Body weight is a component of the mechanical theory of OA (osteoarthritis) pathogenesis. Obesity was also found to be a risk factor for digital OA involving non-weight-bearing joints, which suggested that metabolism influences the occurrence and progression of OA. The metabolic origin of OA has been partially attributed to the involvement of adipokines, such as leptin, the levels of which are significantly and positively correlated with cartilage degeneration in OA patients. However, the mechanisms by which leptin-induced cartilage degeneration occurs are poorly understood. The discovery of chondrogenic progenitor cells (CPCs) opened up new opportunities for investigation. Investigating the effects of leptin on differentiation and proliferation in CPCs would increase our understanding of the roles played by leptin in the aetiology and development of OA. Here, CPCs were harvested using single-cell sorting from rat cartilage tissues to obtain mesenchymal stem-like cells, which possess clonogenicity, proliferation and stemness. High doses of leptin decreased the ability of the CPCs to migrate, inhibited their chondrogenic potential and increased their osteogenic potential, suggesting that leptin changes differentiation fates in CPCs. High doses of leptin induced cell cycle arrest and senescence in CPCs by activating the p53/p21 pathway and inhibiting the Sirt1 pathway. Inhibiting the Sirt1 pathway accelerated cartilage senescence in knockout (KO) mice. Activating the leptin pathway induced higher Ob-Rb expression and was significantly correlated with cartilage degeneration (lower levels of Coll-2) and tissue senescence (higher levels of p53/p21 and lower levels of Sirt1) in OA patients, suggesting that leptin-induced CPCs senescence contributes to the development of OA. Taken together, our results reveal new links between obesity and cartilage damage that are induced by leptin-mediated effects on cell behaviour and senescence.
Controlled release of pesticides by light regulation is one of the most viable strategies recently developed for the highly efficient utilization of agrochemicals. Herein, we report an infrared-light-responsive pesticide delivery system for the controlled release of imidacloprid (IMI) by preparation of functional hollow carbon microspheres (HCMs). After IMI loading and surface functionalization with polyethylene glycol (PEG) and α-cyclodextrin (α-CD), IMI was sequestered in the pesticide system (denoted as HCMs/IMI/PEG/α-CD) as a result of the formation of a PEG/α-CD gel network. Upon the irradiation of infrared light, HCMs with high photothermal conversion efficiency (42.8%) raised the local temperature effectively, leading to the collapse of the gel network and the release of IMI. In comparison to the amount of pesticide release (29%) under sunlight, it could reach 77% driven by infrared light, which was an intriguing improvement. Consequently, HCMs/IMI/PEG/α-CD under infrared light showed significantly higher pest control efficacy on corn borers by 125% than itself alone. This work provides a promising method to intentionally regulate pesticide release and enhance utilization efficiency.
MicroRNA (miRNA) has an important role as a master regulator of gene expression in immune system and is upregulated during T cell differentiation, however its function is not clear yet. In this study, the contribution of miR-31 in T cell activation was investigated. miR-31 was upregulated during the activation of primary T lymphocytes upon T-cell receptor (TCR) stimulation. Ectopic expression of miR-31 increased the expression of interleukin (IL)-2, while knockdown of endogenous miR-31 decreased the IL-2 expression. To gain more insights into the regulatory mechanism, we performed a bioinformatic analysis and found miR-31 potentially targeted kinase suppressor of ras 2 (KSR2), a repression factor of Ras2 kinase. Using reporter gene and western blotting assays, we confirmed that miR-31 could inhibit KSR2 by directly targeting its 3' untranslated region (UTR). Moreover, miR-31 enhanced nuclear factor of activated T cells (NF-AT) activity in Jurkat T cells, and increased transcription activity of IL-2 promoter in primary T cells. In conclusion, our study demonstrated that miR-31 upregulated IL-2 expression via reduction of its up-stream kinase suppressor, KSR2, and is a component of T cell activation.
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