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

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

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

Effect of time at exposure and number of times of exposure of general anesthesia on neurodevelopment in children.

<p>A. Relationship between categories of time at exposure and hazard ratio (HR) of later neurodevelopmental deficits in each analytical group. The line for each individual study is located over the range of time at exposure. The gray thick line indicates the effect of time at exposure (per 1-year early) on neurodevelopmental deficits using a meta-regression analysis. The slope of gray line represents the change in the log HR per 1-year early. The vertical axis is on a log scale. The result of effect of number of times of exposure on neurodevelopmental deficits is shown in B. The gray thick line indicates the effect of number of times of exposure on neurodevelopmental deficits.</p

The literature search process.

<p>The literature search process.</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

Aromatic-Amide-Derived Nonbiaryl Atropisomer as Highly Efficient Ligand for Asymmetric Silver-Catalyzed [3 + 2] Cycloaddition

In this work, we have successfully determined that the aromatic amide-derived nonbiaryl atropisomer/silver complex (silver-Xing-Phos) is an effective catalyst system for the solvent-dependent <i>exo</i>-selective cycloaddition of glycine aldimino esters with chalcones or less-reactive methyl cinnamates to give the corresponding chalcone- or cinnamate-derived pyrrolidines with multiple stereogenic centers in good yields and high diastereoselectivities as well as excellent enantioselectivities. Remarkably, it is the first example of highly enantioselective silver-catalyzed [3 + 2] cycloaddition of methyl cinnamates with glycine aldimino esters

Table1_Intelligence modeling of the flow boiling heat transfer of nanorefrigerant for integrated energy system.docx

To promote the application of nanorefrigerant in Organic Rankine Cycle and Integrated Energy System a reliable model with simple structure and favorable accuracy for predicting the flow boiling heat transfer coefficient (HTC) of nanorefrigerant is essential. In this work, four intelligence models—the radial basis function (RBF), multilayer perceptron (MLP), least squares support vector machine (LSSVM), and adaptive neuro fuzzy inference system (ANFIS)—were developed to predict the flow boiling heat transfer coefficient using nanorefrigerants, based on 765 experimental samples. The performances of these artificial intelligence models were comprehensively evaluated through accuracy analysis, variation trend analysis, and sensitivity analysis. Results indicated that the comprehensive performance of the RBF model was superior than those of other intelligence models and the existing empirical models. The RBF model accurately captured the variation trend of the output as the input variables were varied. Meanwhile, the impact degrees of all input variables in decreasing order were nanoparticle concentration (φ), mass flux (G), thermal conductivity of nanoparticle (kp), and vapor quality (x).</p

Experimental Observation of Fullerene Crystalline Growth from Mesocrystal to Single Crystal

Fullerene hierarchical mesocrystals were first prepared by antisolvent induced precipitation method. Their morphologies and sizes can be controlled by adjusting the antisolvent type and the ratio between the solvent (toluene) and antisolvent (ethyl acetate or tetrahydrofuran). The formation of fullerene mesocrystals and their transformation to single crystal were observed by time-dependent experiments with SEM and TEM. Fullerene mesocrystals can be separated from the solution and are stable for several months. HRTEM revealed that mesocrystals were made up of highly oriented nanoparticles. The formation of fullerene mesocrystals and their transformation to single crystals provide a new way for the construction of fullerene nanostructures with different applications