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.
A wide variety of industrial applications require materials with high strength and ductility. Unfortunately, the strategies for increasing material strength, such as processing to create line defects ...(dislocations), tend to decrease ductility. We developed a strategy to circumvent this in inexpensive, medium manganese steel. Cold rolling followed by low-temperature tempering developed steel with metastable austenite grains embedded in a highly dislocated martensite matrix. This deformed and partitioned (D and P) process produced dislocation hardening but retained high ductility, both through the glide of intensive mobile dislocations and by allowing us to control martensitic transformation. The D and P strategy should apply to any other alloy with deformation-induced martensitic transformation and provides a pathway for the development of high-strength, high-ductility materials.
We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90×10^{6} helium, 8.4×10^{6} carbon, and 7.0×10^{6} ...oxygen nuclei collected by the Alpha Magnetic Spectrometer (AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way.
We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4×10^{6} nuclei ...collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0±0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.
Deformation twinning in pure aluminum has been considered to be a unique property of nanostructured aluminum. A lingering mystery is whether deformation twinning occurs in coarse-grained or ...single-crystal aluminum at scales beyond nanotwins. Here, we present the first experimental demonstration of macrodeformation twins in single-crystal aluminum formed under an ultrahigh strain rate (∼10^{6} s^{-1}) and large shear strain (200%) via dynamic equal channel angular pressing. Large-scale molecular dynamics simulations suggest that the frustration of subsonic dislocation motion leads to transonic deformation twinning. Deformation twinning is rooted in the rate dependences of dislocation motion and twinning, which are coupled, complementary processes during severe plastic deformation under ultrahigh strain rates.
Lignin is a key component in the biomass with a complex polymeric structure of the phenyl-C3 alkyl units. The kraft lignin from the wood pulping process is tested in TG-FTIR and Py-GC-MS. The samples ...are pyrolyzed in TGA coupled with FTIR from 30 to 900°C at the heating rate of 20 and 40K/min. The evolution of phenolic compounds in the initial pyrolysis stage of lignin is determined by FTIR, while the second stage is mainly attributed to the production of the low molecular weight species. A bench-scale fast pyrolysis unit is employed to investigate the effect of temperature on the product yield and composition. It is found that the guaiacol-type and syringol-type compounds as the primary products of lignin pyrolysis are predominant in bio-oil, acting as the significant precursors for the formation of the derivatives such as the phenol-, cresol- and catechol-types. A series of free-radical chain-reactions, concerning the cracking of different side-chain structures and the methoxy groups on aromatic ring, are proposed to demonstrate the formation pathways for the typical compounds in bio-oil by closely relating lignin structure to the pyrolytic mechanisms. The methoxy group (–OCH3) is suggested to work as an important source for the formation of the small volatile species (CO, CO2 and CH4) through the relevant free radical coupling reactions.
Deformation twinning plays a vital role in accommodating plastic deformation of hexagonal-close-packed (hcp) metals, but its mechanisms are still unsettled under high strain rate shock compression. ...Here we investigate deformation twinning in shock-compressed Mg as a typical hcp metal with in situ, ultrafast synchrotron x-ray diffraction. Extension twinning occurs upon shock compression along ⟨112over ¯0⟩ and ⟨101over ¯0⟩, but only upon release for loading along ⟨0001⟩. Such deformation mechanisms are a result of the polarity of deformation twinning, which depends on directionality and relative magnitude of resolved shear stress and may be common for Mg and its alloys in a wide range of strain rates.
Abstract Parkinson's disease (PD) is a progressive neurological disorder that is often associated with various gastrointestinal (GI) symptoms. The link between the alteration of dopaminergic system ...and the symptoms of the GI tract in PD is complicated. To determine the changes in the dopaminergic system in the GI tract in PD, two kinds of rodent PD models were used in the present study. One was 6-hydroxydopamine (6-OHDA) -treated rats in which 6-OHDA was microinjected in the bilateral substantia nigra (SN). The other was 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treated mice in which MPTP was injected intraperitoneally. Immunofluorescence, reverse transcription (RT)-real time polymerase chain reaction (PCR) and Western blot were used to evaluate and compare the levels of mRNA and protein expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the GI tract between normal and rodent PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The results indicated that TH- and DAT-positive cells were widely distributed in the GI tract. There were significant differences in TH and DAT expression in the GI tract between normal and PD models, as well as between 6-OHDA-treated rats and MPTP-treated mice. The protein levels of TH and DAT in the GI tract were significantly increased in 6-OHDA-treated rats, but the protein level of TH was significantly decreased in MPTP-treated mice. In addition, there was visible atrophy of gastric epithelial parietal cells in MPTP-treated mice, although the protein level of DAT was not significantly changed. The different alterations of dopaminergic system in the GI tract of the two kinds of PD models might underline the differences in GI symptoms in PD patients and might be correlated with the disease severity and disease process affecting the GI tract.
To develop a nomogram based on MRI and clinical features to predict progression-free survival (PFS) of 2018 FIGO stage ⅢC1r cervical squamous cell carcinoma (CSCC).
144 consecutive patients with ...stage ⅢC1r CSCC from two independent institutions were stratified into training cohort (from Institution 1, n=100) and independent validation cohort (from Institution 2, n=44). Univariate and multivariate Cox regression analyses of MRI and clinical features before treatment were performed to determine independent risk factors for PFS in training cohort. Nomogram was developed based on them. Concordance index (C-index), calibration curves, and receiver operating characteristic (ROC) analyses were performed to assess and validate the nomogram.
In training cohort, 2009 FIGO stage, maximum length of the primary tumor, short diameter and roundness index of the maximum metastatic lymph node were independent risk factors of PFS in patients with stage IIIC1r CSCC (all P-values < 0.05). Nomogram based on them to predict 1- and 3-year PFS achieved C-indexes of 0.835 (95% confidence interval (CI): 0.809–0.862) and 0.789 (95%CI: 0.683–0.895) in the training and validation cohorts, respectively. Areas under ROC curves for the nomogram to predict 1- and 3-year PFS were 0.891 (95%CI: 0.829–0.954), 0.921 (95%CI: 0.861–0.981) in training cohort, and 0.902 (95%CI: 0.803–0.999), 0.885 (95%CI: 0.778–0.992) in validation cohort, respectively. Calibration curves indicated the nomogram predictions were in good agreement with actual observations.
The nomogram based on MRI and clinical features has high accuracy and stability in predicting PFS of patients with stage IIIC1r CSCC.
•Nomogram based on MRI and clinical features was developed to predict PFS of stage IIIC1r CSCC.•The prediction nomogram achieved a C-index of 0.789 in validation cohort.•Nomogram had good predictive value with AUCs larger than 0.85 in validation cohort.
Here, in an analysis of a 2.92 fb–1 data sample taken at 3.773 GeV with the BESIII detector operated at the BEPCII collider, we measure the absolute decay branching fractions to be B(D0 → K–e+νe) = ...(3.505 ± 0.014 ± 0.033)% and B(D0 → π–e+νe) = (0.295 ± 0.004 ± 0.003)%. From a study of the differential decay rates we obtain the products of hadronic form factor and the magnitude of the CKM matrix element $f$ $^{K}_{+}$(0)|Vcs| = 0.7172 ± 0.0025 ± 0.0035 and $f$ $^{π}_{+}$(0)|Vcd| = 0.1435 ± 0.0018 ± 0.0009.
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