26Background: Severe, steroid-insensitive asthma is a substantial clinical problem accounting 27

Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)–induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited all features of allergic disease, including AHR and eosinophil infiltration, in uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment following RSV-induced exacerbation only partially suppressed AHR and failed to dampen macrophage and neutrophil infiltration or inflammatory cytokine production (TNF-α, MCP-1, and KC). This mimics clinical observations in patients with exacerbations, which is associated with increased neutrophils and often poorly responds to corticosteroid therapy. Interestingly, we also observed increased TNF-α levels in sputum samples from patients with neutrophilic asthma. Although RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF-α and MCP-1 function or depletion of macrophages suppressed features of disease, including AHR and macrophage and neutrophil infiltration. Our findings highlight critical roles for macrophages and inflammatory cytokines (including TNF-α and MCP-1) in viral-induced exacerbation of asthma and suggest examination of these pathways as novel therapeutic approaches for disease management.

Surface passivation of the CdS/Cu 2 ZnSnS 4 photocathode by a HfO 2 layer was found to be very effective for enhancing the photoelectrochemical stability. The dependence of the photoelectrochemical performance, especially the stability of the Cu 2 ZnSnS 4 -based photocathode, on the thickness of the HfO 2 film was systematically investigated. The thickness of the HfO 2 layer obviously influenced the PEC stability and efficiency of the Cu 2 ZnSnS 4 -based photocathode. The CdS/Cu 2 ZnSnS 4 photocathode modified with a 6 nm thick HfO 2 layer showed long-term PEC photocurrent stability of over 10 h while still retaining high half-cell solar-to-hydrogen efficiency (HC-STH) of 2.7%. Finally, we fabricated an unbiased solar water splitting device based on the Pt/HfO 2 /CdS/Cu 2 ZnSnS 4 photocathode in tandem with a BiVO 4 photoanode, and this tandem device not only exhibited an unassisted STH conversion efficiency of 1.046% but also showed a high long-term stability of over 10 h.

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