Purpose
To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC).
Methods
We use bioinformatics overlapping ...subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients’ information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity.
Results
22 GC specific key miRNAs were identified (Fold-change >2,
P
< 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (
P
< 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank
P
< 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (
P
< 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (
P
< 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same.
Conclusion
These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A method named total electron content (TEC) keogram is introduced for surveying the large‐scale irregularities continuously in the polar ionosphere. The TEC keogram is developed from a movie of TEC ...maps along various meridian lines from the dayside to the nightside across the magnetic pole, trying to identify and track several types of ionospheric structures. Through two examples, a clear train of polar cap patches are identified from TEC keogram and confirmed by SuperDARN radar observations. The motion speed of these patches estimated from this tool agrees with SuperDARN radar measurements. Then, the motions of patches relative to the background convection through the whole polar cap are statistically studied for the first time. Moreover, the occurrence dependence of fully tracked patches on months, UT hours, and interplanetary magnetic field conditions is generally consistent with previous reports. These results suggest that the TEC keogram offers a power tool for continuous monitoring and studying of large‐scale plasma irregularities in the polar ionosphere.
Key Points
A tool named TEC keogram is introduced for continuously monitoring the dynamics of large‐scale structures in the polar region
Inspired by auroral keogram, the TEC keogram is developed from a time series of TEC lines obtained from long‐term TEC maps
With this tool, case and statistical studies are carried out to infer the average moving speed and formation mechanism of polar patches
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A sub‐population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our ...study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin‐resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin‐resistant TSCC cells, which displayed CSC‐like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin‐resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/β‐catenin pathway mediated the cancer stem‐like properties in cisplatin‐resistant TSCC cells. Further studies showed that the transfection of active β‐catenin in SOX8 stable‐knockdown cells partly rescued the SOX8 silencing‐induced repression of stem‐like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled‐7 (FZD7) and induced the FZD7‐mediated activation of the Wnt/β‐catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7‐mediated Wnt/β‐catenin pathway.
What's new?
Tongue cancer frequently spreads to the lymph nodes, and while chemotherapy with cisplatin has improved 5‐year survival rates, all too often the cancer becomes resistant to chemotherapy and returns. Here, the authors show that tongue squamous cell carcinoma (TSCC) cells that have acquired cisplatin resistance express more SOX‐8 mRNA than their parent TSCC cells. Getting rid of SOX‐8, they showed, hampered the cells' chemoresistance as well as the epithelial to mesenchymal transition. Adding active beta‐catenin to the cells lacking SOX‐8 partially restored these properties, showing that SOX‐8 acts through the Wnt/beta‐catenin pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A simple, efficient scheme was developed to obtain near-gigaelectronvolt electron beams with energy spreads of few per-mille level in a single-stage laser wakefield accelerator. Longitudinal plasma ...density was tailored to control relativistic laser-beam evolution, resulting in injection, dechirping, and a quasi-phase-stable acceleration. With this scheme, electron beams with peak energies of 780–840 MeV, rms energy spreads of 2.4‰–4.1‰, charges of 8.5–23.6 pC, and rms divergences of 0.1–0.4 mrad were experimentally obtained. Quasi-three-dimensional particle-in-cell simulations agreed well with the experimental results. The dechirping strength was estimated to reach up to 11 TeV/mm/m, which is higher than previously obtained results. Such high-quality electron beams will boost the development of compact intense coherent radiation sources and x-ray free-electron lasers.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
A search for a time-varying ν¯e signal was performed with 621 days of data acquired by the Daya Bay Reactor Neutrino Experiment over 704 calendar days. The time spectrum of the measured ν¯e flux ...normalized to its prediction was analyzed with a Lomb-Scargle periodogram, which yielded no significant signal for periods ranging from 2 hours to nearly 2 years. The normalized time spectrum was also fit for a sidereal modulation under the Standard Model Extension (SME) framework to search for Lorentz and CPT violation (LV-CPTV). Limits were obtained for all six flavor pairs e¯μ¯,e¯τ¯, μ¯τ¯, e¯e¯,μ¯μ¯ and τ¯τ¯ by fitting them one at a time, constituting the first experimental constraints on the latter three. Daya Bay’s high statistics and unique layout of multiple directions from three pairs of reactors to three experimental halls allowed the simultaneous constraint of individual SME LV-CPTV coefficients without assuming others contribute negligibly, a first for a neutrino experiment.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter ...presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θμe mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm241, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CLs for Δm241 < 13 eV2. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CLs for Δm241 < 1.6 eV2.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with ...the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.
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A new alpha-emitting isotope U-214, produced by the fusion-evaporation reaction W-182(Ar-36,4n) U-214, was identified by employing the gas-filled recoil separator SHANS and the recoil-a correlation ...technique. More precise a-decay properties of even-even nuclei U-216,U-218 were also measured in the reactions of Ar-40, Ca-40 beams with W-180,W-182,W- 184 targets. By combining the experimental data, improved alpha-decay reduced widths delta(2) for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N = 126 are deduced. Their systematic trends are discussed in terms of the N-p N-n scheme in order to study the influence of protonneutron interaction on a decay in this region of nuclei. It is strikingly found that the reduced widths of( 214,216)U are significantly enhanced by a factor of two as compared with the NpNn systematics for the 84 <= Z <= 90 and N < 126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the pi 1f (7/2) and nu 1f(5/2) spin-orbit partner orbits, which is supported by the large-scale shell model calculation.
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Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether ...the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-β1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-β1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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