Frontiers in Molecular Biosciences最新文献

{"title":"Multi-omics characterization of β-myrcene-evolved <i>Pseudomonas</i> sp. M1 reveals convergent FleQ mutations and altered catabolic efficiency.","authors":"Filipa Soares, Rafaela Roque, Patrick Hellwig, Dirk Benndorf, Pedro M Santos","doi":"10.3389/fmolb.2026.1800048","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1800048","url":null,"abstract":"<p><p>β-Myrcene is a high-value monoterpene precursor whose high hydrophobicity limits microbial biotransformation. In aqueous medium, β-myrcene forms droplets that <i>Pseudomonas</i> sp. M1 accesses through chemotaxis mediated by the genomic island (GI)-encoded methyl-accepting chemotaxis protein MyrS. To identify genetic targets for strain improvement, we subjected M1 to adaptive laboratory evolution (ALE) for 600 generations under β-myrcene selection and characterized two evolved isolates, M2C19 and M3C22, using comparative genomics, quantitative proteomics, and metabolite profiling. Both lineages independently acquired mutations in the AAA + ATPase domain of FleQ, the master regulator of flagellar biosynthesis, resulting in loss of polar flagella and Tad pilus proteins, and strong reduction of chemotaxis signal transduction (CheA, CheW), putatively impacting response to β-myrcene chemoattractant signal. Despite identical growth rates during exponential phase, evolved strains achieved ∼33% higher final OD₆₀₀ than wild-type M1. Metabolite analysis indicated enhanced pathway flux: M2C19 accumulated myrcenoic acid 10.6-fold above wild-type, while M3C22 accumulated 3.5-fold, and upstream intermediates (myrcen-8-ol, myrcenal) were depleted in both strains. Proteome profiling revealed distinct temporal dynamics of GI induction: M2C19 showed early upregulation of GI proteins, whereas M3C22 displayed delayed induction at early exponential phase with recovery by late exponential phase. Beyond the GI, both evolved strains converged on reduced motility/chemotaxis systems and extensive membrane remodeling, while core metabolic processes diverged. M2C19 broadly upregulating respiration and β-oxidation components, and M3C22 showing systematic downregulation of these pathways at early growth stages. Overall, the results identify FleQ as a major adaptive target during β-myrcene-driven evolution and reveal distinct proteometabolic strategies that improve monoterpene processing under laboratory selection.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1800048"},"PeriodicalIF":3.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive assessment of inflammatory bowel disease activity using a DIA-derived stool peptidomic signature and machine learning.","authors":"Elmira Shajari, David Gagné, Mandy Malick, Patricia Roy, Jean-François Noël, Hugo Gagnon, Maxime Delisle, François-Michel Boisvert, Marie A Brunet, Jean-François Beaulieu","doi":"10.3389/fmolb.2026.1768474","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1768474","url":null,"abstract":"<p><strong>Introduction: </strong>Monitoring disease activity in inflammatory bowel disease (IBD) is essential for guiding therapy and preventing irreversible tissue damage. Colonoscopy, although the gold standard, is invasive and unsuitable for frequent monitoring, while fecal calprotectin lacks accuracy within its diagnostic gray zone (fecal calprotectin 100-250 μg/g). Stool proteomics offers a non-invasive alternative by directly capturing molecular signatures of intestinal inflammation. We conducted a proof-of-concept study to determine whether stool-derived peptides can accurately classify IBD activity (Active vs. Remission) using a fully unbiased and reproducible nested cross-validation machine-learning framework.</p><p><strong>Methods: </strong>A total of 174 stool samples from IBD patients were collected and profiled using SWATH-DIA mass spectrometry. Feature selection was performed within the training loops only (Boruta, LASSO, RFE) across repeated subsampling, retaining peptides consistently identified in ≥70% of runs. Stable features were used to train four classifiers (GLMNet, SVM-Radial, SVM-Linear, Naïve Bayes) under inner 5-fold tuning. Outer test folds provided fully unseen evaluation, and model performance was additionally assessed exclusively on gray zone samples extracted from the outer test splits to quantify diagnostic resolution in this clinically challenging subgroup.</p><p><strong>Results: </strong>Nested cross-validation identified a consensus panel of nine stool-derived peptides from five proteins. Across candidate classifiers, performance was broadly similar, with GLMNet consistently achieving the best trade-off between metrics. For GLMNet, outer-fold mean AUC was 0.93 and balanced accuracy 0.88, with specificity 0.94, sensitivity 0.82, and F1-score 0.85; close agreement between inner- and outer-fold metrics indicated minimal overfitting. Within the calprotectin gray zone subgroup (n = 34), GLMNet maintained good performance (balanced accuracy 0.78, F1 0.79, AUC 0.80), confirming that the peptide signature remains informative in this diagnostically challenging range.</p><p><strong>Conclusion: </strong>A stool-based multi-peptide signature, evaluated with a rigorously nested, leakage-free machine-learning framework, can reliably classify IBD activity and retain discriminative power within the gray zone. This biologically interpretable five-protein panel provides a strong basis for targeted mass-spectrometry assay development and prospective validation as a non-invasive tool for personalized IBD monitoring.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1768474"},"PeriodicalIF":3.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the circRNA-Mediated ceRNA regulatory network in dendritic cells during H37Ra and BCG infection.","authors":"Xiaohong Sun, Shuangshuang Bao, Kaixin Zhou, Yaqi Sun, Qian Gao, Yan Lin","doi":"10.3389/fmolb.2026.1764518","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1764518","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is a chronic infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>), and poses a significant threat to global human health. Dendritic cells (DCs) represent the most potent antigen-presenting cells and play a critical role in host defenses against <i>M.tb</i> infection.</p><p><strong>Methods: </strong>We analyzed GEO datasets to identify differentially expressed circRNAs and mRNAs in <i>M.tb</i>-infected DCs. The downstream miRNAs were predicted using the circBank and CircInteractome databases, while the target mRNAs were predicted using TargetScan and miRanda. A ceRNA regulatory network consisting of 10 circRNAs, 41 miRNAs, and 145 mRNAs was constructed. Protein-protein interaction (PPI) analysis identified 30 hub nodes, which were further subjected to Gene Ontology and KEGG enrichment analyses.Subsequently, the circRNA/miRNA/mRNA regulatory axis was assessed, followed by validation using qRT-PCR and evaluation through ROC curve analysis.</p><p><strong>Results: </strong>Four core genes-<i>STAT1</i>, <i>BCL2</i>, <i>TRAF6</i>, and <i>IL1A</i>-were enriched in tuberculosis,JAK-STAT,and NF-κB pathways. Two ceRNA axes, circNFATC3/miR-150-5p/<i>STAT1</i> and circNFATC3/miR-23a-3p/<i>BCL2</i>, were validated by qRT-PCR, showing expression patterns consistent with high-throughput data. ROC analysis demonstrated strong diagnostic potential (AUC >0.7) for both axes.</p><p><strong>Conclusion: </strong>This study constructed a ceRNA regulatory network in <i>M.tb</i>-infected DCs, identified key molecular modules, and proposed circRNA-associated axes as promising biomarkers for early TB diagnosis and potential therapeutic targets.However, these findings are limited to experimental models of DCs infection and require further validation in clinical samples and <i>in vivo</i> models.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1764518"},"PeriodicalIF":3.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic biomarkers and regulatory mechanisms associated with lysine β-hydroxybutyrylation modification in prostate cancer.","authors":"Yonghui Meng, Jinjun He, An Yan, Bangwei Che, Kaifa Tang, Tao Zhang","doi":"10.3389/fmolb.2026.1778536","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1778536","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a highly prevalent malignant tumor in males. Lysine β-hydroxybutyrylation (Kbhb), an emerging post-translational modification, plays a critical role in tumorigenic processes. However, its functional mechanism in PCa remains elusive. This study aims to identify Kbhb-related prognostic genes in PCa and provide novel insights for its diagnosis, prognosis and treatment.</p><p><strong>Methods: </strong>Candidate genes were obtained through differential expression analysis and intersection analysis. Univariate Cox proportional hazards model and least absolute shrinkage and selection operator (LASSO) regression were employed to screen Kbhb-related prognostic genes, and a risk model was constructed and validated. The expression levels of Kbhb modification and related prognostic genes were validated using Western blotting (WB), real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC). Additionally, clinical correlation analysis, nomogram development and validation, immune infiltration analysis, tumor mutation burden (TMB) analysis, gene set enrichment analysis (GSEA), drug sensitivity prediction, molecular regulatory network analysis, drug targeting analysis, and molecular docking were performed.</p><p><strong>Results: </strong>Three genes--kinesin family member 4A (KIF4A), TPX2 microtubule nucleation factor (TPX2), and aurora kinase B (AURKB)-were identified as Kbhb-related prognostic genes. Results of WB indicated that the butyrylation level of the H3K27 (H3K27-Bu) protein was significantly upregulated in PCa tissues. RT-qPCR and IHC results demonstrated that the expression levels of KIF4A, TPX2, and AURKB were significantly higher in the PCa than normal tissues. A risk model based on these genes demonstrated discriminatory ability (AUC >0.6) and served as an independent prognostic factor alongside prostate-specific antigen (PSA). The prognostic nomogram showed high accuracy (AUC 0.82-0.88). High-risk patients exhibited distinct immune infiltration profiles and higher mutation frequencies in tumor protein 53 (TP53), Titin (TTN), and speckle-type POZ protein (SPOP). Drug sensitivity analysis linked the risk score to 24 compounds, while molecular docking suggested that estradiol and bisphenol A could target the identified hub genes.</p><p><strong>Conclusion: </strong>This study identified KIF4A, TPX2, and AURKB as reliable prognostic biomarkers for PCa. These findings provide a theoretical basis for understanding Kbhb-mediated mechanisms in PCa and offer novel targets for early diagnosis and precision therapy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1778536"},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bamboo shoots-derived nanovesicles (BSNs) induce apoptosis in non-small-cell lung cancer A549 cells through the p53 signaling pathway.","authors":"Ruihua Bai","doi":"10.3389/fmolb.2026.1759968","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1759968","url":null,"abstract":"<p><strong>Introduction: </strong>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Nanovesicles have been demonstrated to be important mediators of intercellular communication in NSCLC. Plant-derived nanovesicles contain lipids, proteins, nucleic acids, and pharmacologically active substances, and have attracted increasing attention as potential anticancer agents due to their easy availability, low toxicity, and demonstrated biological activities. However, the role of edible plant-derived nanovesicles in cancer regulation remains poorly understood.</p><p><strong>Methods: </strong>Bamboo shoot-derived nanovesicles (BSN) were isolated by differential centrifugation and characterized. The human NSCLC cell line A549 was used as an <i>in vitro</i> model. Cellular uptake of BSN was evaluated, and their effects on cell proliferation, migration, and invasion were assessed. Selectivity was examined using non-cancer cells (3T3-L1 and RAW264.7) and another cancer cell line (HeLa). RNA sequencing (RNA-seq) was performed to explore the underlying molecular mechanisms, followed by protein-protein interaction (PPI) network analysis. Apoptosis and signaling pathways were further analyzed by flow cytometry and Western blot.</p><p><strong>Results: </strong>BSN were efficiently internalized by A549 cells and significantly inhibited A549 cell proliferation, migration, and invasion. This inhibitory effect was not observed in non-cancer cells (3T3-L1 and RAW264.7) or in another cancer cell line (HeLa). RNA-seq analysis indicated that BSN treatment mainly affected the cell cycle and p53 signaling pathways. Among the Top 20 core genes identified in the PPI network, 13 were associated with Akt-related pathways. Further experiments demonstrated that BSN promoted apoptosis in A549 cells through modulation of the Akt/p53 signaling pathway.</p><p><strong>Discussion: </strong>These findings indicate that BSN selectively target NSCLC cells and induce apoptosis via the Akt/p53 pathway, thereby exerting anti-tumor effects in A549 cells. This study highlights the potential of bamboo shoot-derived nanovesicles as a promising plant-based therapeutic strategy for NSCLC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1759968"},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics analysis reveals the drug-protein-ceRNA regulatory network in acute ischemic stroke.","authors":"Xiaoli Kong, Zhengyu Chen, Han Lu, Xueting Gao, Xiaoyu Zhou, Hao Su, Jun Teng, Haimeng You, Hongyan Ge","doi":"10.3389/fmolb.2026.1779905","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1779905","url":null,"abstract":"<p><p>Previous studies have shown that non coding RNA (ncRNA) is closely related to the occurrence and development of acute ischemic stroke (AIS), but its systemic regulatory disease profile has not been fully elucidated. We collected peripheral whole blood samples from AIS patients and healthy controls for transcriptome expression profiling analysis of mRNA, micro RNA, and long non coding RNA (lncRNA). In transcriptome data analysis, differentially expressed RNAs were identified, and key functional pathways and microenvironmental changes in AIS were comprehensively analyzed. Based on the ceRNA hypothesis, a competitive regulatory network of ceRNA (lncRNA/miRNA/mRNA) for AIS disease occurrence was constructed. In downstream analysis, the upregulated mRNA in the ceRNA network was combined with drug target molecular information in the Drugbank database to screen and identify three direct targets, NFKBIA, TNFAIP6, and ORM1, all of which play key immunomodulatory and anti-inflammatory roles in the pathological process of AIS; Further combining with the PPI network, FN1 and MMP9 were identified as key predictive targets. Constructing a multi-level and multi-omics network map of drug protein ceRNA to explore the transformation pathway from molecular mechanisms to clinical drug targets. Molecular docking simulation was used to verify that the predicted targets FN1 and MMP9 can bind to current therapeutic drugs such as Acetylsalicylic acid, suggesting the possibility of FN1 and MMP9 as new targets for AIS treatment. This study follows a systematic strategy from constructing transcriptome regulatory networks to downstream clinical drug target validation, providing a new perspective for the occurrence and development of AIS diseases from the RNA regulatory level. The multi-omics landscape reveals potential molecular mechanisms and lays a solid theoretical foundation for identifying novel and reliable diagnostic biomarkers and potential therapeutic targets.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1779905"},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-based antibody subclass maturation drives direct enzymatic inhibition in fabry disease patients receiving enzyme replacement therapy.","authors":"Tomas Baldwin, Hibba Kurdi, Ivan Doykov, Francesca Robertson, Stefania Rosmini, Sabrina Nordin, Joao Augusto, Rebecca Kozor, Julien Baruteau, James Davison, David Moreno-Martinez, Uma Ramaswami, Ravi Vijapurapu, Tarekegn Geberhiwot, Rick Steeds, James Moon, Derralynn Hughes, Kevin Mills, Wendy E Heywood","doi":"10.3389/fmolb.2026.1702751","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1702751","url":null,"abstract":"<p><strong>Background: </strong>Enzyme replacement therapy (ERT) for Fabry disease can elicit anti-drug antibodies (ADAs) that may diminish efficacy and limit clinical benefit.</p><p><strong>Objectives: </strong>To develop and apply a multiplexed proteomic assay for quantitative, subclass-specific ADA and complement profiling in Fabry disease to inform personalized ERT selection.</p><p><strong>Methods: </strong>We created a targeted LC-MS/MS platform to quantify ADA binding across IgG1-4, IgM, and IgA1, and complement proteins C1Qc-C9, in serum from Fabry patients (n = 39) and healthy controls. Neutralizing capacity was measured via enzymatic inhibition assay. Subclass-specific cross-reactivity was assessed for agalsidase alfa, agalsidase beta, and pegunigalsidase alfa.</p><p><strong>Results: </strong>IgG4 binding was significantly higher in Fabry males (p = 0.007), with no sex-based differences for other Ig classes. Complement binding (C1Qc, C3) was elevated in ∼25% of patients, with IgG1, IgG2, IgM, and IgA1 correlating with C1Qc (r > 0.6). Seven patients (three female) exhibited >50% ERT inhibition; IgG4 binding correlated with enzymatic inhibition (p < 0.0025) and elevated lyso-Gb3 in males (p < 0.02). We assessed cross-reactivity of IgG4 in a patient who had received only agalsidase alfa, finding a 49% reduction in IgG4 binding to Pegunigalsidase alfa compared to Agalsidase alfa (p = 0.003) and 45% to Peguingalsidase alfa compared to agalsidase beta (p = 0.035). IgG4 comprised >50% of immune complexes for agalsidase alfa/beta but only 25% for pegunigalsidase alfa, indicating a potentially distinct immunogenic profile.</p><p><strong>Conclusion: </strong>Quantitative subclass-specific ADA and complement profiling reveals sex-specific IgG4 patterns, neutralizing capacity, and ERT-specific immunogenic differences, supporting its utility for personalized therapy in Fabry disease.</p><p><strong>Capsule summary: </strong>A novel multiplex LC-MS/MS assay quantifies ADA subclasses and complement in Fabry disease, uncovering distinct IgG4 patterns and ERT-specific profiles that enhance understanding of treatment immunogenicity.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1702751"},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the manufacturing process on the commutability of erythropoietin control materials for external quality assessment schemes.","authors":"Luisa Toll, Patricia Kaiser, Ingo Schellenberg, Mario Thevis, Folker Wenzel","doi":"10.3389/fmolb.2026.1773497","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1773497","url":null,"abstract":"<p><strong>Introduction: </strong>Erythropoietin (EPO) is a measurand that has not yet been sufficiently standardized in laboratory medicine. This is why quality control within the framework of external quality assessment (EQA) schemes is of great importance. Therefore, the INSTAND e.V. EPO EQA was introduced to support quality assurance of medical laboratories for this measurand. The use of commutable control material (CM) enables the comparison of various measurement systems with one another and allows to assess the level of harmonization between laboratory measurements. This study assessed the suitability of different EPO CMs for use in EPO EQA schemes and the impact of sample preparation, such as dilution, spiking and lyophilization.</p><p><strong>Methods: </strong>Eleven candidate CMs in both frozen and lyophilized forms were analyzed and compared to 80 clinical samples (CS) using a chemiluminescence immunoassay (CLIA) and two different enzyme-linked immunosorbent assay (ELISA) test kits. The commercially available CMs were based on a serum pool that was either diluted with human serum albumin or enriched with various recombinant EPO (rhEPO) preparations. Commutability was assessed oriented towards the principles of difference in bias analysis based on the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group on Commutability.</p><p><strong>Results: </strong>Most CMs remained within the range of the CS bias distribution across all paired method correlations. However, CMs exceeding the limits were also observed in some cases, even the native frozen pooled serum. Dilution and lyophilization affected the inter-method bias to varying degrees. Bias values for CMs enriched with different rhEPO preparations were mostly within the same range, though for CMs containing darbepoetin alfa in some cases higher inter-method bias was observed. Apparent differences in non-selectivity between the assays limited the ability to reliably assess commutability.</p><p><strong>Conclusion: </strong>The findings highlight current methodological challenges regarding the manufacturing of suitable materials and commutability assessment. Further investigations are needed regarding the standardization and harmonization of EPO measurements. Until further data is available, the evaluation within the EPO EQA should remain within method-specific sub-collectives.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1773497"},"PeriodicalIF":3.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postbiotics and phage synergy in precision oral microbiome engineering: systems biology strategies targeting <i>Streptococcus mutans</i> in dental caries.","authors":"Guhanraj Radhamanalan","doi":"10.3389/fmolb.2026.1766853","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1766853","url":null,"abstract":"<p><p>Dental caries continues to represent a major global public health concern and arises from complex ecological shifts within oral biofilms. The dominance of <i>Streptococcus mutans</i>, in combination with broader microbial imbalance and interactions involving the oral virome, plays a central role in disease progression. Although established preventive measures such as fluoride therapy and mechanical plaque control reduce enamel demineralization and microbial load, they do not comprehensively address dysbiosis, virulence regulation, or host-microbial signaling dynamics. Postbiotics are non-viable microbial products or metabolic derivatives with biological activity, are gaining attention as targeted modulators of the oral ecosystem. These agents include organic acids, exopolysaccharides, bacteriocins, and structural components derived from inactivated probiotic cells. Through diverse mechanisms, postbiotics can reduce acidogenic potential, weaken extracellular matrix integrity within biofilms, disrupt bacterial communication systems, and modulate mucosal immune pathways. Such effects may limit colonization efficiency and pathogenic behavior of <i>S. mutans</i> while preserving commensal balance. Emerging strategies propose combining postbiotics with bacteriophage-based approaches, immunomodulatory platforms, and innovative delivery systems such as nanoformulations and bioadhesive matrices to improve site-specific efficacy. Advances in multi-omics technologies, systems biology modeling, and artificial intelligence-driven diagnostics further support the development of personalized interventions tailored to individual microbial signatures. In addition, postbiotic-mediated modulation of viral-bacterial interactions and horizontal gene exchange may contribute to restoring ecological stability and reducing antimicrobial resistance dissemination. This review integrates current knowledge on postbiotic-driven regulation of the oral microbiome and virome and examines their potential role in precision-oriented caries management. Addressing translational challenges, including formulation stability, safety evaluation, regulatory pathways, and comprehensive virome profiling, will be critical for future clinical application.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1766853"},"PeriodicalIF":3.9,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Multi-omics to shed light on the pathogenesis of multifactorial diseases.","authors":"Giuseppina Fanelli, Anastasia Ricci, Michele Menotta, Sara Rinalducci","doi":"10.3389/fmolb.2026.1834409","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1834409","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1834409"},"PeriodicalIF":3.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}