the nugget zone.
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and ...molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC. By RRBS, DNA promoter hypermethylation was identified in HCC from TG mice. Induction of promoter hypermethylation was associated with reduced tet methylcytosine dioxygenase 1 (TET1) expression by COX-2. TET1 could catalyze the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) and prevents DNA hypermethylation. In keeping with this, loss of 5hmC was demonstrated in COX-2-induced HCC. Consistently, COX-2 overexpression in human HCC cell lines could reduce both TET1 expression and 5hmc levels. Integrative analyses of DNA methylation and gene expression profiles further identified significantly downregulated genes including LTBP1, ADCY5 and PRKCZ by promoter methylation in COX-2-induced HCC. Reduced expression of LTBP1, ADCY5 and PRKCZ by promoter hypermethylation was further validated in human HCCs. Bio-functional investigation revealed that LTBP1 inhibited cell proliferation in HCC cell lines, suggesting its potential role as a tumor suppressor in HCC. Gene expression microarrays revealed that signaling cascades (AKT (protein kinase B), STK33 (Serine/Threonine kinase 33) and MTOR (mechanistic target of rapamycin) pathways) were enriched in COX-2-induced HCC. In conclusion, this study demonstrated for the first time that enhanced COX-2 expression in hepatocytes is sufficient to induce HCC through inducing promoter hypermethylation by reducing TET1, silencing tumor-suppressive genes and activating key oncogenic pathways. Inhibition of COX-2 represents a mechanism-based target for HCC prevention.
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