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We study the coefficient of performance (COP) and its bounds of the Canot-like refrigerator working between two heat reservoirs at constant temperatures T h and T c , under two optimization criteria χ and Ω. In view of the fact that an "adiabatic" process takes finite time and is nonisentropic, the nonadiabatic dissipation and the finite time required for the "adiabatic" processes are taken into account. For given optimization criteria, we find that the lower and upper bounds of the COP are the same as the corresponding ones obtained from the previous idealized models where any adiabatic process undergoes instantaneously with constant entropy. When the dissipations of two "isothermal" and two "adiabatic" processes are symmetric, respectively, our theoretical predictions match the observed COP's of real refrigerators more closely than the ones derived in the previous models, providing a strong argument in favor of our approach.

BackgroundInterleukin-33 (IL-33) is increasingly being recognized as a key immunomodulatory cytokine in many neurological diseases.MethodsIn the present study, wild-type (WT) and IL-33−/− mice received intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS) to induce neuroinflammation. Intravital microscopy was employed to examine leukocyte–endothelial interactions in the brain vasculature. The degree of neutrophil infiltration was determined by myeloperoxidase (MPO) staining. Real-time PCR and western blotting were used to detect endothelial activation. Enzyme-linked immunosorbent assay and quantitative PCR were conducted to detect pro-inflammatory cytokine levels in the brain.ResultsIn IL-33−/− mice, neutrophil infiltration in the brain cortex and leukocyte–endothelial cell interactions in the cerebral microvessels were significantly decreased as compared to WT mice after LPS injection. In addition, IL-33−/− mice showed reduced activation of microglia and cerebral endothelial cells. In vitro results indicated that IL-33 directly activated cerebral endothelial cells and promoted pro-inflammatory cytokine production in LPS-stimulated microglia.ConclusionsOur study indicated that IL-33/ST2 signaling plays an important role in the activation of microglia and cerebral endothelial cells and, therefore, is essential in leukocyte recruitment in brain inflammation.Graphical abstractThe role of IL-33/ST2 in LPS induced neuroinflammation

BackgroundChemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation.MethodsWild-type (WT), CXCL1−/−, and CXCR2−/− mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2−/− mice.ResultsExpression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2−/− and CXCL1−/− mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels.ConclusionsCXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation.

BackgroundThe complement system is becoming increasingly recognized as a key participant in many neurodegenerative diseases of the brain. Complement-deficient animals exhibit reduced neuroinflammation.MethodsIn the present study, we administered intracerebroventricularly lipopolysaccharide (LPS) to mimic local infection of the brain and investigated the role of key complement component C3 in brain vasculature endothelial activation and leukocyte recruitment. The degree of neutrophil infiltration was determined by esterase staining. Leukocyte-endothelial interactions were measured using intravital microscopy. Cerebral endothelial activation was evaluated using real-time PCR and Western blotting.ResultsNeutrophil infiltration into the brain cortex and hippocampus was significantly reduced in C3−/− mice and C3aR−/− mice but not in C6−/− mice. We detected markedly attenuated leukocyte-endothelial interactions in the brain microvasculature of C3−/− mice. Accordingly, in response to LPS administration, the brain microvasculature in these mice had decreased expression of P-selectin, E-selectin, intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Depletion of C3 from the circulation also caused reduction in VCAM-1 and E-selectin expression and leukocyte recruitment, suggesting that C3 in the circulation contributed to brain endothelial activation. Furthermore, C3−/− mice exhibited decreased leukocyte recruitment into the brain upon tumor necrosis factor-α (TNF-α) stimulation. C3a activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) and induced the upregulation of VCAM-1 and ICAM-1 expression in murine primary cerebral endothelial cells in vitro.ConclusionsOur study provides the first evidence that C3a plays a critical role in cerebral endothelial activation and leukocyte recruitment during inflammation in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0485-y) contains supplementary material, which is available to authorized users.

Leukocyte migration across the endothelial barrier plays an essential role in CNS inflammation. The migration process requires complex endothelial adhesion molecules concentrated at the junctions of endothelial cells. Recent findings suggest that cerebral endothelial cells play an active role in the pathogenesis of CNS inflammatory diseases. This review describes our current understanding of the effects of various inflammatory mediators of leukocyte migration on cerebral endothelial cells, the mechanisms underlying the leukocyte-endothelial cell interactions, and the crosstalk between endothelial cells and glial cells or platelets. These emerging mechanisms may provide new therapeutic strategies for a variety of CNS inflammatory diseases.

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A direct and practical synthetic route to N-heterocyclic carbene copper complexes of [(NHC)CuX] (X = halide) and [(NHC)2Cu]PF6 types using commercially available copper powder is described. A number of copper-NHC complexes have been obtained in a range of yields from 26 to 99%. The reactions take place in air without removal of moisture and oxygen, and the excess of copper powder can be easily removed via simple filtration after completion. The direct reactions of imidazolium salts and copper powder can also be performed in aqueous media avoiding tedious purification processes. The procedure is also suitable for gram-scale preparation.