Journal of advanced research最新文献

{"title":"Endothelial DANCR deficiency promotes atherosclerotic plaque instability by targeting ribosomal protein L22.","authors":"Shuting Wang, Qiyue Zhang, Rongxia Li, Yixiao Wang, Adalaiti Kamili, Yuqing Han, Zhihui Hou, Yu Chen, Shujun Yang, Weili Zhang","doi":"10.1016/j.jare.2026.08.060","DOIUrl":"10.1016/j.jare.2026.08.060","url":null,"abstract":"<p><strong>Introduction: </strong>Long noncoding RNAs (lncRNAs) are key regulators of vascular endothelial function. The lncRNA differentiation antagonizing non-protein coding RNA (DANCR) is implicated in cell proliferation and inflammatory responses; however, its specific role in atherosclerosis remains undefined.</p><p><strong>Objective: </strong>To investigate the role of DANCR in modulating endothelial adhesive capacity and atherosclerotic plaque instability.</p><p><strong>Methods: </strong>DANCR expression was profiled in vascular tissues and cell lines using RNA fluorescence in situ hybridization and real-time qPCR. Endothelial-specific DANCR-knockout mice were generated and injected with recombinant adeno-associated virus carrying murine PCSK9 to induce atherosclerosis. Chromatin isolation by RNA purification followed by sequencing was performed to identify potential targets of DANCR. Plasma DANCR level was measured in healthy subjects (n = 42) and in patients with mixed plaques detected by coronary computed tomography angiography (n = 30).</p><p><strong>Results: </strong>DANCR expression was predominantly expressed in endothelial cells and was significantly lower by 43% in the endothelium of human carotid plaques than normal vessels. Endothelial-specific knockout of DANCR in mice led to a 78% increase in aortic plaque area and a 1.1-fold elevation in the plaque instability index, characterized by enlarged necrotic cores, elevated type III/I collagen ratio, and increased macrophage infiltration. The ribosomal protein L22 (RPL22) was identified to be a target of DANCR which repressed its transcriptional expression. Endothelial-specific knockdown of RPL22 reversed the plaque progression and instability induced by DANCR deficiency in vivo. In vitro, DANCR reduced endothelial adhesion capacity and the expression of ICAM1 and VCAM1 via inhibition of the RPL22/p53 pathway. Clinically, plasma DANCR level was lower in patients with mixed plaques compared with control subjects.</p><p><strong>Conclusions: </strong>Endothelial DANCR deficiency promotes atherosclerotic plaque instability through activation of the RPL22/p53 pathway, suggesting DANCR as a potential protective factor and therapeutic target in atherosclerosis.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148858042","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":"Band selection framework for hyperspectral images based on discriminability-oriented optimization mechanism.","authors":"Ximei Ma, Dong Zhao, Qier Kang, Zhennao Cai, Lei Liu, Huiling Chen","doi":"10.1016/j.jare.2026.08.051","DOIUrl":"10.1016/j.jare.2026.08.051","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperspectral images suffer from high dimensionality, inter-band redundancy, and noise interference, increasing computational cost and degrading classification performance. Conventional band selection methods often fail to capture complementary and interactive band relationships, while deep learning-based approaches lack interpretability. Moreover, band selection remains a high-dimensional combinatorial optimization problem, requiring balanced discrimination, redundancy suppression, and search efficiency.</p><p><strong>Methods: </strong>To address the limitations of existing swarm intelligence-based band selection methods and the premature convergence of the original ant colony optimization for continuous domains (ACOR) algorithm, an improved ACOR-based framework, termed IACOR-BS, is proposed. First, a spectral relationship representation based on normalized discriminative scores is constructed to evaluate the discriminative capability and correlation of candidate band subsets. Second, an adaptive preprocessing strategy based on normalized matched filter weights is introduced to suppress low-quality and noise-dominated bands before optimization. Finally, k-means-based initialization, adaptive band index correction, and adaptive parameter adjustment are incorporated into ACOR to improve convergence efficiency and search stability.</p><p><strong>Results: </strong>Experiments on four widely used hyperspectral datasets show that IACOR-BS achieves superior or competitive classification performance under both KNN and SVM classifiers. The proposed framework reduces the number of selected bands by approximately 80% compared with the original spectral dimensionality while maintaining classification accuracy comparable to or higher than that of the best-performing methods. Statistical analyses based on the Friedman and Wilcoxon tests further confirm its superiority and robustness across different datasets and experimental settings.</p><p><strong>Conclusion: </strong>IACOR-BS identifies compact and discriminative band subsets, achieving superior or near-optimal classification performance while maintaining strong band compression capability across diverse hyperspectral datasets.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803738","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":"TAL, encoding a transaldolase, increases grain size and promotes grain filling in rice.","authors":"Xiangbo Li, Mingming Xue, Yajun Tao, Youli Yao, Mingyu Huang, Pei Qu, Shenghao Zhou, Yinwen Wang, Liang Chen, Wenhui Bian, Jun Miao, Chen Chen, Zefeng Yang, Guohua Liang, Yong Zhou","doi":"10.1016/j.jare.2026.08.045","DOIUrl":"10.1016/j.jare.2026.08.045","url":null,"abstract":"<p><strong>Introduction: </strong>Grain size and grain filling are critical determinants of rice yield and grain quality. Although transaldolase (TAL) is a key enzyme of the pentose phosphate pathway and is known to be essential for vegetative growth, whether it contributes to the regulation of grain size and filling has yet to be determined.</p><p><strong>Objective: </strong>This study aims to systematically characterize the function of TAL, with particular emphasis on its effects on grain size and grain filling in rice.</p><p><strong>Methods: </strong>We applied CRISPR/Cas9-mediated knockout and RNA interference (RNAi)-mediated knockdown to assess loss-of-function phenotypes. Concurrently, we established stable TAL overexpression lines to evaluate gain-of-function phenotypes. To identify transcriptional regulators upstream of TAL, we integrated multiple molecular approaches: yeast one-hybrid (Y1H) assays for protein-DNA interaction detection, electrophoretic mobility shift assays (EMSAs) for in vitro binding validation, and dual-luciferase (dual-LUC) transient expression assays for in vivo transcriptional regulatory activity quantification.</p><p><strong>Results: </strong>CRISPR/Cas9-mediated knockout of the TAL gene and RNAi-based silencing of TAL affect multiple aspects of rice growth and development, including decreased grain weight and poor grain filling, accompanied by additional pleiotropic effects such as delayed flowering and a marked yield penalty. In contrast, TAL overexpression not only promoted earlier flowering but, more importantly, substantially enhanced grain size and promoted grain filling. Furthermore, TAL was associated with increased net photosynthetic performance and elevated starch accumulation in leaves and mature grains. Biochemical analysis revealed that TAL possesses transaldolase activity and modulates S7P and E4P homeostasis within the pentose phosphate pathway. We confirmed that TAL is localized to chloroplasts in rice protoplasts, and is preferentially expressed in the pericarp and aleurone layer, as well as in the vascular tissues, suggesting a role in assimilate transport during grain filling. Mechanistically, we identified that OsRA2 functions as a potential transcriptional repressor of TAL by binding to its promoter.</p><p><strong>Conclusion: </strong>This study reveals that TAL, as an important regulatory factor in the pentose phosphate pathway, not only affects multiple aspects of rice growth and development, but more importantly, plays a prominent role in regulating grain size and grain filling.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842555","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":"Short-chain fatty acids alleviate acute pancreatitis by targeting IL-17A to inhibit inflammation and restore intestinal barrier function.","authors":"Xueyang Li, Nianshuang Li, Yaoyu Zou, Pan Zheng, Langyi Guan, Maobin Kuang, Jianhua Wan, Jingwen Gao, Guanyue Wei, Junmin Yang, Nonghua Lu, Cong He, Yin Zhu","doi":"10.1016/j.jare.2026.08.056","DOIUrl":"10.1016/j.jare.2026.08.056","url":null,"abstract":"<p><strong>Background & aims: </strong>Acute pancreatitis (AP) is a life-threatening inflammatory disease with a rising incidence in which intestinal barrier dysfunction and bacterial translocation contribute to severe disease progression. Short-chain fatty acids (SCFAs), key microbial metabolites, have been linked to intestinal health, however, their role in AP and the underlying mechanisms remain unclear. This study aimed to investigate whether SCFAs alleviate AP by restoring intestinal barrier function and modulating inflammation, with a focus on the gut microbiota and the interleukin-17A (IL-17A) pathway.</p><p><strong>Methods: </strong>Mouse AP models were induced using caerulein, and mice were treated with exogenous mixed SCFAs, IL-17A/IL-17RA inhibitors, or recombinant IL-17A (rIL-17A). Germ-free mice, antibiotic-treated mice, and fecal microbiota transplantation (FMT) were used to assess the role of the gut microbiota. Fecal SCFA levels, pancreatic/intestinal histopathology, barrier function markers (Occludin, claudin-1, and D-lactate), inflammatory cytokines, and the IL-17A pathway were analyzed via GC-MS, immunohistochemistry, Western blotting, RNA sequencing, and 16S rRNA gene sequencing.</p><p><strong>Results: </strong>Fecal SCFA levels were reduced in AP mice. Exogenous mixed SCFAs ameliorated pancreatic injury, decreased serum amylase/lipase and proinflammatory cytokines (IL-1β, TNF-α, and IFN-γ), and restored intestinal barrier integrity (increased villus length, mucus layer thickness, and tight junction proteins). The protective effects of SCFAs were abrogated in germ-free or antibiotic-treated mice, but FMT from SCFA-treated donors recapitulated these benefits, supporting a contribution of the gut microbiota to SCFA-mediated protection. 16S rRNA sequencing revealed that SCFAs increased Bifidobacterium pseudolongum (B. pseudolongum) abundance, and B. pseudolongum supplementation alone mitigated AP severity. RNA sequencing and functional assays revealed that SCFAssuppressed the intestinal IL-17A/IL-17RA pathway, reducing the Th17 cell proportion and IL-17A-driven inflammation. The inhibition of IL-17A or IL-17RA mimicked the protective effects of SCFAs, whereas rIL-17A exacerbated AP, which was reversed by SCFAs.</p><p><strong>Conclusion: </strong>SCFAs alleviate AP by improving intestinal barrier integrity and suppressing inflammation, with the gut microbiota contributing, at least in part, to these protective effects. These effects involve gut microbiota remodeling, enrichment of B. pseudolongum, and attenuation of the IL-17A/IL-17RA-related signaling. These findings support a microbiota-associated SCFA-IL-17A regulatory axis in AP and suggest that IL-17A-related signaling warrants further investigation as a potential therapeutic target.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842614","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":"Cerebral amyloid-β burden and white matter injury: associations, clues for underlying mechanisms, and implication on cognitive trajectory after lecanemab therapy.","authors":"Ke Shi, Xin-Yu Luo, Tong-Tong Liu, Wen-Zhe Liu, Yuan-Fei Dong, Fei-Bo Zheng, Xin Zhou, Jing-Song Xing, Zhi-Hua Sun, Qiong-Qiong Chen, Li Jiang, Chen-Chen Tan, Lan Tan, Wei Xu","doi":"10.1016/j.jare.2026.08.057","DOIUrl":"10.1016/j.jare.2026.08.057","url":null,"abstract":"<p><strong>Introduction: </strong>White matter hyperintensities (WMH) are linked to cognitive decline and risk of Alzheimer's disease (AD).</p><p><strong>Objectives: </strong>To test whether amyloid-β (Aβ) deposition contributes to white matter injury and whether WMH dynamics can modulate the clinical efficacy of the anti-Aβ therapy.</p><p><strong>Methods: </strong>Twenty patients with early AD who are receiving lecanemab and a matched cohort of 110 untreated AD patients were followed. Linear mixed-effects models were used to examine the interplay between WMH trajectories and lecanemab on cognitive decline. The roles of Aβ burden in predicting baseline severity and progression rates of WMH were evaluated in a larger cohort of 1,031 adults. Finally, cerebrospinal fluid (CSF) proteomic and bioinformatic analyses were performed to identify potential candidate mediators and pathways linking Aβ to WMH progression.</p><p><strong>Results: </strong>Following lecanemab treatment (median = 13 times), 80 % of patients showed WMH reductions, predominantly in periventricular and frontoparietal regions. Compared to the reference cohort, WMH progression is significantly slower among those with anti-Aβ therapy. WMH trajectory significantly modified the relationship between anti-Aβ therapy and cognitive decline, with greater cognitive improvement observed among those with smaller WMH reductions. The levels of Aβ burden were correlated with higher burden and accelerated rates of WMH. Eight proteins in CSF were identified as candidate mediators linking WMH to Aβ. They were enriched in vascular-endothelial, neuro-cytoskeletal, and neuroinflammation pathways.</p><p><strong>Conclusion: </strong>The interplay of Aβ with white matter integrity contributes to cognitive decline in the context of Alzheimer's disease.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835455","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":"Ethanol as a core modulator of flavor perception: unraveling its impact on the taste attributes and thresholds of esters in alcoholic beverages.","authors":"Yunlin Yang, Yimei Zhang, Xinyu Hu, Xi Chen, Hehe Li, Dongrui Zhao, Bowen Wang, Baoguo Sun, Jinyuan Sun","doi":"10.1016/j.jare.2026.08.058","DOIUrl":"10.1016/j.jare.2026.08.058","url":null,"abstract":"<p><strong>Introduction: </strong>Esters are one of the most crucial flavor components in alcoholic beverages. Their sensory characteristics at different ethanol concentrations profoundly influence the quality of the beverage products.</p><p><strong>Objectives: </strong>This study aimed to regulate the flavor quality of alcoholic beverages and to provide a theoretical basis for precise flavor regulation under the trend of healthy and low-alcohol alcoholic beverages.</p><p><strong>Methods: </strong>Quantitative descriptive analysis was used to characterize the taste features of 30 key ester compounds in different ethanol solutions (10%, 20%, 30%, 40%, 46%, 53% ABV). The taste threshold was determined using the ten-cup method, and the sensory difference intensity changes of four representative esters were also measured.</p><p><strong>Results: </strong>The taste characteristics of esters were generally strong sweetness, with most compounds scoring between 3 and 5 points on a 5-point intensity scale. Ethyl lactate exhibited a prominent acidic taste at high ethanol concentrations, while ethyl benzoate and ethyl phenylpropionate exhibited strong bitter tastes. The astringent and stimulating sensations increased significantly with increasing in ethanol volume fraction, and this was particularly evident in the 46%-53% ABV range. The 30 esters were classified into sweet type, bitter type, and ethanol and acid type. Their taste response patterns were related to the molecular structure. As the ethanol concentration increases, the taste threshold of esters showed a decreasing trend. In particular, in the 30-40% ethanol range, the threshold of some esters decreased by more than 98%. With increasing in ethanol, the multiple times of ester concentration required to achieve the same sensory intensity significantly decreased. High ethanol concentrations compressed the perceivable concentration range, enabling the taste system to perceive significant changes within a narrower range.</p><p><strong>Conclusion: </strong>The flavor of esters changed regularly with the ethanol concentration.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835479","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":"Spatial transcriptomic and proteomic approaches for profiling prognostic cell communities in solid tumors.","authors":"Xia Lei, Xuan Cui, Yuanli Ni, Yihan Ding, Yadi Miao, Cheng Qian, Juanjuan Shan","doi":"10.1016/j.jare.2026.08.054","DOIUrl":"10.1016/j.jare.2026.08.054","url":null,"abstract":"<p><strong>Background: </strong>A comprehensive understanding of the complexity and heterogeneity of the tumor microenvironment (TME) is critical for advancing cancer treatment. Recent advances in spatial omics technologies have opened new avenues for an in-depth exploration of the TME. By integrating high-resolution spatial information from omics, spatial omics enables the systematic characterization of the spatial distribution of various cell types within tissues and their interaction networks, providing a panoramic view of the TME. Emerging studies have highlighted that specific spatial structures within the TME are strongly associated with cancer prognosis and treatment responses.</p><p><strong>Aim of review: </strong>This review focuses on the patterns of spatial cell distributions or characteristic cell structures and their relationship with cancer prognosis, underscoring the pivotal role of spatial heterogeneity in tumors. It aims to provide theoretical foundations for precision medicine approaches in prognostic evaluation and therapy design.</p><p><strong>Key scientific concepts of review: </strong>This review discusses how spatial transcriptomics and proteomics enable extraction of spatial metrics including cell density, proximity, and community-level organization. We further summarize the spatial distribution patterns of cells and key cell community structures, emphasizing the pivotal role of spatial heterogeneity in tumors. Furthermore, it highlights critical spatial features, including immune cell infiltration patterns and vascular niches, that are strongly linked to patient outcomes. Additionally, the review discusses the challenges and future prospects of applying spatial omics in clinical applications. As the field evolves, spatial omics holds transformative potential to revolutionize oncology research, enabling novel approaches for risk stratification and improving patient outcomes.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820727","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":"Biochar and nanoparticle composites (nano-modified biochar) as next-generation soil amendments for sustainable salt stress management.","authors":"Haider Sultan, Jingdong Chen, Yusheng Li, Zaid Ulhassan, Hafiz Muhammad Mazhar Abbas, Muhammad Nazim, Heping Wan, Mohammad Faizan, Changli Zeng","doi":"10.1016/j.jare.2026.08.050","DOIUrl":"10.1016/j.jare.2026.08.050","url":null,"abstract":"<p><strong>Background: </strong>Soil salinity is one of the most critical abiotic stressors limiting global agricultural productivity by adversely affecting plant physiology, nutrient dynamics and soil health. Excessive accumulation of soluble salts disrupts osmotic balance, induces ionic toxicity and elevates oxidative stress, thereby impairing plant metabolism and soil ecological stability. In recent years, biochar and engineered nanoparticles (NPs) have emerged as innovative and sustainable soil amendments capable of mitigating salinity-induced deterioration in agroecosystems. Biochar improves soil structure, water retention and cation exchange capacity while promoting microbial activity and nutrient availability. In contrast, nanoparticles enhance stress tolerance by regulating redox balance, improving nutrient use efficiency and modulating antioxidant defense systems.</p><p><strong>Aim of review: </strong>The review aims to critically evaluate the individual and combine role of biochar and nanoparticles as a nano-modified biochar (NP-BC) in alleviating salinity stress in plant-soil systems. The review further explores the mechanistic pathways through which NP-BC improves plant physiological performance, soil biochemical properties and stress resilience under saline conditions and highlight their potential as sustainable tools for managing saline agroecosystems.</p><p><strong>Key scientific concepts of the review: </strong>The integration of biochar with nanoparticles as NP-BC offers a multifunctional approach combining structural, chemical and catalytic properties. This combined system improves ion homeostasis through Na⁺ exclusion and K⁺ retention, enhances osmotic regulation, strengthens antioxidant defense systems, supports soil microbial activity and nutrient cycling under saline conditions. The review provides a comprehensive synthesis of the mechanistic interactions and functional roles of biochar, nanoparticles and NP-BC in mitigating salt stress. Furthermore, it highlights key research gaps related to dosage optimization, long-term environmental implications and field-scale applicability to support the development of next-generation sustainable nano-enabled soil management strategies.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803736","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":"Interleukin-33/IL-1RL1 axis modulates dendritic cell immune responses during the early phase of sepsis via RETREG1-mediated reticulophagy.","authors":"Peng-Yi He, Li-Yu Zheng, Qi Fan, Yu Duan, Yu Chen, Meng-Yao Wu, Tuo Zhang, Shu-Ting Wei, Xin-Yue Cheng, Lei Liu, Shen-Ao Pan, Tian-Zhen Hua, Hui Zhang, Ning Dong, Yao Wu, Ji-Wei Hao, Ren-Qi Yao, Xiao-Mei Zhu, Yong-Ming Yao","doi":"10.1016/j.jare.2026.08.046","DOIUrl":"10.1016/j.jare.2026.08.046","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin-33 (IL-33) is a damage-associated alarmin that may have a profound effect on systemic inflammation. Dendritic cells (DCs) are critically involved in sepsis progression, but the precise regulation of DC function by IL-33 remains unresolved.</p><p><strong>Objectives: </strong>This study explored the role of the IL-33 signaling axis in DC activation during sepsis.</p><p><strong>Methods: </strong>The role of IL-33 was investigated using an in vitro DC system and a cecal ligation and puncture-induced sepsis model in wild-type and interleukin-1 receptor-like 1 (IL-1RL1)-deficient mice. Downstream mechanisms were dissected through proteomic analysis, Western blotting, and genetic ablation. Validation was performed using mice deficient in reticulophagy regulator 1 (RETREG1) and activating transcription factor 6 (ATF6), as well as with the inhibitor of calcium/calmodulin-dependent kinase II (CaMKII).</p><p><strong>Results: </strong>IL-33 stimulation potently enhanced DC function in an IL-1RL1-dependent manner. IL-33 promoted RETREG1-mediated reticulophagy, a process essential for DC activation, as DCs from Retreg1^-/- mice showed markedly attenuated activation responses. Mechanistically, IL-33 induced the nuclear translocation of ATF6, a transcription factor implicated in RETREG1 regulation. Concurrently, IL-33 activated CaMKII, which was associated with increased RETREG1 phosphorylation, thereby potentiating RETREG1-driven reticulophagy.</p><p><strong>Conclusion: </strong>Our findings unveil a novel pathway wherein IL-33 orchestrates DC immune function during early sepsis through a dual mechanism-transcriptional upregulation and functional potentiation of RETREG1. Modulation of IL-33/RETREG1-mediated reticulophagy may inform therapeutic development for septic complications.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803781","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":"Tumor microenvironment-remodeling cell membrane biomimetic nanoplatform for activated imaging and cascade-amplified treatment of breast cancer.","authors":"Boye Zhang, Yuli Chen, Pengyan Qiao, Ruixu He, Shiyuan Fan, Biyue Zhang, Wen Liu, Guodong Ren, Lili Yan, Lixia Guo, Sufang Ma, Chengwu Zhang, Haipeng Diao, Yang Liu, Lihong Li","doi":"10.1016/j.jare.2026.08.053","DOIUrl":"10.1016/j.jare.2026.08.053","url":null,"abstract":"<p><strong>Introduction: </strong>Strategic harnessing and modulation of the tumor microenvironment (TME) can overcome its inherent therapeutic barriers and enhance treatment efficacy. TME hallmarks, including hypoxia, excessive glutathione (GSH), and insufficient H₂O₂, severely limit reactive oxygen species (ROS)-based therapies.</p><p><strong>Methods: </strong>To address this issue, leveraging the high lactate level in TME, we developed BIMLM (BSA-IR780-MnO₂@LOX@Membrane) as a biomimetic nanoplatform integrating lactate oxidase (LOX)-driven lactate exhaustion with MnO₂-coated IR-780 for TME remodeling and self-amplifying ROS generation. BIMLM was fabricated by first preparing MnO₂-coated IR-780 nanoparticles, then immobilizing LOX, and finally cloaking them with tumor cell membranes.</p><p><strong>Results: </strong>After BIMLM accumulates selectively within tumor tissue, intratumoral excess lactate triggers the sequential therapeutic cascades. Specifically, LOX-catalyzed lactate oxidation generates H₂O₂ to induce metabolic starvation by disrupting energy supply. This H₂O₂ is then decomposed by MnO₂ to produce O₂, which simultaneously facilitates cyclic lactate oxidation and enhances photodynamic therapy (PDT). The resulting Mn²⁺ further triggers a Fenton-like reaction, converting the self-supplied H₂O₂ into •OH and thereby amplifying chemodynamic therapy (CDT). Concurrently, GSH depletion increases cellular susceptibility to ROS, further potentiating both PDT and CDT. Notably, coordinated GSH downregulation and ROS upregulation synergistically trigger ferroptosis, which combines with apoptosis to achieve potent tumor suppression.</p><p><strong>Conclusions: </strong>Taken together, the nanoplatform reconfigures the TME through lactate depletion, H₂O₂ elevation, hypoxia alleviation, and GSH scavenging. This series of changes creates a self-amplifying cycle that enhances PDT/CDT efficacy while triggering metabolic starvation and ferroptosis, which collectively enable tumor eradication. This strategy establishes a promising paradigm for high-efficiency tumor therapy.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803786","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}