Discovery of New Tricyclic Oxime Sampangine Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcosis and Candidiasis.

Cryptococcus neoformans (C. neoformans) and Candida albicans (C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2 showed excellent inhibitory activity against C. neoformans (MIC80 = 0.016 µg/mL) and synergized with fluconazole to treat resistant C. albicans (FICI = 0.078). Interestingly, compound WZ-2 effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2 (5 mg/kg) effectively reduced the brain C. neoformans H99 burden. Furthermore, compound WZ-2 alone and its combination with fluconazole also significantly reduced the kidney burden of the drug-resistant strain (0304103) and sensitive strain (SC5314) of C. albicans.

Influencing Factors and Symbiotic Mechanism of the Integration of Medical Care and Disease Prevention during the COVID-19 Pandemic: A Cross-Sectional Survey of Public Hospital Employees.

Background: The COVID-19 outbreak has accelerated the huge difference between medical care and disease prevention in Chinese medical institutions. This study aimed to investigate the relationship between the symbiotic units, environments, models, and effects of the integration of medical care and disease prevention. Methods: This cross-sectional study involved 762 employees of public hospitals in 11 cities in Zhejiang Province by random stratified sampling. We analyzed the influence paths of elements in the mechanism of integration of medical care and disease prevention and the mediating effect of symbiotic models among symbiotic units, symbiotic environments, and effects on this integration. Results: The path coefficient of the symbiotic unit on the symbiosis model was 0.46 (p < 0.001), the path coefficient of the symbiotic environment on the symbiosis model was 0.52 (p < 0.001). The path coefficient of the symbiotic unit and the environment was 0.91 (p < 0.001). The symbiotic models exhibited a partial mediation effect between symbiotic units and the effect of this integration. Sobel test = 3.27, ß = 0.152, and the mediating effect accounted for 34.6%. Conclusions: It is suggested that health policymakers and public hospital managers should provide sufficient symbiotic units, establish collaborative symbiotic models, and improve the effects of integration of medical care and disease prevention in public hospitals.