Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Strategy for the Synthesis of α-Methoxytropones.

α-Methoxytropone is a structural motif found in various natural products and other compounds of interest to the scientific community but remains a synthetic challenge. The present Note describes the synthesis of variously substituted α-methoxytropones and related compounds through an intermolecular 3-hydroxy-4-pyrone-based oxidopyrylium (5 + 2) cycloaddition followed by a samarium iodide-mediated reductive ring-opening. The strategy is highlighted in the synthesis of a novel AC-ring analogue of colchicine to compare it to existing methods.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

Aims: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe.

Design, Setting And Participants: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months).

Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis.

Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. Here we report the generation of human trunk-like structures that model the co-morphogenesis, patterning and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis.

Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution.

Organoid evolution models complemented with integrated single-cell sequencing technology provide a powerful platform to characterize intra-tumor heterogeneity (ITH) and tumor evolution. Here, we conduct a parallel evolution experiment to mimic the tumor evolution process by evolving a colon cancer organoid model over 100 generations, spanning 6 months in time. We use single-cell whole-genome sequencing (WGS) in combination with viral lineage tracing at 12 time points to simultaneously monitor clone size, CNV states, SNV states, and viral lineage barcodes for 1,641 single cells.

Genetic Profile of Linezolid-Resistant Clinical Strains from Moscow.

Background: Linezolid, bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. The number of reported linezolid-resistant clinical strains is still low, and the correlation of molecular determinants with phenotype is not perfect.

Methods: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in and genes.