Journal of Advanced Research最新文献

{"title":"Systematic profiling of human gut bacteria with cyclic di-AMP secretion to enhance anti-tumor immunity","authors":"Linggang Zheng, Jumin Huang, Haoran Ni, Xiaoxian Kuang, Jin Liao, Zepeng Qu, Hongbin Liu, Chen Huang, Lili Yu, Lei Dai, Elaine Lai-Han Leung","doi":"10.1016/j.jare.2026.03.013","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.013","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"53 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448039","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":"Exogenous biostimulants: mechanisms and innovations for enhancing seed germination and resilience under abiotic stress","authors":"Xin Liang, Yaohua Zhai, Jun Li, Jiasui Zhan, Fuguang Li, Wenjing Wang","doi":"10.1016/j.jare.2026.03.023","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.023","url":null,"abstract":"<h3>Background</h3>Seed germination is a critical phase in the plant life cycle that is highly vulnerable to abiotic stresses such as drought, salinity, and extreme temperatures, posing a severe threat to global crop establishment and food security. Climate change is exacerbating these challenges, necessitating innovative strategies to enhance seed resilience.<h3>Aim</h3><em>of Review:</em> This review comprehensively elucidates the physiological and biochemical mechanisms by which abiotic stress inhibits seed germination, focusing on disruptions in reactive oxygen species (ROS) homeostasis, phytohormone signaling, and energy metabolism. We further critically evaluate the potential of diverse exogenous substances including nanomaterials, phytohormones, metabolites, amino acids, and signaling molecules to mitigate these stresses.<h3>Key Scientific Concepts of Review</h3>We synthesize evidence demonstrating that exogenous substances can effectively enhance seed tolerance by modulating antioxidant defences, rebalancing hormonal crosstalk (particularly GA/ABA), and reprogramming energy metabolism. However, the transition from laboratory promise to field application faces significant hurdles, including cost-effectiveness, environmental safety, and short action cycles.<h3>Future Directions</h3>Looking beyond mere efficacy, this review proposes a transformative roadmap to overcome these limitations. We highlight the immense potential of integrating synthetic biology for sustainable biostimulant production, developing biosafe and biodegradable nanomaterials, and engineering stimulus-responsive nano-delivery systems for the targeted, on-demand release of active ingredients. We argue that the convergence of these multidisciplinary strategies is essential to bridge the lab-field gap and usher in a new era of intelligent, efficient, and sustainable seed technology, ultimately supporting the overarching goals of green agriculture and robust food systems.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"36 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448043","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 stress responsive transcription factor ATF4: from molecular structure to disease mechanisms","authors":"Jian-Rong Yuan, Jie Tang, Rui Sheng","doi":"10.1016/j.jare.2026.03.017","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.017","url":null,"abstract":"<h3>Background</h3>Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, regulates cell survival and death via governing the expression of genes involved in integrated stress response, endoplasmic reticulum stress, autophagy, and metabolism. ATF4′s protein level is tightly controlled by translational regulation (via eIF2α phosphorylation), epigenetic modifications, and post-translational modifications (PTMs) under stress, which are linked to cancer, cardiovascular, neurodegenerative, and metabolic diseases.<h3>Aim</h3>This review aims to summarize recent advances in epigenetic- and PTM-mediated regulation of ATF4 stability and function, and to clarify its multifaceted roles in relevant pathological processes.<h3>Key scientific concepts</h3>Emerging evidence highlights that epigenetic modifications and PTMs are critical for fine-tuning ATF4 activity. These regulatory mechanisms not only modulate ATF4-dependent stress responses but also contribute to disease progression, providing potential therapeutic targets for ATF4-associated disorders.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"19 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448040","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":"Evolutionary-Based Deep Learning Network Model using Adaptive Mixing Differential Evolution and Application in Acute Pulmonary Embolism","authors":"Mingjing Wang, Hao ShangGuan, Yang yang, Yeqi Shou, Lizhi Shao, Yazhou Ji, Ali Asghar Heidari, Huiling Chen, Peiliang Wu","doi":"10.1016/j.jare.2026.03.009","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.009","url":null,"abstract":"<h3>Introduction:</h3>Acute pulmonary embolism (APE) is characterized by high incidence and mortality, along with non-specific clinical manifestations. Its common symptoms such as dyspnea, chest pain, cough, and hemoptysis can also appear in other diseases, frequently resulting in the oversight of APE patients and raising the risk of misdiagnosis and mortality. Current clinical risk stratification for pulmonary embolism usually depends on hemodynamic evaluation, the pulmonary embolism severity index, echocardiography, and myocardial injury markers. However, these assessment methods tend to be complex, time-consuming, invasive, and lack repeatability. Therefore, developing a more efficient and accurate tool for APE prediction and analysis is crucial.<h3>Objectives:</h3>To achieve precise prediction and analysis of APE patients using accessible clinical data, we developed an evolutionary-based deep learning network AlexNet model (EDLAlexNet) that leverages blood biochemical indices, vital signs, clinical parameters, and clinical characteristics. The goal is to provide a reliable clinical tool for the assessment and management of APE with high accuracy, specificity, sensitivity, and a favorable AUC.<h3>Methods:</h3>We developed the EDLAlexNet model, which incorporates a novel evolutionary computation method called adaptive mixing differential evolution (MIXDE) integrating Q-learning and opposition-based learning. The performance of the MIXDE algorithm was statistically validated on standard test datasets. Subsequently, the MIXDE-based EDLAlexNet was used to analyze data from intermediate-low-risk and high-risk pulmonary embolism patients.<h3>Result:</h3>The results for APE using EDLAlexNet showed promising performance, achieving an accuracy of 93.76%, specificity of 89.46%, sensitivity of 95.74%, and an AUC of 0.9527. These outcomes demonstrate the model’s effectiveness in precisely predicting and analyzing APE patients.<h3>Conclusion:</h3>Overall, EDLAlexNet, which integrates the MIXDE algorithm, exhibits excellent performance in APE prediction and analysis. It shows potential as a valuable clinical tool for the assessment and management of APE, addressing the limitations of current assessment methods.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"27 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448041","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":"Development of machine perfusion strategies for liver support and beyond","authors":"Boqi Fu, Jinglin Wang, Wenkui Yu, Haozhen Ren","doi":"10.1016/j.jare.2026.03.019","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.019","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"16 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448038","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":"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}