{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:14:32Z","timestamp":1788239672070,"version":"build-2803163510"},"reference-count":26,"publisher":"CSIRO Publishing","issue":"13","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Pre-eclampsia (PE) involves placental dysfunction and immune dysregulation, but the cell-type localization of tryptophan\u2013kynurenine\u2013nicotinamide adenine dinucleotide (Trp\u2013Kyn\u2013NAD+) axis-related genes in PE placentas remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to localize Trp\u2013Kyn\u2013NAD+ axis-related expression across placental cell types and prioritize candidate axis-related markers using public transcriptomic datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The placental microarray dataset GSE75010 was used for discovery, GSE24129 for supportive external evaluation, and the single-cell RNA sequencing dataset GSE173193 for descriptive cell-type localization. Single-cell annotation, combined axis-gene localization, differential-expression and co-expression analyses, fixed four-gene model evaluation, immune-signature analysis, exploratory ligand\u2013receptor expression scoring and transcription factor\u2013gene co-expression analysis were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>Combined single-cell analysis showed non-uniform localization of Trp\u2013Kyn\u2013NAD+ axis-related expression across placental cell types. Microarray-based screening prioritized AFMID, ENPP1, IDO1, and NT5E as candidate axis-related genes. The fixed four-gene model showed moderate internal discrimination, and results from the small external cohort were interpreted as supportive. Candidate genes were also associated with immune-signature variation, and ligand\u2013receptor expression scoring identified exploratory communication-related transcriptional patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>By prioritizing AFMID, ENPP1, IDO1, and NT5E and mapping their cell-type localization, this study placed established IDO1-related evidence within a broader Trp\u2013Kyn\u2013NAD+ axis-related transcriptomic context. AFMID, ENPP1, and NT5E represent additional candidates for evaluation in larger cohorts and experimental systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>These findings provide a cell-type-resolved transcriptomic context for prioritizing Trp\u2013Kyn\u2013NAD+ axis-related candidates for further validation in PE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1071\/rd26131","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:20:13Z","timestamp":1788236413000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated placental microarray and single-cell transcriptomic analysis prioritizes Trp\u2013Kyn\u2013NAD+ axis-related candidate markers in 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