Pregabalin alleviates postherpetic neuralgia by downregulating spinal TRPV1 channel protein

Purpose: To determine the mechanism involved in pregabalin-induced alleviation of postherpetic neuralgia in a rat model.Methods: Ninety-sixty healthy Sprague-Dawley (SD) rats were assigned to sham, model andpregabalin groups (32 rats per group). A model of postherpetic neuralgia (PN) was established. The expressions of IL-1β and TNF-α in spinal cord tissue were determined 7 days after administration of treatments. The proportions of fluorescence areas in astrocytes in the dorsal horn, prefrontal lobe and hippocampus, and level of spinal cord TRPV1 channel protein in each group were evaluated.Results: Relative to model rats, IL-1β and TNF-α in spinal cord of pregabalin rats were significantly reduced (p < 0.05). The areas of fluorescence in astrocytes in dorsal horn of spinal cord, prefrontal lobe and hippocampus of model group were significantly increased, relative to sham, but were decreased in rats in pregabalin group (p < 0.05).Conclusion: Pregabalin significantly alleviates postherpetic neuralgia via mechanisms which may be related to the inflammatory response of spinal dorsal horn and downregulation of TRPV1 channel protein expression. This finding may be useful in developing new drugs for alleviating postherpetic neuralgia

Bluetooth vulnerabilities in data security of mobile phones

This study explored the Bluetooth vulnerabilities of mobile phones and how those vulnerabilities can be utilized by attackers to control mobile phones and gain personal data. The researcher conducted attacks on mobile phones under varying conditions in order to verify the efficacy of two attacks, Bluesnarfing and Bluebugging. This method tested improvements in Bluetooth security features by using attack verification. In other words, if an attack is designed to make use of the vulnerabilities of Bluetooth 1.0, then the newer version, Bluetooth 2.0, should have a proposed solution designed to fix these vulnerabilities. This study demonstrated that the security features of Bluetooth have been improved to defend against Bluesnarfing and Bluebugging. However, other Bluetooth threats were found, including lack of verification for connections following the first connection, over-supported functions, and the implementation of discovery mode. The implementation and design may also cause leakage of users\u27 information leakage

The 3-D numerical simulation research of vacuum injector for linear induction accelerator

Simulation method for voltage in-feed and electron injection of vacuum injector is given, and verification of the simulated voltage and current is carried out. The numerical simulation for the magnetic field of solenoid is implemented, and a comparative analysis is conducted between the simulation results and experimental results. A semi-implicit difference algorithm is adopted to suppress the numerical noise, and a parallel acceleration algorithm is used for increasing the computation speed. The RMS emittance calculation method of the beam envelope equations is analyzed. In addition, the simulated results of RMS emittance are compared with the experimental data. Finally, influences of the ferromagnetic rings on the radial and axial magnetic fields of solenoid as well as the emittance of beam are studied

Bond Stress–Slip Model of BFRP Grid to ECC

The bonding performance between a basalt fiber-reinforced composite material (BFRP) grid and an engineering cementitious composite (ECC) is the basis that affects the synergy between the two. However, the research on the bonding behavior between the FRP grid and ECC is limited; in particular, the theoretical study on the bond–slip intrinsic relationship model and a reliable anchorage length calculation equation is lacking. To study the bond–slip relationship between the BFRP grid and ECC material, we considered the parameters of BFRP grid thickness, anchorage length, ECC substrate protective layer thickness, and grid surface treatment, and conducted center pull-out tests on eight sets of specimens. By analyzing the characteristics of the bond–slip curve of the specimen, a bond–slip constitutive model between the BFRP grid and ECC was established. Combining the principle of equivalent strain energy, the calculation formula of the basic anchorage length of the BFRP grid in the ECC matrix was derived. Research shows that the bonding performance between the BFRP grid and ECC improves with the increase in the grid anchoring length, grid thickness, and ECC layer strength. Sand sticking on the surface of the BFRP grid can enhance the bonding force between the two. The established bond–slip constitutive model curve is in good agreement with the test curve. The bond–slip relationship between the BFRP grid and ECC can be described by the first two stages in the BPE model. The derived formula for calculating the basic anchorage length of the BFRP mesh in the ECC matrix is computationally verified to be reliable in prediction

Progress and Challenges to Hepatitis E Vaccine Development and Deployment

Hepatitis E is a significant cause of acute hepatitis, contributing to high morbidity and mortality rates, and capable of causing large epidemics through fecal–oral transmission. Currently, no specific treatment for hepatitis E has been approved. Given the notably high mortality rate among HEV-infected pregnant women and individuals with underlying chronic liver disease, concerted efforts have been made to develop effective vaccines. The only licensed hepatitis E vaccine worldwide, the HEV 239 (Hecolin) vaccine, has been demonstrated to be safe and efficacious in Phase III clinical trials, in which the efficacy of three doses of HEV 239 remained at 86.6% (95% confidence interval (CI): 73.0–94.1) at the end of 10 years follow-up. In this review, the progress and challenges for hepatitis E vaccines are summarized

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Abstract Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tubular cells (PTC), which are the main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic process that removes long-lived proteins and damaged organelles via lysosome-mediated degradation, which has an antioxidant effect that relieves oxidative stress. The canonical transient receptor potential channel 6 (TRPC6), a nonselective cation channel that allows passage of Ca2+, plays an important role in renal disease. Yet, the relationship between TRPC6 and autophagy, as well as their functions in renal oxidative stress injury, remains unclear. In this study, we found that oxidative stress triggered TRPC6-dependent Ca2+ influx in PTC to inhibit autophagy, thereby rendering cells more susceptible to death. We also demonstrated that TRPC6 knockout (TRPC6-/-) or inhibition by SAR7334, a TRPC6-selective inhibitor, increased autophagic flux and mitigated oxidative stress-induced apoptosis of PTC. The protective effects of TRPC6 ablation were prevented by autophagy inhibitors Chloroquine and Bafilomycin A1. Moreover, this study also shows that TRPC6 blockage promotes autophagic flux via inhibiting the PI3K/Akt/mTOR and ERK1/2 signaling pathways. This is the first evidence showing that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in PTC, and it may become a novel therapeutic target for the treatment of renal oxidative stress injury in the future

Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis

Abstract Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML