Epstein-Barr virus-encoded miR-BART11-3p modulates the DUSP6-MAPK axis to promote gastric cancer cell proliferation and metastasis.

Epstein-Barr virus (EBV)-encoded miRNAs within the BamHI-A rightward transcript (BART) region are abundantly expressed in EBV-associated gastric cancer (EBVaGC), suggesting that they play roles in tumorigenesis. However, how these viral miRNAs contribute to the development of EBVaGC remains largely obscure. In this study, we found that EBV-encoded miR-BART11-3p targets 3' -UTR of dual-specificity phosphatase 6 (DUSP6) mRNA to upregulate ERK phosphorylation and downregulate JNK and p38 phosphorylation. By doing so, miR-BART11-3p promotes gastric cancer (GC) cell proliferation, migration, and invasion in vitro, and facilitates tumor growth in vivo. Restoration of DUSP6 expression reverses the tumor-promoting activity of miR-BART11-3p in AGS GC cells. Consistently, knockdown of DUSP6 ablates the antitumor effects of miR-BART11-3p inhibitors in EBV-positive GC cells. Furthermore, blocking ERK phosphorylation with trametinib inhibited the proliferation, migration, and invasion of miR-BART11-3p-expressing AGS cells. Administration of a miR-BART11-3p antagomir reduced the growth of EBV-positive xenograft tumors. Together, these findings reveal a novel mechanism by which EBV dysregulates MAPK pathways through an EBV-encoded microRNA to promote the development and progression of EBVaGC, which may be harnessed to develop new therapeutics to treat EBVaGC. IMPORTANCE The Epstein-Barr virus (EBV) is the first human tumor virus found to encode miRNAs, which within the BART region have been detected abundantly in EBV-associated gastric cancer (EBVaGC) and play various roles in promoting tumorigenesis. In our study, we observed that EBV-miR-BART11-3p promotes cell proliferation and induces migration and invasion in GC. Interestingly, we showed that miR-BART11-3p upregulates p-ERK and downregulates p-JNK and p-p38 by directly targeting 3'-UTR of dual-specificity phosphatase 6 (DUSP6). Restoration of DUSP6 rescues the effects generated by miR-BART11-3p in GC cells, and blocking ERK phosphorylation with Trametinib augments JNK and p38 phosphorylation and inhibits the effects of miR-BART11-3p-expressing AGS cells, suggesting that miR-BART11-3p promotes cell proliferation, migration, and invasion by modulating DUSP6-MAPK axis in EBVaGC. The findings presented in this study provide new mechanisms into the tumorigenesis in EBVaGC and new avenues for the development of therapeutic strategies to combat EBVaGC targeting miR-BART11-3p or phospho-ERK.

Establishment and characterization of two Epstein-Barr virus-positive gastric cancer cell lines with epitheliotropic M81 strain undergoing distinct viral and altered cellular expression profiles.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer (GC) distinguished by the presence of the EBV genome and limited viral gene expression within malignant epithelial cells. EBV infection is generally thought to be a relatively late event following atrophic gastritis in carcinogenesis, which implies the heterogeneity of EBVaGC. To facilitate the study of the role of EBV in EBVaGC, we established two EBV-positive GC cell lines (AGS-EBV and HGC27-EBV) with an epitheliotropic EBV strain M81 and characterized viral and cellular gene expression profiles in comparison to SNU719, a naturally derived EBV-positive GC cell line. Like SNU719, AGS-EBV and HGC27-EBV stably maintained their EBV genomes and expressed EBV-encoded small RNAs and nuclear antigen EBNA1. Comprehensive analysis of the expression of EBV-encoded miRNAs within the BamHI-A region rightward transcript region, and the transcripts of EBV latent and lytic genes in cell lines, as well as xenografts, reveals that AGS-EBV and HGC27-EBV cells undergo distinct viral expression profiles. A very small fraction of AGS-EBV and SNU719 cells can spontaneously produce infectious progeny virions, while HGC27-EBV does not. AGS-EBV (both M81 and Akata) cells largely mimic SNU719 cells in viral gene expression profiles, and altered cellular functions and pathways perturbed by EBV infection. Phylogenetic analysis of the EBV genome shows both M81 and Akata EBV strains are closely related to clinical EBVaGC isolates. Taken together, these two newly established EBV-positive GC cell lines can serve as models to further investigate the role of EBV in different contexts of gastric carcinogenesis and identify novel therapeutics against EBVaGC.

Metal-Free Half-Metallicity in B-Doped gh-C3N4 Systems.

Half-metallicity rising from the s/p electrons has been one of the hot topics in spintronics. Based on the first-principles of calculation, we explore the magnetic properties of the B-doped graphitic heptazine carbon nitride (gh-C3N4) system. Ferromagnetism is observed in the B-doped gh-C3N4 system. Interestingly, its ground state phase (BC1@gh-C3N4) presents a strong half-metal property. Furthermore, the half-metallicity in BC1@gh-C3N4 can sustain up to 5% compressive strain and 1.5% tensile strain. It will lose its half-metallicity, however, when the doping concentration is below 6.25%. Our results show that such a metal-free half-metallic system has promising spintronic applications.

Simulation and experimental research on trans-media vehicle water-entry motion characteristics at low speed.

The motion characteristics of trans-media vehicles during the water-entry process were explored in this study in an effort to obtain the optimal water-entry condition of the vehicle for developing a novel, single control strategy integrating underwater non-control and in-air control. A water-entry dynamics model is established by combining the water-entry motion characteristics of the vehicle in uncontrolled conditions at low speed with time-varying parameters (e.g. buoyancy, added mass). A water-entry experiment is designed to confirm the effectiveness of the established model. After that, by comparing the experimental results with the simulated results, the model is further modified to more accurately reflect water-entry motion. The change laws of the vehicle's attitude and position during the water-entry process are also obtained by analyzing the simulation of the modified model under different velocity, angle, and angle of attack conditions. The results presented here have guiding significance for the future realization of reaching the stable underwater navigation state of the vehicle after water-entry process.

Research on the water-entry attitude of a submersible aircraft.

BACKGROUND: The water entry of a submersible aircraft, which is transient, highly coupled, and nonlinear, is complicated. After analyzing the mechanics of this process, the change rate of every variable is considered. A dynamic model is build and employed to study vehicle attitude and overturn phenomenon during water entry. Experiments are carried out and a method to organize experiment data is proposed. The accuracy of the method is confirmed by comparing the results of simulation of dynamic model and experiment under the same condition. RESULTS: Based on the analysis of the experiment and simulation, the initial attack angle and angular velocity largely influence the water entry of vehicle. Simulations of water entry with different initial and angular velocities are completed, followed by an analysis, and the motion law of vehicle is obtained. To solve the problem of vehicle stability and control during water entry, an approach is proposed by which the vehicle sails with a zero attack angle after entering water by controlling the initial angular velocity. With the dynamic model and optimization research algorithm, calculation is performed, and the optimal initial angular velocity of water-entry is obtained. CONCLUSIONS: The outcome of simulations confirms that the effectiveness of the propose approach by which the initial water-entry angular velocity is controlled.

Covariance and crossover matrix guided differential evolution for global numerical optimization.

Differential evolution (DE) is an efficient and robust evolutionary algorithm and has wide application in various science and engineering fields. DE is sensitive to the selection of mutation and crossover strategies and their associated control parameters. However, the structure and implementation of DEs are becoming more complex because of the diverse mutation and crossover strategies that use distinct parameter settings during the different stages of the evolution. A novel strategy is used in this study to improve the crossover and mutation operations. The crossover matrix, instead of a crossover operator and its control parameter CR, is proposed to implement the function of the crossover operation. Meanwhile, Gaussian distribution centers the best individuals found in each generation based on the proposed covariance matrix, which is generated between the best individual and several better individuals. Improved mutation operator based on the crossover matrix is randomly selected to generate the trial population. This operator is used to generate high-quality solutions to improve the capability of exploitation and enhance the preference of exploration. In addition, the memory population is randomly chosen from previous generation and used to control the search direction in the novel mutation strategy. Accordingly, the diversity of the population is improved. Thus, CCDE, which is a novel efficient and simple DE variant, is presented in this paper. CCDE has been tested on 30 benchmarks and 5 real-world optimization problems from the IEEE Congress on Evolutionary Computation (CEC) 2014 and CEC 2011, respectively. Experimental and statistical results demonstrate the effectiveness of CCDE for global numerical and engineering optimization. CCDE can solve the test benchmark functions and engineering problems more successfully than the other DE variants and algorithms from CEC 2014.

Half-metallic properties, single-spin negative differential resistance, and large single-spin Seebeck effects induced by chemical doping in zigzag-edged graphene nanoribbons.

Ab initio calculations combining density-functional theory and nonequilibrium Green's function are performed to investigate the effects of either single B atom or single N atom dopant in zigzag-edged graphene nanoribbons (ZGNRs) with the ferromagnetic state on the spin-dependent transport properties and thermospin performances. A spin-up (spin-down) localized state near the Fermi level can be induced by these dopants, resulting in a half-metallic property with 100% negative (positive) spin polarization at the Fermi level due to the destructive quantum interference effects. In addition, the highly spin-polarized electric current in the low bias-voltage regime and single-spin negative differential resistance in the high bias-voltage regime are also observed in these doped ZGNRs. Moreover, the large spin-up (spin-down) Seebeck coefficient and the very weak spin-down (spin-up) Seebeck effect of the B(N)-doped ZGNRs near the Fermi level are simultaneously achieved, indicating that the spin Seebeck effect is comparable to the corresponding charge Seebeck effect.

The role of Coulomb interaction in thermoelectric effects of an Aharonov-Bohm interferometer.

We investigate the thermoelectric effects of an Aharonov-Bohm (AB) interferometer with a quantum dot (QD) embedded in each of its arms, where the intra-dot Coulomb interaction between electrons in each QD is taken into account. Using Green's function methods and the equation of motion (EOM) technique, we find that the Seebeck coefficient and Lorenz number can be strongly enhanced when the chemical potential sweeps the molecular states associated with the Fano line-shapes in the transmission spectra, due to quantum interference effects between the bonding and antibonding molecular states. It is found that enhancement of the thermoelectric effects occurs between the two groups of conductance peaks in the presence of strong intra-dot Coulomb interaction-the reason being that a transmission node is developed in the Coulomb blockade regime. In this case, the maximum value of the Lorenz number approaches 10π(2)k(B)(2)/(3e(2)). Its thermoelectric conversion efficiency in the absence of phonon thermal conductance, described by the figure of merit ZT, approaches 2 at room temperature. Therefore, it may be used as a high-efficiency solid-state thermoelectric conversion device under certain circumstances.

Large-bandgap behavior in transport of electrons through individual DNA molecules caused by coupling with a two-level system.

We propose a model to interpret the large-bandgap behavior in transport of electrons through an individual DNA molecule where the tunneling electrons are coupled with two-level systems (TLS). The TLS can be regarded as the simplest way to describe vibrations and inelastic scattering in the molecules if the two levels represent the low-lying phonon states. The nonlinear current-voltage curves can be derived by the use of the transfer matrices in an equivalent single-particle multichannel network. At low temperatures, the gap of the conduction band is sensitive to the strength of the coupling between the TLS and the conduction electrons. It is shown that the large-bandgap behavior similar to that of semiconductors stems from the inelastic scattering by the TLS.