{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:03:40Z","timestamp":1789376620458,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Provincial Basic and Applied Basic Research Fund Project","award":["2024A1515012734"],"award-info":[{"award-number":["2024A1515012734"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515030086"],"award-info":[{"award-number":["2024A1515030086"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2023B1111030002"],"award-info":[{"award-number":["2023B1111030002"]}]},{"name":"Guangdong Clinical Research Center of Immune Disease","award":["2020B1111170008"],"award-info":[{"award-number":["2020B1111170008"]}]},{"name":"Guangdong Provincial Clinical Teaching Base Undergraduate Teaching Reform Research Project","award":["2025JD074"],"award-info":[{"award-number":["2025JD074"]}]},{"name":"Shenzhen Longhua District Science and Technology Innovation Special Fund","award":["20230516G54634167"],"award-info":[{"award-number":["20230516G54634167"]}]},{"name":"Shenzhen Longhua District Science and Technology Innovation Special Fund","award":["20250106G67331237"],"award-info":[{"award-number":["20250106G67331237"]}]},{"name":"Second Major Talent Development Program of the Third Affiliated Hospital of Sun Yat-Sen University"},{"name":"Guangzhou Pukang Charity Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objectives: We tested whether a database-derived phthalate ester (PAE)\u2013ankylosing spondylitis (AS) candidate panel identifies an inflammatory transcriptional program and characterized its transcription-factor (TF) architecture. Methods: Machine learning prioritization and repeated nested cross-validation were followed by locked-model transfer from GSE73754 to GSE25101. Donor-level single-cell analyses included 96,746 peripheral blood mononuclear cells from 10 AS and 29 healthy-control donors (GSE194315), with corroboration assessed in 25 additional baseline AS patients (GSE277117). Results: Within classical monocytes, the continuous signature covaried with panel-excluded TNF-\u03b1\/NF-\u03baB signaling (\u03c1 = 0.571; q = 0.000729), inflammatory response (\u03c1 = 0.447; q = 0.0108), and eight of 10 AP-1-related TF activities. Target-excluded TF activities covaried with CXCL8 (8\/10) and IL1B (10\/10). AP-1-gene\/CXCL8 co-expression received partial corroboration in the additional AS cohort (JUN\u2013CXCL8: \u03c1 = 0.92). Among 16 genes prioritized from 473 shared candidates, CXCL8, IL2RB, STAT5B and TNF were stable. The locked 14-gene model achieved an area under the receiver-operating-characteristic curve of 0.770 (DeLong 95% confidence interval, 0.596\u20130.943), supporting partial rank transportability. Secondary analyses showed a lower CD56bright fraction among natural killer (NK) cells in AS (\u22122.699 percentage points; 95% confidence interval, \u22124.575 to \u22120.611; q = 0.0498) and reduced NK-cell JUN expression (log2 fold change = \u22120.995; adjusted p = 0.0497). Conclusions: The PAE\u2013AS signature identifies an AP-1\/CXCL8-associated classical-monocyte inflammatory program, with partial cross-cohort corroboration and secondary NK alterations, providing candidates for exposure-informed mechanistic studies.<\/jats:p>","DOI":"10.3390\/genes17091113","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Database-Derived Phthalate Ester\u2013Ankylosing Spondylitis Signature Identifies an AP-1\/CXCL8 Inflammatory Classical-Monocyte Program"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-0688","authenticated-orcid":false,"given":"Xiqing","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Xuqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Wenyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Dan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xinlei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-0600","authenticated-orcid":false,"given":"Jieruo","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Xiaoyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-4201","authenticated-orcid":false,"given":"Yutong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial Spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00296-023-05274-w","article-title":"Recent Updates in Enthesitis-Related Arthritis","volume":"43","author":"Naveen","year":"2023","journal-title":"Rheumatol. 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