PubMed · 42688201
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Geraldine H O'Sullivan Coyne, Alice P Chen. 2026-08-19. Editorial: Women in science-precision medicine 2023.. https://doi.org/10.3389/fmed.2026.1927814
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Metagenomic community state types (mgCSTs) capture within-species genetic and functional diversity and community structure of the vaginal microbiome, enabling precise links between microbiome composition, function, and health-related risk. VISTA, the Vaginal Inference of Subspecies and Typing Algorithm, is a two-step classifier that assigns mgCSTs to vaginal metagenomes, providing standardized, scalable classifications.
Calcific aortic valve disease (CAVD) is a progressive fibrocalcific illness for which no effective pharmaceutical treatment exists. This study investigated whether carbamoylated high-density lipoprotein (C-HDL), a defective type of HDL that can develop during inflammation, contributes to CAVD progression and the involved molecular pathways. Male ApoE-/- mice were divided into three groups: CAVD model, cyanate-treated, and inhibitor, and analyzed after 12 weeks. C57BL/6 mice on a regular diet served as blank controls. Serum paraoxonase-1 (PON1), aortic valve calcification, cluster of differentiation 31 (CD31), phosphorylated nuclear factor kappa B p65 (p-p65), NOTCH receptor 1 (NOTCH1), and runt-related transcription factor 2 (RUNX2) were evaluated. In parallel, using RNA sequencing (RNA-seq), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) network analysis, and quantitative real-time polymerase chain reaction. Cyanate treatment reduced serum PON1 levels, increased von Kossa-positive calcium deposition, and raised CD31, p-p65, NOTCH1, and RUNX2 levels compared with the model group, but Gly partially corrected these effects. Transcriptomic research identified 270 C-HDL-associated differentially expressed genes (DEGs) enriched in pathways associated with inflammatory signaling and NF-κB activity. Five potential hub genes (BIRC6, PIK3R1, ATM, IFIH1, and DDX58) were discovered and verified using qRT-PCR. These data show that C-HDL may accelerate CAVD by disrupting valve endothelial homeostasis and stimulating inflammatory signaling, and they identify potential molecular targets for future functional validation.
The prevalence of non-susceptibility to ceftolozane-tazobactam (C/T) among Pseudomonas aeruginosa remains low, but novel mechanisms of C/T resistance are of concern. Herein, we describe a novel P. aeruginosa genotype associated with high-level C/T resistance (>256/4 µg/mL) in a single patient. Whole-genome sequencing of the isolate was compared to that of a susceptible isolate cultured from the same patient 2 months earlier. Analysis of the sequences revealed two different P. aeruginosa high-risk clones: sequence type (ST)111 followed by ST235. The C/T-resistant ST235 isolate contained five copies of a genetic element composed of an L2 β-lactamase gene (blaL2) and a truncated ampRL2 transcriptional regulator gene, which are commonly found together in Stenotrophomonas maltophilia strains and have not been reported to mediate resistance to C/T. Comparative genomic analysis with other P. aeruginosa isolates failed to identify alternative explanations for the observed C/T resistance. We found that exogenous expression of blaL2 increased C/T minimum inhibitory concentrations (MICs) in genetically distinct P. aeruginosa strains. A screen of our archived isolates identified two P. aeruginosa clinical isolates, PS2045 and PS2046, with one and two copies, respectively, of the genetic element containing blaL2 and truncated ampRL2. Interestingly, disruption of the gene blaL2 but not the truncated ampRL2 in PS2045 led to a decrease in C/T MIC. Thus, we report a novel mechanism of C/T resistance in P. aeruginosa partially mediated by an L2 β-lactamase independently of its canonical regulator, AmpRL2.