Mitoquinone mitigates paraquat-induced A549 lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion.

Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury.

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3ß Pathway.

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3ß (p-GSK-3ß) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3ß in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3ß regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3ß (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.

Protective effect of ginsenoside Rg1 on LPS-induced apoptosis of lung epithelial cells.

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity in the critical care units. Though, it was commonly accepted that inflammation and apoptosis of lung epithelial cells played an essential role in the pathogenesis of ALI, the underlying mechanism remain unknown. In our study, we found that LPS-induced cell apoptosis could be counteracted by elevated cell autophagy. In LPS-treated MLE-12 cells, suppression of autophagy via 3-MA could aggravate LPS-induced apoptosis, while activation of autophagy via Rapamycin could effectively impair the apoptosis of MLE-12 cells induced by LPS. In order to further discover the molecular regulation mechanism between apoptosis and autophagy in LPS-treated MLE-12 cells, we demonstrated that autophagy could induced the expression of Nrf2, followed with the decrease of p-p65. Targeted inhibition of Nrf2 could induce enlarged cell apoptosis via increasing the level of p-p65. In addition, we demonstrated that ginsenoside Rg1 protected MLE-12 cells from LPS-induced apoptosis via augmenting autophagy and inducing the expression of Nrf2. Our data implicates that activation of autophagy and Nrf2 by ginsenoside Rg1 may provide a preventive and therapeutic strategy for ALI.

Estimation of nitrogen runoff loss from croplands in the Yangtze River Basin: A meta-analysis.

Nitrogen (N) runoff loss from croplands due to excessive anthropogenic N additions is a principal cause of non-point source water pollution worldwide. Quantitative knowledge of regional-scale N runoff loss from croplands is essential for developing sustainable agricultural N management and efficient water N pollution control strategies. This meta-analysis quantifies N runoff loss rates and identifies the primary factors regulating N runoff loss from uplands (n = 570) and paddy (n = 434) fields in the Yangtze River Basin (YRB). Results indicated that total N (TN) runoff loss rates from uplands and paddy fields consistently increased from upstream to downstream regions. Runoff depth, soil N content and fertilizer addition rate (chemical fertilizer + manure) were the major factors regulating variability of TN runoff loss from uplands, while runoff depth and fertilizer addition rate were the main controls for paddy fields. Multiple regression models incorporating these influencing factors effectively predicted TN runoff loss rates from uplands (calibration: R2 = 0.60, n = 242; validation: R2 = 0.55, n = 104) and paddy fields (calibration: R2 = 0.70, n = 189; validation: R2 = 0.85, n = 82). Models estimated total cropland TN runoff loss load in YRB of 0.54 (95% Cl: 0.23-1.33) Tg, with 0.30 (95% Cl: 0.15-0.56) Tg from uplands and 0.24 (95% Cl: 0.08-0.77) Tg from paddy fields in 2017. Guangxi, Jiangxi, Fujian, Hunan and Henan provinces within the YRB were identified as cropland TN runoff loss hotspots. Models predicted that TN runoff loss loads from croplands in YRB would decrease by 0.8-13.7% for five scenarios, with higher TN load reductions occurring from scenarios with decreased runoff amounts. Reducing upland TN runoff loss should focus primarily on soil N utilization and runoff management, while reducing N fertilizer addition and runoff provided the most sensitive strategies for paddy fields. Integrated management of water, soil and fertilizer is required to effectively reduce cropland N runoff loss.

Long-term (1980-2015) changes in net anthropogenic phosphorus inputs and riverine phosphorus export in the Yangtze River basin.

Quantitative information on long-term net anthropogenic phosphorus inputs (NAPI) and its relationship with riverine phosphorus (P) export are critical for developing sustainable and efficient watershed P management strategies. This is the first study to address long-term (1980-2015) NAPI and riverine P flux dynamics for the Yangtze River basin (YRB), the largest watershed in China. Over the 36-year study period, estimated NAPI to the YRB progressively increased by ∼1.4 times, with NAPIA (chemical fertilizer input + atmospheric deposition + seed input) and NAPIB (net food/feed imports + non-food input) contributing 65% and 35%, respectively. Higher population, livestock density and agricultural land area were the main drivers of increasing NAPI. Riverine total phosphorus (TP), particulate phosphorus (PP) and suspended sediment (SS) export at Datong hydrological station (downstream station) decreased by 52%, 75% and 75% during 1980-2015, respectively. In contrast, dissolved phosphorus (DP) showed an increase in both concentration (∼7-fold) and its contribution to TP flux (∼16-fold). Different trends in riverine P forms were mainly due to increasing dam/reservoir construction and changes in vegetation/land use and NAPI components. Multiple regression models incorporating NAPIA, NAPIB, dam/reservoir storage capacity and water discharge explained 84% and 92% of the temporal variability in riverine DP and PP fluxes, respectively. Riverine TP flux estimated as the sum of DP and PP fluxes showed high agreement with measured values (R2 = 0.87, NSE = 0.84), indicating strong efficacy for the developed models. The model forecasted an increase of 50% and 7% and a decrease of 15% and 22% in riverine DP flux from 2015 to 2045 under developing, dam building, NAPIA and NAPIB reduction scenarios, respectively. This study highlights the importance of including enhanced P transformation from particulate to bioavailable forms due to river regulation and changes in land-use, input sources and legacy P pools in development of P pollution control strategies.

Rice-shaped porous ZnMn2O4 microparticles as advanced anode materials for lithium-ion batteries.

In this work, novel rice-shaped porous ZnMn2O4 microparticles made of nanoparticles were successfully prepared for the first time by the calcination of Zn0.33Mn0.67CO3 precursors synthesized using a facile triethanolamine-assisted solvothermal method. The effect of solvothermal reaction time on the crystallinity and morphology of Zn0.33Mn0.67CO3 precursors is discussed. The obtained ZnMn2O4 microparticles have lengths of ca. 1.6 µm and widths of ca. 0.9 µm, while the primary nanoparticles are in sizes of ca. 25-70 nm. As a potential anode material for lithium-ion batteries, the ZnMn2O4 microparticles give a large reversible discharge capacity of 892 mA h g-1 at 0.2 A g-1, superior cyclability (95% capacity retention after 550 cycles at 2 A g-1), and excellent rate capability (571 mA h g-1 at 5 A g-1). The outstanding electrochemical performances of the microparticle materials benefit from the suitable micro-/nanoparticle sizes, hierarchical porous structures, and strong interconnected 3D frameworks, which shorten the path lengths for ionic transport, accommodate volume expansion/contraction, and maintain the structural integrity of electrodes during the cycling process.