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Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.

BackgroundThe amount of gaseous tritium stored and released in fusion reactor is higher than that in current fission reactors, so that tritium is an important source of potential radioactivity in fusion reactor.PurposeThis study aims to investigate the environmental impact of gas tritium emission from fusion reactor for achieving the safety and environmental friendliness of fusion reactor in the future.MethodsTypical factory sites along the eastern coast of China with the highest frequency east wind direction was selected as the research object, and the Gauss model was employed to predict the atmospheric dispersion of gaseous tritium release and the dry deposition of tritium gas (HT), soil oxidation and re-evaporation of HTO. The radiation dose of 1 g HT in the case of short-term released from fusion reactor to the public in the surrounding environment was calculated.ResultsCalculation results show that the effective dose of inhalation internal irradiation of HT released at 10 m height for adults at 500~3 000 m west of the release point ranges from 0.38 mSv to 0.1 mSv. The dose caused by the re-evaporation effect of HTO at different distances is the main source of the dose of gaseous tritium. The proportion of the HT deposited to soil being oxidized to HTO and the atmosphere condition are the key parameter determining the effective dose of the tritium gas.ConclusionsThe study shows that the effective dose of HT released from fusion reactor to public is higher than which released from fission reactor, hence further attention to the environmental impact of the tritium is needed in the research on the fusion reactor subsequently.

Taking the 180~300 km ultra-low orbit satellite as the research object, the aerodynamic drag characteristics of the typical shapes were studied by using the direct simulation Monte Carlo (DSMC) method in the free molecular flow simulation method, which can accurately simulate the three-dimensional complex shapes. By comparing the theoretical drag coefficients of spheres and plates at different velocity rates and the aerodynamic experimental data of 70° bluff body shapes at different velocity rates with the DSMC calculation results, the adaptability of the three-dimensional DSMC method to shape and mesh is verified. The drag characteristics of several typical satellite shapes were calculated and compared, and the pressure difference drag, shear drag, total drag and dimensionless drag coefficients with altitude and shape were obtained. The optimized design of the shape of the ultra-low orbit satellite can reduce the drag by about 10%, which can effectively improve its on-orbit operation characteristics and reduce the design requirements of the own related systems of the satellite.

The non-rigid airship is a low-rigidity and inflatable aircraft which has obvious fluid-structure interaction characteristics. In this paper, the unsteady explicit dynamic fluid-structure interaction analysis framework of non-rigid airship is constructed based on the parametric section (PARSEC) method, the radial basis function (RBF), and the Delaunay mapping method. The reliability and accuracy of the numerical method are verified by the cases of plate impact and the aeroelasticity of NACA0014 wing. The calculation framework is also suitable for unsteady bidirectional fluid-structure interaction analysis of thin-envelope aerostats such as high-altitude balloon. Finally, the time domain and frequency domain responses of one non-rigid airship are simulated by the above framework. The research results show that there is an approximately linear relationship between the dominant frequency of vibration and the pressure difference of the airship.

In projects, mixed soil slurry between cut-off wall and coarse-grained soil always exists. It may influence on or change mechanical properties of interface between coarse-grained soil and structure. The mechanical behaviors of the interface between coarse-grained soil and concrete were investigated by simple shear tests under mixed soil slurry. The significant dilatancy and stress-strain softening can be achieved through the results, which also indicate that the cement content play an important role in the shear strength of the interface. The peak strength and the position when the dilatancy occurs are related to both normal stress and cement content. An elasto-plastic constitutive model for interface considering mixed soil slurry was formulated in the framework of generalized potential theory. The entire model parameters can be identified by experimental tests. Finally, the predictions of the model have been compared with experimental results, and results show the model is reasonable and practical.

Large-eddy simulation (LES) with dynamic one-equation subgrid-scale stress model was utilized to study the characteristics of turbulent flow over sea-surface generalized as two-dimensional wavy wall with different wave steepness. The statistical characteristics of turbulent field and pressure distribution were presented in detail. The simulation results showed that the separation zones induce stronger convection as the wave steepness increases. Reynolds shear stress near the wall boundary showed positive correlation with the wave steepness, while in the outer region, time-averaged turbulent fields seemed to be insensitive with the wall boundary. The equivalent velocity profiles obtained from the spatial averaging of the time-averaged velocity indicated that lower velocity occurred as the increase of wave steepness due to the increased pressure-induced form drag. The vortex structures were also visualized and showed vertically-bent characteristics which induced negative Reynolds shear stress at the stoss side as the increase of wave steepness that is equivalent to the effect of wave age.

BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.

The 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprise tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel.

The 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprise tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel.

Airships, as the significant UAV, have a need for greater autonomy in their new missions. Therefore, airship flight control systems require precise dynamic modeling, taking into account the effect of flexibility and the interaction with aerodynamic forces. This research effort develops an efficient modeling of the autonomous flexible airship. The formalisation used is based on the Lagrange method. The resulting model includes the rigid body motion, the elastic deformation, and the coupling between them. Based on the precise flexible dynamic model, a novel backstepping nonlinear controller with integral action is proposed for motion control systems. The resulting feedback controller is able to adapt to actuator performance limitations, such as limitations in magnitude and rate of change of rudder, than conventional backstepping controller without integral action. With the deformation considered, the presented controller could resist the flexible uncertainty effect, and the system’s trajectory tracking ability is significantly improved. The approach guarantees exponential stability of a compensated tracking error in the sense of Lyapunov.

BackgroundGenome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.MethodsAnalyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.ResultsAssuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability