Nationwide Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in China.

Objectives: Extended high-risk human papillomavirus (hrHPV) genotype testing has recently been introduced in routine cervical cancer screening. Changes in national and regional hrHPV genotype prevalence offer an objective baseline indicator of the future impact of mass HPV vaccination and HPV-based cervical screening.

Methods: This retrospective study reports nationwide hrHPV genotyping results from July 2018 to June 2019 in 29 KingMed Diagnostics laboratories throughout China.

Uncovering New Mutations Conferring Azole Resistance in the Gene.

The opportunistic pathogen has developed worldwide resistance to azoles largely through mutations in cytochromeP450 enzyme Cyp51. In this study, we indicated that azole situation results in emergence of azole-resistant mutations. There are previously identified azole-resistant mutations (M220K, M220I, M220R, G54E and G54W mutations) and we successfully identified in this study two new mutations (N248K/V436A, Y433N substitution) conferring azole resistance among 18 independent stable azole-resistant isolates.

and Efficacy of a Synergistic Combination of Itraconazole and Verapamil Against .

The incidence of aspergillosis continues to rise sharply, while the progress made in expanding the antifungal drug arsenal remains extremely slow, indicating an urgent need for new strategies. Previous studies have shown that the calcium signaling pathway, which is evolutionarily conserved in mammals and fungi, is involved in regulating the tolerance of azoles in fungi. In this study, we performed a preliminary screening among various combinations of different clinical calcium channel blockers and different antifungal drugs.

The Aspergillus fumigatus transcription factor AceA is involved not only in Cu but also in Zn detoxification through regulating transporters CrpA and ZrcA.

Copper (Cu) and zinc (Zn) are essential nutrients for both pathogens and hosts; however, their excess accumulation is toxic for all cells. The Aspergillus transcription factor AceA has been identified having function for Cu detoxification through up-regulation of the expression of the P-type ATPase, CrpA. Here, we demonstrate that Aspergillus fumigatus CrpA is involved in both Cu and Zn detoxification and a putative metallothionein AfCrdA plays a major function in Cu detoxification, and a putative transporter AfZrcA has a dominant role in Zn detoxification, but all three members are transcriptionally dependent on AfAceA.

Cu-sensing transcription factor Mac1 coordinates with the Ctr transporter family to regulate Cu acquisition and virulence in Aspergillus fumigatus.

Copper (Cu) is an essential trace element and is regarded as an important virulence factor in fungal pathogens. Previous studies suggest that a putative Cu-sensing transcription factor Mac1 and the Cu transporter Ctr family play important roles during fungal development and virulence. However, how Cu importers of the Ctr family are involved in the Cu acquisition and what is the functional relationship between them have not been fully investigated yet.

Erg4A and Erg4B Are Required for Conidiation and Azole Resistance via Regulation of Ergosterol Biosynthesis in Aspergillus fumigatus.

Unlabelled: Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen Aspergillus fumigatus remains limited. In this study, we found that two endoplasmic reticulum-localized sterol C-24 reductases encoded by both erg4A and erg4B homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis.

Comparative evaluation of nonylphenol isomers on steroidogenesis of rat Leydig Cells.

Nonylphenol (NP) has been proven to be one of the most investigated xenohormones interacting with the estrogen receptor. Technical nonylphenol (t-NP) contains at least 20 para-substituted isomers. It has been shown that NP isomers vary in their estrogenic potency.