Temporal and spatial variations and the relationships of land use pattern and ecosystem services in Qinghai-Tibet Plateau, China.

The Qinghai-Tibet Plateau is the key and largest ecological hotspot globally with enormous multiple ecosystem services. The vast and unique alpine ecosystems in this area have been subjected to the increased human disturbances, such as intensified land use. To explore the magnitude, spatiotemporal pattern and transformation process of land use in the Qinghai-Tibet Plateau and their impacts on the major ecosystem services during 1980-2020, we used the Integrated Valuation of Ecosystem Services and Trade-offs model to simulate the spatiotemporal variations of three types of ecosystem services, including habitat quality, carbon storage, and water yield. We analyzed the impacts of land use change on ecosystem services. The findings revealed that land use pattern remained generally stable from 1980 to 2020, with alpine grassland and desert as the dominant land use types. Habitat quality had generally enhanced, while carbon storage and water yield increased firstly and then declined. The magnitudes of three services gradually increased from the northwest to the southeast, corresponding to the spatial transformation pattern from desert via grassland to forest. The correlation between land use intensity and ecosystem services showed significant spatial heterogeneity, particulaly in counties greatly affected by land use intensity which concentrated predominantly in the mid-west, southern, and mid-east regions of the Qinghai-Tibet Plateau. The results have certain guiding significance for formulating land use policy and regulating land use pattern of alpine ecosystems in the Qinghai-Tibet Plateau.

Metformin inhibits ovarian granular cell pyroptosis through the miR-670-3p/NOX2/ROS pathway.

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and that NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance in women, whereas its role in OGC pyroptosis is unknown. This study aimed to investigate the impact of metformin on OGC pyroptosis and the underlying mechanisms. The results showed that treating a human granulosa-like tumor cell line (KGN) with metformin significantly decreased LPS-induced expression of miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; and the secretion of IL-1ß, IL-6, IL-18, and TNF-α were also diminished. These effects were amplified by adding N-acetyl-L-cysteine (NAC), a pharmacological inhibitor of ROS. In contrast, metformin's anti-pyroptosis and anti-inflammatory effects were robustly ameliorated by NOX2 overexpression in KGN cells. Moreover, bioinformatic analyses, RT-PCR, and Western blotting showed that miR-670-3p could directly bind to the NOX2 (encoded by the CYBB gene in humans) 3'UTR and decrease NOX2 expression. Metformin-induced suppression of NOX2 expression, ROS production, oxidative stress, and pyroptosis was significantly alleviated by transfection with the miR-670-3p inhibitor. These findings suggest that metformin inhibits KGN cell pyroptosis via the miR-670-3p/NOX2/ROS pathway.