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Zika virus (ZIKV) is a neurotropic flavivirus. The outbreak of ZIKV in 2016 created a global health emergency. However, the underlying pathogenic mechanisms remain elusive. We investigated the host response features of in vivo replication in a mouse model of ZIKV infection, by performing a series of transcriptomic and bioinformatic analyses of ZIKV and mock‐infected brain tissue. Tissue damage, inflammatory cells infiltration and high viral replication were observed in the brain tissue of ZIKV infected mice. RNA‐Seq of the brain indicated the activation of ferroptosis pathways. Enrichment analysis of ferroptosis regulators revealed their involvement in pathways such as mineral absorption, fatty acid biosynthesis, fatty acid degradation, PPAR signaling pathway, peroxidase, and adipokinesine signalling pathway. We then identified 12 interacted hub ferroptosis regulators (CYBB, HMOX1, CP, SAT1, TF, SLC39A14, FTL, LPCAT3, FTH1, SLC3A2, TP53, and SLC40A1) that were related to the differential expression of CD8+ T cells, microglia and monocytes. CYBB, HMOX1, SALT, and SLAC40A1 were selected as potential biomarkers of ZIKV infection. Finally, we validated our results using RT‐qPCR and outside available datasets. For the first time, we proposed a possible mechanism of ferroptosis in brain tissue infected by ZIKV in mice and identified the four key ferroptosis regulators. [ABSTRACT FROM AUTHOR]

[Display omitted] • Posaconazole dry powder inhalers (DPIs) for pulmonary delivery mitigated adverse effects related to systemic administration. • Posaconazole nanocrystal-agglomerated particles in DPIs exhibited improved solubility and dissolution. • Optimized posaconazole DPIs demonstrated high pulmonary deposition and superior relative bioavailability in the lungs. • High drug loading in posaconazole DPIs reduced excipient use and the total amount of inhalable powder needed. Invasive pulmonary aspergillosis poses a significant threat to immunocompromised patients, characterized by high mortality rates. Posaconazole (PSZ), a second-generation triazole antifungal, exhibits broad-spectrum activity but suffers from limited pulmonary concentrations and notable systemic side effects when administered orally or intravenously. This study focuses on optimizing PSZ nanocrystals-agglomerated particles for dry powder inhalers (DPIs) to enhance solubility, dissolution rates, and pulmonary deposition, ultimately improving therapeutic efficacy while minimizing systemic adverse effects. We employed wet medium milling and spray-drying techniques to formulate PSZ nanocrystals-agglomerated DPIs. Various stabilizers including HPMC, HPC, Soluplus, and PVPK30, were systematically evaluated to optimize physicochemical properties. Aerosolization performance was assessed using the Next Generation Impactor, while antifungal efficacy was evaluated through in vitro and in vivo studies. The optimized PSZ DPIs demonstrated significant enhancements in solubility and dissolution rates, with a fine particle fraction (FPF) of 78.58 ± 3.21%, ensuring optimal lung delivery. In vitro experiments revealed potent effects with minimal cytotoxicity to lung cells. In vivo studies indicated that the optimized formulation achieved a C max /AUC 0→∞ ratio in lung tissues that was 27.32 and 6.76-fold higher than that of the oral suspension, highlighting increased local drug concentrations. This approach presents a scalable, cost-effective strategy for the pulmonary delivery of PSZ, ensuring high drug loading and promising clinical outcomes in treating pulmonary fungal infections. [ABSTRACT FROM AUTHOR]

Background: The antiviral activity and underlying mechanism of Patchouli alcohol remain unclear., Methods: This study evaluated the cytotoxicity, optimal methods for drug administration, anti-influenza A activity of Patchouli alcohol. The antiviral mechanism of Patchouli alcohol was also assessed via qRT-PCR, western blot, hemagglutination inhibiting (HAI) assay, and hemolysis inhibiting assay., Results: Patchouli alcohol was shown to have low cytotoxicity and its strongest antiviral effect was associated with premixed administration. Patchouli alcohol inhibited virus replication during the early lifecycle stages of influenza A virus infection and specifically prevented expression of the viral proteins, HA and NP. In both the HAI and hemolysis inhibiting assays, Patchouli alcohol was able to block HA2-mediated membrane fusion under low pH conditions. Patchouli alcohol had lower binding energy with HA2 than HA1., Conclusion: These findings suggest that Patchouli alcohol could be a promising membrane fusion inhibitor for the treatment of influenza A infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Zhang, Zhang, Lai, Long, Huang, Zhan, Liu, Lai, Zhang, Pan, Su and Li.)

Objective: To identify the biomarkers as early warning signals for severe COVID-19., Methods: We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19., Results: The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels ( P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 ( P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI : 1.046-1.526, P =0.015) with an AUC of 0.831 (95% CI : 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750., Conclusions: An increased NLR can serve as an early warning signal of severe COVID-19.