RESUMEN
Historical documents provide evidence for regional droughts preceding the political turmoil and fall of Beijing in 1644 CE, when more than 20 million people died in northern China during the late Ming famine period. However, the role climate and environmental changes may have played in this pivotal event in Chinese history remains unclear. Here, we provide tree-ring evidence of persistent megadroughts from 1576 to 1593 CE and from 1624 to 1643 CE in northern China, which coincided with exceptionally cold summers just before the fall of Beijing. Our analysis reveals that these regional hydroclimatic extremes are part of a series of megadroughts along the Pacific Rim, which not only impacted the ecology and society of monsoonal northern China, but likely also exacerbated external geopolitical and economic pressures. This finding is corroborated by last millennium reanalysis data and numerical climate model simulations revealing internally driven Pacific sea surface temperature variations and the predominance of decadal scale La Niña-like conditions to be responsible for precipitation decreases over northern China, as well as extensive monsoon regions in the Americas. These teleconnection patterns provide a mechanistic explanation for reoccurring drought spells during the late Ming Dynasty and the environmental framework fostering the fall of Beijing in 1644 CE, and the subsequent demise of the Ming Dynasty.
RESUMEN
A close relationship between epigenetic regulation and obesity has been demonstrated in several recent studies. Histone methyltransferase enhancer of Zeste homolog 2 (Ezh2), which mainly catalyzes trimethylation of histone H3K27 to form H3K27me3 was found to be required for the differentiation of white and brown adipocytes in vitro. Here, we investigated the effects of the Ezh2-specific inhibitor GSK126 in a mouse model of obesity induced by a high-fat diet (HFD). We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo.
