BackgroundBrain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson’s disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown.MethodsCre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation.ResultsWe show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model.ConclusionsThese findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

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The problem of global asymptotic stability analysis and controller synthesis for a class of discrete linear time-delay systems with state saturation nonlinearities is investigated. With the introduction of a free matrix whose infinity norm is less than or equal to 1, the state of discrete linear time-delay systems with state saturation is bounded by a convex hull, which makes it feasible to apply a suitable Lyapunov functional to obtain a sufficient condition for global asymptotic stability. It is also shown that this condition can be extended to controller synthesis and discrete time-delay systems with partial state saturation. The obtained results are expressed in terms of matrix inequalities that can be solved by the presented iterative linear matrix inequality approach. The effectiveness of these results is demonstrated by some numerical examples.

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Torsional rotor vibrations are undesirable phenomena which are very difficult to control in rotating systems. A common method for reducing vibrations involves the use of dynamic absorbers. However, if their physical parameters are constant, the frequency range of efficiency of dynamic absorbers is tight, making them unsuitable for systems with variable speeds. The use of smart materials, due to their variable and controllable mechanical properties, may be a powerful tool for increasing the frequency range. Electrorheological (ER) fluids are attractive materials that undergo very fast reversible changes in their rheological properties upon the application of an electric field. In this study, an electrorheological dynamic torsional absorber, called the Smart ER Dynamic Absorber, has been designed in order to reduce torsional rotor vibrations. Under shear mode, the ER absorber can exhibit various torsional damping and stiffness characteristics when an electric field is applied. A nonlinear empirical model of the dynamic behavior of ER materials has been developed. An On-Off control strategy has been applied and absorber efficiency measured. The results show that the ER dynamic absorber exhibits very good performances.