Journal of Advanced Research最新文献

{"title":"Locus coeruleus-hippocampus noradrenergic activation alleviates sepsis-associated encephalopathy by promoting astrocytic AQP4-related autophagy via α2A-AR","authors":"Juntao Weng, Yueyue Yang, Chenyu Li, Sandong Cao, Xiaoxia Xu, Gaolin Qiu, Dijia Wang, Xiaowen Zheng, Hu Liu, Zhilai Yang, Jiqian Zhang, Qunlin Zhang, Yao Lu, Qiying Shen, Daqing Ma, Xuesheng Liu, Bin Mei","doi":"10.1016/j.jare.2026.03.024","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.024","url":null,"abstract":"<h3>Introduction</h3>Sepsis-associated encephalopathy (SAE) is a frequent and devastating complication of sepsis, yet effective targeted therapies remain unavailable. The locus coeruleus-hippocampus noradrenergic (LC-HP-NA) system is critical for neurocognitive regulation; however, its role and mechanisms in SAE remain poorly understood.<h3>Objectives</h3>This study aims to confirm that LC-HP-NA activation alleviates sepsis-induced long-term neurocognitive impairment, and clarify the underlying mechanism, focusing on hippocampal astrocytic α₂A-adrenoceptor (α₂A-AR) and aquaporin-4 (AQP4)-related autophagy.<h3>Methods</h3>Using chemogenetics to activate the LC-HP-NA, genetic manipulation (astrocytic α₂A-AR knockdown and AQP4 overexpression), in vivo sepsis mouse models, and in vitro lipopolysaccharide (LPS)-stimulated primary astrocyte cultures. Techniques included microdialysis, western blotting, immunofluorescence, Transmission Electron Microscope and behavioral tests.<h3>Results</h3>Sepsis impaired the LC-HP-NA system and long-term neurocognition, with increased hippocampal astrocytic AQP4 expression and inhibited autophagy. LC-HP-NA activation elevated hippocampal noradrenaline release, promoted astrocytic autophagy, suppressed astrocyte reactivity, restored synaptic structures, and improved long-term cognitive function. Notably, knockdown of hippocampal astrocytic α₂A-AR or overexpression of astrocytic AQP4 eliminated the neuroprotective effects of LC-HP-NA activation. Mechanistically, in LPS-stimulated astrocytes, α₂A-AR activation reduced AQP4 expression, enhanced PPAR-γ/mTOR-dependent autophagy, and decreased astrocyte reactivity, mediated by the cyclic adenosine monophosphate (cAMP)/ protein kinase A (PKA) signaling pathway.<h3>Conclusion</h3>LC-HP-NA activation alleviates SAE via astrocytic α₂A-AR, promoting AQP4-dependent autophagy through the cAMP/PKA. This provides a therapeutic target for SAE.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"268 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring cardiolipin homeostasis mitigates cerebral ischemia–reperfusion injury by suppressing ATG5-mediated neuronal autophagy-dependent ferroptosis","authors":"Weichen Dong, Wenxin Zhang, Li Huang, Lulu Xiao, Yuanfei Luo, Linying Yuan, Yike Jiang, Anyu Liao, Hongting Zhao, Zhihui Liu, Jia Wang, Ying Zhao, Yulong Cai, Mengna Peng, Dong Yang, Yi Xie, Kuanyu Li, Wusheng Zhu","doi":"10.1016/j.jare.2026.03.014","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.014","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"26 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugated bile acids facilitate cholangiocyte senescence to promote cholestatic liver diseases via STING signaling","authors":"Guifang Fan, Xin Li, Yiran Li, Shuni Duan, Wenqing Qin, Yajing Li, Rong Sun, Kaihong Xie, Zixuan Huo, Jiaorong Qu, Runping Liu","doi":"10.1016/j.jare.2026.03.020","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.020","url":null,"abstract":"<h3>Introduction</h3>Cholestatic liver disease can progress to advanced stages if left untreated and is lack of effective therapeutic options, highlighting the urgent need for new therapeutic targets.<h3>Objectives</h3>We aim to investigate the involvement of conjugated bile acids and STING signaling in the progression of cholestatic liver diseases.<h3>Methods</h3>We studied cholestatic liver injury in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), as well as in <em>Abcb4</em>^-/- mice and in mice subjected to bile duct ligation (BDL). Single-cell RNA sequencing (scRNA-seq) of clinical samples, bulk RNA sequencing (RNA-seq) of isolated primary hepatic cells, and abundant biochemical analysis were analyzed to reveal the damage-response pattern during cholestasis.<h3>Results</h3>We found that STING activation was correlated with the severity of liver injuries in patients with PBC and PSC, as well as in BDL and <em>Abcb4</em>^-/- mice. <em>Tmem173</em>^-/- mice exhibited significant protection against cholestasis-induced ductular reaction, inflammation, and fibrosis. Mechanistically, our results uncovered the cellular heterogeneity of the damage-response pattern during cholestasis. In cholangiocytes, substantial accumulation of conjugated primary bile acids significantly induced mitochondrial damage through the opening of the mitochondrial permeability transition pore, resulting in the production and leakage of oxidized DNA, which facilitates the establishment of senescence-associated secretory phenotype (SASP) by activating STING. The chemoattractive SASP of cholangiocytes then promoted the infiltration and activation of macrophages. Additionally, damage-associated molecular patterns derived from cholangiocytes further triggered the activation of inflammasome and non-lethal pyroptosis in macrophages, which were abrogated by pharmacological or genetic blockade of STING.<h3>Conclusion</h3>The present study delineates a novel intrahepatic damage-response map during cholestasis and underscores STING signaling as a promising therapeutic target for cholangiopathies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"127 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TaWAK5 perceives OGs to activate drought responses in wheat","authors":"Jingyi Wang, Long Li, Chaonan Li, Matthew Reynolds, Manuel Spannagl, Jörg-Peter Schnitzler, Yang Zhao, Zilong Ma, Jiemeng Xu, Xinguo Mao, Ruilian Jing","doi":"10.1016/j.jare.2026.03.018","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.018","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"16 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue-resolved molecular landscape reveals hepatic regulatory networks and metabolic mediators underlying feed efficiency in chickens","authors":"Wenxin Zhang, Fangren Lan, Yuejie Han, Ronglang Cai, Junnan Zhang, Guiqin Wu, Guangqi Li, Yiyuan Yan, Ning Yang, Huadong Yin, Congjiao Sun","doi":"10.1016/j.jare.2026.03.021","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.021","url":null,"abstract":"<h3>Introduction</h3>Residual feed intake (RFI) is a key indicator of feed efficiency in poultry and is regulated by coordinated physiological processes across multiple tissues. Improving feed efficiency is essential for sustainable poultry production; however, its genetic and molecular basis, particularly the relationship between feed efficiency and fat deposition during the extended laying period, remains incompletely understood.<h3>Objectives</h3>This study aimed to identify the molecular features underlying feed efficiency and to elucidate its molecular relationship with fat deposition during the extended laying period in laying hens.<h3>Methods</h3>Whole-genome resequencing was integrated with multi-tissue transcriptomic and metabolomic profiling of 248 laying hens. Genetic association analyses, multi-tissue <em>cis</em>-eQTL mapping, cross-omics integration analyses, and molecular subtyping were combined with machine learning and hepatocyte-based functional assays to prioritize and evaluate candidate genes and metabolites associated with RFI at 100 weeks of age (100wRFI).<h3>Results</h3>Genetic analyses highlighted a genomic locus associated with 100wRFI. Integrative multi-omics analyses prioritized putative causal genes and metabolites across tissues, among which <em>PCCB</em> emerged as a recurrent multi-tissue candidate forming a liver-centered gene–metabolite–phenotype axis with PE(18:0/20:4(8Z,11Z,14Z,17Z)). Functional perturbation of <em>PCCB</em> in hepatocytes was associated with altered hepatic lipogenesis, redox status, mitochondrial membrane potential, and inflammatory signaling. Multi-tissue molecular features associated with 100wRFI showed stable predictive performance for fat deposition–related traits, and lysophosphatidylinositol LPI(18:1) was identified as a putative metabolic mediator promoting hepatic lipid accumulation in vitro.<h3>Conclusions</h3>This study delineates the tissue-resolved molecular landscape of feed efficiency in hens during the extended laying period and highlights hepatic regulatory networks linking lipid metabolism, cellular homeostasis, and feed efficiency. These findings underscore the close molecular coupling between feed efficiency and fat deposition and provide a resource and framework for future functional studies and strategies to improve feed efficiency.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"16 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrono-nutrition in precision nutrition: Integrating chronotype into personalized dietary interventions","authors":"Ping Chen, Yage Wang, Mengke Yuan, Xiaofang Li, Zhuojun Li, Chunmei Li, Kaikai Li","doi":"10.1016/j.jare.2026.03.006","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.006","url":null,"abstract":"BACKGROUNDThe promise of precision nutrition lies in its ability to move beyond one size fits all dietary advice. While current approaches successfully incorporate factors like genetics and metabolism, a critical personal variable, the individual's innate chronotype, remains largely overlooked. Chronotype dictates the temporal organization of an individual's physiology, profoundly influencing metabolism and the response to food intake throughout the 24-hour day. Integrating this dimension is essential for the next evolution of personalized dietary strategies.AIM OF REVIEWThis review aims to synthesize the scientific foundation for integrating chronotype into precision nutrition. We will critically evaluate the evidence linking chronotype to differential metabolic outcomes and delineate the tissue-specific circadian mechanisms that underpin these phenotypes. Furthermore, we assess the development and efficacy of chronotype-tailored dietary interventions and propose a framework for their implementation in personalized health, identifying key challenges and future research priorities.KEY SCIENTIFIC CONCEPTS OF REVIEWThe central paradigm is that an individual's chronotype constitutes a fundamental metabolic phenotype, predictive of daily patterns in nutrient metabolism, hormonal secretion, and energy homeostasis. This phenotype emerges from a hierarchical network of circadian clocks, spanning from the central brain clock to peripheral oscillators in metabolic organs like the liver and gut. The timing of food intake acts as a potent synchronizer for this system; when misaligned with the endogenous chronotype, it can precipitate metabolic dysfunction, whereas aligned chrono-nutrition reinforces metabolic coherence. Thus, true dietary personalization necessitates moving beyond static composition to dynamic timing, strategically aligning eating windows with an individual's unique circadian rhythm to optimize health.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"2 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMOC2 accelerates myocardial fibrosis following myocardial infarction by promoting lipid peroxidation through inhibition of the LKB1/AMPKα/FOXO3 pathway","authors":"Xing Yun, Yan Ling, Liang Gaoyuan, Xie Saiyang, Li Mengyao, Zhao Nan, Zhao Yingying, Deng Wei, Tang Qizhu","doi":"10.1016/j.jare.2026.03.022","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.022","url":null,"abstract":"INTRODUCTIONMyocardial infarction (MI) initiates a cascade of pathological events leading to cardiac remodeling, characterised by abnormal activation of cardiac fibroblasts, excessive extracellular matrix deposition, and progressive ventricular fibrosis, all of which contribute to heart failure. The secreted modular calcium-binding protein 2 (SMOC2), an extracellular matrix-associated protein, has been implicated in several fibrotic diseases. However, its specific role and underlying mechanisms in post-MI cardiac fibrosis remain largely undefined.OBJECTIVESThis study aimed to investigate the role of SMOC2 in myocardial remodeling following MI and to elucidate the molecular mechanisms by which SMOC2 influences cardiac fibroblast activation, fibrosis, and cardiac dysfunction.RESULTSUsing a mouse model of left anterior descending artery (LAD) ligation and neonatal rat cardiac fibroblasts (NRCFs) subjected to hypoxia/reoxygenation (H/R), we observed a significant upregulation of SMOC2 expression after MI and in fibroblasts under H/R stress. Fibroblast-specific SMOC2 overexpression aggravated myocardial injury, inflammation, and fibrosis, whereas SMOC2 knockout markedly alleviated these effects and improved cardiac function. Mechanistically, SMOC2 interacted with integrin αvβ5 to inhibit the LKB1/AMPKα/FOXO3 signalling pathway, leading to reduced antioxidant defence, enhanced lipid peroxidation, and elevated oxidative stress. Integrated RNA sequencing and metabolomic analyses consistently revealed that SMOC2 disrupted lipid metabolism during cardiac remodeling.CONCLUSIONSMOC2 promotes cardiac injury and fibrosis following MI by suppressing the LKB1/AMPKα/FOXO3 signalling pathway through interaction with integrin αvβ5, thereby enhancing lipid peroxidation and oxidative stress. These findings suggest that targeting SMOC2 or reactivating the AMPKα/FOXO3 axis may serve as a potential therapeutic strategy to mitigate maladaptive cardiac remodeling after myocardial infarction.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"189 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal dynamic and GhGLR4.8-mediated reorganization of 3D chromatin architecture during Fusarium oxysporum f. Sp. Vasinfectum infection in cotton","authors":"Shiming Liu, Xianhui Huang, Xiaojun Zhang, Dingyi Yang, Yuejin Wang, Maojun Wang, Shuangxia Jin, Xianlong Zhang, Longfu Zhu","doi":"10.1016/j.jare.2026.03.002","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.002","url":null,"abstract":"Plants evolve sophisticated strategies to rapidly regulate gene expression in response to environmental stress. Epigenetic regulation and highly dynamic three-dimensional (3D) chromatin reorganization are critical mechanisms mediating transcriptional reprogramming under stress conditions. However, to what extent biotic stress induces chromatin reorganization and the underlying mechanisms remain inadequately understood.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indoor aerosols induced blood-brain barrier leakiness and β-amyloid1-42 aggregation","authors":"Jinping Wang, Baoteng Wang, Kunpeng Zhu, Jiaxing Zhang, Guoying Zhang, Shankui Liu, Wijayalath Pedige Dasun Vimukthi, Yanlin Zhang, Fang Cao, Chi Yang, Xiao Sun","doi":"10.1016/j.jare.2026.03.015","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.015","url":null,"abstract":"Introduction: Exposure to indoor aerosols that include fine particulate matter 2.5 (PM2.5) and microorganisms has been implicated in various health issues, including neurodegenerative diseases.Objectives: The major components of indoor aerosols could induce the blood–brain barrier (BBB) leakiness and β amyloid (Aβ) aggregation, potentially exacerbating Alzheimer’s disease (AD) pathology.Methods: The main components of aerosols were collected by an intelligent sampler and an airborne microorganism sampler, respectively. The PM2.5 was characterized with SEM and UV–vis spectrophotometer. The microorganisms were identified by 16S rRNA gene sequencing. The Aβ aggregation was studied by thioflavin T kinetic assay and circular dichroism spectroscopy. The BBB models were constructed by seeding astrocytes and human brain microvascular endothelial cells on the membrane of transwell inserts. Moreover, the BBB leakiness induced by PM2.5, <em>Staphylococcus aureus</em> (<em>S. aureus</em>)<em>,</em> and the Aβ aggregates was evaluated by immunofluorescence imaging and transwell assay both <em>in vitro</em> and <em>in vivo</em>.Results: The PM2.5 owns the size of 112 ± 35.41 nm and the surface charge of −0.125 mV. PM2.5 and <em>S. aureus</em> can independently disrupt the BBB integrity both <em>in vitro</em> and <em>in vivo</em> by down-regulating adherens and tight junction proteins including zonula occludens-1, VE-cadherin, occludin, and claudin-5. Furthermore, PM2.5 and <em>S. aureus</em> accelerated Aβ aggregation into neurotoxic oligomers and fibrils. In combined exposures, PM2.5 + Aβ or <em>S. aureus</em> + Aβ act synergistically to exacerbate BBB permeability and cytotoxicity of endothelial cells, astrocytes, and neuron cells, creating a vicious cycle of the BBB dysfunction and neurodegeneration.Conclusions: These findings establish PM2.5 and <em>S. aureus</em> as dual environmental drivers of BBB compromise and Aβ pathology, offering novel mechanistic insights and emphasizing the urgent need for strategies to mitigate indoor aerosol-related health risks for AD patients.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"6 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Species-specific tryptophan metabolism drives bioactivity divergence in Apis cerana and Apis mellifera honeys","authors":"Yan Liu, Yunyun Hu, Qian Luo, Xuan Yang, Bei Fan, Fengzhong Wang, Xinran Wang, Jinhui Zhou","doi":"10.1016/j.jare.2026.03.007","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.007","url":null,"abstract":"<em>Introduction</em>: The honeys produced by <em>Apis mellifera ligustica</em> Spinola (<em>A. mellifera</em>) and <em>Apis cerana cerana</em> Fabricius (<em>A. cerana</em>) are the two predominant varieties in terms of global yield, each recognized for its distinct functional properties. Our previous studies identified the characteristic markers distinguishing <em>A. cerana</em> honey and <em>A. mellifera</em> honey. However, the mechanistic links between species-specific metabolism and functional properties remain unclear, presenting a formidable challenge. <em>Objective</em>: This study aimed to elucidate how bee species-specific metabolism shapes honey bioactivity. <em>Methods</em>: We used topological and enrichment analyses to map the characteristic markers onto metabolic pathways. Also, we quantified the <em>in vitro</em> antioxidant capacity of both honeys and their respective markers via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. We further evaluated the anti-inflammatory efficiency of these honeys in lipopolysaccharide-stimulated Caco-2 cells by measuring cytokine expression and cellular responses. <em>Results</em>: Tryptophan metabolism primarily contributed to the formation of honey in both <em>A. cerana</em> and <em>A. mellifera</em>. <em>A. cerana</em> preferentially metabolized tryptophan via the indoleacetic acid pathway, yielding higher concentrations of methyl indole-3-acetate (MIA), whereas <em>A. mellifera</em> favored the kynurenine pathway, producing elevated levels of kynurenic acid (KYNA). Both compounds enhanced intestinal barrier integrity through their antioxidant and anti-inflammatory activities, despite differing in their specific mechanisms and efficacy. MIA exhibited superior anti-inflammatory and antioxidant properties compared with KYNA, which directly correlated with the enhanced bioactivity of <em>A. cerana</em> honey. KYNA primarily strengthened barrier function by upregulating the expression of tight junction proteins Zonula occludens protein-1(ZO-1), claudin-1, and occludin, whereas MIA demonstrated greater efficacy in suppressing the expression of inflammatory proteins. Correlation analyses confirmed MIA and KYNA as the key drivers of the intestinal barrier–protective activities of honey. The complementary mode of action—KYNA providing structural reinforcement and MIA offering anti-inflammatory modulation—highlights the synergistic bioactivity underlying the protective properties of honey. Conclusion: These findings provide a mechanistic understanding of how bee species-specific tryptophan metabolism in <em>A. cerana</em> and <em>A. mellifera</em> drives the bioactivity divergence in honey, with MIA and KYNA linked to differential antioxidant and intestinal anti-inflammatory activities.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"29 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}