Journal of advanced research最新文献

{"title":"TREM2 signaling in cardiovascular disease: macrophage heterogeneity, timing, and therapeutic opportunity.","authors":"Ke Yang, Xuefang Ma, Binyan Wang, Aodi Fan, Haohao Gao, Yakun Yang, Haixia Li, Xiangyu Zhu, WeiYing Hu, Jingyu Ni, Han Zhang, Tian Li, Lan Li, Guanwei Fan","doi":"10.1016/j.jare.2026.08.040","DOIUrl":"10.1016/j.jare.2026.08.040","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases remain the leading cause of global morbidity and mortality, with pathogenesis extending beyond hemodynamic derangements to involve chronic, maladaptive immune-metabolic crosstalk. Macrophage functional identity has evolved beyond the M1/M2 paradigm toward a model of high heterogeneity and dynamic plasticity, wherein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) serves as a pivotal molecular hub.</p><p><strong>Aim of review: </strong>This review systematically delineates the spatiotemporal dynamics and functional duality of TREM2⁺ macrophages across major cardiovascular conditions, including atherosclerosis, myocardial infarction, heart failure and sepsis-induced cardiomyopathy. It further evaluates the current evidence and limitations of soluble TREM2 (sTREM2) as a candidate biomarker and critically appraises translational strategies targeting this pathway.</p><p><strong>Key scientific concepts of review: </strong>TREM2 integrates lipid sensing, efferocytosis, metabolic reprogramming, and immune modulation to exert highly context-dependent effects. In early disease stages, TREM2⁺ macrophages participate in lipid accumulation and inflammation initiation, whereas in later phases, they contribute to plaque stabilization, tissue repair coordination and microenvironmental homeostasis. sTREM2 may serve as a dynamic indicator of macrophage activation and functional transition, but its clinical utility for risk stratification and therapeutic monitoring remains investigational. Translational approaches include agonistic antibodies, small-molecule agonists, gene/RNA-based therapies, and localized delivery systems. However, clinical progress is challenged by profound context dependency, sexual dimorphism, undefined therapeutic windows, and the absence of cardiovascular-specific clinical validation. Future advancement requires integrating multiomics technologies, biomarker-guided trials, and systems biology to move TREM2 from mechanistic insight toward precision cardiovascular immunomodulation.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763051","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":"Soil pH regulates organic carbon pool by changing microbial life-history strategy.","authors":"Xiyuan Xu, Kunkun Fan, Ning Ling, Jiasui Li, Teng Yang, Gui-Feng Gao, Yuying Ma, Li Nie, Jiabao Zhang, Haiyan Chu","doi":"10.1016/j.jare.2026.08.028","DOIUrl":"10.1016/j.jare.2026.08.028","url":null,"abstract":"<p><strong>Introduction: </strong>The stability of the vast soil carbon pool, crucial for climate regulation, depends on microbial processes that govern carbon loss as CO₂ or its stabilization in soil. Microbial life-history strategies, representing tradeoffs between resource acquisition (A-strategy) and growth yield (Y-strategy), are central to soil organic carbon (SOC) dynamics. However, how abiotic factors modulate these strategies and, in turn SOC fate remains unclear.</p><p><strong>Objectives: </strong>Using the black soil region of Northeast China, which harbors substantial yet vulnerable SOC reserves, this study aimed to identify the dominant abiotic driver shaping microbial life-history strategies and to elucidate how this driver influences SOC stabilization pathways.</p><p><strong>Methods: </strong>We conducted a field survey combining metagenomic profiling of microbial attributes (diversity, functional potential, and inferred life-history strategy) with measurements of soil properties including extracellular enzyme activities and SOC fractions. This integrative approach traced the pathway from abiotic drivers to microbial traits and ultimately to carbon allocation.</p><p><strong>Results: </strong>Soil pH emerged as the key environmental gradient, with a threshold at pH 6.43 marking a systemic shift in microbial ecology and carbon processing. Acidic soils (pH 4.60-6.43) favored A-strategists, characterized by large genomes, enriched carbohydrate-active enzymes, and high extracellular enzyme activity, enabling polymer degradation and humification but limiting mineral-associated organic carbon (MAOC) formation. In contrast, neutral soils (pH 6.43-8.87) supported Y-strategists with streamlined genomes and biosynthetic metabolism, promoting microbial necromass accumulation and MAOC stabilization. Distinct functional guilds underpinned the A- and Y-strategies and frequent horizontal gene transfer in acidic soils further reinforced the A-strategy dominance under low pH.</p><p><strong>Conclusion: </strong>Our findings reveal a mechanistic link between microbial life-history strategies and SOC stabilization, demonstrating that pH may shape the balance between A- and Y-strategists and their contrasting carbon pathways. This insight enhances predictive models of SOC dynamics and highlights pH management as a key lever for agroecosystems carbon retention.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698574","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":"R-loop Scarlet-RL suppresses scarlet transcription to mediate attraction to plant volatile in migratory locusts.","authors":"Zongyuan Ma, Yajing Sun, Jing Qu, Lihan Zhao, Jiaqi Yu","doi":"10.1016/j.jare.2026.08.027","DOIUrl":"10.1016/j.jare.2026.08.027","url":null,"abstract":"<p><strong>Introduction: </strong>The ABC transporter Scarlet is known for its role in pigment deposition within insect eye pigment granules. However, its extraocular functions remain largely unexplored.</p><p><strong>Objectives: </strong>To investigate the role of Scarlet(LOCMI17149) in olfactory modulation and its regulatory mechanisms in the brains of the migratory locusts.</p><p><strong>Methods: </strong>The expression patterns and functions of scarlet(LOCMI17149) were analyzed by quantitative PCR (qPCR), fluorescence in situ hybridization and RNAi knockdown. Enzyme linked immunosorbent assay (ELISA) was employed to measure the xanthurenic acid (XA) titer. Pharmacological interventions were performed to validate the role of XA and scarlet(LOCMI17149) in multi-unit electrophysiology. DNA-RNA immunoprecipitation (DRIP), chromatin immunoprecipitation (ChIP) and qPCR were conducted to measure the levels of R-loop and histone modification.</p><p><strong>Results: </strong>Among the four Scarlet orthologs, one scarlet(LOCMI17149) is predominantly expressed in the antennae and brain. This expression pattern implicates its roles in olfactory processing. RNAi knockdown of scarlet(LOCMI17149) impaired olfactory preference for plant volatiles and common odorants (indole and β-ionone). This behavioral deficit caused by scarlet(LOCMI17149) RNAi knockdown is linked to a metabolic shift, characterized by decreased 3-hydroxykynurenine (3-HK) and elevated levels of its metabolite XA in the brain. Intracerebral injection of XA recapitulates the olfactory impairment and implicates it as a key behavioral effector. Local field potential (LFP) and electroantennogram (EAG) analysis support that XA suppresses the neurophysiological activity in the antennae and brains of locusts. Furthermore, we discover that an R-loop structure (Scarlet-RL) forms at scarlet(LOCMI17149) locus. Knockdown of Scarlet-RL with antisense oligonucleotides (ASO) increases scarlet(LOCMI17149) mRNA expression, indicating that Scarlet-RL acts as a transcriptional repressor in scarlet(LOCMI17149) transcription. Scarlet-RL mediates the synthesis of nascent mRNAs through histone modification. This study provides the first evidence that Scarlet-RL directly controls the transcription of this chemosensory regulator, revealing a novel epigenetic mechanism that orchestrates insect olfactory preference.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709082","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":"Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription.","authors":"Xiaoyan Wu, Yajun Luo, Caiyi Wu, Jiayao Ni, Yong Xu, Ming Kong, Tao Zhang","doi":"10.1016/j.jare.2026.08.032","DOIUrl":"10.1016/j.jare.2026.08.032","url":null,"abstract":"<p><strong>Introduction: </strong>Identified as a pathological hallmark of all forms of chronic kidney disease (CKD), renal fibrosis contributes to renal failure when dysregulated. In this process, renal fibroblasts act as the primary source of myofibroblasts, which play a pivotal role as the central effector cells.</p><p><strong>Objectives: </strong>This study investigated the role for the lysine methyltransferase Suv39h1 in regulating fibroblast-myofibroblast transition (FMyT) and renal fibrosis.</p><p><strong>Methods: </strong>Fibroblast- and myofibroblast-specific gene knockout in mice was achieved by using the Col1a2-Cre^ERT2 and Postn-Cre^ERT2 drivers. The model of renal fibrosis was established by unilateral ureteral obstruction (UUO) or diabetic nephropathy (DN). Transcriptomic alterations were evaluated by RNA-seq.</p><p><strong>Results: </strong>Our data showed that the transcriptional upregulation of Su39h1 might be implicated in the process of FMyT, as evidenced by its consistent induction in model systems. Suv39h1 deletion attenuated renal fibrosis in three animal models, consistent with its inhibition of FMyT in fibroblasts. Moreover, the conditional ablation of Suv39h1 within Postn-expressing mature myofibroblasts resulted in a significant abrogation of the pathological remodeling associated with renal fibrosis in mice. Notably, the targeted inhibition of Suv39h1 by chaetocin effectively suppressed fibroblast activation in vitro and ameliorated the progression of renal fibrosis in mice. Transcriptomic analysis revealed CXCL10 as a downstream target of Suv39h1. Furthermore, CXCL10 knockdown abolished the protective effect of Suv39h1 insufficiency on renal fibrosis. Mechanistically, CXCL10 regulated FMyT by suppressing the Hippo/YAP pathway.</p><p><strong>Conclusion: </strong>We identify Suv39h1-mediated regulation as a previously unrecognized regulator of renal fibrogenesis.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709118","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":"Optimizing energy efficiency and occupant comfort in smart buildings using SMOTE-augmented deep learning approaches.","authors":"Shahid Mahmood, Jinping Guan, Asifa Iqbal, El-Sayed M El-Kenawy, Sarah M Alhammad, Marwa M Eid","doi":"10.1016/j.jare.2026.08.035","DOIUrl":"10.1016/j.jare.2026.08.035","url":null,"abstract":"<p><strong>Introduction: </strong>The architecture and construction sector is a major consumer of energy and a significant contributor to greenhouse gas emissions, emphasizing the need for intelligent, energy-efficient, and sustainable building systems. Although deep learning techniques have shown strong potential for thermal comfort prediction and building energy management, existing studies remain limited by localized experimental settings, class imbalance, and insufficient comparative evaluation of advanced deep learning models, restricting their practical applicability.</p><p><strong>Objectives: </strong>This study aims to develop a robust deep learning framework for optimizing energy efficiency and occupant thermal comfort by addressing class imbalance and improving prediction accuracy.</p><p><strong>Methods: </strong>A unified framework incorporating data visualization, missing value treatment, label encoding, feature normalization, and the Synthetic Minority Over-sampling Technique (SMOTE) was developed. Multiple deep learning architectures, including Deep Neural Networks (DNN), Deep Flatten DNN, Bi-LSTM, and Attention-based LSTM, were comparatively evaluated. The novelty of the proposed framework lies in integrating SMOTE-based class balancing with the comparative evaluation of multiple deep learning architectures within a unified prediction framework.</p><p><strong>Results: </strong>The Attention-based LSTM model achieved the highest thermal comfort prediction accuracy of 91%, outperforming the Bi-LSTM (89%), Deep Flatten DNN (88%), and DNN (87%). It also achieved superior Precision, Recall, and F1-score, with an 8-percentage-point improvement over the previously reported GNN model on the same dataset.</p><p><strong>Conclusion: </strong>The proposed SMOTE-augmented framework improves the accuracy and robustness of thermal comfort prediction, providing an effective solution for intelligent, energy-efficient, and sustainable building energy management with strong potential for real-world applications.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709159","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":"Broad-spectrum light-responsive deep eutectic solvents for ambient microalgae disintegration with intact fractions.","authors":"Huan Wang, Jianfeng Ma, Bing Song, Hongguo Wu, Song Yang, Hu Li","doi":"10.1016/j.jare.2026.08.034","DOIUrl":"10.1016/j.jare.2026.08.034","url":null,"abstract":"<p><strong>Introduction: </strong>Rationally integrating microalgae valorization is pivotal to sustainable and cost-competitive biorefineries. However, a trade-off exists between effective disintegration of recalcitrant microalgae and retention of biomolecular integrity.</p><p><strong>Objectives: </strong>This study aims to develop a mild, light-responsive pretreatment platform that reconciles structure integrity-efficiency trade-off without relying on energy-intensive external reinforcement.</p><p><strong>Methods: </strong>An \"(in)organic hybridizing dual-amplification\" maneuver is delivered to construct a ternary deep eutectic solvent (DES) system composed of Fe³⁺, α-hydroxycarboxylic acid, and water. The system's performance is evaluated under ambient light irradiation for a short duration (2 h). Mechanistic insights are obtained through theoretical calculations and spectroscopy, while the economic viability was assessed via life cycle cost analysis.</p><p><strong>Results: </strong>Under ambient light, this light-responsive DES system fractionates microalgae into lipids (extraction efficiency of 91.6%, based on saponifiable lipids), conserving functional fatty acids, carbohydrates amenable to digestibility, and high-recovery protein (80.4%, comprising 16.2% soluble and 64.2% natively conformation-preserved fraction). Furthermore, both the extracted microalgal lipids and microbial lipids synthesized from carbohydrates can be converted into ASTM D6751-compliant biodiesel, with the DES retaining efficiency and stability after six recycles. Life cycle cost analysis verifies the economic competitiveness of the developed protocol. Mechanism studies revealed that α-hydroxycarboxylic acid, featuring dual H-bond donor/acceptor characters, cooperates with Fe³⁺ and water to form a supramolecular network that competitively reconfigures the cell wall hydrogen-bonding architecture and lowers constituents' binding energy. Meanwhile, Fe³⁺ forms photo-active complexes with α-hydroxycarboxylic acid as electron shuttles, coupling broad-spectrum ligand-to-metal charge transfer with oxidant-free photo-Fenton process, propelling controllable Fe-redox cycling and sustained radical generation for efficient and facile microalgae disintegration cooperatively.</p><p><strong>Conclusion: </strong>The dual-amplification strategy successfully overcomes the kinetic constraints of traditional photo-Fenton processes and the recalcitrance of cell walls. By enabling efficient, ambient-light-driven disintegration while preserving component integrity, this work provides a scalable and sustainable technological strategy for biomass biorefining.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703111","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":"Candidalysin drives pyroptosis of intestinal epithelium to exacerbate IBS by suppressing HDAC2-mediated deacetylation of GSDMD-K194.","authors":"Ao Liu, Yan Ai, Pengcheng Yang, Li Zhang, Gaichao Hong, Bernd Schnabl, Keshu Xu, Kailin Cai, Xiaohua Hou, Huikuan Chu","doi":"10.1016/j.jare.2026.08.010","DOIUrl":"10.1016/j.jare.2026.08.010","url":null,"abstract":"<p><strong>Introduction: </strong>Gut dysbiosis contributes to irritable bowel syndrome (IBS) pathogenesis and fungi exert independent effects on IBS patients, independent of bacterial influence. IBS patients exhibit elevated fecal Candida levels but the specific role of Candida in IBS remains unclear.</p><p><strong>Objectives: </strong>This study investigated the contributions of Candida albicans (C. albicans) and its toxin candidalysin to IBS pathophysiology and elucidated the underlying mechanisms.</p><p><strong>Methods: </strong>Fecal C. albicans in healthy controls and diarrhea-predominant IBS (IBS-D) patients were detected. Restraint stress murine models were gavaged with C. albicans, C. albicans mutant strains lacking candidalysin (ece1Δ/Δ) or PBS. RNA-seq of intestinal organoids treated with candidalysin and pyroptosis proteins were detected. Gsdmd^-/- mice were generated to evaluate the relationship of candidalysin and pyroptosis. Mass spectrometry, co-immunoprecipitation, and acetylome profiling were employed to characterize GSDMD post-translational modifications.</p><p><strong>Results: </strong>C. albicans abundance was significantly higher in IBS-D patients than controls (31% vs 13%). C. albicans exacerbated barrier disruption, visceral sensitization and inflammation in restraint stress mice by candidalysin. While these pathophysiologic abnormalities were attenuated in Gsdmd^-/- mice. Mechanistically, candidalysin downregulated histone deacetylase 2 (HDAC2) in intestinal epithelial cells, which directly interacted with GSDMD. Acetylome profiling identified GSDMD-K194 as a critical acetylation site. Pharmacological HDAC2 inhibition exacerbated GSDMD-mediated pyroptosis, which was abolished by K194 mutagenesis.</p><p><strong>Conclusion: </strong>Candidalysin exacerbates IBS by inducing pyroptosis in intestinal epithelial cells in vivo, specifically through the inhibition of HDAC2-mediated deacetylation of GSDMD-K194. These findings identify fungal toxins and HDAC2/GSDMD-mediated pyroptosis as pathophysiological mediators in IBS and propose mycobiota-directed therapeutic strategies.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703149","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":"Generation of 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide-resistant rice (Oryza sativa L.) germplasm based on enhanced DNA shuffling and CRISPR-mediated base editing.","authors":"Le Chen, Dongshu Guo, Zhou Yang, Yaru Jin, Xiao Li, Jingjing Deng, Weiwu Wang, Baolong Zhang, Yuwen Yang","doi":"10.1016/j.jare.2026.08.011","DOIUrl":"10.1016/j.jare.2026.08.011","url":null,"abstract":"<p><strong>Introduction: </strong>Weeds significantly threaten rice production. While herbicides are the most efficient weed-control method, prolonged use accelerates resistant weed emergence. 4-Hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides offer potential for managing resistant weeds in rice, but the availability of resistant rice mutants is limited.</p><p><strong>Objectives: </strong>This study aimed to optimize the method of DNA shuffling to conduct directed evolution of the rice HPPD gene, discover novel resistance mutations, and generate herbicide-resistant rice germplasm.</p><p><strong>Methods: </strong>We developed an efficient DNA shuffling method utilizing flanking sequences and segmented amplification to construct random mutation libraries of rice HPPD and maize (Zea mays L.) HPPD genes. Mutant libraries were screened via chromogenic reaction in Escherichia coli. CRISPR-mediated adenine base editing was adopted to generate rice mutants, and hydroponic assays were conducted to evaluate herbicide resistance. The crystal structure of rice HPPD was determined by X-ray crystallography, while mutant structures and ligand docking were simulated with AlphaFold3.</p><p><strong>Results: </strong>Flanking sequences enhanced single-stranded DNA amplification efficiency, and segmented amplification reduced nonsense mutations. A resistant mutant, OsHPPD-mHelix, was obtained. Enzyme kinetics analysis demonstrated that its K_i for mesotrione was increased approximately 2.5-fold compared to that of wild-type OsHPPD, while its enzyme activity was not significantly affected. Using the mutation sites contained in OsHPPD-mHelix as hotspots, genome-edited rice was further generated. It was found that the mesotrione resistance of rice carrying the E423G mutation was approximately 2.2-fold higher than that of wild-type rice. Structural and molecular dynamics analyses suggested the E423G mutation promotes a closed terminal α-helix conformation, with free energy landscapes indicating reduced mesotrione binding stability, potentially explaining the resistance mechanism.</p><p><strong>Conclusion: </strong>This study provides an efficient DNA shuffling technology and novel herbicide-resistant rice germplasm, enriching the toolbox for rice gene-directed evolution and resistant variety cultivation.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698251","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":"Dual-functional bacterial extracellular vesicles with therapeutic oligonucleotides for synergistic treatment of ischemia/reperfusion injury in the brain.","authors":"Kangmin Park, Sung Bin Ahn, Jihun Oh, Jae Young Park, Chowon Lee, Minji Kang, Dong Yun Lee, Minhyung Lee","doi":"10.1016/j.jare.2026.08.031","DOIUrl":"10.1016/j.jare.2026.08.031","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemia/reperfusion (I/R) injury refers to secondary damage that occurs following ischemic stroke when reperfusion is achieved using thrombolytic agents. The abrupt restoration of blood flow induces excessive production of reactive oxygen species (ROS), inflammatory cytokines, and infiltration of immune cells, resulting in additional tissue injury. Although the anti-inflammatory effects of LpEVs have been researched, their potential as gene delivery vehicles has not been investigated.</p><p><strong>Objectives: </strong>LpEV, which possesses anti-inflammatory properties and a lipid membrane structure, has the potential to be utilized as a gene delivery vehicle. Our study focuses on whether LpEVs act as delivery vehicles for anti-miRNA-181a oligonucleotides (AMO181a) and exert therapeutic effects on I/R injury.</p><p><strong>Methods: </strong>LpEVs were isolated by PEG precipitation method. Physical characterization of LpEVs was performed by dynamic light scattering. In vitro cytokine assays were performed to evaluate the anti-inflammatory effect. For delivery of AMO181a, cholesterol-conjugated AMO181a (AMO181a-chol) was loaded into the LpEVs by hydrophobic interaction. Delivery efficiency of AMO181a was evaluated in Neuro2A cells by flow cytometry. The therapeutic effects of LpEVs and AMO181a were measured in the ischemia/reperfusion animal models.</p><p><strong>Results: </strong>Anti-inflammatory effects of LpEVs were confirmed in the activated macrophages in vitro, reducing pro-inflammatory cytokines. Also, LpEVs decreased the infarct volume in an I/R animal model. Delivery efficiency of AMO181a-chol by LpEVs was higher than that of naked AMO181a-chol and comparable to the AMO181a-chol/polyethylenimine (25 kDa, PEI25k) complex in vitro and in vivo. Furthermore, LpEVs did not induce cytotoxicity. As a result, AMO181a-chol-loaded LpEVs had higher therapeutic effects than controls including LpEV alone, naked AMO181a-chol, and AMO181a-chol/PEI25k.</p><p><strong>Conclusion: </strong>LpEVs may be useful for the treatment of ischemia/reperfusion injury with dual functions of its own anti-inflammatory effects and for delivery of therapeutic oligonucleotides.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703079","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 biparatopic antibody targeting the Cε2 and Cε3 domains of IgE disrupts IgE-FcεRI interaction.","authors":"Lixia Zhu, Peiyi Zheng, Qingyu Cheng, Yongshan Gao, Xiaojiao Fan, Xiaoxue Huang, Chengbing Yao, Yuhua Shang, Bofeng Li, Tengchuan Jin","doi":"10.1016/j.jare.2026.08.033","DOIUrl":"10.1016/j.jare.2026.08.033","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic anti-IgE antibodies that block the interaction between immunoglobulin E (IgE) and its high-affinity receptor (FcεRI) have been a popular direction for the treatment of allergic diseases.</p><p><strong>Objectives: </strong>Although both the Cε2 and Cε3 domains of IgE play important roles in stabilizing the IgE:FcεRI complex, most of those anti-IgE antibodies target only the Cε3 domain of IgE. Here, we develop a biparatopic antibody (SA25-A4-IgG1Fc) targeting both the Cε2 and Cε3 domains of IgE, which disrupts IgE-FcεRI interaction.</p><p><strong>Methods: </strong>We link nanobody A4 and SA25 by a (GGGGS)₄ linker, and fuse with a human IgG1Fc tag to generate SA25-A4-IgG1Fc. The FcεRI disruption effect of SA25-A4-IgG1Fc is tested by enzyme-linked immunosorbent assay, flow cytometry, surface plasmon resonance, and food allergic humanized mice.</p><p><strong>Results: </strong>We identify an alpaca nanobody A4, which recognizes the Cε2 domain of IgE with nanomolar affinity, and a shark nanobody SA25, which binds the Cε3 domain of IgE competitively with FcεRⅠ. Targeting both the Cε2 and Cε3 domains of IgE, the biparatopic antibody (SA25-A4-IgG1Fc) binds to IgE with picomolar affinity, and blocks IgE-FcεRI interaction with greater potency than omalizumab in vitro. In addition, SA25-A4-IgG1Fc also removes IgE from human basophils and mast cells with high efficacy, and inhibits ovalbumin (OVA)-induced IgE-dependent food allergy in IgE/FcεRⅠ humanized mice in vivo.</p><p><strong>Conclusion: </strong>Our results demonstrate that the biparatopic antibody SA25-A4-IgG1Fc is a promising inhibitor for the treatment of food allergy, and provide a novel idea for the development of anti-IgE antibodies.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703131","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}