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Background: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. Methods: In this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7-/- mice) blockages of α7 nAChR. Results: As shown in our in vivo studies, BBB injury was significantly reduced in α7-/- mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7-/- animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). Conclusions: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. Methods: In this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7−/− mice) blockages of α7 nAChR. Results: As shown in our in vivo studies, BBB injury was significantly reduced in α7−/− mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7−/− animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). Conclusions: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders. [ABSTRACT FROM AUTHOR]

A grid fusion lifting surface suitable for large subsonic angles of attack was designed. The influence of the grid position, grid diversion angle, and grid number on the aerodynamic performance of the grid fusion lifting surface under subsonic conditions was studied by numerical simulations. Based on the summary and analysis of the grid in the hypersonic state, the CFD numerical simulation method, which solves unsteady Reynolds averaged Navier-Stokes equations, was used to complete the research of the flow mechanism of the grid fin in the subsonic state. At low speed and subsonic conditions, the results show that the negative front grid fusion lift surface has better aerodynamic characteristics with a high angle of attack. Under subsonic conditions, the stall angle of attack of the front grid fusion lifting surface with a diversion angle of 20° increases by 16°, and the maximum lift coefficient increases by 22.1% compared to that of the conventional flat wing. The number of grids has an insignificant effect on the aerodynamic performance of the grid fusion lifting surface at a large angle of attack. [ABSTRACT FROM AUTHOR]