Janus kinase signaling activation mediates peritoneal inflammation and injury in vitro and in vivo in response to dialysate.

Peritoneal membrane pathology limits long-term peritoneal dialysis (PD). Here, we tested whether JAK/STAT signaling is implicated and if its attenuation might be salutary. In cultured mesothelial cells, PD fluid activated, and the pan-JAK inhibitor P6 reduced, phospho-STAT1 and phospho-STAT3, periostin secretion, and cleaved caspase-3. Ex vivo, JAK was phosphorylated in PD effluent cells from long-term but not new PD patients. MCP-1 and periostin were increased in PD effluent in long term compared with new patients. In rats, twice daily, PD fluid infusion induced phospho-JAK, mesothelial cell hyperplasia, inflammation, fibrosis, and hypervascularity after 10 days of exposure to PD fluid. Concomitant instillation of a JAK1/2 inhibitor virtually completely attenuated these changes. Thus, our studies directly implicate JAK/STAT signaling in the mediation of peritoneal membrane pathology as a consequence of PD.

Warfare rather than agriculture as a critical influence on fires in the late Holocene, inferred from northern Vietnam.

Fire has played an essential role in the development of human civilization. Most previous research suggests that frequent-fire regimes in the late Holocene were associated with intensification of human activities, especially agriculture development. Here, we analyze fire regimes recorded in the Song Hong delta area of Vietnam over the past 5,000 years. In the prehistoric period, 2 long-term, low-charcoal abundance periods have been linked to periods of low humidity and cool climate, and 5 short-term fire regimes of 100-150 years in duration occurred at regular intervals of approximately 700 years. However, over the last 1,500 years, the number, frequency, and intensity of fire regimes clearly increased. Six intensified-fire regime periods in northern Vietnam during this time coincided with changes of Vietnamese dynasties and associated warfare and unrest. In contrast, agricultural development supported by rulers of stable societies at this time does not show a positive correlation with intensified-fire regime periods. Thus, warfare rather than agriculture appears to have been a critical factor contributing to fire regimes in northern Vietnam during the late Holocene.