Journal of advanced research最新文献

{"title":"Comparative diagnostic performance of robotic, electromagnetic navigation, and fluoroscopy bronchoscopy for lung cancer in peripheral pulmonary lesions: a prospective, multicenter, parallel-controlled trial.","authors":"Changhao Zhong, Junfeng Huang, Li Xu, Zhending You, Feng Wang, Jiayuan Sun, Junhong Jiang, Dan Liu, Jian'an Huang, Huaping Zhang, Hongjia Li, Zhaohui Li, Wei He, Zikai Lin, Xiangyuan Zheng, Linzhi He, Jing Liu, Difei Chen, Guangzhi Wang, Shiyue Li","doi":"10.1016/j.jare.2026.09.008","DOIUrl":"10.1016/j.jare.2026.09.008","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral pulmonary lesions (PPLs) are difficult to access bronchoscopically due to their distal location. Although robotic, electromagnetic navigation, and fluoroscopy-guided systems have been developed, inconsistent study designs have limited direct comparison of their diagnostic performance.</p><p><strong>Objectives: </strong>This study aimed to compare the diagnostic performance and lesion-specific advantages of robotic bronchoscopy system (RBS), electromagnetic navigation bronchoscopy(ENB), and fluoroscopy bronchoscopy(FB) for PPLs.</p><p><strong>Methods: </strong>In this multicenter, prospective, parallel-controlled trial, consecutive patients with suspected PPLs from 7 centers were assigned to the RBS, ENB or FB groups according to a predefined cyclic sequence for biopsy between 2019 and 2023. Subgroup analyses of diagnostic yield were performed according to lesion characteristics. Machine-learning models and a web-based platform were developed for clinical evaluation.</p><p><strong>Results: </strong>A total of 270 patients were included, with 90 patients in each group. RBS achieved a higher overall diagnostic yield than ENB and FB (87.8%, 83.3% and 63.3%, respectively; P < 0.001). Strict diagnostic yield was also highest in the RBS group (81.1% vs 61.1% and 47.8%; P < 0.001). In the subgroup analysis, RBS performed better for 15-30 mm lesions and lesions within 15 mm of the pleura (P < 0.005), whereas ENB showed a diagnostic yield comparable to RBS for malignant, larger and solid lesions. Navigation and biopsy success rates in the RBS group were 100%, with more precise trajectories and lower displacement than the other two techniques (P < 0.001). Based on lesion characteristics, internally developed models (all AUC > 0.96) were integrated into a visualization platform to estimate the technique-specific diagnostic success for individualized PPLs.</p><p><strong>Conclusion: </strong>This multicenter study demonstrates that RBS, ENB and FB have distinct diagnostic advantages across different PPL subgroups. RBS showed better diagnostic performance in selected challenging lesions, whereas ENB achieved comparable performance in malignant, solid, or larger lesions. The image-based prediction platforms may further support individualized selection of transbronchial navigation strategies for PPL or lung cancer diagnosis.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019216","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":"AASIA: A comprehensive protein structural interactome database for agricultural animals.","authors":"Jiajun Li, Mengdi Yuan, Linyang Jiang, Dianke Li, Zhongtao Yin, Feng Zhu, Wenyu Shi, Zhuocheng Hou, Ziding Zhang","doi":"10.1016/j.jare.2026.09.015","DOIUrl":"10.1016/j.jare.2026.09.015","url":null,"abstract":"<p><strong>Introduction: </strong>Agricultural animals are essential for global food production and sustainable agriculture. Improving disease resistance and economically important traits is critical for ensuring food security. Proteome-wide protein-protein interactions (PPIs), termed as interactomes, underlie key biological processes in cells, making them critical for deciphering the genome-phenome relationship. However, species-specific PPI resources remain limited for most agricultural animals.</p><p><strong>Objectives: </strong>Motivated by the rapid development of deep learning and breakthroughs in AI-driven protein structure prediction, we attempted to develop an integrated structural interactome resource for agricultural animals.</p><p><strong>Methods: </strong>We predicted species-specific interactomes through an integrative prediction pipeline that combines interolog mapping, domain-domain interaction inference, and deep learning. The 3D complex structures of all predicted PPIs were further generated using ESMFold.</p><p><strong>Results: </strong>We established AASIA (Agricultural Animals Structural Interactome Atlas; https://aasia.zzdlab.com), a user-friendly database comprising 410,421 high-confidence PPIs and corresponding complex structures across five key species, including Anas platyrhynchos, Bos taurus, Gallus gallus, Ovis aries, and Sus scrofa.</p><p><strong>Conclusions: </strong>AASIA provides the first proteome-scale structural interactome resource for five key agricultural animals. By integrating interaction prediction with structural modeling, it enables mechanistic insight into agriculturally relevant traits and supports applications in variant interpretation, multi-omics integration, and molecular breeding.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009624","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":"Rhizosphere micro-environment restructuring by foliar 24-epibrassinolide enhances wheat resilience to polyethylene nanoplastics.","authors":"Ming Zhuang, Xiaodong Zheng, Chengkui Qiao, Lijun Han, Junling Dun, Shiyu Wang, Mengyuan Cao, Linlin Guo, Fajun Tian, Caixia Wang","doi":"10.1016/j.jare.2026.09.010","DOIUrl":"10.1016/j.jare.2026.09.010","url":null,"abstract":"<p><strong>Introduction: </strong>The stress effects of nanoplastics (NPs) on wheat growth have been increasingly reported. The plant growth regulator 24-epibrassinolide (EBL) shows potential in mitigating abiotic stress, but the mechanisms by which it alleviates NPs toxicity-particularly through root metabolites, rhizosphere metabolites, and rhizosphere microbial communities-remain unclear.</p><p><strong>Objectives: </strong>This study aimed to investigate how EBL mitigates polyethylene nanoplastics (PE-NPs) stress in wheat, focusing on plant growth, root metabolism, rhizosphere metabolites, and rhizosphere microbial communities.</p><p><strong>Methods: </strong>Wheat seedlings were treated with PE-NPs with or without exogenous EBL. Growth parameters, photosynthesis, oxidative damage, and antioxidant enzyme activities were measured. Integrated metabolomics and mass spectrometry imaging (MSI) technologies were employed to characterize metabolic alterations and to spatially visualize metabolite distributions. Rhizosphere metabolites were analyzed using triple quadrupole mass spectrometry, and rhizosphere microbial communities were characterized through high-throughput sequencing, with functional profiles inferred based on 16S rRNA data.</p><p><strong>Results: </strong>EBL treatment significantly alleviated PE-NPs toxicity, increasing shoot and root lengths by 6 % and 14 % and enhancing fresh weights by 16 % and 32 %, respectively. It improved photosynthetic efficiency, reduced malondialdehyde (MDA) accumulation in shoots (29 %) and roots (25 %), and enhanced antioxidant activity and increased jasmonic acid levels. Metabolomics and spatial metabolomics revealed changes in flavonoid biosynthesis, starch/sucrose metabolism, and purine metabolism in wheat roots. Rhizosphere metabolite analysis showed enrichment of galactose, starch/sucrose, and alpha-linolenic acid metabolism. Additionally, EBL enhanced the abundance of Actinobacteriota and Acidobacteriota and increased predicted plastic-degradation-related functions based on FAPROTAX analysis, improved soil physicochemical properties, and increased available nitrogen and phosphorus levels.</p><p><strong>Conclusion: </strong>Exogenous EBL alleviated PE-NPs toxicity in wheat by improving photosynthetic performance, reprogramming root metabolism, and reshaping rhizosphere metabolite and microbial profiles. These findings provide new insights into EBL-mediated tolerance to PE-NPs and support further evaluation of foliar EBL as a plant-centered strategy for improving wheat resilience under nanoplastic stress.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149003214","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":"METTL16 maintains photoreceptor integrity via splicing fidelity, mRNA stability, and translational regulation.","authors":"Jiangbo Ren, Wenjing Liu, Ron Zou, Kuanxiang Sun, Mu Yang, Xianjun Zhu, Zhenglin Yang","doi":"10.1016/j.jare.2026.09.012","DOIUrl":"10.1016/j.jare.2026.09.012","url":null,"abstract":"<p><strong>Introduction: </strong>N6-methyladenosine (m⁶A) RNA modification is essential for retinal homeostasis. Pathogenic mutations in U6 snRNA have recently been identified in families with retinitis pigmentosa (RP), underscoring the importance of precise RNA processing in photoreceptor survival. METTL16 installs m⁶A at A43 of U6 snRNA, but its retinal role remains unknown.</p><p><strong>Objectives: </strong>To define the role of METTL16 in photoreceptor maintenance and determine how its deficiency contributes to retinal degeneration.</p><p><strong>Methods: </strong>We generated rod-specificMettl16knockout (RKO) mice. Visual function was comprehensively evaluated by electroretinography, light-dark box test, and optomotor response. Retinal morphology was examined using immunohistochemical staining. Multi-omics profiling (RNA-seq, proteomics, MeRIP-seq) systematically identified differentially expressed genes and downstream targets. Translational efficiency was assessed through SUnSET assay and polysome profiling.</p><p><strong>Results: </strong>RKO mice exhibited progressive visual impairment, photoreceptor degeneration, and synaptic defects. Mechanistically, METTL16 deficiency disrupted multiple layers of RNA regulation. In the nucleus, loss of U6 snRNA A43 m⁶A modification impaired 5' splice-site selection, causing aberrant exon skipping in RP-associated genes, including Tulp1 and Pde6g, before overt degeneration. METTL16 deficiency also altered m⁶A-associated regulation of selected transcripts, including Tor1b and Nlgn2. In the cytoplasm, METTL16 associated with translation-related factors, and its loss was accompanied by reduced global translation efficiency and decreased levels of several phototransduction proteins.</p><p><strong>Conclusion: </strong>These findings identify METTL16 as a regulator of photoreceptor integrity through U6 snRNA modification and m⁶A-associated transcript regulation, with additional evidence supporting a potential role in translational control. They provide a mechanistic link between RNA dysregulation and retinal degeneration.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979205","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":"Multi-omics integration identifies GmISO5 as a key regulator of seed isoflavone biosynthesis and implicates it in the response to soybean mosaic virus.","authors":"Xinkang Feng, Daqian Sun, Hui Liu, Li Chu, JiaJia Li, Delin Li, Hao Zhang, Xueqing Wang, Tianli Ge, Haiyang Zheng, Shiyu Guo, Xiangguang Zhao, Jinyu Li, Tuanjie Zhao, Yinghui Li, Xiaobo Wang, Lijuan Qiu","doi":"10.1016/j.jare.2026.09.011","DOIUrl":"10.1016/j.jare.2026.09.011","url":null,"abstract":"<p><strong>Introduction: </strong>Isoflavones are specialized metabolites that accumulate abundantly in soybean seeds, contributing to nutritional quality, human health benefits, and plant defense. Although the core isoflavone biosynthetic pathway has been well characterized, its upstream regulatory network and potential relationship with plant stress responses remain incompletely understood.</p><p><strong>Objectives: </strong>This study aimed to identify key regulators of seed isoflavone accumulation and to assess whether the identified regulator is associated with the soybean response to soybean mosaic virus (SMV) infection.</p><p><strong>Methods: </strong>We integrated genome-wide and transcriptome-wide association analyses with CRISPR/Cas9-mediated knockout, transcriptome profiling, molecular interaction assays, co-expression network analysis, and population genetic analysis.</p><p><strong>Results: </strong>GmISO5 was identified as a major genetic determinant of seed isoflavone content. CRISPR/Cas9-mediated knockout of GmISO5 reduced total seed isoflavones by approximately 80% and broadly altered the expression of isoflavone-pathway genes. Molecular assays demonstrated that GmISO5 directly binds to and activates the promoters of GmHIDH and GmCHS1, which encode 2-hydroxyisoflavanone dehydratase and chalcone synthase, respectively, demonstrating direct regulation at distinct steps of the isoflavone biosynthetic pathway. Transcriptome profiling and co-expression network analysis further placed GmISO5 within an isoflavone-enriched regulatory module. Following SMV inoculation, GmISO5 knockout lines exhibited more severe symptoms and higher viral accumulation, implicating GmISO5 in the response to SMV infection. Population genetic analyses showed that the low-isoflavone haplotype (GmISO5^Low) reached 91% frequency in improved cultivars, suggesting that its enrichment may have resulted from indirect selection for seed-weight and oil-content traits associated with GmISO5^Low rather than direct selection for reduced isoflavone accumulation.</p><p><strong>Conclusion: </strong>GmISO5 is a key regulator of soybean seed isoflavone accumulation that directly activates GmHIDH and GmCHS1. The increased SMV susceptibility of GmISO5 knockout lines further implicates GmISO5 in the soybean response to SMV infection, although whether reduced isoflavone accumulation directly causes the altered SMV phenotype remains to be established.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964058","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":"IGFBP7 promotes sepsis-induced multiple organ dysfunction by enhancing OGDH-mediated succinate accumulation.","authors":"Shuai-Shuai Xie, Yu-Hang Dong, Long Xu, Ze-Hui Dong, Ying-Ying Gao, Wei Li, Wen-Xian Ma, Ya-Xin Ru, Tian Zhao, Rui Hou, Lei-Xiang Zhang, Qin Yang, Juan Jin, Jia-Gen Wen, Xiao-Ming Meng","doi":"10.1016/j.jare.2026.09.013","DOIUrl":"10.1016/j.jare.2026.09.013","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a life-threatening systemic inflammatory syndrome frequently complicated by multiple organ dysfunction, yet the molecular mechanisms driving organ failure during sepsis remain poorly understood. Insulin-like growth factor-binding protein 7 (IGFBP7) has been implicated in various organ diseases; however, its role in sepsis-induced multiple organ dysfunction remains unclear.</p><p><strong>Objectives: </strong>This study aimed to determine whether IGFBP7 contributes to the pathogenesis of sepsis-induced multiple organ dysfunction and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Circulating IGFBP7 levels were measured in patients and mice with sepsis. Global and organ-specific Igfbp7 knockout mice were used to evaluate the role of IGFBP7 in cecal ligation and puncture (CLP)-induced sepsis. Liquid chromatography-tandem mass spectrometry was used to investigate the downstream mechanisms.</p><p><strong>Results: </strong>Serum IGFBP7 levels were markedly elevated in patients with sepsis and positively correlated with indices of organ dysfunction. IGFBP7 expression was also increased in the circulation and multiple organs of septic mice. Global or organ-specific deletion of Igfbp7 significantly alleviated CLP-induced multiple organ injury and inflammatory responses. Mechanistically, IGFBP7 interacted with 2-oxoglutarate dehydrogenase (OGDH) and was associated with reduced OGDH-sirtuin 5 association, increased overall OGDH succinylation, enhanced OGDH activity, and excessive succinate accumulation. Succinate accumulation disrupted mitochondrial homeostasis, promoted oxidative stress, and amplified proinflammatory responses. Importantly, anti-IGFBP7 treatment restored mitochondrial integrity, improved organ function, and reduced systemic inflammation.</p><p><strong>Conclusion: </strong>These findings identify IGFBP7 as a critical metabolic regulator in sepsis and highlight an IGFBP7-OGDH-succinate axis that contributes to mitochondrial dysfunction and inflammatory injury. Targeting IGFBP7 may represent a potential therapeutic strategy for sepsis-induced multiple organ dysfunction.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148964017","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":"Erratum to \"Phyllosphere microbiomes in grassland plants harbor a vast reservoir of novel antimicrobial peptides and biosynthetic diversity\" [J. Adv. Res. 87 (2026) 39-54].","authors":"Hongzhang Zhou, Yu Gao, Baiyila Wu, Gang Xu, Limei Tian, Yunlei Sun, Fuyu Yang, Kuikui Ni","doi":"10.1016/j.jare.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.jare.2026.09.009","url":null,"abstract":"","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957699","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":"Corrigendum to \"GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean\" [J. Adv. Res. 73 (2025) 187-198].","authors":"Ze-Hao Hou, Yuan Gao, Jia-Cheng Zheng, Meng-Jie Zhao, Ying Liu, Xiao-Yu Cui, Zhi-Yong Li, Ji-Tong Wei, Tai-Fei Yu, Lei Zheng, Yuan-Chen Jiao, Shu-Hui Yang, Jia-Min Hao, Jun Chen, Yong-Bin Zhou, Ming Chen, Lijuan Qiu, You-Zhi Ma, Zhao-Shi Xu","doi":"10.1016/j.jare.2026.08.063","DOIUrl":"https://doi.org/10.1016/j.jare.2026.08.063","url":null,"abstract":"","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922149","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":"Advancing gene feature selection: a synergistic approach with co-expression networks and genetic algorithms.","authors":"Zhilin Wang, Weiping Ding, Jinquan Zhang, Ali Asghar Heidari, Mingjing Wang, Huiling Chen","doi":"10.1016/j.jare.2026.08.064","DOIUrl":"10.1016/j.jare.2026.08.064","url":null,"abstract":"<p><strong>Introduction: </strong>Gene feature selection is essential in bioinformatics and medical research, as it identifies gene subsets closely associated with specific diseases or biological traits from high-dimensional gene datasets. High-dimensional gene data causes the curse of dimensionality, leading to sparsity, complex inter-feature relationships, and significant noise. These issues undermine the reliability of conventional statistical methods in capturing underlying biological information. While gene feature selection can enhance classification model accuracy and reduce computational complexity, existing methods often struggle to handle the complexities of high-dimensional medical gene data.</p><p><strong>Objectives: </strong>To address the limitations of current methods, we designed a synergistic gene feature selection approach (CJWGA) that integrates co-expression networks and genetic algorithms. The goal is to efficiently perform gene feature selection, significantly reduce the size of feature subsets, and achieve high predictive accuracy across multiple gene datasets.</p><p><strong>Methods: </strong>The CJWGA decomposes feature selection into two key steps: preprocessing of co-expression networks and iterative selection using genetic algorithms. A preprocessing gene selection approach (IMGCNet) is proposed to screen module genes based on conditional mutual information. For joint mutual information, a combined information entropy crossover operator (CIECO) and a joint adaptive mutation operator (JAMO) are designed for the nondominated sorting genetic algorithm, aiming to balance intensification and diversification.</p><p><strong>Results: </strong>Experimental results demonstrate that the proposed CJWGA achieves remarkable performance. It significantly reduces the size of feature subsets while maintaining high predictive accuracy across multiple gene datasets.</p><p><strong>Conclusion: </strong>Overall, the synergistic CJWGA approach, integrating co-expression networks and improved genetic algorithms, exhibits excellent performance in gene feature selection. It addresses the challenges of high-dimensional medical gene data and holds potential as a valuable tool for gene feature selection in bioinformatics and medical research.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A proactive immune training strategy to generate anticipatory immunity against viral evasion.","authors":"Shugang Qin, Yuqin Teng, Jinxiu Xin, Yupei Zhang, Letao Huang, Siyu Zhao, Xiangyu Jiao, Xiaoling Yin, Shenbin Liu, Ju Sun, Weitong Xu, Yongmei Xie, Jiyan Liu, Lingxiang Kong, Xiangrong Song","doi":"10.1016/j.jare.2026.08.059","DOIUrl":"10.1016/j.jare.2026.08.059","url":null,"abstract":"<p><strong>Introduction: </strong>RNA viruses rapidly evolve to evade host immunity, posing a significant challenge to conventional vaccines. Natural infection, however, provides a blueprint for broad immunity by training the immune system against a diverse antigenic landscape. This study addresses the problem of creating a vaccine that mimics this complex training process.</p><p><strong>Objectives: </strong>We aimed to develop and validate a novel vaccination paradigm, \"Proactive Immune Training\" (PIT), designed to enhance cross-reactive neutralization breadth against variants within the predicted evolutionary space.</p><p><strong>Methods: </strong>Using SARS-CoV-2 as a model, we constructed a 600-mutant mRNA library (m-library) based on 30 predicted high-frequency mutation sites. This library was encapsulated in proprietary lipid nanoparticles (LNPs) to form the PIT vaccine. We then evaluated a sequential prime-boost regimen consisting of a single-antigen (SA) vaccine followed by a PIT boost (SA + PIT) in BALB/c mice, assessing humoral and cellular immunity, and performing deep sequencing of B-cell and T-cell receptor repertoires.</p><p><strong>Results: </strong>The SA + PIT regimen induced significantly broader and more potent neutralizing antibodies against a range of SARS-CoV-2 variants compared to conventional regimens. This enhanced protection was mechanistically linked to a profound diversification of the T-cell and B-cell receptor repertoires, a hallmark of superior immune adaptability.</p><p><strong>Conclusion: </strong>The PIT strategy successfully guides the immune system to generate a broad and adaptive immunological response. This proactive, training-based paradigm offers a powerful and versatile framework for developing next-generation vaccines against highly variable pathogens.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914642","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}