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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. Exvivo andin 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+/- mice. Finally, we demonstrate that Klotho protein treatment can protect against IS-induced thrombosis and atherosclerosis in apoE-/- 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. [ABSTRACT FROM AUTHOR]

The effect of sympathetic stimulation on thrombopoiesis is not well understood. Here, we demonstrate that both continual noise and exhaustive exercise elevate peripheral platelet levels in normal and splenectomized mice, but not in dopamine β-hydroxylase-deficient (Dbh–/–) mice that lack norepinephrine (NE) and epinephrine (EPI). Further investigation demonstrates that sympathetic stimulation via NE or EPI injection markedly promotes platelet recovery inmice with thrombocytopenia induced by 6.0 Gy of total-body irradiation and in mice that received bone marrow transplants after 10.0 Gy of lethal irradiation. Unfavorably, sympathetic stress-stimulated thrombopoiesis may also contribute to the pathogenesis of atherosclerosis by increasing both the amount and activity of platelets in apolipoprotein E–deficient (ApoE–/–) mice. In vitro studies reveal that both NE and EPI promote megakaryocyte adhesion, migration, and proplatelet formation (PPF) in addition to the expansion of CD34+ cells, thereby facilitating platelet production. It is found that α2-adrenoceptor-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation is involved in NE- and EPI-induced megakaryocyte adhesion and migration, and PPF is regulatedbyERK1/2 activation-mediatedRhoAGTPase signaling.Our data deeply characterize the roleof sympathetic stimulationin the regulation of thrombopoiesis and reevaluate its physiopathological implications. [ABSTRACT FROM AUTHOR]

The western flower thrips (WPT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), an invasive insect pest in China, causes great economic losses worldwide. To understand the effects of heat shock on WFT population dynamics, we constructed life tables to quantify the effects of heat shock on the growth rate, survival, and fecundity of WFT offspring. WFT adults and 2nd instars were heat shocked at 45 °C, and the treatment was repeated after a 24-h recovery period. Heat-shocked and control insects were reared on the leaves of purple cabbage (Brassica oleracea L.; Brassicales: Brassicaceae), and various lifetable and development parameters of their F1 offspring were evaluated. The duration of the immature period of the offspring of heat-shocked adults was not significantly shorter than that of the control, whereas the duration of the immature period of the offspring of the heatshocked 2nd instars was longer than that of the other treatments, indicating that heat-shock of second instars slowed the development of their offspring. The preoviposition period during the adult stage and the total oviposition period of the F1 offspring of the heat-shocked adults were significantly longer than those of the control. The fecundities of the F1 offspring of the heat-shocked 2nd instars and adults were 81.8 and 70.6 eggs/female, respectively, both of which were significantly less than that of the control (149.1). The use of heated tents might be effective for the prevention and control of WFT infestations in greenhouses. Our life-table analysis of the effects of heat shock on F1 survival and reproduction provides a strong basis for future studies of thermal treatments for the control of WFT. [ABSTRACT FROM AUTHOR]

Human growth hormone (hGH) is known to play a functional role in regulating hematopoiesis, although its direct effect on thrombopoiesis is unclear. In this study, we show for the first time that hGH has a distinct capacity to promote the differentiation of human primary megakaryocytes derived from umbilical cord blood CD34+ cells. In particular, hGH is potent in facilitating proplatelet formation and platelet production from cultured megakaryocytes. The stage- and time-specific activations of extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathways are involved in the action of hGH. Fusion with hGH enhances the effect of a tandem dimer of thrombopoietin mimetic peptide (dTMP) on thrombopoiesis, manifested by a significant acceleration and increase of platelet production, indicating that hGH may exert a complementary and synergistic effect with c-Mpl ligands on thrombopoiesis. Accordingly, the administration of dTMP-growth hormone fusion protein led to a rapid platelet recovery in mice with severe thrombocytopenia induced by 6.5 Gy total body irradiation, thereby markedly abridging the duration of thrombocytopenia crisis (platelets <150 × 109/L), in comparison with high doses of dTMP. These findings demonstrate the functional role of growth hormone in promoting thrombopoiesis and provide a promising avenue for the treatment of severe thrombocytopenia. [ABSTRACT FROM AUTHOR]

We experimentally observe the bond stretching time of one-photon and net-two-photon dissociation pathways of singly ionized H2 molecules driven by a polarization-skewed femtosecond laser pulse. By measuring the angular distributions of the ejected photoelectron and nuclear fragments in coincidence, the cycle-changing polarization of the laser field enables us to clock the photon-ionization starting time and photon-dissociation stopping time, analogous to a stopwatch. After the single ionization of H2, our results show that the produced H+2 takes almost the same time in the one-photon and net-two-photon dissociation pathways to stretch to the internuclear distance of the one-photon coupled dipole-transition between the ground and excited electronic states. The spatiotemporal mapping character of the polarization-skewed laser field provides us a straightforward route to clock the ultrafast dynamics of molecules with sub-optical-cycle time resolution. [ABSTRACT FROM AUTHOR]

We experimentally visualize the dissociative frustrated double ionization of hydrogen molecules by using few-cycle laser pulses in a pump-probe scheme, in which process the tunneling ionized electron is recaptured by one of the outgoing nuclei of the breaking molecule. Three internuclear distances are recognized to enhance the dissociative frustrated double ionization of molecules at different instants after the first ionization step. The recapture of the electron can be further steered to one of the outgoing nuclei as desired by using phase-controlled two-color laser pulses. Both the experimental measurements and numerical simulations suggest that the Rydberg atom is favored to emit to the direction of the maximum of the asymmetric optical field. Our results on the one hand intuitively visualize the dissociative frustrated double ionization of molecules, and on the other hand open the possibility to selectively excite the heavy fragment ejected from a molecule. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the value and compliance rate of voiding vesicoureteral urosonography in pediatric vesicoureteral reflux (VUR)., Methods: This is a retrospective study. A total of 80 children with high-risk VUR admitted to Children's Hospital affiliated to Capital Medical University from December 2018 to December 2020 were selected. All patients underwent voiding urosonography (VUS) and fluoroscopic voiding cystourethrography (VCUG). The sensitivity and compliance of voiding vesicoureteral urosonography were compared, and its application value was evaluated., Results: A total of 160 PUUs were examined, and all cases were normal. Among them, 56 PUUs had reflux (35.00%, 56/160), 46 PUUs had reflux under both examination methods (28.75%, 46/160), and 10 PUUs were only detected under VUS (6.25%, 10/160). Thirty-four cases of VUR (42.50%, 34/80) were diagnosed by VUS, among which 15 cases were bilateral reflux and 4 cases were unilateral reflux. Twenty-five cases (35.00%, 25/80) were diagnosed by VCUG, among which 10 cases were bilateral regurgitation and five cases were unilateral regurgitation. No significant difference was observed in the detection rate of reflux between the two methods (P=0.432). A total of 146 PUUs were found to be consistent between the two methods (91.25%, 160), including 2 Grade-I reflux, 6 Grade-II reflux, 14 Grade-III reflux, 12 Grade-IV reflux, eight Grade-V reflux, and 104 without reflux, demonstrating SATISFACTORY consistency between the two groups (Kappa=0.885)., Conclusion: Voiding vesicoureteral urosonography has a high coincidence rate in the detection of vesicoureteral reflux in children., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)