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The aircraft hydraulic system is very important for the actuation system and its failure has led to a number of catastrophic accidents in the past few years. The reasons for hydraulic loss can be leakage, blockage, and structural damage. Fortunately, the development of more electric aircraft (MEA) provides a new means of solving this difficult problem. This paper designs an active fault tolerant control (AFTC) method for MEA suffering from total hydraulic loss and actuation system failure. Two different kinds of scenarios are considered: leakage/blockage and vertical tail damage. With the application of the dissimilar redundant actuation system (DRAS) in MEA, a switching mechanism can be used to change the hydraulic actuation (HA) system into an electro-hydrostatic actuation (EHA) system when the whole hydraulic system fails. Taking account of the gap between HA and EHA, a degraded model is built. As for vertical tail damage, engine differential thrust control is adopted to help regain lateral-directional stability. The engine thrust dynamics are modeled and the mapping relationship between engine differential thrust and rudder deflection is formulated. Moreover, model reference control (MRC) and linear quadratic regulator (LQR) are used to design the AFTC method. Comparative simulation with the NASA generic transportation model (GTM) is carried out to prove the proposed strategy.

Triptolide, an active ingredient extracted from the Chinese herb Tripterygium wilfordii Hook f., has multiple pharmacological properties, including anti-inflammatory, immune-modulatory, and anti-proliferative activities. However, the hepatotoxicity of triptolide always limits its clinical applications.Farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays a key role in hepatoprotection through the maintenance of liver metabolism homeostasis. This study explored the role of FXR in triptolide-induced cytotoxicity and investigated whether activation of FXR can protect against triptolide-induced liver injury.The role of FXR in triptolide-induced cytotoxicity was investigated in HepG2 cells. In addition, the protective effect of the selective FXR agonist GW4064 on triptolide-induced hepatotoxicity was explored in BALB/c mice.HepG2 cells were transient transfected with FXR expression plasmid or FXR-siRNA. The cytotoxicity was compared using the MTT assay. The extent of liver injury was assessed by histopathology and serum aminotransferases. The expression of FXR and its target genes were detected by Western blot and qRT-PCR.The transient overexpression of FXR protected against triptolide-induced cell death, whereas FXR knockdown with a specific small interfering RNA resulted in increased cytotoxicity. In BALB/c mice, treatment with the FXR agonist GW4064 attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and lipid peroxidation. Moreover, the livers of GW4064-treated mice showed increased expression of FXR and several related target genes involved in phase II and phase III xenobiotic metabolism.Taken together, these results indicate that activation of FXR attenuates triptolide-induced hepatotoxicity and provide direct implications for the development of novel therapeutic strategies against triptolide-induced hepatotoxicity.

Cisplatin is a potent anti-cancer agent for various types of tumors. However, the clinical use of cisplatin is often limited by its nephrotoxicity. This study reports that WZ tablet (WZ, a preparation of an ethanol extract of Schisandra sphenanthera) mitigates cisplatin-induced toxicity in renal epithelial HK-2 cells and in mice. Pretreatment of HK-2 cells with WZ ameliorated cisplatin-induced cytotoxicity caused by oxidative stress, as was demonstrated by reductions in the levels of reactive oxygen species (ROS) and increased levels of glutathione (GSH). WZ facilitated the nuclear accumulation of the transcription factor NF-E2-related factor 2 (Nrf2) and the subsequent expression of its target genes such as NAD(P)H:quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCL). Protective effects of WZ on cisplatin-induced nephrotoxicity were also observed in mice. WZ attenuated cisplatin-induced renal dysfunction, structural damage and oxidative stress. The nuclear accumulation of Nrf2 and its target genes were increased by WZ treatment. Taken together, these findings demonstrated WZ have a protective effect against cisplatin-induced nephrotoxicity by activation of the Nrf2 mediated defense response, which is of significant importance for therapeutic intervention in cisplatin induced renal injury.

Background Tanshinone IIA (Tan), the main active component of Salvia miltiorrhiza, has been demonstrated to have antioxidant activity. Acetaminophen (APAP), a widely used antipyretic and analgesic, can cause severe hepatotoxicity and liver failure when taken overdose. Oxidative stress has been reported to be involved in APAP-induced liver failure. Purpose This study aimed to investigate the effect of Tan on APAP-induced hepatotoxicity and the underlying mechanisms involved. Study Design C57BL/6 J mice were divided into six groups: (1) control, (2) APAP group, (3) APAP + Tan (30 mg/kg) group, (4) Tan (30 mg/kg) group, (5) APAP + Tan (10 mg/kg) group, (6) Tan (10 mg/kg) group. Mice in group 3 and 5 were pre-treated with specified dose of Tan by gavage and subsequently injected with an overdose of APAP intraperitoneally (i.p., 300 mg/kg). The effect of Tan on Nrf2 pathway was investigated in HepG2 cells and mice. Methods Plasma aspartate transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), liver glutathione (GSH), glutathione transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) levels were determined after mice were sacrificed. Lipid peroxidation and histological examination were performed. The effect of Tan on the Nrf2 pathway was detected by western blotting and qRT-PCR. Results Tan pretreatment reduced APAP-induced liver injury. Tan was able to activate Nrf2 and increase the expression levels of Nrf2 target genes, including glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1), in a dose-dependent manner in HepG2 cells. Consistent with our observations in HepG2 cells, Tan increased nuclear Nrf2 accumulation and upregulated mRNA and protein levels of the Nrf2 target genes GCLC, NQO1 and HO-1 in C57BL/6 J mice compared with mice treated with APAP alone. Conclusions Our results demonstrate that Tan pretreatment could protect the liver from APAP-induced hepatic injury by activating the Nrf2 pathway. Tan may provide a new strategy for the protection against APAP-induced liver injury.

Diammonium glycyrrhizinate (DG), an active compound extracted and purified from liquorices root, has been reported to exhibit antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effect and underlying mechanisms of DG on the hepatotoxicity induced by valproic acid (VPA). DG at the dose of 60mg/kg was orally administered with VPA (100mg/kg) to mice once daily for 14 consecutive days. DG treatment attenuated VPA-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. DG prevented VPA-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. The effects of VPA and DG on Nrf2 expression in HepG2 cells were in consistent with that of mice. Furthermore, an increase in the nuclear levels of nuclear factor-kappaB (NF-κB) was observed in the livers of VPA-treated mice that coincided with induction of inflammatory cytokines. In contrast, DG inhibited NF-κB translocation and that subsequently decreased inflammatory cytokines. Taken together, these results demonstrate that DG attenuates VPA-induced liver injury through increasing the expression of Nrf2 mediated phase II/antioxidant enzymes and simultaneously decreasing the expression of inflammatory mediators.

Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF), has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2) in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN), attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

The aircraft cabin environment smoke accident can threaten the flight safety seriously. According to the incomplete statistics, the cabin smoke accident happens one time in every 5,000 flights. As a result, more attention is paid on the airworthiness validation of the cabin smoke to ensure the aircraft safety. However, lacking the knowledge of the diffusion law of cabin smoke sometimes makes the validation experiment of the cabin smoke dangerous and expensive. With the rapid progress of computer technology, computational fluid dynamics (CFD) is widely used. In addition, utilizing computer modeling and simulation before the validation experiment can significantly improve the operability and feasibility of the experiment. This paper analyzes the flow regularity of smoke in the aircraft cabin and the influence of ventilation on cabin smoke diffusion by Fluent, which could prove analysis/calculation to be one of airworthiness compliance validation methods and decrease the costs of ground test and flight test which is able to reduce cost and increase efficiency.

With the commercial aircraft widely used, flight accidents related to the aircraft cabin happened sometimes, which is a serious threat to the flight safety. According to incomplete statistics, there are 1.5 times of accidents related to the aircraft cabin environment throughout the world. In some accidents, smoke containing toxic air enter the cabin and threaten the passengers. In recent years more and more attention is paid to the aircraft cabin environment, which is mainly about two areas: one is the research on the unsteady distribution law of cabin air environment and the nonlinear diffusion mechanism of pollutants via the technology of Computational Fluid Dynamic(CFD),the other is the research on parameters characteristic of components in the ECS(Environment Control System) with the system simulation. However, research accomplished related to the two areas above is mostly under normal condition of aircraft ECS, attention to the simulation of cabin air environment accident is more and more needed. Furthermore, it is necessary that 1D ECS simulation model and 2D CFD model are combined together, considering the complete parameters time history from 1D ECS components to the 2D aircraft cabin when doing the research on cabin environment accident. This paper describe a cabin environment smoke accident simulation with a 1D-2D co-simulation technology.