Journal of Advanced Research最新文献

{"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}

{"title":"Rejuvenation of THY1+ nucleus pulposus-derived stem cells promotes intervertebral disc regeneration through FGF10-FGFR1-CREB pathway and mitochondrial fission","authors":"Haoxin Zhai, Zexin Wang, Shaoyi Wang, Zhicheng Liu, Dawang Zhao, Yiming Zhang, Kaiwen Liu, Xiangzhen Kong, Qunbo Meng, Hanwen Gu, Lin Chen, Yuanqiang Zhang, Lei Cheng","doi":"10.1016/j.jare.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.008","url":null,"abstract":"<h3>Introduction</h3>Intervertebral disc degeneration (IVDD), a major cause of low back pain, is primarily characterized by compromised regeneration ability of nucleus pulposus-derived stem cells (NPSCs) owing to their senescence. The role of NPSCs as major regenerative cells in IVDD is garnering attention. However, the drivers and mechanisms of NPSCs reactivation and regeneration are poorly understood, limiting the development of targeted therapies. The fibroblast growth factor (FGF) family has shown increasing promise in tissue regeneration; however, the key factors involved in IVDD remain unclear.<h3>Objectives</h3>To elucidate the regenerative driver of NPSCs and the underlying anti-senescence mechanism to provide a potential therapeutic strategy.<h3>Methods</h3>Single cell RNA sequencing (scRNA-seq) and bulk RNA sequencing were performed to identify the key NPSCs clusters and regenerative drivers in IVDD. Clinical IVDD samples were collected to determine the alterations in the NPSCs subset proportion and the expression of regeneration factors. Further, NPSCs senescence and in vivo models were used to investigate the specific mechanisms and therapeutic effects.<h3>Results</h3>Thy-1 membrane glycoprotein (THY1)⁺ NPSCs, which are depleted in IVDD, were the key cells involved in intervertebral disc degeneration based on scRNA-seq. THY1⁺ NPSCs exhibited stemness and regeneration potential. The RNA-seq analysis of senescent THY1⁺ NPSCs indicated fibroblast growth factor 10 (FGF10) as a pivotal rejuvenation factor. Multiplex fluorescence staining demonstrated diminished FGF10 expression in IVDD. FGF10 mitigated THY1⁺ NPSCs senescence by interacting with fibroblast growth factor receptor 1 (FGFR1). The FGF10-FGFR1 axis inhibited CREB phosphorylation and further alleviated ARG2-DRP1-related mitochondrial fission, reversing THY1⁺ NPSC senescence. Inhibition of CREB and downregulation of ARG2 regulate cellular senescence via modulation of mitochondrial fission. The transplantation of FGF10-overexpression NPSCs prominently alleviated nucleus pulposus degeneration and demonstrated regeneration potential <em>in vivo</em>.<h3>Conclusion</h3>Our findings elucidate the pivotal roles of THY1⁺ NPSCs and FGF10 in intervertebral disc regeneration and NPSCs activation, respectively, contributing to the development of regenerative therapeutic strategies for IVDD","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"15 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384032","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":"Microglia Dld-K127 lactylation promotes Parkinson’s disease via regulating the metabolism of lactate-pyruvate transformation","authors":"Guoqing Wang, Guichun Gong, Xinxing Yang, Yanran Qian, Yujia Zhao, Daidi Li, Mei Liu, Zucai Xu, Feng Zhang","doi":"10.1016/j.jare.2026.03.016","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.016","url":null,"abstract":"Microglial activation represents a central pathological hallmark of Parkinson’s disease (PD), characterized by a distinct metabolic reprogramming from oxidative phosphorylation toward glycolysis during pro-inflammatory activation. This metabolic shift drives lactate accumulation and subsequent protein lactylation, which has been increasingly implicated in PD development. However, the molecular mechanisms through which protein lactylation exerts its pathological effects remain largely unknown.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"14 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393132","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":"T-cell epitope supplementation enhanced cross-protection against H7N9 AIV in chickens via upregulated HA epitope-specific T cell and CD4 T cell-mediated help","authors":"Xiaoli Hao, Xinjie Yuan, Jiongjiong Wang, Zhonglong Song, Xiaona Li, Chuang Meng, Yi Yang, Tao Qin, Jiao Hu, Min Gu, Shunlin Hu, Xiaoquan Wang, Xiaowen Liu, Daxin Peng, Xiufan Liu, Shaobin Shang","doi":"10.1016/j.jare.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.012","url":null,"abstract":"The continuous circulation of H7N9 avian influenza viruses (AIVs) in poultry poses a significant public health threat. T cell-mediated immunity favors enhanced and broad protection against viruses. However, it remains challenging to exploit avian T-cell immunity for improving vaccine efficacy. Here, we showed that vaccine-induced hemagglutinin (HA)-specific T-cell responses promoted broad protection against heterologous H7N9 in poultry. Four conserved epitopes of H7N9 HA recognized by chicken T cells were identified, including two CD4 T-cell epitopes (P12, P15), one CD8 T-cell epitope (P4), and one dual-recognized epitope peptide (P10). These peptides were pooled (PP) and incorporated into an H7N9 whole inactivated virus (WIV) vaccine via a DDA/TDB nanoparticle platform (H7N9 WIV + PP) for better delivery and presentation of diverse T-cell epitopes. The results showed that H7N9 WIV + PP vaccination elicited more robust humoral and cellular immune responses than the H7N9 WIV alone and conferred broad protection against antigenically divergent H7N9 virus challenge. Mechanistically, pooled T-cell epitope supplementation enhanced the elicitation of HA peptide-specific T-cell responses, which in turn boosted HA-specific antibodies via peptide-specific CD4&lt;sup&gt;+&lt;/sup&gt; T-cell help while concurrently mobilizing protective CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T-cell immunity and effector molecules. Our study offers a novel strategy for developing broad-spectrum poultry vaccines against evolving AIV strains. Introduction: The persistent circulation of H7N9 avian influenza viruses (AIVs) in poultry continues to threaten public health. While T cell-mediated immunity is known to enhance and promote cross-protective antiviral responses, exploiting avian T-cell immunity for improved vaccine efficacy remains challenging. Hemagglutinin (HA)-specific T-cell responses may serve as a key mechanism to broaden protection against antigenically diverse H7N9 strains. Objectives: This study aimed to determine whether HA-specific T-cell responses can enhance heterologous protection against H7N9 in poultry and whether T-cell epitope-supplemented vaccines can improve both humoral and cellular immunity. Methods: Conserved HA epitopes recognized by chicken T cells were identified using immunological assays, resulting in two CD4 epitopes (P12, P15), one CD8 epitope (P4), and one dual-recognized epitope (P10). These peptides were pooled (PP) and incorporated into an H7N9 whole inactivated virus (WIV) vaccine formulated with a DDA/TDB nanoparticle adjuvant (H7N9 WIV + PP). Immune responses and protection were assessed following homologous and heterologous H7N9 virus challenge. Results: The H7N9 WIV + PP vaccine elicited stronger humoral and cellular immune responses compared with WIV alone. Birds receiving H7N9 WIV + PP displayed significantly improved protection against antigenically divergent H7N9 challenge. Mechanistically, pooled epitope supplementation enhanced HA peptide-spe","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"32 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384033","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":"The MaEIL9-MaZIP5–MaSCL8 module integrates MaBEL1 and synergistically modulates banana fruit ripening","authors":"Fan Liu, Xueli Sun, Ou Sheng, Tongxin Dou, Jiangshan Jian, Qiaosong Yang, Chunhua Hu, Guiming Deng, Weidi He, Huijun Gao, Tao Dong, Chunyu Li, Yaoyao Li, Cancan Liu, Ganjun Yi, Fangcheng Bi","doi":"10.1016/j.jare.2026.03.001","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.001","url":null,"abstract":"<h3>Introduction</h3>Fruit ripening is a genetically predetermined developmental process that is governed by a complex multilevel regulatory network requiring the orchestration of spatiotemporal expression of many genes and proteins. The GAI-RGA- and −SCRs (GRASs) are plant-exclusive transcription factors, which play pivotal regulatory roles in modulating growth, developmental processes, and environmental stress adaptation. However, the functional characterization and molecular mechanisms of GRASs in fruit ripening regulation remain poorly understood.<h3>Objectives</h3>This research was designed to elucidate the regulatory mechanism of MaSCL8 controlling banana ripening processes.<h3>Methods</h3>Yeast one-hybrid assay, dual luciferase reporter assay, and electrophoretic mobility shift assay were used to look for downstream target genes and upstream regulators of <em>MaSCL8</em>. We further performed luciferase complementation imaging and yeast two-hybrid assays to screen and verify MaSCL8-interacting proteins. Finally, the function of <em>MaSCL8</em> was analyzed by stable overexpression in tomato and transient overexpression in banana.<h3>Results</h3>This study demonstrated that a <em>GRAS</em> gene, <em>MaSCL8</em>, positively regulates banana fruit ripening. MaSCL8 functioned as a nuclear-localized transcriptional activator and could physically interact with the promoter regions of <em>MaAMY3</em>, <em>MaBAM9b</em>, <em>MaEXPA15</em>, <em>MaEXP21</em>, <em>MaPL3</em>, and <em>MaACO1,</em> consequently enhancing their transcription. <em>MaSCL8</em> overexpression in tomato and banana accelerated ripening processes by inducing the transcription of ethylene biosynthesis and softening related genes. Interestingly, MaBEL1 formed a heterodimer with MaSCL8, enhancing the MaSCL8-activated transcription of its target genes. In addition, we found that MaEIL9-MabZIP5 transcriptional cascade act upstream of <em>MaSCL8</em> and activate the expression of <em>MaSCL8</em> by physically interacting with its promoter.<h3>Conclusion</h3>Our findings indicate the MaEIL9–MaZIP5–MaSCL8 module cooperates with MaBEL1, contributing to banana ripening by improving ethylene production, starch degradation and cell wall disassembly. These results advance the fundamental understanding of GRAS-mediated ripening mechanisms.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384034","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":"Co-delivery nanoparticle targeting CAF for simultaneous activating T cell plus NKT cell attack in solid tumor","authors":"Yucheng Xiang, Lie Zhang, Jing Ye, Yu Chen, Qiao Ren, Bingyin Su, Xiaohong Xu, Quan Zhang","doi":"10.1016/j.jare.2026.03.011","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.011","url":null,"abstract":"<h3>Introduction</h3>Tumor fibrosis promotes immunosuppression by creating physical barrier that limits immune cell infiltration, posing challenges for immunotherapy. Therefore, it is essential to design a reasoned therapeutic strategy to surmount the tumor immune privilege by activating antitumor immunity and simultaneously destroying the physiological barriers of tumor microenvironment.<h3>Objectives</h3>Aim to develop a fibroblast-activated protein-α (FAP-α) responsive nanoparticle delivery system, (α-GC/NAV)-CPC, which encapsulates navitoclax (NAV) and alpha-galactosylceramide (α-GC). Upon reaching tumor site, the nanoparticles would be disassembled by FAP-α in tumor. The released α-GC activates natural killer T (NKT) and in parallel, the released NAV eliminates cancer associated fibroblasts (CAFs), ultimately breaking down physical barrier and realizing potent anti-tumor activity.<h3>Methods</h3>To maintain the self-assembly ability and FAP-α responsiveness, the designed amphiphilic block polymers consist of PEG chain as the hydrophilic domain, terminal cholesterol as the hydrophobic domain and FAP-α degradable amino acid residue sequence linkage (Ala-Thr-Gly-Pro-Ala). At the tissue level, the tumor specific fibrosis barrier destroying ability of (α-GC/NAV)-CPC was investigated. Subsequently, the NAV and α-GC were co-encapsulated into nanoparticles. The tumor accumulation, tumoricidal and anti-metastasis efficacy were validated in triple negative breast cancer-bearing models.<h3>Results</h3>This strategy can efficiently break down the cancer associated fibroblast based physical barrier. Encapsulated NAV can significantly decrease tumor interstitial fluid pressure (IFP), indicating as 4.9-fold lower than saline control group. Consequently, enhanced tumor infiltration and penetration of immune cells were observed. By quantitative flow-cytometry analysis, the abundances of NKT and T cells in tumors after (NAV/α-GC)-CPC treatment increased over 5 times and 4 times respectively, compared with saline treatment. Encouragingly, in <em>in vivo</em> models, (α-GC/NAV)-CPC treatment even led to 66.7% of mice achieving tumor eradication without recurrence. In further pulmonary metastasis challenge, mice treated with (α-GC/NAV)-CPC rarely displayed lung metastatic nodules.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"226 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380672","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}