{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:08:15Z","timestamp":1789567695606,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PA2024GDSK0092"],"award-info":[{"award-number":["PA2024GDSK0092"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PA2025GDGP0026"],"award-info":[{"award-number":["PA2025GDGP0026"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2308085MC107"],"award-info":[{"award-number":["2308085MC107"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dairy Science and Technology Innovation Fund of China Dairy Industry Association for Mengniu Special Program","award":["CDIAKCJJ-MN-2025-09"],"award-info":[{"award-number":["CDIAKCJJ-MN-2025-09"]}]},{"name":"Engineering Research Center of Bio-Process of Ministry of Education"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Red kidney bean phytohemagglutinin (PHA) is an isolectin system of erythroagglutinating (PHA-E) and leucoagglutinating (PHA-L) subunits, but the biological significance of the natural ratio remains unclear. Here, natural PHA fractions with stepwise PHA-E\/PHA-L ratios (N1 = 0.85, N2 = 1.24, N3 = 1.80) were tested in a BALB\/c mouse sensitization model. The fractions induced nonlinear, qualitatively distinct responses. N1 and N2 both increased ileal epithelial length by approximately 10.2% relative to PBS; N2 additionally showed the highest IgG2a\/IgG1 ratio, a prominent IL-17A response, and restored ZO-1 and occludin expression to PBS levels. N3 evoked the strongest IL-4-dominant Th2-like response and the highest sIgA level among PHA fractions, yet shortened the epithelium by 14.3% with a weaker barrier-gene expression. These phenotypes coincided with fraction-specific gut microbiota remodeling. Thus, the PHA isoform ratio critically determines immune, intestinal, and microbial outcomes and warrants consideration in bean lectin safety evaluation.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05871","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:01:39Z","timestamp":1788793299000},"page":"28723-28739","source":"Crossref","is-referenced-by-count":0,"title":["Isoform Ratio Rather\nthan Total Content Determines\nNonlinear Bioactivity of Red Kidney Bean Phytohemagglutinin in Mice"],"prefix":"10.1021","volume":"74","author":[{"given":"Rong","family":"Zhang","sequence":"first","affiliation":[{"name":"Hefei University of Technology , , , ,","place":["Hefei, Anhui, P. R. China, 230009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330047"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Jin","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , , ,","place":["Hefei, Anhui, P. R. China, 230009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , , ,","place":["Hefei, Anhui, P. R. China, 230009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Meng","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , , ,","place":["Hefei, Anhui, P. R. China, 230009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-4928","authenticated-orcid":true,"given":"Shudong","family":"He","sequence":"additional","affiliation":[{"name":"Hefei University of Technology , , , ,","place":["Hefei, Anhui, P. R. China, 230009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026091609094029300_cit1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1385232","article-title":"Legumes and common beans in sustainable diets:\nnutritional quality, environmental benefits, spread and use in food\npreparations","volume":"11","author":"Lisciani","year":"2024","journal-title":"Front. Nutr."},{"key":"2026091609094029300_cit2","doi-asserted-by":"publisher","DOI":"10.1093\/fqsafe\/fyae003","article-title":"Innovations\nin measuring and mitigating phytohemagglutinins, a key food safety\nconcern in beans","volume":"8","author":"Lu","year":"2024","journal-title":"Food Qual. Saf."},{"issue":"1","key":"2026091609094029300_cit3","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.seppur.2008.04.004","article-title":"Phytohemagglutinin isolectins extracted and purified from red kidney\nbeans and its cytotoxicity on human H9 lymphoma cell line","volume":"63","author":"Ren","year":"2008","journal-title":"Sep. Purif. Technol."},{"issue":"4","key":"2026091609094029300_cit4","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1093\/glycob\/cwu004","article-title":"Phytohemagglutinin\nfrom Phaseolus vulgaris (PHA-E) displays\na novel glycan recognition mode using a common legume lectin fold","volume":"24","author":"Nagae","year":"2014","journal-title":"Glycobiology"},{"issue":"24","key":"2026091609094029300_cit5","doi-asserted-by":"publisher","DOI":"10.3390\/foods14244247","article-title":"Toward standardized\nmeasurement of active phytohemagglutinin in common bean, Phaseolus vulgaris L","volume":"14","author":"Thompson","year":"2025","journal-title":"Foods"},{"issue":"1","key":"2026091609094029300_cit6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/j.1432-1033.1984.tb08162.x","article-title":"Biosynthesis\nand processing of phytohemagglutinin in developing bean cotyledons","volume":"141","author":"Vitale","year":"1984","journal-title":"Eur. J. Biochem."},{"issue":"9","key":"2026091609094029300_cit7","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1089\/jmf.2014.0120","article-title":"Toxicity\nassessment of common beans (Phaseolus vulgaris L.) widely consumed by tunisian\npopulation","volume":"18","author":"Nciri","year":"2015","journal-title":"J. Med. Food"},{"issue":"20","key":"2026091609094029300_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e39471","article-title":"From inflammation\nto immune regulation: The dual nature\nof dietary lectins in health and disease","volume":"10","author":"Konozy","year":"2024","journal-title":"Heliyon"},{"key":"2026091609094029300_cit9","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2025.10017","article-title":"Legume lectin phytohemagglutinin\nreduces transepithelial electrical resistance by counteracting the\nchaperone function of heat shock protein-70","volume":"14","author":"Dokladny","year":"2025","journal-title":"J. Nutr. Sci."},{"issue":"8","key":"2026091609094029300_cit10","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain\nfatty acids: linking\ndiet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev.\nImmunol."},{"issue":"W1","key":"2026091609094029300_cit11","doi-asserted-by":"publisher","first-page":"W420","DOI":"10.1093\/nar\/gkac373","article-title":"IBS 2.0: an\nupgraded illustrator for the visualization of biological sequences","volume":"50","author":"Xie","year":"2022","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"2026091609094029300_cit12","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2025.100768","article-title":"Isolation, purification,\nand characterization of a lectin from Cassia senna seeds with analgesic\nand gastroprotective effects","volume":"5","author":"Dafalla","year":"2025","journal-title":"Phytomed. Plus"},{"key":"2026091609094029300_cit13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.fct.2013.08.004","article-title":"A BALB\/c mouse model for assessing\nthe potential allergenicity of proteins: comparison of allergen dose,\nsensitization frequency, timepoint and sex","volume":"62","author":"Chen","year":"2013","journal-title":"Food Chem. Toxicol."},{"issue":"1","key":"2026091609094029300_cit14","doi-asserted-by":"publisher","DOI":"10.3390\/foods14010109","article-title":"Synergistic synbiotic-containing\nlactiplantibacillus plantarum and fructo-oligosaccharide alleviate\nthe allergenicity of mice induced by soy protein","volume":"14","author":"Bai","year":"2025","journal-title":"Foods"},{"issue":"6","key":"2026091609094029300_cit15","doi-asserted-by":"publisher","DOI":"10.3390\/foods13060934","article-title":"Polygonatum sibiricum saponin prevents immune dysfunction and strengthens\nintestinal mucosal barrier function in cyclophosphamide-induced immunosuppressed\nBALB\/c mice","volume":"13","author":"Zhao","year":"2024","journal-title":"Foods"},{"issue":"19","key":"2026091609094029300_cit16","doi-asserted-by":"publisher","DOI":"10.3390\/foods14193376","article-title":"Grifola frondosa polysaccharides\nalleviated cyclophosphamide-induced\nintestinal injury based on microbiota, metabolite and immune axis\nmodulation","volume":"14","author":"Wu","year":"2025","journal-title":"Foods"},{"issue":"1","key":"2026091609094029300_cit17","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/bioinformatics\/btp610","article-title":"Methods\nfor combining peptide intensities to estimate relative protein abundance","volume":"26","author":"Carrillo","year":"2010","journal-title":"Bioinformatics"},{"issue":"12","key":"2026091609094029300_cit18","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1074\/mcp.M800104-MCP200","article-title":"Label-free\nquantitative analysis\nof one-dimensional PAGE LC\/MS\/MS proteome: application on angiotensin\nII-stimulated smooth muscle cells secretome","volume":"7","author":"Gao","year":"2008","journal-title":"Mol. Cell. Proteomics"},{"issue":"8","key":"2026091609094029300_cit19","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1074\/mcp.M115.056911","article-title":"CONSTANd: A normalization method\nfor isobaric labeled spectra by constrained optimization","volume":"15","author":"Maes","year":"2016","journal-title":"Mol. Cell. Proteomics"},{"issue":"9","key":"2026091609094029300_cit20","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.1016\/S0021-9258(17)40456-X","article-title":"Biological\nand biochemical properties\nof Phaseolus vulgaris isolectins","volume":"252","author":"Leavitt","year":"1977","journal-title":"J. Biol. Chem."},{"issue":"19","key":"2026091609094029300_cit21","doi-asserted-by":"publisher","first-page":"16928","DOI":"10.1074\/jbc.M112382200","article-title":"The high specificities\nof phaseolus vulgaris erythro- and leukoagglutinating lectins for\nbisecting GlcNAc or \u03b21\u20136-linked branch structures, respectively,\nare attributable to Loop B","volume":"277","author":"Kaneda","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026091609094029300_cit22","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2024.101913","article-title":"The tissue glycome as regulator of\nimmune activation and tolerance mediated by C-type lectins and Siglecs","volume":"76","author":"Nardini","year":"2024","journal-title":"Semin. Immunol."},{"key":"2026091609094029300_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2024.101925","article-title":"Roles for Siglec-glycan\ninteractions in regulating immune cells","volume":"77","author":"Lin","year":"2025","journal-title":"Semin.\nImmunol."},{"issue":"4","key":"2026091609094029300_cit24","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1084\/jem.138.4.939","article-title":"Phytohemagglutinin\nmitogenic proteins: structural evidence for a family of isomitogenic\nproteins","volume":"138","author":"Miller","year":"1973","journal-title":"J. Exp. Med."},{"key":"2026091609094029300_cit25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02379","article-title":"Editorial: lectins\nand their ligands in shaping immune responses","volume":"10","author":"Lepenies","year":"2019","journal-title":"Front. Immunol."},{"issue":"39","key":"2026091609094029300_cit26","doi-asserted-by":"publisher","first-page":"26770","DOI":"10.1021\/acsnano.4c07360","article-title":"Carbohydrate-lectin\ninteractions reprogram dendritic cells to promote type 1 anti-tumor\nimmunity","volume":"18","author":"Lensch","year":"2024","journal-title":"ACS Nano"},{"key":"2026091609094029300_cit27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.871713","article-title":"The role of\nintestinal mucosal barrier\nin autoimmune disease: a potential target","volume":"13","author":"An","year":"2022","journal-title":"Front.\nImmunol."},{"issue":"6","key":"2026091609094029300_cit28","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/S2468-1253(24)00390-X","article-title":"The intestinal barrier: a pivotal\nrole in health, inflammation, and cancer","volume":"10","author":"Neurath","year":"2025","journal-title":"Lancet\nGastroenterol. Hepatol."},{"issue":"1","key":"2026091609094029300_cit29","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-024-01026-5","article-title":"The role of the mucosal\nbarrier system in maintaining\ngut symbiosis to prevent intestinal inflammation","volume":"47","author":"Okumura","year":"2025","journal-title":"Semin. Immunopathol."},{"issue":"2","key":"2026091609094029300_cit30","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3390\/pathogens3020390","article-title":"Secretory\nIgA is\nconcentrated in the outer layer of colonic mucus along with gut bacteria","volume":"3","author":"Rogier","year":"2014","journal-title":"Pathogens"},{"issue":"11","key":"2026091609094029300_cit31","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1038\/s41423-024-01218-x","article-title":"Type 17 immunity: novel\ninsights\ninto intestinal homeostasis and autoimmune pathogenesis driven by\ngut-primed T cells","volume":"21","author":"Ohara","year":"2024","journal-title":"Cell. Mol. Immunol."},{"issue":"4","key":"2026091609094029300_cit32","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.immuni.2015.09.003","article-title":"Interleukin-23-Independent IL-17 production\nregulates intestinal epithelial permeability","volume":"43","author":"Lee","year":"2015","journal-title":"Immunity"},{"key":"2026091609094029300_cit33","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jff.2015.10.022","article-title":"Dietary Phaseolus\nvulgaris extract alleviated diet-induced obesity, insulin resistance\nand hepatic steatosis and alters gut microbiota composition in mice","volume":"20","author":"Song","year":"2016","journal-title":"J. Funct. Foods"},{"issue":"30","key":"2026091609094029300_cit34","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add8766","article-title":"Lectin-Seq: a method to profile lectin-microbe interactions\nin native communities","volume":"9","author":"McPherson","year":"2023","journal-title":"Sci. Adv."},{"issue":"1","key":"2026091609094029300_cit35","doi-asserted-by":"publisher","DOI":"10.1093\/ismejo\/wrae133","article-title":"Diversity alone\ndoes not reliably\nindicate the healthiness of an animal microbiome","volume":"18","author":"Williams","year":"2024","journal-title":"ISME J."},{"issue":"11","key":"2026091609094029300_cit36","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1136\/gutjnl-2024-333378","article-title":"What defines a healthy gut microbiome?","volume":"73","author":"Van Hul","year":"2024","journal-title":"Gut"},{"issue":"3","key":"2026091609094029300_cit37","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.tree.2024.11.008","article-title":"The costs\nand benefits of a dynamic host microbiome","volume":"40","author":"Gillingham","year":"2025","journal-title":"Trends\nEcol. Evol."},{"issue":"1","key":"2026091609094029300_cit38","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-09351-7","article-title":"Short-chain fatty acids mediate interactions between immune responses\nand commensal bacteria in high altitude yaks","volume":"9","author":"Guo","year":"2026","journal-title":"Commun. Biol."},{"issue":"12","key":"2026091609094029300_cit39","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1016\/j.immuni.2025.11.006","article-title":"A host-centric view\nof the microbiota metabolome","volume":"58","author":"Yamada","year":"2025","journal-title":"Immunity"},{"issue":"1","key":"2026091609094029300_cit40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53832-y","article-title":"Identification of gut microbiome features associated with host metabolic\nhealth in a large population-based cohort","volume":"15","author":"Keshet","year":"2024","journal-title":"Nat.\nCommun."},{"issue":"1","key":"2026091609094029300_cit41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ymeth.2006.07.008","article-title":"A mouse model for food\nallergy using intraperitoneal\nsensitization","volume":"41","author":"Dearman","year":"2007","journal-title":"Methods"},{"issue":"3","key":"2026091609094029300_cit42","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.jcmgh.2018.05.010","article-title":"Experimental\nmodels for studying\nfood allergy","volume":"6","author":"Kanagaratham","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"issue":"18","key":"2026091609094029300_cit43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251810231","article-title":"Lectin-based approaches to analyze\nthe role of glycans and their clinical application in disease","volume":"25","author":"Ideo","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"10","key":"2026091609094029300_cit44","doi-asserted-by":"publisher","DOI":"10.1016\/j.waojou.2024.100969","article-title":"Fecal microbiota transplantation\nalleviates food allergy in neonatal mice via the PD-1\/PD-L1 pathway\nand change of the microbiota composition","volume":"17","author":"Huang","year":"2024","journal-title":"World\nAllergy Organ. J."},{"issue":"11","key":"2026091609094029300_cit45","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1021\/acschembio.1c00689","article-title":"A useful guide to\nlectin binding:\nmachine-learning directed annotation of 57 unique lectin specificities","volume":"17","author":"Bojar","year":"2022","journal-title":"ACS Chem. Biol."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c05871","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28723\/68405722\/acs.jafc.6c05871.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/36\/28723\/68405722\/acs.jafc.6c05871.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:34:39Z","timestamp":1789565679000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/36\/28723\/5422602\/Isoform-Ratio-Rather-than-Total-Content-Determines"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":45,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,7]]},"published-print":{"date-parts":[[2026,9,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c05871","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}