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• Upregulated glucokinase (GCK) involved in diabetic sympathetic neuropathy. • Upregulated GCK with P2X3 receptor to develop diabetic cardiac sympathy. • GCK shRNA inhibited the elevated sympathetic activity and blood pressure. • GCK shRNA reduced ATP currents co-transfected with GCK and P2X3. • GCK shRNA improved the dysfunctional cardiac function in T2DM rats. Glucokinase (GCK) may be involved in inflammatory pathological changes, while the P2X3 receptor in the stellate ganglia (SG) is related to diabetic cardiac autonomic neuropathy. In this study, we explored the relationship between the upregulated GCK in SG and diabetic cardiac sympathy. The expression and location of GCK and P2X3 in SG of type 2 diabetes mellitus (T2DM) rats were assessed. Changes in cardiac function were determined by measuring blood pressure, sympathetic nerve activity, heart rate, and heart rate variability. P2X3 agonist-activated currents in isolated stellate ganglion neurons and cultured human embryonic kidney 293 (HEK293) cells were recorded using whole-cell patch clamp techniques. The upregulated expression of GCK in SG of T2DM rats was decreased after treatment with GCK short hairpin RNA (shRNA). GCK shRNA treatment also improved the blood pressure, sympathetic nerve activity, heart rate, and heart rate variability in T2DM rats. By contrast, the expression of P2X3 and tumor necrosis factor α (TNF-α) was lessened by GCK shRNA treatment. In addition, adenosine triphosphate (ATP)-activated currents in stellate ganglion neurons and HEK293 cells co-transfected with GCK and P2X3 receptor plasmids were reduced after GCK shRNA treatment. In T2DM rats, knockdown of GCK relieved the diabetic cardiac sympathy mediated by P2X3 receptor-involved upregulation of GCK in SG. [ABSTRACT FROM AUTHOR]

• Platelet microRNAs were screened for links with platelet reactivity in healthy subjects. • The associated microRNAs were validated in clopidogrel-treated patients with ACS. • Platelet miR-223/126/150 influenced the clopidogrel antiplatelet effect. [ABSTRACT FROM AUTHOR]

• The system matrix was used to derive the axial displacement equation of the studied zoom system. • The merit functions constructed accurately reflected the design requirements of the zoom system. • Particle swarm optimization was used to optimize the mathematical model globally. • Numerical and Optical design software simulation and were employed to verify the design method. • A simple and effective tool was provided for the trajectory optimization of multi-component zoom system. In this paper, we propose a systematic approach to design a four-component zoom system with fixed spacing between focal points based on matrix optics to achieve a relatively high zoom ratio. In the method, the zoom trajectory under each chosen paraxial design is determined through matrix method, which is challenging but meaningful to achieve a globally optimized design for the complex zoom system. The elements of the system matrix imply the working state of the optical system, and axial displacement equation for the desired zoom system are derived by restricting specific matrix elements. Properly selected trajectory of the particular component described by means of a parametric function can make the model become solvable explicitly. Then the paraxial design problem is transformed into the optimization of these parameters with regard to the merit functions encompassing the primary aberration terms, compactness, smoothness of the trajectories. We adopt Particle Swarm Optimization (PSO) algorithm to globally optimize the parameters to retrieve the optimum zoom trajectory in specific design criteria. The proposed method is demonstrated through two specific examples under different configurations, both of which have acquired a final zoom ratio of 8X. The simulation results demonstrate that our proposed method can be a practical and powerful tool for paraxial design of complex multi-group zoom optical systems. [ABSTRACT FROM AUTHOR]

• A multiplex fluorescence immunoassay was developed for simultaneous detection OPs based on Au@Pt nanozyme catalysis. • The Au@Pt nanozyme can directly catalyzes non-fluorescent Amplex™ Red into fluorescent resorufin without labelling procedure. • The pesticide antibodies and bio-barcodes were labelled on AuNPs to form AuNPs probes for amplify the signal. • The carboxy modified thiol oligonucleotides and amino modified 96-well plate provided a multi-residue detection for pesticides with high sensitivity and selectivity. • The developed method can detect small molecule contaminants without the use of expensive natural enzyme. Organophosphate pesticides (OPs) are often used as insecticides and acaricides in agriculture, thus improving yields. OP residues may pose a serious threat, due to inhibition of the enzyme acetylcholinesterase (AChE). Therefore, a competitive bio-barcode immunoassay was designed for simultaneous quantification of organophosphate pesticide residues using AuNP signal amplification technology and Au@Pt catalysis. The AuNP probes were labelled with antibodies and corresponding bio-barcodes (ssDNAs), MNP probes coated with ovalbumin pesticide haptens and Au@Pt probes functionalized with the complementary ssDNAs were then prepared. Subsequently, pesticides competed with MNP probes to bind the AuNP probes. The recoveries of the developed assay were ranged from 71.26 to 117.47% with RSDs from 2.52 to 14.52%. The LODs were 9.88, 3.91, and 1.47 ng·kg−1, for parathion, triazophos, and chlorpyrifos, respectively. The assay was closely correlated with the data obtained from LC-MS/MS. Therefore, the developed method has the potential to be used as an alternative approach for detection of multiple pesticides. [ABSTRACT FROM AUTHOR]

• Celiac ganglion projects its postganglionic fibers to the liver. • Upregulated P2Y12 in celiac ganglia and liver of type 2 diabetic rats. • P2Y12 shRNA inhibited sympathetic activity and elevated hepatic glycogen. • P2Y12 shRNA reduced NLRP3 inflammasome formation and IL-1β production. • P2Y12 shRNA improve dysfunctional glucokinase to reduce hyperglycemia. The celiac ganglion projects its postganglionic (including purinergic) fibers to the liver. P2Y12 receptor is one of the P2Y family members. We found that the expression levels of P2Y12 receptor in both celiac ganglia and liver were increased in type 2 diabetes mellitus (T2DM) rats which also displayed an enhanced activity of celiac sympathetic nerve discharge (SND). In addition, a marked decrease of hepatic glucokinase (GK) expression was accompanied by reduced hepatic glycogen synthesis in T2DM rats, whereas meanwhile the levels of NLRP3, active caspase-1, NF-κB, and interleukin-1β were elevated. All these abnormal alterations could be largely reversed after treatment of short hairpin RNA (shRNA) targeting P2Y12. Our results indicate that the silence of P2Y12 by shRNA may effectively correct the anomalous activity of celiac SND and improve the dysfunctional hepatic glucokinase by counteracting hepatocyte inflammation and likely pyroptosis due to activated NLRP3 inflammasome and caspase-1 signaling, thereby attenuating hyperglycemia in T2DM rats. [ABSTRACT FROM AUTHOR]