Integrin alphaIIbbeta3-dependent Reactive Oxygen Species Production in Platelets

Excessive Reactive Oxygen Species (ROS) is associated with all known cardiovascular risk factors and is believed to play an important role for the onset of cardiovascular diseases. As a family of multisubunit enzymes complexes, NADPH oxidases deliberately generate superoxide and/or hydrogen peroxide. Evidence shows that NADPH oxidase are the key generators of ROS in the blood vessel wall and other tissues during cardiovascular disease progression. Studies from both human and animal platelet has suggested the role of NADPH-dependent ROS in platelet activation and thrombosis. However, the mechanism of how ROS production is regulated during platelet activation, and the effect of NOX-dependent ROS on platelet function remains unclear. This study focuses on illustrating the mechanism of how does integrin αIIbβ3 regulate ROS production and NOX activity in platelets. Integrin outside-in signaling is shown to be important for ROS production and NOX2 activation. Data here demonstrated P47phox phosphorylation and ROS production could be induced by integrin-ligation without need for other stimuli, and it is augmented by outside-in signaling activator, MnCl2, while disrupted by selective outside-in inhibitor, mP6. And the absence of β3 is shown to almost completely abolished p47phox activation, even in CRP-stimulated platelets. In addition, it has demonstrated that NOX1 and NOX2 knockout platelets was defect in stable adhesion, which is not further inhibited by mp6. This could possibly suggest ROS reversely inhibits integrin outside-in signaling. However, platelet spreading is not affected by NOX knockout. Along with previous data showing that NOX1/2 knockout mainly affected platelet granule secretion, and second wave of platelet aggregation, which requires integrin outside-in signaling, we concluded NOX-dependent ROS is important for integrin outside-in signaling and its functional consequences. Altogether, this study, provided insight as how ROS production in activated platelets is regulated, forming a theoretical foundation for new antithrombotic strategy basing on intervening integrin outside-in pathway-regulated NOX activity

Integrin alphaIIbbeta3-dependent Reactive Oxygen Species Production in Platelets

Excessive Reactive Oxygen Species (ROS) is associated with all known cardiovascular risk factors and is believed to play an important role for the onset of cardiovascular diseases. As a family of multisubunit enzymes complexes, NADPH oxidases deliberately generate superoxide and/or hydrogen peroxide. Evidence shows that NADPH oxidase are the key generators of ROS in the blood vessel wall and other tissues during cardiovascular disease progression. Studies from both human and animal platelet has suggested the role of NADPH-dependent ROS in platelet activation and thrombosis. However, the mechanism of how ROS production is regulated during platelet activation, and the effect of NOX-dependent ROS on platelet function remains unclear. This study focuses on illustrating the mechanism of how does integrin αIIbβ3 regulate ROS production and NOX activity in platelets. Integrin outside-in signaling is shown to be important for ROS production and NOX2 activation. Data here demonstrated P47phox phosphorylation and ROS production could be induced by integrin-ligation without need for other stimuli, and it is augmented by outside-in signaling activator, MnCl2, while disrupted by selective outside-in inhibitor, mP6. And the absence of β3 is shown to almost completely abolished p47phox activation, even in CRP-stimulated platelets. In addition, it has demonstrated that NOX1 and NOX2 knockout platelets was defect in stable adhesion, which is not further inhibited by mp6. This could possibly suggest ROS reversely inhibits integrin outside-in signaling. However, platelet spreading is not affected by NOX knockout. Along with previous data showing that NOX1/2 knockout mainly affected platelet granule secretion, and second wave of platelet aggregation, which requires integrin outside-in signaling, we concluded NOX-dependent ROS is important for integrin outside-in signaling and its functional consequences. Altogether, this study, provided insight as how ROS production in activated platelets is regulated, forming a theoretical foundation for new antithrombotic strategy basing on intervening integrin outside-in pathway-regulated NOX activity

Controllable Growth of Semiconductor Heterostructures Mediated by Bifunctional Ag₂S Nanocrystals as Catalyst or Source-Host

We demonstrate that Ag2S nanocrystals are the bifunctional mediator for controllable growth of semiconductor heterostructures including more complicated multisegments heterostructures in solution-phase, which is a new type of nanomediator and quite different from the metal nanoparticle catalyst. The intrinsic high Ag+ ion mobility makes Ag2S nanocrystals not only exhibit excellent catalytic function for growth of metal sulfide heterostructures but also act as a source-host for growth of ternary semiconductor heterostructures, for example, Ag2S-AgInS2. The semiconductors grow epitaxially from or inward in Ag2S nanocrystals forming single-crystalline heterostructures. Moreover, the method developed here also can construct multisegments heterostructures, for example, Ag2S-CdS-ZnS, AgInS2-Ag2S-AgInS2. The interfacial structure is still stable even if the lattice mismatch is quite large, which is a unique feature of this method

A Nonmetal Catalyst for Molecular Hydrogen Activation with Comparable Catalytic Hydrogenation Capability to Noble Metal Catalyst

A Nonmetal Catalyst for Molecular Hydrogen Activation with Comparable Catalytic Hydrogenation Capability to Noble Metal Catalys

In Situ Synthesis of Porous Fe₃O₄/C Microbelts and Their Enhanced Electrochemical Performance for Lithium-Ion Batteries

The porous Fe₃O₄/C microbelts (FCBs) were synthesized by simple electrospinning method, combined with carbonization of the precursor microbelts at high temperature in N₂ flow. Compared with α-Fe₂O₃ microbelt, the FCBs show better cyclic performance. The high capacity of 710 mA h g^–1 is still maintained after 50 cycles. The excellent performance of FCBs in lithium-ion batteries can be attributed to the highly stable porous belt structure of FCBs and to the substantial structure carbon matrix surrounded Fe₃O₄ nanoparticles. The synthesis method is simple, cheap, and green and could be extended to fabricate other carbon composites

Experimental Evidence for the Interface Interaction in Ag/C₆₀ Nanocomposite Catalyst and Its Crucial Influence on Catalytic Performance

New model catalysts are important for studying the interface interaction and their influence on the catalytic performance. In this paper, a novel Ag/C60 nanocomposite catalyst (Ag/C60 NCC) has been designed, prepared, and applied for the first time in the hydrogenation of aromatic nitro compounds. A new band at 1100 cm−1 appears in the Fourier transform infrared (FTIR) spectra of the Ag/C60 NCC, and the peak of the Ag (2) mode of C60 shifts clearly from 1468 to 1464 cm−1 in the Raman spectrum. X-ray photoelectron (XPS) spectrum of Ag 3d electron can be curve fitted into two pairs of peaks, corresponding to neutral Ag and Ag+, and the half-peak breadth is also broadened. Ag/C60 NCC exhibits excellent activity and selectivity in the hydrogenation of chloronitrobenzenes and nitrobenzaldehydes, whereas Ag nanocrystals (NCs), the mixture of Ag NCs, and C60 NCs do worse. These results evidence the presence of the charge transfer from Ag to C60 and clearly indicate the catalytic performance’s dependence on the interface interaction between Ag NCs and support C60 NCs

Publication bias and influence analysis of meta-analysis.

<p>A. Funnel plots of studies included in the meta-analysis. The vertical axis represents ln[HR] and the horizontal axis means the standard error of ln[HR]. Horizontal line and sloping lines in funnel plot represent summary HR and expected 95% CIs for a given standard error, respectively. Area of each circle represents contribution of the study to the pooled OR. B. Influence of individual studies on the pooled HR. The vertical axis indicates the overall HR and the two vertical axes indicate its 95% CI. Every hollow round indicates the pooled OR when the left study is omitted in this meta-analysis. The two ends of every broken line represent the respective 95% CI.</p

Current Clinical Evidence on the Effect of General Anesthesia on Neurodevelopment in Children: An Updated Systematic Review with Meta-Regression

<div><p>Background</p><p>Several epidemiological studies have been conducted to address the later effect of anesthesia on neurodevelopment in children. However, the results are still inconclusive.</p><p>Methods</p><p>We here conducted a systematic review and meta-analysis to summarize the currently available clinical and epidemiologic evidence on the association of anesthesia/surgery with neurodevelopmental outcomes in children by searching PubMed, EMBASE, and Web of Science database (from January-1 2000 to February-1, 2013). The evaluation of neurodevelopment includes language and learning disabilities, cognition, behavioral development, and academic performance. Both retrospective and prospective studies were included. Data were abstracted from seven eligible studies. We estimated the synthesized hazard ratios (HR) and 95% confidence interval (CI) according to inter-study heterogeneity.</p><p>Results</p><p>The pooled HR for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.25 (95% CI, 1.13–1.38, P<0.001; random-effects model) in children undergoing the first anesthesia before the age of 4-year. Then we analyzed the factors for this association using meta-regression method. It showed that it was the number of times of exposure (HR = 1.75, 95% CI 1.31–2.33; P<0.001) rather than the time at exposure before 4-year (HR = 1.08, 95% CI 0.87–1.34 for the effect of per 1-year early exposure; P = 0.47) is a risk factor for neurodevelopmental impairment.</p><p>Conclusion</p><p>The current clinical evidence suggests modestly elevated risk of adverse neurodevelopmental outcomes in children who were exposed to anesthesia/surgery during early childhood, especially for those with multiple times of exposure. Due to limitation of retrospective studies, prospective investigations are needed to determine whether anesthesia/surgery is causative.</p></div

Characteristics of eligible studies for meta-analysis.

<p>CI, confidence interval; HR, hazard ratio; PB, Population-based.</p><p>data from paper by Flick et al using the same study population but with different cut-off of timing at exposure.</p><p>during infancy (probably within 36 months).</p><p>evaluated by the 9-star Newcastle-Ottawa Scale.</p

Individual study and overall hazard ratios of relationships between general anesthesia and neurodevelopmental impairment in children.

<p>The size of each square is proportional to the weight of the study. For the combined result, the length of the diamond represents the 95% CI of the summary.</p