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Influenza A virus (IAV) H1N1 infection is a constant threat to human health and it remains so due to the lack of an effective treatment. Since melatonin is a potent antioxidant and anti-inflammatory molecule with anti-viral action, in the present study we used melatonin to protect against H1N1 infection under in vitro and in vivo conditions. The death rate of the H1N1-infected mice was negatively associated with the nose and lung tissue local melatonin levels but not with serum melatonin concentrations. The H1N1-infected AANAT-/- melatonin-deficient mice had a significantly higher death rate than that of the WT mice and melatonin administration significantly reduced the death rate. All evidence confirmed the protective effects of melatonin against H1N1 infection. Further study identified that the mast cells were the primary targets of melatonin action, i.e., melatonin suppresses the mast cell activation caused by H1N1 infection. The molecular mechanisms involved melatonin down-regulation of gene expression for the HIF-1 pathway and inhibition of proinflammatory cytokine release from mast cells; this resulted in a reduction in the migration and activation of the macrophages and neutrophils in the lung tissue. This pathway was mediated by melatonin receptor 2 (MT2) since the MT2 specific antagonist 4P-PDOT significantly blocked the effects of melatonin on mast cell activation. Via targeting mast cells, melatonin suppressed apoptosis of alveolar epithelial cells and the lung injury caused by H1N1 infection. The findings provide a novel mechanism to protect against the H1N1-induced pulmonary injury, which may better facilitate the progress of new strategies to fight H1N1 infection or other IAV viral infections.

As a global biodiversity hotspot, southwestern China has been increasingly disturbed by human activities and has been undergoing rapid urbanization in recent years. In order to provide recommendations for conservation strategies, this paper explores the disequilibrium between land use and amphibian diversity. Four types of suitable habitat that are suitable for amphibians to inhabit (including farmland, woodland, grassland, and water habitat) were assessed and compared. Through fitting 20 models for species–area relationships (SARs), we found that different habitat types had different best-fitted SAR models. However, the conventional power law model had the advantage of being estimated without extreme values, and the estimation usually did not involve numerical problems. As such, we compared the debt mapping patterns derived from the best-fit SAR models and the power models. Regardless of the SAR models used, current amphibian richness was more strongly correlated with the past habitat area, suggesting that amphibian extinction debt existed in the region. Distribution of debt magnitude in different habitats presented congruent results: 1) The debt magnitude predicted in different habitats varied in decreasing order with grassland, water habitats, woodland, and farmland. 2) Debt magnitude in the region near the Chengdu Plain was high, while the extinction debt magnitude in the western region near the Qinghai-Tibet Plateau was low. This followed expectations, as there is a profound impact of human activities in the Chengdu Plain that threatens the survival of amphibian species in that area. In summary, our results suggest that some specific habitats (grasslands and water) and areas (Chengdu Plain) need greater conservation effort to better protect the habitats of amphibians and reduce the extinction risks of species.