{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:18:34Z","timestamp":1784035114085,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"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. Plant Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Understanding the chemical linkage from non-volatile precursors in leaf to flavor compounds in mainstream smoke is critical for evaluating the contrasting sensory perceptions of different tobacco phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To elucidate this mechanism, we systematically compared high-quality Zimbabwe tobacco leaf and China Hehua tobacco dust using a multi-platform analytical strategy, including cascade membrane ultrafiltration, UV-\n                      <jats:italic>vis<\/jats:italic>\n                      ,\n                      <jats:sup>1<\/jats:sup>\n                      H NMR, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results indicated that the bulk macromolecules were predominantly carbohydrates and highly conserved across both tobacco leaves, while trace chemical divergences drive their distinct sensory profiles. Zimbabwe tobacco smoke particulates were enriched in aromatic pyrazoles and other N-heterocycles, fueled by a nitrogen-rich precursor matrix in the uncombusted extract of Zimbabwe tobacco leaf. Conversely, Hehua smoke featured sweet-toned furans and heavy alkanes, originating from an altered chemical balance alongside a carbon-hydrogen-oxygen (CHO) fraction that is relatively more aliphatic and lipid-rich. Furthermore, by tracking nontargeted markers in the smoke particulates generated from filtrates and retentates attained through the cascade filtration stages, potential macromolecular interactions were found influencing the combustion transformation. Specific macromolecular fractions of the 50 to 300 kDa range in the Hehua matrix exhibit pronounced co-enrichment with free small-molecule precursors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The observed co-enrichment suggests that these specific macromolecular fractions may act as carriers during their transfer into mainstream smoke. This novel comparative framework successfully bridges the analytical gap between uncombusted tobacco precursors and flavors in smoke particulates, establishing a chemical foundation for the digital quality evaluation and targeted formulation of substitute tobacco materials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpls.2026.1868514","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:40:15Z","timestamp":1784032815000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the linkage between non-volatile precursors and particulate-phase flavor compounds in mainstream smoke via multi-platform analysis and cascade ultrafiltration"],"prefix":"10.3389","volume":"17","author":[{"given":"Yi-Han","family":"Zhang","sequence":"first","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yan","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Min","family":"He","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ru","family":"Wang","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shen","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Bo","family":"Ji","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of China National Tobacco Corporation","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Jiang","family":"He","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of China National Tobacco Corporation","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Juan","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of China National Tobacco Corporation","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Zhengzhou Tobacco Research Institute of China National Tobacco Corporation","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Shaanxi University of Science and Technology","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Shaanxi University of Science and Technology","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ke","family":"Zang","sequence":"additional","affiliation":[{"name":"China Tobacco Hebei Industry Co., Ltd.","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1021\/acs.chemrestox.3c00150","article-title":"Nontargeted analysis in tobacco research: challenges and opportunities","volume":"36","author":"Adeniji","year":"2023","journal-title":"Chem. Res. Toxicol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S53","DOI":"10.1016\/j.fct.2004.01.001","article-title":"An overview of the effects of tobacco ingredients on smoke chemistry and toxicity","volume":"42","author":"Baker","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/mrc.1939","article-title":"Tobacco smoke particulate matter chemistry by NMR","volume":"45","author":"Barsanti","year":"2007","journal-title":"Magn. Reson. Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.etp.2005.05.010","article-title":"Analysis of complex mixtures \u2013 Cigarette smoke","volume":"57","author":"Borgerding","year":"2005","journal-title":"Exp. Toxicol. Pathol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"17957","DOI":"10.1021\/acsomega.8b02136","article-title":"A solution NMR approach to determine the chemical structures of carbohydrates using the hydroxyl groups as starting points","volume":"3","author":"Brown","year":"2018","journal-title":"ACS Omega"},{"key":"B6","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.phytochem.2004.01.019","article-title":"Metabolic fingerprinting of wild type and transgenic tobacco plants by 1H NMR and multivariate analysis technique","volume":"65","author":"Choi","year":"2004","journal-title":"Phytochemistry"},{"key":"B7","first-page":"403","article-title":"Tobacco research and development","volume-title":"Zimbabwe\u2019s Agricultural Revolution Revisited","author":"Cole","year":"2024"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7313","DOI":"10.3390\/molecules15107313","article-title":"Plant phenolics: extraction, analysis and their antioxidant and anticancer properties","volume":"15","author":"Dai","year":"2010","journal-title":"Molecules"},{"key":"B9","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1021\/acs.chemrestox.8b00097","article-title":"Free-base nicotine determination in electronic cigarette liquids by 1H NMR spectroscopy","volume":"31","author":"Duell","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2023.101532","article-title":"Widely targeted metabolomic analysis reveals that volatile metabolites in cigar tobacco leaves dynamically change during fermentation","volume":"35","author":"Fan","year":"2023","journal-title":"Biochem. Biophys. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.foodchem.2007.05.091","article-title":"Chlorogenic acid and caffeine contents in various commercial brewed coffees","volume":"106","author":"Fujioka","year":"2008","journal-title":"Food Chem."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2023.1264739","article-title":"Aroma precursors of cigars from different tobacco parts and origins, and their correlations with sensory characteristics","volume":"14","author":"Geng","year":"2023","journal-title":"Front. Plant Sci."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/beverages11050125","article-title":"The impact of brewing methods on the quality of a cup of coffee","volume":"11","author":"Genovese","year":"2025","journal-title":"Beverages"},{"key":"B14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jhazmat.2010.08.126","article-title":"Multivariate chemometric discrimination of cigarette tobacco blends based on the UV\u2013Vis spectrum of their hydrophilic extracts","volume":"185","author":"Giokas","year":"2011","journal-title":"J. Hazard. Mater."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1039\/C8RA08395A","article-title":"Microfiltration of raw soy sauce: membrane fouling mechanisms and characterization of physicochemical, aroma and shelf-life properties","volume":"9","author":"Guo","year":"2019","journal-title":"RSC Adv."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2024.1476807","article-title":"Characterization of the key aroma compounds in cigar filler tobacco leaves from different production regions","volume":"15","author":"Jiang","year":"2024","journal-title":"Front. Plant Sci."},{"key":"B17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1385\/0-89603-215-9:149","article-title":"The application of nuclear magnetic resonance to structural studies of polysaccharides","volume-title":"Spectroscopic Methods and Analyses: Nmr, Mass Spectrometry, and Metalloprotein Techniques","author":"Jones","year":"1993"},{"key":"B18","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/nmeth.2551","article-title":"LipidBlast in silico tandem mass spectrometry database for lipid identification","volume":"10","author":"Kind","year":"2013","journal-title":"Nat. Methods"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17124262","article-title":"The political economy of tobacco in Mozambique and Zimbabwe: a triangulation mixed methods protocol","volume":"17","author":"Lencucha","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5736","DOI":"10.1039\/d5ay00531k","article-title":"Deciphering the differences in aroma components of tobacco from different origins based on HS-GC-IMS and multivariate statistical analysis","volume":"17","author":"Li","year":"2025","journal-title":"Anal. Methods"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5005","DOI":"10.1007\/s00216-013-6869-2","article-title":"Metabolomics for unknown plant metabolites","volume":"405","author":"Nakabayashi","year":"2013","journal-title":"Anal. Bioanal. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1080\/03610470.2021.2003669","article-title":"Identification and categorization of volatile sulfur flavor compounds in roasted malts and barley","volume":"81","author":"Parr","year":"2023","journal-title":"J. Am. Soc Brew. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"48196","DOI":"10.1021\/acsomega.4c05472","article-title":"Development and application of a quantitative model for proximate and ultimate analysis of flue-cured tobacco based on near-infrared spectroscopy","volume":"9","author":"Peng","year":"2024","journal-title":"ACS Omega"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1021\/ed500578c","article-title":"1H NMR spectroscopy-based configurational analysis of mono- and disaccharides and detection of \u03b2-glucosidase activity: an undergraduate biochemistry laboratory","volume":"92","author":"Periyannan","year":"2015","journal-title":"J. Chem. Educ."},{"key":"B25","volume-title":"The Chemical Components of Tobacco and Tobacco Smoke","author":"Rodgman","year":"2013"},{"key":"B26","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.aca.2010.06.029","article-title":"Quantification of organic acids in beer by nuclear magnetic resonance (NMR)-based methods","volume":"674","author":"Rodrigues","year":"2010","journal-title":"Anal. Chim. Acta"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25194529","article-title":"Volatile phenols\u2014Important contributors to the aroma of plant-derived foods","volume":"25","author":"Schieber","year":"2020","journal-title":"Molecules"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1007\/s13361-016-1469-y","article-title":"Untargeted metabolomics strategies-challenges and emerging directions","volume":"27","author":"Schrimpe-Rutledge","year":"2016","journal-title":"J. Am. Soc Mass Spectrom."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying small molecules via high resolution mass spectrometry: communicating confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"388","DOI":"10.2478\/s11535-011-0028-6","article-title":"Total phenolic content and antioxidant activity of plants used in traditional Romanian herbal medicine","volume":"6","author":"Spiridon","year":"2011","journal-title":"Cent. Eur. J. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"12273","DOI":"10.1021\/acs.analchem.1c01841","article-title":"CRB-SWATH: a method for enhancing untargeted precursor ion extraction and automatically constructing their tandem mass spectra from swath datasets by chromatographic retention behaviors","volume":"93","author":"Wang","year":"2021","journal-title":"Anal. Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.1021\/acs.analchem.2c05480","article-title":"Biogenic solution map based on the definition of the metabolic correlation distance between 4-dimensional fingerprints","volume":"95","author":"Wang","year":"2023","journal-title":"Anal. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"23204","DOI":"10.1021\/acs.analchem.5c03451","article-title":"CRB-FCC: a standardized nontargeted analysis for formula assignment and structure annotation","volume":"97","author":"Wang","year":"2025","journal-title":"Anal. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6069","DOI":"10.1080\/10408398.2022.2027339","article-title":"Oleogels prepared with low molecular weight gelators: texture, rheology and sensory properties, a review","volume":"63","author":"Wang","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.trac.2007.12.001","article-title":"Quantitative metabolomics using NMR","volume":"27","author":"Wishart","year":"2008","journal-title":"TrAC Trends Anal. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0168-8510(01)00126-9","article-title":"Prospects for tobacco control in Zimbabwe: a historical perspective","volume":"57","author":"Woelk","year":"2001","journal-title":"Health Policy"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2025.1703429","article-title":"Metabolomic analysis of Yunnan cigar tobacco leaves: impact of geography and climate on flavor characteristics and machine learning-based origin traceability","volume":"16","author":"Wu","year":"2026","journal-title":"Front. Plant Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.microc.2009.12.001","article-title":"Multivariate statistical analysis of tobacco of different origin, grade and variety according to polyphenols and organic acids","volume":"95","author":"Xiang","year":"2010","journal-title":"Microchem. J."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2024.465554","article-title":"Nontarget analysis of natural flavor metabolites in tobacco extracts","volume":"1740","author":"Xu","year":"2025","journal-title":"J. Chromatogr. A"},{"key":"B40","doi-asserted-by":"publisher","first-page":"6789","DOI":"10.1021\/es0629054","article-title":"Mechanism involved in the evolution of physically irreversible fouling in microfiltration and ultrafiltration membranes used for drinking water treatment","volume":"41","author":"Yamamura","year":"2007","journal-title":"Environ. Sci. Technol."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2025.1687831","article-title":"Unraveling the molecular basis of sensory attributes in smoking spices: a nontargeted metabolite analysis using liquid chromatography high resolution mass spectrometry","volume":"12","author":"Yang","year":"2025","journal-title":"Front. Mol. Biosci."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2025.1657415","article-title":"Untargeted metabolomics based on HS-SPME-GC-MS revealing the dynamic evolution of aroma components during cigar aging","volume":"16","author":"Yang","year":"2025","journal-title":"Front. Plant Sci."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/membranes13010077","article-title":"Reduction of ultrafiltration membrane fouling by the pretreatment removal of emerging pollutants: a review","volume":"13","author":"Zhang","year":"2023","journal-title":"Membranes"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/07373937.2026.2642377","article-title":"Unraveling the key chemical components transformation and aroma formation mechanisms during tobacco curing-drying process: a comprehensive review","volume":"44","author":"Zhao","year":"2026","journal-title":"Drying Technol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2023.1123100","article-title":"Integrative analysis of sensory evaluation and non-targeted metabolomics to unravel tobacco leaf metabolites associated with sensory quality of heated tobacco","volume":"14","author":"Zhao","year":"2023","journal-title":"Front. Plant Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"20220326","DOI":"10.1515\/chem-2022-0326","article-title":"Untargeted metabolomics revealing changes in aroma substances in flue-cured tobacco","volume":"21","author":"Zou","year":"2023","journal-title":"Open Chem."}],"container-title":["Frontiers in Plant Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2026.1868514\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:40:16Z","timestamp":1784032816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2026.1868514\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":46,"alternative-id":["10.3389\/fpls.2026.1868514"],"URL":"https:\/\/doi.org\/10.3389\/fpls.2026.1868514","relation":{},"ISSN":["1664-462X"],"issn-type":[{"value":"1664-462X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"article-number":"1868514"}}