{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:27:03Z","timestamp":1786645623131,"version":"build-2736575974"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key Research and Development Plan of Heilongjiang Province","award":["Grant No. GA21C007"],"award-info":[{"award-number":["Grant No. GA21C007"]}]},{"name":"The Heilongjiang Provincial Science and Technology Tackling Program","award":["Grant No. 2022ZXJ03C01"],"award-info":[{"award-number":["Grant No. 2022ZXJ03C01"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Smoking cessation decreases lung cancer progression; however, its effects on precancerous lesions and the underlying mechanisms remain unclear. This study established a mouse model of precancerous pulmonary nodules and employed single-cell RNA sequencing (scRNA-seq) and immune repertoire sequencing (IR-seq) to elucidate the regulatory mechanisms by which smoking cessation influences the development of lung precancerous lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A B[a]P-induced mouse model of pulmonary precancerous lesions was established after 6 weeks of B[a]P treatment. Lung nodules were identified via micro-MRI, and histopathological features were assessed by H&amp;E staining. After confirming the establishment of precancerous lesions in smoking-exposed mice, graded B[a]P withdrawal for 4 and 8 weeks was implemented. Nodule size was measured using Generic Medical Imaging software. scRNA-seq and IR-seq analyzed immune cell composition, proportions, signaling, and gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>B[a]P withdrawal reduced new lung nodule formation and decreased the diameter, area, and volume of existing nodules. It alleviated cellular atypia, reduced inflammation, and altered the tumor microenvironment by increasing T-, B-, and NK cells while reducing monocytes and neutrophils. Concurrently, B[a]P withdrawal downregulated Vim, GPX1, Atf3, CD44, and Arpc5 and upregulated Hsph1, Hsp90aa, and Hspa1b. B[a]P withdrawal upregulated CD80 and ICOS, suppressed intercellular communication via Icam1-(Itgal+Itgb2), Ppia-Bsg, and Thbs1-Cd47 pathways. The APP-CD74 pathway emerged as a novel regulator in precancerous lesions. IR-seq revealed restored T- and B-cell receptor diversity, CDR3 sequence alterations, and V(D)J gene regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>B[a]P withdrawal reduces lung nodules, inhibits progression, potentially by enhancing immune surveillance by modulating immune cells, signaling pathways, and gene expression, while promoting ferroptosis, suppressing inflammation, and preventing tumor stem cell-like traits. These findings may provide mechanistic insights into the beneficial effects associated with smoking cessation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356148","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:27:51Z","timestamp":1786642071000},"page":"e0356148","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulatory effects of smoking cessation on the cellular microenvironment and differentially expressed genes in precancerous lesions of pulmonary nodules in mice based on single-cell RNA sequencing and immune 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