The fungus Cryptococcus neoformans is considered the leading cause of death in immunocompromised patients. Despite numerous investigations concerning its molecular epidemiology, there are only a few studies addressing the impacts of varying factors on genotype-phenotype correlations. It remains largely unknown whether genetic and environmental variabilities among isolates from different sources may have dramatic consequences on virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and 7 from a natural environment, to investigate factors influencing the outcome of C. neoformans infection. MLST analysis clearly identified sequence type (ST) 5 as the prevalent sequence type in all clinical isolates and interestingly, genotypic diversities were observed in isolates from both HIV-uninfected individual and natural environment but not those from HIV-infected patients. Moreover, we found that compared to those from HIV-infected patients, the isolates from HIV-uninfected individuals exhibited enhanced virulence-associated traits including significantly elevated capsule production and melanin formation, increases in survival in human cerebrospinal fluid (CSF), less effective uptake by host phagocytes, and higher mortality in a mouse model of cryptococcosis. Consistently, pathogenic phenotypes were associated with CD4 counts of patients, implying environmental impact on within-host C. neoformans virulence. Importantly, a large-scale whole-genome sequencing analysis revealed that genomic variations within genes related to specific functions may act as a vital driving force of host intrinsic virulence evolution. Taken together, our results support a strong genotype-phenotype correlation suggesting that the pathogenic evolution of C. neoformans could be heavily affected by both genetic and environmental factors.
Due to the sea water intrusion and the development trend of using large-scale ships, more stringent requirements are put forward for the safety of water delivery process and the mooring equipment operation for the sea shiplock. The maximum loads for the mooring equipment of sea shiplock, i.e., floating mooring column (FMC), are generally occurred at the end of water delivery. The superimposed effect of turbulent flow and marine corrosive environment can accelerate the failure of the floating mooring column structure for the sea shiplock, which leads to the safety incidents, including the structural damage of FMC and the breakage of mooring lines for the ship, etc. The safety of the FMC is mostly influenced by three factors, including the ship’s tonnage, the water flow environment of the locked room, and the lock operation technologies; among these, the water flow environment can be considered the most significant. In practice, because the mooring load of an FMC due to water delivery from the shiplock is very complicated, there is currently no mature approach to condition monitoring. This investigation aims to address a large sea shiplock, and the optimal regulation approach for water delivery of shiplock is established based on a load monitoring methodology for FMCs. The detection accuracy of the FMC mooring loads is controlled by simulation verification with errors less than 10%. During the optimized water delivery process, the exerted loads on the FMCs are noticeably reduced to be lower than the maximum design rating. The innovative approach is essentially based on an inversion calculation of the load response model for obtaining the mooring loads of FMCs, with the monitored load results used to regulate and optimize the water delivery process of the shiplocks. The research results can fill a part of the research gap of FMC mooring load condition monitoring method in shiplock water delivery, and provide technical support for the safety of shiplock water delivery process and mooring equipment operation.
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