The limitations of conventional cancer therapies have driven the development of precise, low-toxicity strategies. Natural products with bioactivity and self-assembly potential offer a basis for designing multifunctional nanomedicines combining chemotherapy, chemodynamic therapy (CDT), and immunotherapy.
{"title":"Smart nano-assembly from traditional Chinese medicine: manganese-enhanced polysaccharide platform for orchestrated cancer chemo-immunotherapy","authors":"Zhen Lin, Mingming Rong, Wanyu Tang, Zixian Yang, Yifei Xu, Jing Xu, Yuanqiang Guo","doi":"10.1016/j.jare.2026.03.030","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.030","url":null,"abstract":"The limitations of conventional cancer therapies have driven the development of precise, low-toxicity strategies. Natural products with bioactivity and self-assembly potential offer a basis for designing multifunctional nanomedicines combining chemotherapy, chemodynamic therapy (CDT), and immunotherapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"57 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465766","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}
Pub Date : 2026-03-17DOI: 10.1016/j.jare.2026.03.036
Liuyang He, Jie Chen, Meng Yuan, Lei Xia, Jie Pan, Yewen Xie, Chunjian Qi
Introduction
The CD47-SIRPα Axis functions as a key innate immune checkpoint that enables tumors to evade phagocytosis and immune surveillance. Blockade of this interaction has emerged as a promising anticancer immunotherapy strategy.
Objective
The study aimed to develop a macrophage-targeting delivery system using whole β-glucan particles (WGPs) with an immune-stimulatory property to deliver small interfering RNA against SIRPα (siSIRPα), thereby abrogating SIRPα-mediated phagocytosis inhibition and enhancing antitumor immunity.
Methods
Dectin-1-dependent uptake of WGP-siSIRPα was confirmed with bone marrow derived macrophages (BMDMs) from WT and Dectin-1-/- using immunofluorescences and flow cytometry. Cytoskeletal dynamics and lysosomal escape of siSIRPα in BMDMs were visualized by immunofluorescences. Phenotype of BMDMs was characterized via transcriptomics, flow cytometry, ELISA and ROS detection. WGP-siSIRPα mediated T-cell activation was assessed using flow cytometry. In vitro phagocytosis of macrophages was evaluated by confocal microscopy. Therapeutic efficacy was evaluated in subcutaneous B16 melanoma (C57BL/6 mice) and 4 T1 breast cancer (BALB/c mice) models following oral administration of WGP-siSIRPα.
Results
WGP-mediated siSIRPα delivery, dependent on Dectin-1 receptor, achieved robust SIRPα silencing and significantly downregulated expression of SIRPα in macrophages, accompanied by cytoskeletal reorganization and effective lysosomal escape. WGPs promoted M0-to-M1 polarization in macrophages, which synergistically augmented T-cell responses through enhanced antigen presentation. Enhanced phagocytosis of tumor cells with high CD47 expression was observed following siSIRPα delivery. Orally administered WGP-siSIRPα significantly inhibited tumor growth in both B16 melanoma and 4 T1 breast cancer models, associated with decreased SIRPα expression in tumor-associated macrophages (TAMs) and increased M1 polarization within the tumor microenvironment (TME).
Conclusion
These findings establish a proof-of-concept for an oral WGP-based delivery platform and demonstrate a novel siRNA-mediated approach to CD47-SIRPα blockade, which potentiates macrophage-driven antitumor immune responses.
{"title":"Oral Delivery of siSIRPα via Yeast-Derived β-Glucan Particles Enhances Macrophage-Mediated Antitumor Immunity by Blocking the CD47-SIRPα Axis","authors":"Liuyang He, Jie Chen, Meng Yuan, Lei Xia, Jie Pan, Yewen Xie, Chunjian Qi","doi":"10.1016/j.jare.2026.03.036","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.036","url":null,"abstract":"<h3>Introduction</h3>The CD47-SIRPα Axis functions as a key innate immune checkpoint that enables tumors to evade phagocytosis and immune surveillance. Blockade of this interaction has emerged as a promising anticancer immunotherapy strategy.<h3>Objective</h3>The study aimed to develop a macrophage-targeting delivery system using whole β-glucan particles (WGPs) with an immune-stimulatory property to deliver small interfering RNA against SIRPα (<em>siSIRPα</em>), thereby abrogating SIRPα-mediated phagocytosis inhibition and enhancing antitumor immunity.<h3>Methods</h3>Dectin-1-dependent uptake of WGP-<em>siSIRPα</em> was confirmed with bone marrow derived macrophages (BMDMs) from WT and Dectin-1<sup>-/-</sup> using immunofluorescences and flow cytometry. Cytoskeletal dynamics and lysosomal escape of <em>siSIRPα</em> in BMDMs were visualized by immunofluorescences. Phenotype of BMDMs was characterized via transcriptomics, flow cytometry, ELISA and ROS detection. WGP-<em>siSIRPα</em> mediated T-cell activation was assessed using flow cytometry. <em>In vitro</em> phagocytosis of macrophages was evaluated by confocal microscopy. Therapeutic efficacy was evaluated in subcutaneous B16 melanoma (C57BL/6 mice) and 4 T1 breast cancer (BALB/c mice) models following oral administration of WGP-<em>siSIRPα</em>.<h3>Results</h3>WGP-mediated <em>siSIRPα</em> delivery, dependent on Dectin-1 receptor, achieved robust SIRPα silencing and significantly downregulated expression of SIRPα in macrophages, accompanied by cytoskeletal reorganization and effective lysosomal escape. WGPs promoted M0-to-M1 polarization in macrophages, which synergistically augmented T-cell responses through enhanced antigen presentation. Enhanced phagocytosis of tumor cells with high CD47 expression was observed following <em>siSIRPα</em> delivery. Orally administered WGP-<em>siSIRPα</em> significantly inhibited tumor growth in both B16 melanoma and 4 T1 breast cancer models, associated with decreased SIRPα expression in tumor-associated macrophages (TAMs) and increased M1 polarization within the tumor microenvironment (TME).<h3>Conclusion</h3>These findings establish a proof-of-concept for an oral WGP-based delivery platform and demonstrate a novel siRNA-mediated approach to CD47-SIRPα blockade, which potentiates macrophage-driven antitumor immune responses.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"52 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465941","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}
Pub Date : 2026-03-15DOI: 10.1016/j.jare.2026.03.025
Qinyong Dong, Tingjie Huang, Yaling Bi, Jiawen Ji, Mufan Hu, Chunran Zhou, Xiaoying Wan, Peijuan Miao, Xi Wang, Huan Yu, Jiaqi Li, Canping Pan
Stalk rot caused by Fusarium graminearum (F. graminearum) poses a serious threat to maize production, further exacerbated by contamination with the mycotoxin deoxyninylenol (DON). Although selenium nanoparticle (SeNP) priming technology shows potential for enhancing crop resistance, the systematic regulatory mechanisms by which it reprograms plant defense responses against this pathogen remain unclear.
{"title":"Unleashing antifungal power: Nanopriming with selenium boosts JA signaling, suppresses pathogen enzymes, and activates phytoalexins for enhanced Fusarium graminearum resistance in maize","authors":"Qinyong Dong, Tingjie Huang, Yaling Bi, Jiawen Ji, Mufan Hu, Chunran Zhou, Xiaoying Wan, Peijuan Miao, Xi Wang, Huan Yu, Jiaqi Li, Canping Pan","doi":"10.1016/j.jare.2026.03.025","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.025","url":null,"abstract":"Stalk rot caused by <ce:italic>Fusarium graminearum</ce:italic> (<ce:italic>F. graminearum</ce:italic>) poses a serious threat to maize production, further exacerbated by contamination with the mycotoxin deoxyninylenol (DON). Although selenium nanoparticle (SeNP) priming technology shows potential for enhancing crop resistance, the systematic regulatory mechanisms by which it reprograms plant defense responses against this pathogen remain unclear.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"50 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465775","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}
The design of multifunctional catalysts demonstrating exceptional efficiency in complete water electrolysis reactions across various pH environments represents a critical advancement for large-scale generation of renewable hydrogen. This study presents an exceptionally effective catalytic system consisting of cobalt-decorated Co9S8/MoS2 heterostructures supported on ultrathin nitrogen-doped graphene nanosheets (denoted as Co-Co9S8/MoS2@NG). The hybrid architecture integrates transition metal sulfides with conductive graphene substrates through strategic cobalt decoration and nitrogen doping, achieving optimized electronic configurations for enhanced catalytic performance. The Co9S8/MoS2@NG composite demonstrates outstanding catalytic performance and durability across various pH conditions for oxygen generation processes, achieving overpotentials of 210, 238, and 230 mV at 10 mA/cm2 in alkaline, neutral, and acidic environments respectively. Notably, this bifunctional catalyst also shows remarkable efficiency in hydrogen production applications. When implemented in a customized water-splitting electrolyzer utilizing Co-Co9S8/MoS2@NG for both anode and cathode functions, the system achieved operational voltages of 1.58, 1.55, and 1.56 V under alkaline, neutral, and acidic conditions correspondingly. The synthesized Co-Co9S8/MoS2@NG composite demonstrates remarkable catalytic performance, requiring only 1.52 V to maintain 10 mA/cm2 current density across alkaline, neutral, and acidic electrolytes. This material surpasses commercial Pt/C||Ir/C systems (showing 1.64 V, 1.68 V, and 1.66 V in corresponding media) while maintaining competitiveness with state-of-the-art catalysts documented in recent studies. These findings demonstrate the multifunctional capabilities of Co-Co9S8/MoS2@NG as an efficient tri-electrode material for enhanced water electrolysis systems, offering new possibilities for sustainable energy conversion technologies.
{"title":"Co-decorated Co9S8/MoS2 heterostructures anchored to ultrathin graphene nanosheets as trifunctional electrocatalysts for self-powered universal-pH overall water splitting","authors":"Ailing Feng, Xu Zhu, Shijiu Ding, Peitao Liu, Yue Peng, Yanqing Zu, Xiaodong Li, Yanan Chen, Pengfei Bi","doi":"10.1016/j.jare.2026.03.028","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.028","url":null,"abstract":"The design of multifunctional catalysts demonstrating exceptional efficiency in complete water electrolysis reactions across various pH environments represents a critical advancement for large-scale generation of renewable hydrogen. This study presents an exceptionally effective catalytic system consisting of cobalt-decorated Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf> heterostructures supported on ultrathin nitrogen-doped graphene nanosheets (denoted as Co-Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf>@NG). The hybrid architecture integrates transition metal sulfides with conductive graphene substrates through strategic cobalt decoration and nitrogen doping, achieving optimized electronic configurations for enhanced catalytic performance. The Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf>@NG composite demonstrates outstanding catalytic performance and durability across various pH conditions for oxygen generation processes, achieving overpotentials of 210, 238, and 230 mV at 10 mA/cm<ce:sup loc=\"post\">2</ce:sup> in alkaline, neutral, and acidic environments respectively. Notably, this bifunctional catalyst also shows remarkable efficiency in hydrogen production applications. When implemented in a customized water-splitting electrolyzer utilizing Co-Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf>@NG for both anode and cathode functions, the system achieved operational voltages of 1.58, 1.55, and 1.56 V under alkaline, neutral, and acidic conditions correspondingly. The synthesized Co-Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf>@NG composite demonstrates remarkable catalytic performance, requiring only 1.52 V to maintain 10 mA/cm<ce:sup loc=\"post\">2</ce:sup> current density across alkaline, neutral, and acidic electrolytes. This material surpasses commercial Pt/C||Ir/C systems (showing 1.64 V, 1.68 V, and 1.66 V in corresponding media) while maintaining competitiveness with state-of-the-art catalysts documented in recent studies. These findings demonstrate the multifunctional capabilities of Co-Co<ce:inf loc=\"post\">9</ce:inf>S<ce:inf loc=\"post\">8</ce:inf>/MoS<ce:inf loc=\"post\">2</ce:inf>@NG as an efficient tri-electrode material for enhanced water electrolysis systems, offering new possibilities for sustainable energy conversion technologies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"57 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465772","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}
Cardiovascular and cerebrovascular diseases (CCVDs) have surpassed cancer as a significant global health challenge. As essential responders of the immune system, macrophages play a critical role in maintaining and remodeling CCVD homeostasis. They are involved in various functions, including the clearance of apoptotic cells, regulation of inflammatory responses, enhancement of electrical conduction, and facilitation of tissue development and repair. Ion channels not only participate in the electrophysiological activities of macrophages but also directly influence tissue immune responses and inflammatory processes. The regulatory role of ion channels in macrophage function in CCVDs has attracted considerable attention.
Aim
of Review: This review aims to systematically elucidate the specific expression and functional regulation of macrophage ion channels within the cardiovascular and cerebrovascular systems and analyzes the functional heterogeneity of these channels across distinct tissue-specific macrophage subsets. It further explores their mechanistic roles in the progression and repair of CCVDs.Key Scientific Concepts of Review: This review elucidates the fundamental functions and electrophysiological basis of macrophages in the heart, vasculature, and brain, including parenchymal resident macrophages (microglia) of the brain. It further discusses the variation in ion channel expression across macrophages of different tissue origins and polarization states and how this heterogeneity dictates their specific functional roles. Additionally, this review summarizes the pathophysiological contributions of macrophage ion channels to major cardiovascular and cerebrovascular disorders, as well as the underlying molecular mechanisms. Furthermore, it provides an in-depth analysis of the functional mechanisms of key ion channels, critically discusses existing controversies and limitations in current research, and offers our perspectives along with feasible solutions. Finally, this review explores future research directions and emerging trends in this field, along with the clinical potential of targeting macrophage ion channels as a novel therapeutic strategy for CCVDs.
{"title":"Ion channels in macrophages: dynamic regulation in cardiovascular and cerebrovascular diseases and therapeutic potential","authors":"Xiangqin Tian, Yangyang Jia, Changye Sun, Yongkun Sun, Zhikun Guo, Xianwei Wang","doi":"10.1016/j.jare.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.003","url":null,"abstract":"<h3>Background</h3>Cardiovascular and cerebrovascular diseases (CCVDs) have surpassed cancer as a significant global health challenge. As essential responders of the immune system, macrophages play a critical role in maintaining and remodeling CCVD homeostasis. They are involved in various functions, including the clearance of apoptotic cells, regulation of inflammatory responses, enhancement of electrical conduction, and facilitation of tissue development and repair. Ion channels not only participate in the electrophysiological activities of macrophages but also directly influence tissue immune responses and inflammatory processes. The regulatory role of ion channels in macrophage function in CCVDs has attracted considerable attention.<h3>Aim</h3><strong>of Review:</strong> This review aims to systematically elucidate the specific expression and functional regulation of macrophage ion channels within the cardiovascular and cerebrovascular systems and analyzes the functional heterogeneity of these channels across distinct tissue-specific macrophage subsets. It further explores their mechanistic roles in the progression and repair of CCVDs.<strong>Key Scientific Concepts of Review:</strong> This review elucidates the fundamental functions and electrophysiological basis of macrophages in the heart, vasculature, and brain, including parenchymal resident macrophages (microglia) of the brain. It further discusses the variation in ion channel expression across macrophages of different tissue origins and polarization states and how this heterogeneity dictates their specific functional roles. Additionally, this review summarizes the pathophysiological contributions of macrophage ion channels to major cardiovascular and cerebrovascular disorders, as well as the underlying molecular mechanisms. Furthermore, it provides an in-depth analysis of the functional mechanisms of key ion channels, critically discusses existing controversies and limitations in current research, and offers our perspectives along with feasible solutions. Finally, this review explores future research directions and emerging trends in this field, along with the clinical potential of targeting macrophage ion channels as a novel therapeutic strategy for CCVDs.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147448037","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}
Pub Date : 2026-03-13DOI: 10.1016/j.jare.2026.03.023
Xin Liang, Yaohua Zhai, Jun Li, Jiasui Zhan, Fuguang Li, Wenjing Wang
Background
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.
Aim
of Review: 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.
Key Scientific Concepts of Review
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.
Future Directions
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.
{"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}
Pub Date : 2026-03-13DOI: 10.1016/j.jare.2026.03.017
Jian-Rong Yuan, Jie Tang, Rui Sheng
Background
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.
Aim
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.
Key scientific concepts
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.
{"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}
Pub Date : 2026-03-13DOI: 10.1016/j.jare.2026.03.009
Mingjing Wang, Hao ShangGuan, Yang yang, Yeqi Shou, Lizhi Shao, Yazhou Ji, Ali Asghar Heidari, Huiling Chen, Peiliang Wu
Introduction:
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.
Objectives:
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.
Methods:
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.
Result:
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.
Conclusion:
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.
{"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}
Pub Date : 2026-03-13DOI: 10.1016/j.jare.2026.03.019
Boqi Fu, Jinglin Wang, Wenkui Yu, Haozhen Ren
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