Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)derived exosomes (N-Exos) and degenerated CESC-derived exosomes (D-Exos) in vitro and in vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N-Exos and D-Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. N-Exos were more conducive to autophagy activation than D-Exos. The apoptotic rate of NPCs decreased obviously after treatment with N-Exos compared to D-Exos. N-Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP.

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Background: Particulate air pollution, especially PM2.5, is highly correlated with various adverse health impacts and, ultimately, economic losses for society, however, few studies have undertaken a spatiotemporal assessment of PM2.5-related economic losses from health impacts covering all of the main cities in China. Methods: PM2.5 concentration data were retrieved for 190 Chinese cities for the period 2014–2016. We used a log-linear exposure–response model and monetary valuation methods, such as value of a statistical life (VSL), amended human capital (AHC), and cost of illness to evaluate PM2.5-related economic losses from health impacts at the city level. In addition, Monte Carlo simulation was used to analyze uncertainty. Results: The average economic loss was 0.3% (AHC) to 1% (VSL) of the total gross domestic product (GDP) of 190 Chinese cities from 2014 to 2016. Overall, China experienced a downward trend in total economic losses over the three-year period, but the Beijing–Tianjin–Hebei, Shandong Peninsula, Yangtze River Delta, and Chengdu-Chongqing regions experienced greater annual economic losses. Conclusions: Exploration of spatiotemporal variations in PM2.5-related economic losses from long-term health impacts could provide new information for policymakers regarding priority areas for PM2.5 pollution prevention and control in China.

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