The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the ...role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p enhanced cell migration/invasion in vitro, cancer metastasis in vivo, and particularly the EMT characterized by loss of epithelial markers and gain of mesenchymal features in NPC cells. Furthermore, mechanistic studies disclosed that EBV-miR-BART7-3p targeted a major human tumor suppressor PTEN, modulating PI3K/Akt/GSK-3β signaling and eventually leading to the high expression and nuclear accumulation of Snail and β-catenin, which favor EMT. Knockdown of PTEN could phenocopy the effect of EBV-miR-BART7-3p, whereas re-expression of PTEN resulted in a phenotypic reversion. Moreover, these findings were supported by an observation of an EBV-positive cell model in which silencing of endogenous EBV-miR-BART7-3p partially attenuated cell migration/invasion and altered EMT protein expression pattern via reverting PI3K/Akt, Snail and β-catenin expression. Thus, this study suggests a novel mechanism by which EBV-miR-BART7-3p modulates the EMT and metastasis of NPC cells, and a clinical implication of EBV-miR-BART7-3p as a potential biomarker or therapeutic target.
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new ...players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor-interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR-873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
The intrinsic magnetic topological insulatorMnBi2Te4exhibits rich topological effects such as quantum anomalous Hall effect and axion electrodynamics. Here, by combining the use of synchrotron and ...laser light sources, we carry out comprehensive and high-resolution angle-resolved photoemission spectroscopy studies onMnBi2Te4and clearly identify its topological electronic structure. In contrast to theoretical predictions and previous studies, we observe topological surface states with diminished gap forming a characteristic Dirac cone. We argue that the topological surface states are mediated by multidomains of different magnetization orientations. In addition, the temperature evolution of the energy bands clearly reveals their interplay with the magnetic phase transition by showing interesting differences between the bulk and surface states, respectively. The investigation of the detailed electronic structure ofMnBi2Te4and its temperature evolution provides important insight into not only the exotic properties ofMnBi2Te4, but also the generic understanding of the interplay between magnetism and topological electronic structure in magnetic topological quantum materials.
This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 ...m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.
This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at ...Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.
Nearly 500 basidiomycetous yeast species were accepted in the latest edition of The Yeasts: A Taxonomic Study published in 2011. However, this number presents only the tip of the iceberg of yeast ...species diversity in nature. Possibly more than 99 % of yeast species, as is true for many groups of fungi, are yet unknown and await discovery. Over the past two decades nearly 200 unidentified isolates were obtained during a series of environmental surveys of yeasts in phyllosphere and soils, mainly from China. Among these isolates, 107 new species were identified based on the phylogenetic analyses of nuclear ribosomal DNA (rDNA) D1/D2 domains of the large subunit (LSU), the small subunit (SSU), and the internal transcribed spacer region including the 5.8S rDNA (ITS) and protein-coding genes both subunits of DNA polymerase II (RPB1 and RPB2), the translation elongation factor 1-α (TEF1) and the mitochondrial gene cytochrome b (CYTB), and physiological comparisons. Forty-six of these belong to 16 genera in the Tremellomycetes (Agaricomycotina). The other 61 are distributed in 26 genera in the Pucciniomycotina. Here we circumscribe eight new genera, three new families and two new orders based on the multi-locus phylogenetic analyses combined with the clustering optimisation analysis and the predicted similarity thresholds for yeasts and filamentous fungal delimitation at genus and higher ranks. Additionally, as a result of these analyses, three new combinations are proposed and 66 taxa are validated.
Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances
. It has long been speculated that magnetars are the engine powering ...repeating bursts from FRB sources
, but no convincing evidence has been collected so far
. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts
. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare
. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.
Two-dimensional (2D) materials have been studied extensively as monolayers, vertical or lateral heterostructures. To achieve functionalization, monolayers are often patterned using soft lithography ...and selectively decorated with molecules. Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe
can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.
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