Journal of Advanced Research最新文献

{"title":"Corrigendum to “Urolithin A inhibits breast cancer progression via activating TFEB-mediated mitophagy in tumor macrophages“ [J. Adv. Res. 69 (2025) 125–138]","authors":"Bowen Zheng, Yuying Wang, Baian Zhou, Fengyuan Qian, Diya Liu, Danrong Ye, Xiqian Zhou, Lin Fang","doi":"10.1016/j.jare.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.012","url":null,"abstract":"<strong>Error description in the original figure:</strong>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"105 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932655","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":"PTPN22 as a therapeutic target in intervertebral disc degeneration: Modulating mitophagy and pyroptosis through the PI3K/AKT/mTOR axis","authors":"Haibo Liang, Shu Yang, Yeheng Huang, Yuxuan Zhu, Qihang Wu, Zhouwei Wu, Sunlong Li, Yifeng Shi, Zhenya Chen, Haiming Jin, Xiangyang Wang","doi":"10.1016/j.jare.2025.05.017","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.017","url":null,"abstract":"<h3>Introduction</h3>Intervertebral disc degeneration (IDD) is a predominant risk factor for low back pain (LBP). However, the mechanisms underlying IDD progression remain unclear.<h3>Objectives</h3>The protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with various chronic inflammatory and autoimmune conditions. However, its role in the progression of IDD remains obscure. This investigation delves into the function of PTPN22 within IDD and examines its molecular mechanisms.<h3>Methods</h3>The expression levels of PTPN22 in human and rat degenerative nucleus pulposus (NP) cells were analyzed using Western blot and immunohistochemistry. Following PTPN22 knockdown via lentiviral transfection, pyroptosis, extracellular matrix (ECM) degradation, mitophagy, and mitochondrial function were assessed using Western blot, immunofluorescence, Calcein-AM/PI staining, qPCR, Seahorse, JC-1, and MitoSOX assays. The roles of autophagy and the PI3K/AKT/mTOR pathway were further investigated using the autophagy inhibitor 3-MA, Baf-A1, and the PI3K agonist 740Y-P. A puncture-induced rat model was established, and the effects of LV-shPTPN22 on IDD were evaluated through imaging and histological analyses.<h3>Results</h3>We noted an upregulation of PTPN22 in degenerative NP cells. A deficiency in PTPN22 was found to enhance mitophagy, thereby alleviating hydrogen peroxide (H₂O₂)-induced mitochondrial dysfunction and consequently mitigating NP cell pyroptosis and ECM degradation. Inhibition of the PI3K/AKT/mTOR pathway appears to play a pivotal role in the protective effects of PTPN22 deficiency against IDD. Experiments conducted in vivo revealed that PTPN22 knockdown significantly curtails the progression of IDD.<h3>Conclusion</h3>In summary, PTPN22 knockdown alleviates IDD progression by reducing pyroptosis and ECM degradation through enhanced mitophagy. This highlights PTPN22 as a critical contributor to IDD and a promising therapeutic target.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"12 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930996","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":"Dynamic profiling of BMSC-dECM reveals accumulation of core matrisome proteins suppresses osteogenic differentiation and bone regeneration","authors":"Mei Li, Weilai Zhu, Mingyu Hu, Xufeng Mao, Bowen Weng, Jing Peng, Shuishui Yin, Haijiao Mao, Jiyuan Zhao","doi":"10.1016/j.jare.2025.05.023","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.023","url":null,"abstract":"<h3>Introduction</h3>The extracellular matrix (ECM) of bone mesenchymal stem cells (BMSCs) plays a critical role in tissue development and regeneration. Rather than being inert, the ECM exhibits a dynamic structure that determines cell fate.<h3>Objectives</h3>The aim of this study is to investigate the dynamic composition, functional properties, and underlying mechanisms of BMSC-ECM during osteogenic differentiation. We propose that dynamic alterations in BMSC-ECM, particularly in critical matrix proteins, are essential to regulate osteogenic differentiation and bone regeneration.<h3>Methods</h3>Dynamic ECM from BMSCs was collected at different time points during culture with or without osteogenic induction, followed by decellularization. A mouse tibial defect model was introduced to assess bone regeneration in vivo. Proteomics was used to analyze the dynamic protein composition pattern, while a comparative transcriptomic analysis further determined the impact of dynamic BMSC-dECM on cellular mRNA profile.<h3>Results</h3>Decellularized ECMs (dECMs) from late noninduced BMSCs exhibited distinct functional properties compared to the other groups. While early noninduced, early osteogenic (Os)-induced and late Os-induced dECMs promoted bone regeneration, late noninduced dECM dramatically inhibited this process. The protein composition of dECMs, rather than the structure or total ECM content, was the key factor determining their dynamic function. Accumulation of core matrisome during noninduced culture resulted in the inhibition of its function. Consistently, the gene expression profiles of replanted BMSCs on early noninduced/Os-induced dECM and late Os-induced dECM were similar, leaving the late noninduced dECM separate. Moreover, the core matrisome of the external dECM negatively regulated intracellular gene expression. Versican (VCAN) and Asporin (ASPN) might be the key ECM proteins influencing bone regeneration.<h3>Conclusions</h3>Accumulation of the core matrisome during noninduction led to solidification and the inactivation of bone regeneration. Targeting the core matrisome might effectively avoid the drawbacks of noninduced dECM, providing novel strategies for developing highly bioactive stem cell-derived dECM.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931178","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":"Palmitoylated COX-2Cys555 reprogramed mitochondrial metabolism in pyroptotic inflammatory injury in patients with post-acute COVID-19 syndrome","authors":"Jia-Shen Wu, Chi-Yu Xu, Su-Min Mo, Xin-Mou Wu, Ze-Bang Du, Lin Che, Yi-Ling Zhang, Kai-Li Yang, Ting-Dong Li, Sheng-Xiang Ge, Tian-Ying Zhang, Zhong-Ning Lin, Yu-Chun Lin","doi":"10.1016/j.jare.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.005","url":null,"abstract":"<h3>Introduction</h3>The complex interplay between protein palmitoylation, mitochondrial dynamics, and inflammatory responses plays a pivotal role in respiratory diseases. One significant features of post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is the occurrence of a storm of inflammatory cytokines related to the NOD-like receptor protein 3 (NLRP3). However, the specific mechanisms via which palmitoylation affects mitochondrial function and its impact on the NLRP3 inflammasome under pathological respiratory conditions remain to be elucidated.<h3>Objective</h3>This study aimed to investigate how protein palmitoylation influences the inflammatory responses and mitochondrial dynamics in respiratory diseases, such as those induced by the SARS-CoV-2 spike S protein in PACS, thereby providing a therapeutic target for inflammatory lung injury.<h3>Methods</h3><em>In vivo</em> experiments were conducted using AdV5-pADM-CMV-COVID-19-S (AdV5-S) nasal drip-treated C57BL/6 mice to assess NLRP3 inflammasome activation and inflammatory response. <em>In vitro</em> experiments were performed using pCMV-S-transfected human lung epithelial BEAS-2B cells to analyze the effects of DHHC5-mediated palmitoylation of cyclooxygenase-2 (COX-2) at cysteine 555 (COX-2^Cys555) on mitochondrial metabolism and NLRP3 inflammasome activation.<h3>Results</h3>Palmitoylation of COX-2^Cys555 enhanced its interaction with hexokinase 2 (HK2) to regulate mitochondrial metabolic reprogramming, leading to NLRP3 inflammasome activation and pyroptosis. Pharmacological and genetic suppression of palmitoylation diminished the mitochondrial localization of palmitoylated COX-2 and its interaction with HK2, thereby reducing mitochondrial metabolic reprogramming. Furthermore, genetic intervention targeting DHHC5 (sh<em>Dhhc5</em>) alleviated NLRP3 activation and pyroptosis, mitigating the chronic inflammatory damage associated with PACS.<h3>Conclusion</h3>This study highlights the regulatory role of COX-2^Cys555 palmitoylation in mitochondrial metabolism and lung inflammatory injury, and suggests potential therapeutic targets to combat respiratory pathogenesis linked to palmitoylated COX-2.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"27 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930997","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":"Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease","authors":"Songsong Wang, Qiang Jia, Xiaoli Liu, Yihan Ma, Ying Yang, Xue Rong, Yang Wang, Haiyang Wang, Fusheng Liu, Shenshen Yang, Yubo Li, Liwen Han","doi":"10.1016/j.jare.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.014","url":null,"abstract":"<h3>Introduction</h3>Non-alcoholic fatty liver disease (NAFLD) is a multifactorial chronic condition that requires a systematic approach for effective management. Multi-effect therapeutic drugs derived from traditional Chinese medicine are increasingly being recognized as promising alternatives for NAFLD intervention. Hyperoside, a natural flavone glycoside found in <em>Cuscuta chinensis Lam</em>, <em>Forsythia suspensa</em>, and <em>Crataegus pinnatifida Bge</em>, has been shown to effectively mitigate NAFLD in rats. However, the underlying mechanism through which hyperoside alleviates NAFLD remains unclear.<h3>Objective</h3>This study aims to explore the specific mechanisms by which hyperoside intervenes in the progression of NAFLD.<h3>Methods</h3>In this study, a high-fat diet was used to induce the NAFLD model in rats. An integrated analysis, including mass spectrometry-based lipidomics, TMT-based proteomics, 16S rRNA sequencing, and bile acid-targeted metabolomics, was employed to identify significantly altered metabolites and proteins. Western blotting, molecular docking, and isothermal titration calorimetry were conducted to analyze the direct targets of action.<h3>Results</h3>The results indicate that hyperoside activates farnesoid X receptor (FXR), promoting fatty acid oxidation and the efflux of bile acids from the liver. Additionally, hyperoside inhibits hepatic ATP citrate lyase (ACLY) and works synergistically with activated FXR to suppress de novo lipogenesis. Hyperoside also inhibits intestinal microbes linked to bile-salt hydrolase (BSH) activity, which enhances the production of ileal bile acids (BAs), particularly conjugated BAs, thus reducing the liver toxicity of endogenous BAs.<h3>Conclusion</h3>Our findings suggest that hyperoside alleviates NAFLD by modulating fatty acid and bile acid metabolism through FXR and ACLY, suggesting its potential as a multi-effect candidate drug for the treatment of NAFLD.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"39 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931179","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":"Epigallocatechin gallate prevents and alleviates type 2 diabetes mellitus (T2DM) through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats","authors":"Hongzhe Zeng, Changwei Liu, Liwei Wan, Liyuan Peng, Kuofei Wang, Fang Zhou, Wenwen Fang, Shuai Wen, Qixian Bai, Xiaomei Yang, Linmei Liu, Jie Zeng, Jian’an Huang, Zhonghua Liu","doi":"10.1016/j.jare.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.002","url":null,"abstract":"<h3>Introduction</h3>As the main active ingredient of the first FDA-approved phytochemical drug, epigallocatechin gallate (EGCG) can effectively alleviate glucolipid metabolic disorders. However, existing studies mainly focuses on the treatment of EGCG in disease models, with limited focus on its preventive effect on diseases in healthy models.<h3>Objectives</h3>This study investigated how EGCG prevents and alleviates T2DM through gut microbiota and multi-organ interactions in Wistar healthy rats and GK T2DM rats.<h3>Methods</h3>The GK T2DM rat strain was established through repeated selective breeding of Wistar rats with glucose intolerance. Whether and how EGCG prevents and alleviates T2DM were evaluated, including glucose production and absorption efficiency, glucose transport, glucose metabolism, glucose excretion, T2DM-related tissue damage, gut microbiota, and liver transcriptome.<h3>Results</h3>The health benefits of EGCG are primarily reliant on the involvement of the gut microbiota. Our study showed that although the specific microbial communities involved differ, the bidirectional interaction between EGCG and gut microbiota is widespread in healthy rats and T2DM rats. EGCG intervention elevated the relative abundance of specific microbial communities, which in turn promoted the metabolic processing of EGCG in the gut, producing numerous EGCG metabolites that may contribute to preventing and alleviating T2DM. In healthy rats, EGCG intervention selectively enhanced insulin secretion and serum insulin levels to prevent T2DM. In T2DM rats, EGCG intervention selectively lowered blood glucose levels, improved insulin resistance, delayed glucose production and absorption, and promoted urinary glucose excretion to alleviate T2DM. In both healthy and T2DM rats, EGCG intervention universally reduced gut microbiota-derived lipopolysaccharides, maintained systemic oxidative stress homeostasis, alleviated liver and kidney damage, increased muscle glycogen content, and promoted beige thermogenesis in white fat, thus demonstrating potential for preventing and alleviating T2DM.<h3>Conclusion</h3>As a natural active ingredient, EGCG could prevent and alleviate T2DM through gut microbiota and multi-organ interactions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"126 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931002","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":"Basic mechanism of mobilizing cell movement during invasion of glioblastoma and target selection of targeted therapy","authors":"Jie Xu, Pengfei Shi, Liqun Yang, Hongjuan Cui","doi":"10.1016/j.jare.2025.04.042","DOIUrl":"https://doi.org/10.1016/j.jare.2025.04.042","url":null,"abstract":"<h3>Background</h3>Glioblastoma (GBM), also known as glioblastoma multiforme, is a rapidly growing and highly invasive malignant tumor. Due to the inability to clearly distinguish between glioblastoma and normal tissue, surgery cannot achieve safe resection, often leading to poor patient prognosis and inevitable tumor recurrence. According to previous studies, GBM invasion is related to intercellular adhesion, matrix degradation, extracellular matrix and its related adhesion molecules, as well as the molecular matrix of protein hydrolases in the microenvironment of GBM cells and stromal cells.<h3>Aim of review</h3>The aim is to enhance our understanding of the molecular mechanisms underlying GBM invasion and to advance research on targeted therapies for inhibiting GBM invasion.<h3>Key scientific concepts of review</h3>This article describes the protein hydrolases that may affect GBM cell invasion, changes in the cytoskeleton during motility, and the regulatory mechanisms of intracellular signaling pathways in GBM invasion. In addition, we also explored the possibility of targeted therapy against invasion related molecules in GBM.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"104 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920902","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":"Dynamic regulation and targeted interventions of macrophages in ischemia–reperfusion injury","authors":"Ping Lu, Ruotong Shen, Jingjing Yang, Longlong Wu, Rong Wang","doi":"10.1016/j.jare.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.006","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process characterized by oxidative stress and inflammatory responses during tissue reperfusion, leading to severe organ dysfunction. Macrophages, as key immune cells, play a pivotal role in the pathogenesis of IRI, exhibiting dynamic functions that influence both tissue damage and repair. Despite extensive research, the precise mechanisms underlying macrophage-mediated IRI remain incompletely understood, necessitating a comprehensive review to explore their multifaceted roles and potential therapeutic targets.Aim of Review: This review aims to elucidate the diverse roles of macrophages in IRI, focusing on their involvement in programmed cell death mechanisms, communication with other immune cells, and regulatory effects on key organs affected by IRI. The review also explores potential therapeutic strategies targeting macrophages to mitigate IRI-induced injury.Key Scientific Concepts of Review: This article reviews the multifaceted roles of macrophages in IRI and explores various modes of macrophage programmed cell death induced by IRI, including gasdermin D-mediated pyroptosis, lipid peroxidation-associated ferroptosis, PARP-1-mediated PAR-dependent cell death, PANoptosis regulated by the PANoptosome, and the formation of macrophage extracellular traps (METs) induced by both reactive oxygen species-dependent and −independent pathways. Additionally, it discusses intercellular communication between macrophages and other immune cells in IRI, focusing on the bidirectional regulatory effects between macrophages and neutrophils, as well as their synergistic role in resolving inflammation. Moreover, the regulatory mechanisms of macrophages in IRI affecting key organs, such as the brain, lung, heart, kidneys and liver, have been systematically summarized. Finally, innovative therapeutic strategies targeting macrophages, including precise approaches such as regulating cell polarization, inhibiting excessive METs formation, and utilizing nano-drug delivery systems, are thoroughly analyzed. This review provides a significant theoretical foundation for clinical translational research on IRI.Ischemia-Reperfusion Injury (IRI) refers to the functional and structural alterations that occur when blood flow is restored following a period of ischemia. IRI is not only a key factor in the pathological progression of many diseases but also contributes to delayed graft recovery. Although the role of IRI has been extensively studied in various organs, the precise mechanisms and pathways involved remain poorly understood and are highly contentious. Beyond ischemia, reperfusion itself can exacerbate tissue and organ damage, particularly through inflammatory processes. Under normal conditions, macrophages protect the body from infection and regulate tissue inflammation. During ischemia, macrophages are activated by diverse signals and initiate an inflammatory response by releasing oxygen s","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"3 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926515","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":"TaPP2C-a5 fine-tunes wheat seed dormancy and germination with a Triticeae-specific, alternatively spliced transcript","authors":"Qian Zhang, Xiaofen Yu, Ya’nan Wu, Ruibin Wang, Yufan Zhang, Fu Shi, Hongyan Zhao, Puju Yu, Yuesheng Wang, Mingjie Chen, Junli Chang, Yin Li, Guangyuan He, Guangxiao Yang","doi":"10.1016/j.jare.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.007","url":null,"abstract":"<h3>Introduction</h3>The sessile plants often experience environmental conditions not ideal for growth, and therefore have evolved strategies to survive and adapt to stress conditions. Abscisic acid (ABA) regulates plant development and abiotic stress response. Clade A type 2C protein phosphatases (PP2Cs), act as co-receptors of ABA, negatively regulate ABA signalling. However, the biological function and detailed molecular mechanism of clade A <em>PP2Cs</em> in ABA signalling pathway remain to be elucidated in wheat.<h3>Objectives</h3>To analyze the mechanisms of stress response and development mediated by ABA signal precisely regulated by TaPP2C-a5 at the post-transcriptional level in wheat, providing candidate genes for wheat improvement.<h3>Methods</h3>Based on our previous results of <em>TaPP2Cs</em> gene family analysis, the function and detailed regulation mechanisms of <em>TaPP2C-a5</em> gene in seed dormancy and germination as well as drought response mediated by ABA signaling pathway were explored through reverse genetics technology.<h3>Results</h3>We found that class A <em>TaPP2C-a5</em> underwent alternative splicing (AS) to produce two transcripts encoding TaPP2C-a5.1 and TaPP2C-a5.2, respectively. Both <em>TaPP2C-a5.1</em> and <em>TaPP2C-a5.2</em> were highly expressed in mature seeds, and were upregulated by exogenous ABA in seedlings. Overexpression of <em>TaPP2C-a5.1</em> and <em>TaPP2C-a5.2</em> coordinately negatively regulated seed dormancy and ABA-mediated seed germination as well as post-germination developmental arrest in wheat. <em>TaPP2C-a5.1</em> negatively regulated drought stress response, while <em>TaPP2C-a5.2</em> did not participate in drought stress response. The homologous genes of <em>TaPP2C-a5</em> underwent the same AS as <em>TaPP2C-a5</em> in tetraploid wheat, but not in rice.<h3>Conclusion</h3>Our results revealed that <em>TaPP2C-a5</em> gene underwent AS and was involved in the regulation of seed dormancy and germination, as well as drought stress response mediated by the ABA signaling at the post-transcriptional level. Our work not only provide a potential target gene to improve PHS resistance, but also emphasize alternative splicing as a strategy with evolution contexts to fine-tune ABA signaling and its involvement in certain biological process.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"125 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920903","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":"SA supplementation during lactation promotes learning and memory by reducing H3K27me3 levels","authors":"Chengqing Huang, Shu Ai, Mengmeng Wang, Changqing Li, Kun Wang, Ming Nie, Heyujia Zhang, Xiaozhen Gu, Hui-Li Wang","doi":"10.1016/j.jare.2025.04.047","DOIUrl":"https://doi.org/10.1016/j.jare.2025.04.047","url":null,"abstract":"<h3>Introduction</h3>Sialic acid (SA) is an essential nutrient for brain development and cognition. Infants lack the capacity to synthesize sufficient SA independently, requiring reliance on maternal or exogenous sources. For early nutritional supplementation, elucidating how SA affects learning and memory is necessary.<h3>Objectives</h3>This study aimed to elucidate the critical time window for SA supplementation that best supports cognitive functions and hippocampal neural mechanisms.<h3>Methods</h3>The MWM experiment was conducted to elucidate the critical time window and dose of SA supplementation. Morphological and electrophysiological studies were used to observe the structural and functional responses of hippocampal neurons that are exposed to SA. RNA sequencing, Western Blot, immunofluorescence, and electrophysiology were used to screen and validate possible neural mechanisms.<h3>Results</h3>Our results show that SA supplementation during, but not after, the lactation period significantly improves learning and memory. SA promotes neurite outgrowth and increases synaptic transmission without affecting the intrinsic membrane properties of hippocampal CA1 neurons. The effect of SA on CA1 neuronal function is independent of the DG-CA3-CA1 loop. Also, long-term effects on synaptic plasticity are primarily due to intracellular epigenetic changes of H3K27me3 rather than direct binding of extracellular SA to membrane proteins. Consequently, our study indicates that decreased H3K27me3 promotes the glutamate-glutamine cycle under SA, thereby contributing to enhanced learning and memory.<h3>Conclusion</h3>Consequently, our study finds that decreased H3K27me3 promotes the glutamate-glutamine cycle under the influence of SA, thereby contributing to enhanced learning and memory. The potential implication of our findings is that SA in early life may contribute to the optimization of children’s comprehensive cognitive function.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"35 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915758","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}