Key Points• Uremic solute IS increases platelet activity via activation of ROS/p38MAPK signaling.• Klotho counteracts ISinduced thrombosis by restraining platelet hyperactivity.Thrombosis is a common complication of chronic kidney disease (CKD), but the causes and mechanisms of CKD-associated thrombosis are not well clarified. Here, we show that platelet activity is remarkably enhanced in CKD mice, with increase of serum indoxyl sulfate (IS), a typical uremic toxin, which cannot be effectively cleared by routine dialysis. Ex vivo and in vitro experiments reveal that IS displays a distinct ability to enhance platelet activities, including elevated response to collagen and thrombin, increases in plateletderived microparticles, and platelet-monocyte aggregates. The flow chamber assay and carotid artery thrombosis model demonstrate that IS-induced platelet hyperactivity contributes to thrombus formation. Further investigations disclose that reactive oxygen species (ROS)-mediated p38MAPK signaling plays a key role in IS-induced platelet hyperactivity. Moreover, we show that Klotho, which is expressed dominantly in the kidneys, has the capacity to counteract IS-induced platelet hyperactivity by inhibiting ROS/p38MAPK signaling, whereas Klotho reduction may aggravate the effect of IS on platelet activation in CKD and klotho 1/2 mice. Finally, we demonstrate that Klotho protein treatment can protect against IS-induced thrombosis and atherosclerosis in apoE 2/2 mice. Our findings uncover the mechanism of platelet hyperactivity induced by IS and provide new insights into the pathogenesis and treatment of CKD-associated thrombosis.

We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.

Key Points NE and EPI promote megakaryocyte adhesion, migration, and proplatelet formation via α2-adrenoceptor-ERK1/2 signaling. Sympathetic stimulation enhances platelet production, which may facilitate recovery of thrombocytopenia or aggravate atherosclerosis.

A tornado climatology in China was derived based on a recently completed data set with details on 4763 tornadoes in the period 1948–2012. The tornadoes were rated on the Fujita scale, and design basis tornado wind speeds were estimated. Annual tornadoes were estimated 108 (±44) in China, among which 0–4 exceed F3 on the Fujita scale. Three strongest tornadoes in the data set were rated F4. Assessing from frequency distribution of ratings, tornadoes in China could be mostly of the non‐supercell type. In average of all the country, most tornadoes occur in summer (June–August, about 64%). The peak month is July (31%). Geographically, the majority of tornadoes is distributed in eastern China, with the most frequent tornado occurrence being in the coastal provinces. There are southern type and northern type of tornado occurrence in eastern China. The former peaks in spring, while the latter peaks in summer. Two belts of design basis tornado wind speeds higher than 70 m s−1 were identified (on probability of 10−7 per year). One extends approximately along the coastline of China from south to north, while the other crosses this belt from east to west, approximately upstream of the Yangtze River. The Yangtze River Delta and Pearl River Delta have design basis tornado wind speeds higher than 90 m s−1, with maxima of 105 and 95 m s−1, respectively. However, by transferring into the enhanced Fujita scale, the wind speed is much lower, with the corresponding maxima being 82 and 76 m s−1 respectively.