Isoorientin Ameliorates APAP-Induced Hepatotoxicity via Activation Nrf2 Antioxidative Pathway: The Involvement of AMPK/Akt/GSK3β

Oxidative stress has been highlighted as therapeutic targets for acetaminophen (APAP)-induced hepatotoxicity. Isoorientin (Iso), a well-known flavonoid-like compound, has been shown to have antioxidant potential. However, the effect of Iso on APAP-induced liver injury has not yet been elucidated. The present study investigated the hepatoprotective effect of Iso and its underlying mechanism. C57BL/6J mice were used to evaluate the hepatoprotective effect of Iso in vivo and HepG2 cells were utilized to further decipher the mechanisms of Iso -induced Nrf2 activation. We found that Iso treatment significantly reduced APAP-induced hepatotoxicity by reducing the lethality, histopathological liver changes, and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum. These effects were accompanied by decreased malondialdehyde (MDA) formation and myeloperoxidase level (MPO), and by decreased superoxide dismutase (SOD) and glutathione (GSH) depletion. Moreover, Iso induced Nrf2 activation and translocation as well as upstream AMPK/Akt/GSK3β activation. Furthermore, Iso effectively alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, Bax mitochondrial translocation, and apoptosis-inducing factor and cytochrome c release. Further mechanistic investigations revealed that the activation of Nrf2 by Iso via the AMPK/Akt/GSK3β pathway contributed to the hepatoprotective activity of Iso in vitro. In addition, the Iso-mediated inhibition of APAP-induced the lethality, histopathological changes and mitochondrial dysfunction observed in WT mice was nearly absent in Nrf2-/- mice. In summary, Iso ameliorated APAP-induced hepatotoxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway

ISAC from the Sky: UAV Trajectory Design for Joint Communication and Target Localization

Unmanned aerial vehicles (UAVs) as aerial base stations (BSs) are able to provide not only the communication service to ground users, but also the sensing functionality to localize targets of interests. In this paper, we consider an airborne integrated sensing and communications (ISAC) system where a UAV, which acts both as a communication BS and a mono-static radar, flies over a given area to transmit downlink signal to a ground communication user. In the meantime, the same transmitted signal is also exploited for mono-static radar sensing. We aim to optimize the UAV trajectory, such that the performance for both communication and sensing (C$\&$S) is explicitly considered. In particular, we first formulate the trajectory design problem into a weighted optimization problem, where a flexible performance trade-off between C$\&$S is achieved. As a step forward, a multi-stage trajectory design approach is proposed to improve the target estimation accuracy. While the resultant optimization problem is difficult to solve directly, we develop an iterative algorithm to obtain a locally optimal solution. Finally, numerical results show that the target estimation error obtained by the trade-off approach is about an order of magnitude better than a communication-only approach with a slight decrease on communication performance

Microstructure Sensitivity on Environmental Embrittlement of a High Nb Containing TiAl Alloy under Different Atmospheres

Mechanical properties in different atmospheres, including oxygen, vacuum, air and H2, of high Nb containing TiAl alloys with the compositions of Ti–45Al–8.5Nb–(0.2W, 0.2B, 0.02Y) have been investigated in this work. Three different microstructure types, nearly lamellar, gamma phase increased nearly lamellar and fully lamellar are selected for revealing the microstructure sensitivity of environmental embrittlement. The results show that the three types of microstructures are all affected by the hydrogen–induced environmental embrittlement. Although the fracture mode of the experimental alloy is cleavage fracture in all atmospheres, the proportions of transgranular and intergranular fractures are different, especially comparing the fracture surfaces in oxygen and hydrogen. Performance comparison results show that the nearly lamellar microstructure is the most susceptible to the hydrogen–induced environmental embrittlement, while the gamma phase increased microstructure is the most stable one; the fully lamellar microstructure results in moderate susceptibility to the atmospheres. Combined with the hydrogen absorption kinetic analysis, it indicates that γ phase at the interface of lamellar colony significantly inhibits the hydrogen–induced environmental embrittlement, while the effect of β phase is just the opposite. In addition, the correlation between microstructure and hydrogen–induced environmental embrittlement is revealed and the corresponding mechanism is also discussed in this work

A comprehensive research on petroleum hydrocarbon’s migration processes in Jiaozhou Bay

Petroleum hydrocarbon (PHC) pollution in marine bays has been more and more serous along with the rapid development of industry and economic, and understanding the migration processes in marine bays is essential to environmental protection.This paper provided a comprehensive research on the migration processes and laws in Jiaozhou Bay, Shandong Province of China using investigation data on 1984-1988. As a result, the annual changes of PHC contents, the changes of PHC’s sources and the land-ocean migration process were defined. These findings provided solid theory basis for better understanding the transporting processes and laws of pollutants in marine bay waters

PM2.5 increases susceptibility to acute exacerbation of COPD via NOX4/Nrf2 redox imbalance-mediated mitophagy

The increasing abundance of fine particulate matter (PM2.5) in the environment has increased susceptibility to acute exacerbation of COPD (AECOPD). During PM2.5 exposure, excessive reactive oxygen species (ROS) production triggers a redox imbalance, which contributes to damage to organelles and disruption of homeostasis. At present, there are limited data on whether NOX4/Nrf2 redox imbalance increases susceptibility to acute exacerbation of COPD (AECOPD), and the underlying mechanism is unclear. Therefore, the current study was aimed to evaluate the role of NOX4/Nrf2 redox balance on AECOPD induced by PM2.5-CS-exposure. Here, we report that PM2.5 exacerbates cytotoxicity by enhancing NOX4/Nrf2 redox imbalance-mediated mitophagy. First, exposure to a low-dose of PM2.5 (200 μg/ml) significantly exacerbated oxidative stress and mitochondrial damage by increasing the ROS overproduction, enhancing the excessive NOX4/Nrf2 redox imbalance, decreasing the mitochondrial membrane potential (MMP), and enhancing the mitochondrial fragmentation that were caused by a low-dose of CSE (2.5%). Second, coexposure to PM2.5 and CSE (PM2.5-CSE) induced excessive mitophagy. Third, PM2.5 exacerbated CS-induced COPD, as shown by excessive inflammatory cell infiltration, inflammatory cytokine production and mucus hypersecretion, goblet cell hyperplasia, NOX4/Nrf2 redox imbalance, and mitophagy, these effects triggered excessive ROS production and mitochondrial damage in mice. Mechanistically, PM2.5-CS-induced excessive levels of mitophagy by triggering redox imbalance, leading to greater cytotoxicity and AECOPD; however, reestablishing the NOX4/Nrf2 redox balance via NOX4 blockade or mitochondria-specific ROS inhibitor treatment alleviated this cytotoxicity and ameliorated AECOPD. PM2.5 may exacerbate NOX4/Nrf2 redox imbalance and subsequently enhance mitophagy by increasing the ROS and mito-ROS levels, thereby increasing susceptibility to AECOPD

Geometric Shape Induced Small Change of Seebeck Coefficient in Bulky Metallic Wires

In this paper, we report the results of slight changes in the thermopower of long W, Mo, Zn, Cu, brass, and Ti wires, that resulted from changes in the wire’s diameter or cross-sectional area. The samples used in the tests had a round shape with a diameter that ranged from tens of micron to 2 mm, which was much larger than the corresponding mean free paths of these materials. Nevertheless, a small change in thermopower, at the order of 1–10 nV/K, was repeatedly observed when the wire diameter was changed, or when the cross-sectional area of the wire was altered by mechanical methods, such as grinding or splitting. The results are consistent with previous observations showing that the thermopower in metallic thin film stripes changes with their width, from 100 μm to as little as 70 nm, implying a universal, geometric-boundary-related size effect of thermopower in metal materials, that occurs at the nanometer scale and continuously decreases all the way to the millimeter scale. This effect could be applied in the manufacturing of high-temperature sensors with simple structures

Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway

Objective: Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on acetaminophen-induced hepatotoxicity remains unclear. Methods: The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately. Results: In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3β pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3β phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated. Conclusion: Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3β/Nrf2 antioxidant pathway