Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia-reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. Mice were exposed to lower limb RIPC or sham ischemia. After 24 h, mice with RIPC demonstrated decreased myocardial infarct size and improved cardiac contractility following 30-min ischemia and 120-min reperfusion (I-30/R-120). These effects of RIPC were completely blocked by anti-IL-10 receptor antibodies. In IL-10 knockout mice, RIPC cardioprotection was lost, but it was mimicked by exogenous IL-10. Administration of IL-10 to isolated perfused hearts increased phosphory-lation of the protein kinase Akt and limited infarct size after I-30/R-120. In wild-type mice, RIPC increased plasma and cardiac IL-10 protein levels and caused activation of Akt and endothelial nitric oxide synthase in the heart at 24 h, which was also blocked by anti-IL-10 receptor antibodies. In the gastrocnemius muscle, RIPC resulted in immediate inactivation of the phosphatase PTEN and activation of Stat3, with increased IL-10 expression 24 h later. Myocyte-specific PTEN inactivation led to increased Stat3 phosphorylation and IL-10 protein expression in the gastrocnemius muscle. Taken together, these results suggest that RIPC induces late protection against myocardial IR injury by increasing expression of IL-10 in the remote muscle, followed by release of IL-10 into the circulation, and activation of protective signaling pathways in the heart. This study provides a scientific basis for the use of RIPC to confer systemic protection against IR injury.

Deep-sea fan sediments provide an excellent geological archive for paleoenvironment reconstruction. Grain size, clay mineral and elemental (Ti, Fe, Ca) compositions were measured for a core retrieved from a submarine fan in the Okinawa Trough. Varimax-rotated Principal Component Analysis (V-PCA) on time-evolution of grain size spectrum reveals that, since the Holocene, sediment was transported mainly by the benthic nepheloid layer (33%) and upper layers (33%) which is driven by the East Asian winter monsoon (EAWM). The intensification of the Kuroshio Current during the Holocene, masks the fluvial signal of the summer monsoon and obstructs clay minerals derived from the Yellow River, a major contributor prior to 12 ka BP. A new grain size index (GSI), which represents the EAWM well, exhibits a negative correlation with the d 18 O record in Dongge Cave, China during the Holocene when sea level was relatively steady. This anticorrelation suggests the southward migration of the Intertropical Convergence Zone (ITCZ). The consistency among our records and rainfall records in Peru, Ti counts in the Cariaco Basin, monsoon records in Oman and the averaged summer insolation pattern at 30 N further support the ITCZ's impact on monsoon systems globally. Cross-Correlation Analyses for GSI and log(Ti/Ca) against d 18 O record in Dongge Cave reveal a decoupling between the East Asian winter and summer monsoon during 5500-2500 cal yr BP, with greater complexity in the last 2500 years. This can be attributed to exacerbated ENSO mode fluctuations and possibly anthropogenic interference superimposed on insolation and ITCZ forcing.