BackgroundNeuroinflammation is a hallmark that leads to selective neuronal loss and/or dysfunction in neurodegenerative disorders. Microglia-derived lysosomal cathepsins are increasingly recognized as important inflammatory mediators to trigger signaling pathways that aggravate neuroinflammation. However, cathepsin H (Cat H), a cysteine protease, has been far less studied in neuroinflammation, compared to cathepsins B, D, L, and S. The expression patterns and functional roles of Cat H in the brain in neuroinflammation remain unknown.MethodsC57BL/6J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze expression and localization of Cat H in the brain. Nitrite assay was used to examine microglial activation in vitro; ELISA was used to determine the release of Cat H and proinflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ). Cat H activity was analyzed by cellular Cat H assay kit. Flow cytometry and in situ cell death detection were used to investigate neuronal death. Data were evaluated for statistical significance with one-way ANOVA and t test.ResultsCat H mRNA was only present in perivascular microglia and non-parenchymal sites under normal conditions. After LPS injection, Cat H mRNA expression in activated microglia in different brain regions was increased. Twenty-four hours after LPS injection, Cat H mRNA expression was maximal in SNr; 72 h later, it peaked in cerebral cortex and hippocampus then decreased and maintained at a low level. The expression of Cat H protein exhibited the similar alterations after LPS injection. In vitro, inflammatory stimulation (LPS, TNF-α, IL-1β, IL-6, and IFN-γ) increased the release and activity of Cat H in microglia. Conversely, addition of Cat H to microglia promoted the production and release of NO, IL-1β, and IFN-γ which could be prevented by neutralizing antibody. Further, addition of Cat H to Neuro2a cells induced neuronal death.ConclusionsTaken together, these data indicate that the up-regulated microglial Cat H expression, release, and activity in the brain lead to neuronal death in neuroinflammation. The functional link of Cat H with microglial activation might contribute to the initiation and maintenance of microglia-driven chronic neuroinflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0268-x) contains supplementary material, which is available to authorized users.

Experimental measurements of hydrodynamics and the volumetric mass transfer coefficient of oxygen (VMTCO) in an internal loop airlift reactor with different types of draft tubes are reported for the two‐phase systems, air/water and air/carboxyl methyl cellulose (CMC) solution, and a three‐phase system, air/water/resin particle, respectively. The properties of convergence‐divergence draft tubes with three different structural parameters are compared with those of the conventional column draft tube. The results indicate that gas holdups in convergence‐divergence draft tubes are higher than those in conventional draft tubes, the volumetric mass transfer coefficient of oxygen increases with increasing superficial air flow rates. The convergence‐divergence draft tubes all show higher mass transfer capacity than the traditional ones. A 10% higher mass transfer coefficient is observed for the three structural parameters. In the air/CMC system, the volumetric mass transfer coefficient of oxygen decreases with increasing bulk viscosity, while in the three‐phase system VMTCO increases with the resin particle loading. The correlation equation of the volumetric mass transfer coefficient with the operating conditions and structural parameters is established.

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Gas holdup and liquid circulation of one conventional draft tube and three different convergence-divergence draft tubes in an internal loop airlift reactor were investigated. Experiments were carried out in two-phase systems with air-water and air-CMC (carboxyl methyl cellulose) solution and three-phase system with air-water-resin particles. The two-phase drift-flux model was used to estimate gas holdup for three-phase Newtonian and two-phase non-Newtonian systems. It is shown that gas holdup in convergence-divergence draft tubes is higher than that in a conventional draft tube and increases with superficial gas velocity. Variation of the structural parameters of convergence-divergence draft tubes has little effect on gas holdup in the two-phase and three-phase system. The mathematical model, which is based on a drift-flux model, was developed to describe the liquid circulation velocity in the reactor satisfactorily.

In the present study, the dry reforming of methane (DRM) has been simulated in fluidized-bed reactors using the multiphase particle-in-cell model. The model was meticulously built to investigate the effect of a wide range of superficial gas velocities covering particulate, aggregative, and lean-phase flow regimes on bed hydrodynamics, conversion, and yields of product gases. Constant values for catalyst loading, CH4:CO2:N2 ratio (1:1:1.3), and catalyst and gas properties were maintained in all simulations. The simulation results obtained are in good agreement with the experimental data reported in the literature. The results show that under different gas velocities, conversion is relatively indiscernible in the particulate regime. In contrast, for the inhomogeneous phases, the turbulent fluidized bed had the best reactor performance with high CH4 and CO2 conversion rates, good CO + H2 productivity, and high CO/H2 molar ratio. This is due to the vigorous turbulent flow and relatively high gas-solid contact. Due to gas bypassing and backmixing triggered by bubbling, the bubbling fluidized bed generally had the worst performance and below that of the fast-fluidized bed. The present study demonstrates that the performance of DRM reactions in fluidized-bed reactors is strongly related to the hydrodynamics. Moreover, it shows the significance of gas velocity on DRM conversion, yield, and overall reactor performance.