{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:16:58Z","timestamp":1788239818153,"version":"build-2803163510"},"reference-count":61,"publisher":"Frontiers Media SA","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:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microglial neuroinflammation contributes to the progression of neurodegenerative diseases, yet it remains challenging to attenuate inflammatory responses while preserving cellular function. The effects of (R)-nicotine, diosmetin, their combined administration, and galantamine on heterogeneous BV2 transcriptional states have not been compared at single-cell resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LPS-stimulated BV2 microglial-like cells were treated with (R)-nicotine, diosmetin, their combination (DR), or galantamine. Single-cell RNA sequencing was performed with three biological replicates per group and integrated with RNA velocity and SCENIC regulon inference to characterize treatment-associated state redistribution, inferred local transcriptional directionality and regulon-activity patterns. Functional validation included CCK-8 metabolic activity assays, multiplex cytokine ELISA, BDNF\/GDNF quantification, qPCR, and high-content immunofluorescence analysis of iNOS and Arg1 at single-cell resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LPS decreased the relative abundance of the\n                      <jats:italic>\n                        Itgae\n                        <jats:sup>+<\/jats:sup>\n                        \/Plk4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      cluster while increasing the\n                      <jats:italic>\n                        Nmur1\n                        <jats:sup>+<\/jats:sup>\n                        \/Limk2\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      cluster and inflammatory effector programs. DR treatment suppressed pro-inflammatory cytokine release without significantly reducing CCK-8-assessed metabolic activity, increased the\n                      <jats:italic>\n                        Itgae\n                        <jats:sup>+<\/jats:sup>\n                        \/Plk4\n                        <jats:sup>+<\/jats:sup>\n                      <\/jats:italic>\n                      cluster proportion, and increased BDNF\/GDNF relative to LPS. RNA velocity and SCENIC analyses suggested that DR and galantamine showed distinct transcriptional and regulatory patterns: DR attenuated Batf-associated inflammatory regulons and was associated with increased Atf3-linked stress-response activity, whereas galantamine preferentially engaged DNA repair and genome-maintenance programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that the DR condition was associated with remodeling of LPS-challenged BV2 microglial-like states, attenuation of inflammatory programs, and increased neurotrophic outputs relative to LPS, without significantly reducing CCK-8-assessed metabolic activity. This study provides a single-cell characterization of distinct treatment-associated responses to (R)-nicotine, diosmetin, their combined administration, and galantamine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1901868","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:27:05Z","timestamp":1788236825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell transcriptomics reveals distinct microglial state remodeling associated with the (R)-nicotine\/diosmetin combination and galantamine in LPS-challenged BV2 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Yihan","family":"Liu","sequence":"first","affiliation":[{"name":"Beijing Life Science Academy","place":["Beijing, China"]},{"name":"China National Tobacco Quality Supervision & Test Centre","place":["Zhengzhou, 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