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.
Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains ...unclear.
SAP was induced in rats. RELMα protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELMα. To investigate the effect of RELMα overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELMα protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown.
RELMα expression was significantly up-regulated in APALI and was related to the lung injury index. RELMα overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELMα knockdown had opposite effects. In addition, RELMα knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats.
RELMα is associated with lung injury severity in SAP. RELMα augments inflammatory activity by increasing inflammatory cytokine release.
A new technique is developed to directly grow Cu nanowire (CuNW) on Si substrate with electro-chemical deposition to produce height-controlled hydrophilic nanowired surfaces for enhancing pool ...boiling performance. For broader heat transfer applications, CuNW and Si nanowires (SiNW) with various nanowire heights were fabricated and examined under pool boiling with water. The heat transfer performance of the samples with NW arrays is enhanced with increasing NW heights regardless of the NW materials. The surface with the tallest NW structure (35 μm-tall SiNW) yielded a heat flux of 134 W/cm
2 at 23 K wall superheat, about 300% higher than a plain Si surface at the same wall superheat.
► A new technique is developed to directly grow copper nanowire on silicon substrate. ► Increasing nanowire height improves boiling performance. ► Optimal results were obtained in pool boiling with 35 nm long nanowires.
Magnetic holes (MHs), with a scale much greater than ρi (proton gyroradius), have been widely reported in various regions of space plasmas. On the other hand, kinetic‐size magnetic holes (KSMHs), ...previously called small‐size magnetic holes, with a scale of the order of magnitude of or less than ρi have only been reported in the Earth's magnetospheric plasma sheet. In this study, we report such KSMHs in the magnetosheath whereby we use measurements from the Magnetospheric Multiscale mission, which provides three‐dimensional (3‐D) particle distribution measurements with a resolution much higher than previous missions. The MHs have been observed in a scale of 10–20 ρe (electron gyroradii) and lasted 0.1–0.3 s. Distinctive electron dynamics features are observed, while no substantial deviations in ion data are seen. It is found that at the 90° pitch angle, the flux of electrons with energy 34–66 eV decreased, while for electrons of energy 109–1024 eV increased inside the MHs. We also find the electron flow vortex perpendicular to the magnetic field, a feature self‐consistent with the magnetic depression. Moreover, the calculated current density is mainly contributed by the electron diamagnetic drift, and the electron vortex flow is the diamagnetic drift flow. The electron magnetohydrodynamics soliton is considered as a possible generation mechanism for the KSMHs with the scale size of 10–20 ρe.
Key Points
Magnetosheath kinetic‐size magnetic holes are found with electron flow vortex caused by diamagnetic drift
At the 90° pitch angle, the 34–66 eV electron flux decreased while 109–1024 eV electron flux increased inside the MHs
Quasi‐2‐D EMHD soliton theory is applicable to the observations
Forkhead box M1 (FOXM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FOXM1 has multiple functions in tumorigenesis ...and its elevated levels are frequently associated with cancer progression. Here, we characterized the role of ERK/FOXM1 signaling in mediating the metastatic potential of ovarian cancer cells. Immunohistochemical (IHC), immunoblotting and semi-quantitative RT-PCR analyses found that both phospho-ERK and FOXM1 were frequently upregulated in ovarian cancers. Intriguingly, the overexpressed phospho-ERK (p<0.001) and FOXM1 (p<0.001) were significantly correlated to high-grade ovarian tumors with aggressive behavior such as metastasized lymph node (5 out of 6). Moreover, the expressions of phospho-ERK and FOXM1 had significantly positive correlation (p<0.001). Functionally, ectopic expression of FOXM1B remarkably enhanced cell migration/invasion, while FOXM1C not only increased cell proliferation but also promoted cell migration/invasion. Conversely, inhibition of FOXM1 expression by either thiostrepton or U0126 could significantly impair FOXM1 mediated oncogenic capacities. However, the down-regulation of FOXM1 by either thiostrepton or U0126 required the presence of p53 in ovarian cancer cells. Collectively, our data suggest that over-expression of FOXM1 might stem from the constitutively active ERK which confers the metastatic capabilities to ovarian cancer cells. The impairment of metastatic potential of cancer cells by FOXM1 inhibitors underscores its therapeutic value in advanced ovarian tumors.
Domestic chickens (Gallus gallus domesticus) fulfill various roles ranging from food and entertainment to religion and ornamentation. To survey its genetic diversity and trace the history of ...domestication, we investigated a total of 4938 mitochondrial DNA (mtDNA) fragments including 2843 previously published and 2095 de novo units from 2044 domestic chickens and 51 red junglefowl (Gallus gallus). To obtain the highest possible level of molecular resolution, 50 representative samples were further selected for total mtDNA genome sequencing. A fine-gained mtDNA phylogeny was investigated by defining haplogroups A-I and W-Z. Common haplogroups A-G were shared by domestic chickens and red junglefowl. Rare haplogroups H-I and W-Z were specific to domestic chickens and red junglefowl, respectively. We re-evaluated the global mtDNA profiles of chickens. The geographic distribution for each of major haplogroups was examined. Our results revealed new complexities of history in chicken domestication because in the phylogeny lineages from the red junglefowl were mingled with those of the domestic chickens. Several local domestication events in South Asia, Southwest China and Southeast Asia were identified. The assessment of chicken mtDNA data also facilitated our understanding about the Austronesian settlement in the Pacific.
Abstract
Black widows are millisecond pulsars ablating their companions. The material blown from the companion blocks the radio emission, resulting in radio eclipses. The properties of the eclipse ...medium are poorly understood. Here, we present direct evidence of the existence of magnetic fields in the eclipse medium of the black widow PSR J2051−0827 using observations made with the Five-hundred-meter Aperture Spherical radio Telescope. We detect a regular decrease in rotation measure (RM) in the egress of the eclipse, changing from 60 to −28.7 rad m
−2
. The RM gradually changes back to normal when the line of sight moves away from the eclipse. The estimated line-of-sight magnetic field strength in the eclipse medium is ∼0.1 G. The RM reversal could be caused by a change in the magnetic field strength along the line of sight due to binary orbital motion. The RM reversal phenomenon has also been observed in some repeating fast radio bursts (FRBs), and the study of spider pulsars may provide additional information about the origin of FRBs.
Recently, a triple-network model suggested the abnormal interactions between the executive-control network (ECN), default-mode network (DMN) and salience network (SN) are important characteristics of ...addiction, in which the SN plays a critical role in allocating attentional resources toward the ECN and DMN. Although increasing studies have reported dysfunctions in these brain networks in Internet gaming disorder (IGD), interactions between these networks, particularly in the context of the triple-network model, have not been investigated in IGD. Thus, we aimed to assess alterations in the inter-network interactions of these large-scale networks in IGD, and to associate the alterations with IGD-related behaviors.
DMN, ECN and SN were identified using group-level independent component analysis (gICA) in 39 individuals with IGD and 34 age and gender matched healthy controls (HCs). Then alterations in the SN-ECN and SN-DMN connectivity, as well as in the modulation of ECN versus DMN by SN, using a resource allocation index (RAI) developed and validated previously in nicotine addiction, were assessed. Further, associations between these altered network coupling and clinical assessments were also examined.
Compared with HCs, IGD had significantly increased SN-DMN connectivity and decreased RAI in right hemisphere (rRAI), and the rRAI in IGD was negatively associated with their scores of craving.
These findings suggest that the deficient modulation of ECN versus DMN by SN might provide a mechanistic framework to better understand the neural basis of IGD and might provide novel evidence for the triple-network model in IGD.
PDF
