Journal of advanced research最新文献

{"title":"A dual-bioeffect nanoengineered piezoelectric-photothermal hydrogel induces endochondral ossification and promotes critical-sized bone regeneration.","authors":"Chang Xu, Baoxing Tian, Jie Luo, Liang Chen, Baoshuai Bai, Xingqi Song, Ximing Wang, Chuang Hu, Qian Zhou, Yuhua Diao, Guangdong Zhou, Dong Lei, Lunli Gong, Jianfei Tang, Mengjie Hou","doi":"10.1016/j.jare.2026.10.025","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.025","url":null,"abstract":"<p><strong>Introduction: </strong>Critical-sized bone defects remain a major clinical challenge in orthopedics. Current strategies including inert implants and autologous bone grafts suffer from complications like loosening, infection, and donor site morbidity. Piezoelectric and photothermal stimuli synergistically regulate bone regeneration, and black phosphorus nanosheets (BPNSs) possess both effects and biodegradability, but are prone to oxidation and aggregation.</p><p><strong>Objectives: </strong>This study aims to develop an injectable biomimetic hydrogel with dual piezoelectric-photothermal bioeffects for minimally invasive and efficient repair of irregular critical-sized bone defects.</p><p><strong>Methods: </strong>BPNS@rhCOL1MA composite system was constructed by embedding BPNSs into recombinant human methacrylated type I collagen hydrogel. Physicochemical characterization, in vitro cell assays, transcriptomic analysis, and in vivo validation in a rabbit rib defect model were performed.</p><p><strong>Results: </strong>The material exhibited stable network, injectability, and controllable dual-responsive properties. It significantly enhanced osteogenic differentiation of BMSCs in vitro. Transcriptomics revealed activation of electrical/thermal signal transduction and angiogenesis pathways. In vivo, it markedly improved new bone formation, bone mineral density, and mechanical properties.</p><p><strong>Conclusion: </strong>This work first integrates the dual bioeffects of BPNSs with injectable human-derived collagen hydrogel, providing a novel strategy for minimally invasive repair of irregular bone defects.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced nanocarrier delivery and therapeutic systems for natural drug molecules: mechanisms, applications, and future perspectives.","authors":"Yuan Zhang, Tian Li, Yao Chen, Jun Ge","doi":"10.1016/j.jare.2026.10.024","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.024","url":null,"abstract":"<p><strong>Background: </strong>Natural drug molecules often face challenges such as poor water solubility and low bioavailability, which limit their clinical efficacy. Nanocarrier technology offers a promising strategy to address these bottlenecks by improving solubility, protecting active ingredients, and enabling targeted delivery.</p><p><strong>Aim: </strong>of Review: This review systematically surveys the state-of-the-art progress of diverse nanocarrier systems for the delivery of natural drug molecules. It uniquely emphasizes the rational design of nanocarriers, the elucidation of molecular-level interaction mechanisms between natural drugs and nanocarriers, and strategies for achieving specific target recognition and controlled release. Key Scientific Concepts of Review: This review illustrates how the strategic design of various nanocarriers can overcome the inherent physicochemical and biopharmaceutical limitations of natural drug molecules. By elucidating their interaction mechanisms, this review provides an essential foundation for the rational design of nanocarrier-natural drug systems. Furthermore, it critically analyzes translational bottlenecks such as biocompatibility and scalable manufacturing and proposes future directions for next-generation nanocarrier platforms by integrating cutting-edge interdisciplinary approaches, including multistimuli-responsive systems, AI-driven design, and biomimetic strategies.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mir338-CDK8-mitochondrial axis governs lineage-specific osteogenesis and defines Runx2 pleiotropy in cranial sutures.","authors":"Hanshu Zhang, Xueying Ma, Junyan Peng, Qinhao Shen, Runze Jin, Yu Jia, Yu Zhou, Zhi Chen, Huan Liu","doi":"10.1016/j.jare.2026.10.029","DOIUrl":"10.1016/j.jare.2026.10.029","url":null,"abstract":"<p><strong>Introduction: </strong>Developmental pattern formation critically depends on gene regulatory networks that enable context-dependent interpretation of molecular cues, yet how cells from distinct embryonic lineages in shared microenvironments produce divergent outcomes remains a central unresolved question. The murine skull provides a key model: the neural crest-derived posterior frontal (PF) suture fuses, while the mesoderm-derived sagittal (SAG) suture remains patent. A recently identified paradox exists: Runx2 haploinsufficiency impacts both sutures, but Mir338 cluster ablation selectively rescues the SAG suture, suggesting lineage-specific regulatory constraints.</p><p><strong>Objectives: </strong>This study aims to resolve this paradox by investigating how embryonic origin dictates osteoprogenitor responses to Runx2-Mir338 signaling.</p><p><strong>Methods: </strong>We employed multi-omics (miRNA-seq, RNA-seq, scRNA-seq) and lineage tracing to define transcriptional heterogeneity, dissect Runx2 and Mir338-mediated lineage-specific regulation of osteoblastic subclusters, and identify differentially expressed mitochondrial-related genes and Cyclin-dependent kinase 8 (Cdk8). These findings were functionally validated through in vivo and in vitro assays.</p><p><strong>Results: </strong>We uncover that embryonic origin dictates osteoprogenitor responses to Runx2-Mir338 signaling through lineage-specific mitochondrial dynamics. In mesoderm-derived SAG sutures, Runx2 haploinsufficiency disrupts mitochondrial fragmentation, a process critical for ossification, via dysregulation of NADH: ubiquinone oxidoreductase subunit S5 (NDUFS5). We identify CDK8 as a novel direct target of Mir338 and a Runx2-activated gene that promotes mitochondrial fragmentation. This dual regulation of CDK8 establishes a dosage-sensitive \"toggle switch\" unique to SAG sutures, where restoring mitochondrial function via direct mitochondrial transplantation rescues ossification defects. In contrast, neural crest-derived PF sutures exhibit intrinsically low CDK8 expression, partially modulated by DNA methylation, rendering them unresponsive to Runx2-Mir338 modulation and mitochondrial rescue.</p><p><strong>Conclusion: </strong>Our findings resolve the paradox of Runx2 pleiotropy by bridging positional identity, mitochondrial metabolism, and miRNA-mediated regulation, offering a redefined conceptual framework for understanding developmental processes and informing precision therapeutic strategies for congenital skeletal disorders.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aebp1 drives a ceramide-gated Calhm2 calcium influx that injures podocytes in diabetic kidney disease.","authors":"Aiping Duan, Yucui Jiang, Xia Wang, Zige Chen, Ping Dong, Zhaochen Guo, Weisong Qin, Hao Bao","doi":"10.1016/j.jare.2026.10.017","DOIUrl":"10.1016/j.jare.2026.10.017","url":null,"abstract":"<p><strong>Introduction: </strong>Podocyte injury is a critical determinant of diabetic kidney disease (DKD) and other proteinuric nephropathies; however, the mechanisms linking lipotoxicity to cytoskeletal disruption remain unclear.</p><p><strong>Objectives: </strong>This study aimed to identify a central regulator linking lipotoxicity to podocyte injury, decipher its downstream pathway to pathological calcium influx, and assess its translational potential as a non-invasive biomarker of disease progression.</p><p><strong>Methods: </strong>Integrated transcriptomic-proteomic analysis of diabetic glomeruli identified Adipocyte Enhancer-Binding Protein 1 (Aebp1). Its function was investigated using renal overexpression and podocyte-specific knockout mouse models of diabetic and adriamycin (ADR) nephropathy. Mechanistic studies combined in vitro and in vivo analyses, including intracellular calcium kinetic assays and direct protein-lipid interaction assays (e.g., surface plasmon resonance). Clinical validation was conducted in a biopsy-proven DKD cohort, correlating urinary Aebp1 levels with histological severity and longitudinal estimated glomerular filtration rate (eGFR) decline.</p><p><strong>Results: </strong>Aebp1 was identified as a progressively upregulated gene in the diabetic glomeruli. In mice, renal overexpression of Aebp1 induced proteinuria and glomerulosclerosis, whereas podocyte-specific knockout conferred protection against injury in diabetic mice. Mechanistically, Aebp1 activated NF-κB signaling, leading to Neu3 upregulation and pathogenic ceramide accumulation in the podocytes. We found that ceramide can directly bind to and activate Calhm2, a calcium channel not previously implicated in kidney physiology, suggesting a novel lipid-gated pathway linking lipotoxicity to pathological calcium influx in podocytes. This mechanism has been validated in ADR-induced nephropathy. Clinically, urinary Aebp1 serves as an independent predictor of histologically confirmed glomerulosclerosis severity and predicts the clinical endpoint of ≥ 30% eGFR decline.</p><p><strong>Conclusion: </strong>This study identifies a potential pathway in which Aebp1 promotes ceramide accumulation which may activate the Calhm2 calcium channel, thus linking lipotoxicity to calcium dysregulation and podocyte injury in DKD and other proteinuric conditions. Urinary Aebp1 is a potential clinically non-invasive biomarker for predicting histological damage and functional decline in DKD.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TERT is a therapeutic target for tertiary stroke prevention.","authors":"Siwei Luo, Tianyu Gu, Meiling Liang, Ying Zhou, Guangpu Su, Xuemin Xie, Wenxin Yang, Miao Chen, Chi Kwan Tsang","doi":"10.1016/j.jare.2026.10.016","DOIUrl":"10.1016/j.jare.2026.10.016","url":null,"abstract":"<p><strong>Introduction: </strong>Tertiary stroke prevention aims to mitigate long-term disability and improve life quality for stroke survivors. While primary and secondary stroke prevention strategies have been extensively investigated, tertiary prevention remains a critically understudied area, and there is currently no clinically approved drug for tertiary stroke prevention.</p><p><strong>Objectives: </strong>We previously discovered a transcription-regulatory function of telomerase reverse transcriptase (TERT) in cultured primary neurons. Here, we further explored the in vivo role of TERT in neural repair and functional recovery after ischemic stroke.</p><p><strong>Methods: </strong>We performed single-nucleus RNA sequencing (snRNA-seq) analysis in a photothrombosis (PT)-induced permanent ischemic stroke mouse model to characterize TERT expression in the cerebral peri-infarct tissue, which was verified by PT and middle cerebral artery occlusion (MCAO) mouse model with immunofluorescence analysis. CUT&Tag-sequencing was used to profile the whole-genome TERT binding loci and transcriptional activity in the isolated neurons from the peri-infarct tissue. We further used phospho-proteomic analysis to identify the signaling mechanism of TERT regulation in neurons.</p><p><strong>Results: </strong>snRNA-seq revealed TERT expression was increased in neurons in the peri-infarct tissue during the critical post-stroke recovery period in PT mice. This result was confirmed by immunofluorescent imaging in the PT and MCAO stroke models. Intravenous delivery of brain-targeted AAV-mediated neuron-specific overexpression of TERT significantly bolstered neural repair and functional recovery in the PT stroke model. Additionally, pharmacological upregulation of TERT expression in post-stroke recovery period by oral gavage of cycloastragenol (CAG) conferred prominent neural repair, improved sensorimotor functional recovery and alleviated post-stroke depression-like behaviors. Knockdown of neuronal TERT abolished the spontaneous and CAG-induced neural repair-promoting effect in PT mice. Mechanistically, we discovered that neuronal TERT is a transcriptional co-regulator of CREB-target genes including GAP43, EVL, NR4A3, and NRP2 which are associated with enhanced axon sprouting, dendritic branching and synaptogenesis in recovery phase of PT stroke. We further demonstrated that CAG upregulates TERT expression by promoting STAT3 phosphorylation at serine 727 in a DAPK1-dependent manner.</p><p><strong>Conclusion: </strong>Overall, these results demonstrate that TERT is a promising therapeutic target for tertiary stroke prevention.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The oval bed nucleus of the stria terminalis endocannabinoid signaling constrains post-traumatic stress disorder-like behaviors.","authors":"Hongyu Zuo, Jie Li, Jianfeng Li, Xia Zhang, Bin Zhang","doi":"10.1016/j.jare.2026.10.015","DOIUrl":"10.1016/j.jare.2026.10.015","url":null,"abstract":"<p><strong>Introduction: </strong>Post-traumatic stress disorder (PTSD) develops when acute threat responses fail to resolve, resulting in persistent anxiety, avoidance, and hyperarousal. However, the specific neural circuits and molecular mechanisms governing the transition from acute stress to enduring pathology remain incompletely understood. Objectives This study aimed to determine whether endocannabinoid (eCB) signaling within posterior basolateral amygdala (pBLA) to oval bed nucleus of the stria terminalis (ovBNST) projections constrains the maladaptive transition from social threat to PTSD-like anxiety and defensive states.</p><p><strong>Methods: </strong>Using a modified 5-day chronic social defeat stress (CSDS) paradigm, we employed a multimodal experimental strategy that included in vivo fiber photometry, molecular analyses, optogenetic manipulation, pharmacological intervention, and genetic perturbation to interrogate neuronal activity and modulate eCB signaling dynamics in the ovBNST, followed by stress-related behavioral assays. Genetic suppression of 2-arachidonoylglycerol (2-AG) synthesis was employed to evaluate circuit-specific eCB function.</p><p><strong>Results: </strong>Both acute social defeat and trauma re-experiencing enhanced ovBNST neuronal activity and eCB signaling. CSDS reduced pBLA Cnr1 mRNA expression and ovBNST cannabinoid type-1 receptor (CB1R) protein levels, leading to heightened ovBNST excitability, likely due to diminished presynaptic inhibition of glutamate release from pBLA-ovBNST terminals. Pharmacological inhibition of 2-AG degradation in the ovBNST or optogenetic activation of CB1Rs in pBLA-ovBNST projections reversed CSDS-induced social avoidance and anxiety-like behaviors. In contrast, genetic suppression of 2-AG synthesis exacerbated PTSD-like phenotypes.</p><p><strong>Conclusion: </strong>These findings identify a social threat-responsive pBLA-ovBNST circuit in which eCB signaling modulates glutamatergic transmission to promote resilience against PTSD-like behavioral states. Restoring eCB homeostasis within this pathway may represent a promising therapeutic strategy for PTSD intervention.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential modulation of the cGAS-STING pathway promotes spinal cord injury repair.","authors":"Qianqian Peng, Ling Luo, Min Yuan, Hui Li, Lü Chen, Xin Wu, Maolin Han, Shirong Wen, Changlai Zhu, Yun Gu","doi":"10.1016/j.jare.2026.10.023","DOIUrl":"10.1016/j.jare.2026.10.023","url":null,"abstract":"<p><strong>Introduction: </strong>The cGAS-STING pathway is a central innate immune sensor of cytosolic DNA. Spinal cord injury (SCI) triggers sterile inflammation, but the spatiotemporal role of this pathway in injured spinal cord repair remains unclear. Understanding its phase-dependent functions may enable precise immunomodulation to improve recovery.</p><p><strong>Objectives: </strong>This study aimed to investigate the dynamic activation of the cGAS-STING pathway after SCI and to determine whether a time-sequenced pharmacological strategy, consisting of early activation followed by late inhibition, could enhance functional repair.</p><p><strong>Methods: </strong>A mouse thoracic compressive SCI model was used. Pathway expression and cellular localization were assessed by western blot, immunofluorescence, and transcriptomics. Sustained or sequential modulation was performed using STING agonists and antagonists. Motor recovery was evaluated by the Basso Mouse Scale and footprint analysis. Axonal integrity, myelin preservation, and glial scarring were analyzed histologically. Myeloid cells (including microglia) were depleted with PLX5622, and neuron-microglia cocultures were established for mechanistic studies.</p><p><strong>Results: </strong>cGAS-STING was significantly activated predominantly in myeloid cells (mainly microglia, with a smaller contribution from infiltrating macrophages) after SCI. Sustained activation or inhibition failed to improve recovery. Sequential treatment (ADU-S100 days 0-10 → C-176 days 11-28) markedly enhanced motor function, axonal integrity, and myelin preservation while reducing glial scarring. Mechanistically, early activation boosted microglial phagocytosis and clearance; late inhibition resolved inflammation and promoted the expression of anti-inflammatory and axon-associated genes. Myeloid cell depletion completely abolished these benefits.</p><p><strong>Conclusion: </strong>The cGAS-STING pathway exerts phase‑dependent, biphasic functions in SCI. A precisely timed \"activation followed by inhibition\" strategy optimally harnesses myeloid cell dynamics to coordinate debris clearance and inflammation resolution, offering a novel immunomodulatory paradigm for central nervous system repair.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat-inactivated probiotic-fermented tamarind pulp alleviates constipation by modulating gut tryptophan catabolism and the AhR NLRP3 axis.","authors":"Xi Gui, Chunmei Yuan, Siyan Huang, Kaijun Huang, Lan Wu, Zibo Song, Tao Wang, Zhijia Liu, Xuebo Liu, Mingdao Mu, Junjie Yi, Chuanqi Chu","doi":"10.1016/j.jare.2026.10.014","DOIUrl":"10.1016/j.jare.2026.10.014","url":null,"abstract":"<p><strong>Introduction: </strong>Constipation is a common gastrointestinal disorder with gut dysbiosis, and existing laxatives often have limitations, necessitating the development of safer and more effective nutritional interventions.</p><p><strong>Objective: </strong>This study aimed to investigate the alleviating effects and potential mechanisms of probiotic-fermented tamarind pulp (FTP) on loperamide-induced constipation in mice.</p><p><strong>Methods: </strong>A constipated mouse model was established and treated with low and high-dose FTP (LD‑FTP and HD‑FTP). Assessments included gastrointestinal transit, histopathology, serum neurotransmitters/inflammatory factors, gut microbiota (16S rRNA amplicon sequencing), functional predictions generated using PICRUSt2, and fecal metabolomics (LC-MS).</p><p><strong>Results: </strong>FTP dose-dependently alleviated loperamide‑induced constipation. Compared with the model group, HD‑FTP increased small intestinal transit rate by 57.2% (to 92.95%, p < 0.001) and fecal water content by 65.9% (to 70.52%, p < 0.001), both effects superior to the positive control bisacodyl. HD‑FTP also reduced serum IL‑6, IL‑1β, and TNF‑α by 60.0%, 43.5%, and 45.4%, respectively (all p < 0.001), and elevated total short-chain fatty acids (SCFAs) by 107.4% (p < 0.001). FTP exhibited significantly superior constipation‑alleviating efficacy compared to unfermented tamarind pulp (UFTP). FTP also increased microbial richness, enriched potentially beneficial SCFA-producing taxa, and restored microbial metabolic pathways associated with SCFA biosynthesis. Notably, fermentation enhanced tryptophan metabolism toward indole and serotonin pathways, which correlated with increased aryl hydrocarbon receptor (AhR) activation and reduced NLRP3 inflammasome signaling in the colon.</p><p><strong>Conclusion: </strong>FTP effectively alleviated constipation by improving intestinal function, reducing inflammation, and remodeling the gut microbiota-metabolite axis. Mechanistically, fermentation-driven tryptophan catabolism and quercetin biotransformation converge on the AhR-NLRP3 axis. These findings highlight FTP as a superior nutritional strategy over UFTP.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A JAZ-VQ-WRKY transcriptional feedback loop enforces homeostasis in cytotoxic alkaloid biosynthesis.","authors":"Yaojie Zhang, Qi Liu, Pin Liu, Xiaofan Ni, Hang Liu, Shuyi Qian, Hangyu Wen, Ling Li, Jingya Zhao, Yuliang Wang, Qifang Pan, Xueqing Fu, Kexuan Tang","doi":"10.1016/j.jare.2026.10.018","DOIUrl":"10.1016/j.jare.2026.10.018","url":null,"abstract":"<p><strong>Introduction: </strong>Plants face the challenge of balancing the production of defense-related secondary metabolites, requiring inducible \"accelerators\" and intrinsic \"braking\" systems to avoid overproduction. While the phytohormone jasmonate (JA) is a well-established accelerator, the molecular nature of the braking machinery and its coordination with JA signaling remain unclear. The medicinal plant Catharanthus roseus produces cytotoxic terpenoid indole alkaloids (TIAs) and serves as an ideal system to address this question.</p><p><strong>Objectives: </strong>This study aims to identify the core JA-induced transcription factors regulating TIAs synthesis, and to elucidate how their activity is precisely constrained to prevent metabolic runaway, thereby deciphering the molecular mechanisms by which plants achieve metabolic homeostasis.</p><p><strong>Methods: </strong>We used DNA affinity purification sequencing (DAP-seq), yeast one-hybrid (Y1H), and dual luciferase reporter (Dual-LUC) assays to identify and validate the direct binding and transactivation of the transcription factor CrWRKY4 on TIAs pathway genes. Gene knockout was achieved in hairy roots using an optimized CRISPR/Cas9 system. Protein interactions were analyzed using yeast two-hybrid (Y2H), bimolecular complementation (BiFC), and immunoprecipitation (Co-IP) techniques. The functional role of the regulatory module was systematically elucidated through subcellular localization studies, electrophoresis mobility shift assay (EMSA), and metabolite quantification (UPLC-QQQ-MS/MS).</p><p><strong>Results: </strong>We identified a JA-inducible master regulator transcription factor, CrWRKY4, it directly binds and activates multiple TIAs pathway genes. Concurrently, two co-repressors, CrVQ4 and CrVQ9, were characterized and inhibit CrWRKY4's DNA-binding capacity. Moreover, CrJAZ1 interacts with VQ proteins and interferes with the VQ-WRKY regulatory complex. Crucially, CrWRKY4 directly activates the expression of CrVQ4, CrVQ9, and CrJAZ1, forming an intrinsic negative feedback loop. Upon JA signaling, the repressive CrJAZ1-CrVQ4/9 module is relieved, allowing CrWRKY4 to activate TIAs gene expression.</p><p><strong>Conclusion: </strong>This study elucidates a core regulatory mechanism comprising the CrJAZ1-CrVQ4/9-CrWRKY4 module. This module forms a self-braking transcriptional circuit by integrating JA signal.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic dissection of starch and protein quality traits and their potential co-regulation with grain yield in maize.","authors":"Huangai Li, Cheng Wang, Jia Wei, Zhiwei Liu, Yan Long, Xiangyuan Wan","doi":"10.1016/j.jare.2026.09.017","DOIUrl":"10.1016/j.jare.2026.09.017","url":null,"abstract":"<p><strong>Background: </strong>Kernel starch and protein contents are major determinants of maize grain quality and end-use value, whereas yield remains the primary breeding objective. These traits are genetically complex and interrelated, potentially sharing genetic effects while exhibiting trade-offs. Recent advances in quantitative genetics, genome-wide association studies, and multi-omics have generated vast but scattered datasets on maize quality traits. However, an integrated analysis of research trends, genetic architecture, and systematic mining of candidate genes underlying starch and protein contents and their relationships with grain yield is lacking.</p><p><strong>Aim of review: </strong>This review aims to systematically summarize research progress and emerging trends in the genetic and molecular regulation of maize starch and protein contents, to mine and prioritize candidate genes for these quality traits, and to elucidate their genetic basis in relation to yield-related traits. By integrating bibliometric analysis with genetic and multi-omics evidence, the review provides a coherent framework and valuable resources to support the joint improvement of grain quality and yield in modern maize breeding.</p><p><strong>Key scientific concepts of review: </strong>The review highlights three major scientific concepts. First, bibliometric analyses reveal a transition from classical QTL mapping toward genome-wide and system-level approaches, reflecting a shift in maize quality research paradigms. Second, by integrating functionally characterized maize genes, QTLs/QTNs, multi-omics integrative networks, and maize orthologs of regulators from rice and wheat, the review summarizes experimentally supported regulatory relationships, identifies genomic hotspots, and generates prioritized candidate gene resources for further investigation. Third, this review identifies genomic regions and candidate genes that are co-localized with or jointly associated with grain quality and yield traits, providing candidate genetic resources for investigating potential multi-trait effects and quality-yield trade-offs. Together, these insights demonstrate the value of integrative analysis for gene resource mining and outline a conceptual and practical roadmap for multi-omics-assisted precision maize breeding.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}