A novel mechanism for the protection against acute lung injury by melatonin: mitochondrial quality control of lung epithelial cells is preserved through SIRT3-dependent deacetylation of SOD2.

The mitochondrial quality control of lung epithelial cells is disturbed during sepsis, which contributes to abnormal mitochondrial function and acute lung injury. Melatonin is one of the primary hormones secreted by the pineal gland, displaying favorable antioxidative actions in sepsis and cardiopulmonary disease. However, the potential roles and molecular basis of melatonin in lipopolysaccharide (LPS)-treated lung epithelial cells have not been explored and reported. Herein, we investigated whether melatonin could protect against sepsis-induced acute lung injury (ALI) and LPS-treated lung epithelial cells through the mitochondrial quality control as well as its possible molecular targets. Wild type and Sirt3 knockout mice were intratracheally instilled with LPS for 12 h to construct an in vivo acute lung injury model. Both A549 lung epithelial cells and primary alveolar type II (AT-II) cells were used to explore the possible roles of melatonin in vitro by incubating with small interfering RNA against Sirt3. To determine the involvement of the melatonin receptor, cells and mice were treated with si Mtnr1b and luzindole. Melatonin pretreatment significantly inhibited pathological injury, inflammatory response, oxidative stress, and apoptosis in LPS-treated lung tissues and LPS-treated lung epithelial cells. Furthermore, melatonin also shifted the dynamic course of mitochondria from fission to fusion, inhibited mitophagy and fatty acid oxidation in LPS-treated lung epithelial cells in vitro and in vivo. However, SIRT3 inhibition abolished the protective roles of melatonin in acute lung injury. Mechanistically, we found that melatonin increased the activity and expression of SIRT3, which further promoted the deacetylation of SOD2 at K122 and K68. More importantly, melatonin exerted pulmonary protection by activating MTNR1B but not MTNR1A during ALI. Collectively, melatonin could preserve the mitochondrial quality control of lung epithelial cells through the deacetylation of SOD2 in a SIRT3-dependent manner, which eventually alleviated sepsis-induced injury, inflammation, oxidative stress, and apoptosis. Thus, melatonin may serve as a promising candidate against ALI in the future.

Spatial sampling design optimization of monitoring network for terrestrial ecosystem in China.

The rapid socioeconomic development leads to the deterioration of ecological environment. Ecosystem assessment has been conducted worldwide, e.g. the Millennium Ecosystem Assessment to assess consequences of ecosystem change for human well-being. To enhance ecosystem assessment in China, this study proposes the design of a monitoring network for the terrestrial ecosystem consisting of core stations and localized points. With focus on ecosystem services of NPP, water conservation, soil retention and sandstorm prevention, core stations of the monitoring network for observing all four services are first selected by assessing and improving spatial representativeness in ecoregions of forest, grassland and desert ecosystems. Then a spatial sampling method is applied to choose localized points for observing each specific service. Eventually expert's knowledge is used to make final decisions of added stations and points by utilizing existing networks and considering factors such as topography, spatial coverage. Combining both aforementioned approaches and experts knowledge, 60 core stations and 176 localized points are finally determined for the monitoring network. For the forest ecosystem, 39 core stations are decided with 31 selected from existing networks and eight newly added core stations improve spatial representativeness by 51.58 %, 68.11 % and 75.55 % in Temperate grasslands, Temperate desert and Alpine vegetation in Tibet Plateau respectively. For the grassland and desert ecosystem, 21 core stations are chosen with 18 from existing networks and three newly added core stations improve the representativeness by 21.60 % and 44.88 % in Tibet alpine grassland and Grassland in southern mountain areas respectively. Priorities in the implementation phase should be given to instruments installation for monitoring all four services in core stations from existing networks and setting up new stations in regions where representativeness are significantly improved.