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PubMed2026

Comparative phylogenomics and transcriptional regulatory networks of AQPs, HSPs, and LEA proteins in salt-stressed Portulaca oleracea.

Soil salinization severely threatens global food security, necessitating systematic investigations of halophytes like Portulaca oleracea to decode the molecular mechanisms of environmental resilience. Utilizing an integrated framework of deep learning-based genome annotation (58,817 predicted genes; 96.5% BUSCO completeness), multi-tissue RNA-Seq, phylogenomics, and gene regulatory network (GRN) inference, the synergistic orchestration of 78 aquaporins (AQPs), 525 heat shock proteins (HSPs), and 119 late embryogenesis abundant (LEA) proteins was elucidated. The active transcriptome, encompassing 39,065 expressed loci, revealed a systemic growth-defense trade-off. Tissues displayed distinct adaptive mechanisms: leaves modulated intracellular water balance via specialized AQPs, whereas adult roots maintained proteostasis through robust HSP20/HSP70 induction. Phylogenomic clustering across 154 species demonstrated that salinity tolerance constitutes an evolutionary mosaic, identifying 81 halophyte-exclusive orthogroups and 1129 species-specific clusters. Comparative topology across six independent GRNs (4.2M-5.3 M edges) unmasked a highly modular transcriptional reprogramming strategy governed by a core apparatus of 22 stress-exclusive regulators, with functional enrichment heavily prioritizing protein dimerization and chromatin remodeling. Theoretically, the distinct convergence of Trihelix transcription factors with guard cell differentiation pathways offers a candidate transcriptomic framework to explain the plant's characteristic C4-CAM photosynthetic plasticity under severe osmotic pressure. Practically, these evolutionary blueprints and specific master switches transcend single-gene transgenic limitations. Utilizing these root-sustained and stress-inducible targets under localized promoters provides a naturally optimized, network-level precision engineering roadmap to transfer robust, compartmentalized halotolerance to sensitive glycophytic crops.

Gene Regulatory Networks↗

PubMed2026

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗

PubMed2026

"Clinical efficacy and expression of antimicrobial resistance genes after using a novel herbal mouthwash compared to chlorhexidine: A Randomised controlled trial in generalised gingivitis patients".

OBJECTIVES: Chlorhexidine, the gold-standard mouthwash, has several disadvantages, like promotion of antimicrobial resistance. Herbal mouthwashes are emerging as alternatives to chlorhexidine. However, its impact on antimicrobial resistance remains unclear. The aim of the study was to compare the clinical efficacy and the expression of antimicrobial resistance genes of chlorhexidine with a novel herbal mouthwash. DESIGN: Sixty patients with generalised gingivitis were randomly assigned to two groups using block randomisation. After professional mechanical plaque removal patients were instructed to use either chlorhexidine or a novel herbal mouthwash (patented composition) for two weeks. Tetracycline resistance (tetM) and macrolide efflux (mefI) gene expression in subgingival plaque were analysed using real-time polymerase chain reaction. Intragroup comparisons were performed with a paired t-test and Wilcoxon signed-rank test for parametric and nonparametric data. Intergroup comparisons employed unpaired t-test, chi-square test, and Mann-Whitney test. RESULTS: A significant reduction in bleeding, plaque, pocket depth and and patient reported outcomes were noticed in both groups. But reduction in plaque was more significant in chlorhexidine group. tetM and mefI genes significantly upregulated in the chlorhexidine group, while it was downregulated with herbal mouthwash (fold change 1.79 ± 0.74 and 0.60 ± 0.43 for tetM, and 1.83 ± 0.87 and 0.51 ± 0.44 for mefI). However, patients' perception of taste, freshness, and overall satisfaction was better in the chlorhexidine group. CONCLUSIONS: The increased expression of antimicrobial resistance genes following chlorhexidine use warrants careful consideration. Herbal mouthwash is an effective, safer alternative with comparable clinical benefits and less impact on antimicrobial resistance.

Humans↗

PubMed2026

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-κB, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

Reassessment of the effect of oral l-arginine on blood pressure: A systematic review and meta-analysis based on ambulatory blood pressure monitoring.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of oral l-arginine supplementation on ambulatory blood pressure (ABP). METHODS: A systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases was conducted from their inception through March 1, 2026. Randomized controlled trials (RCTs) assessing the effects of oral l-arginine intervention were included. Outcome measures included 24-h systolic blood pressure (24h SBP), 24-h diastolic blood pressure (24h DBP), daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), nighttime systolic blood pressure (nSBP), and nighttime diastolic blood pressure (nDBP). Meta-analysis was performed using Stata 17.0. The weighted mean difference (WMD) was used as the effect size, and the results were pooled with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs comprising 202 participants were included. Meta-analysis results demonstrated that oral l-arginine significantly reduced 24h SBP (WMD = -4.23 mmHg, 95% CI [-5.87, -2.58]; P < 0.01) and 24h DBP (WMD = -3.04 mmHg, 95% CI [-4.48, -1.59]; P < 0.01). Significant reductions were also observed for dSBP (WMD = -4.16 mmHg, 95% CI [-5.90, -2.41]; P < 0.01) and dDBP (WMD = -4.25 mmHg, 95% CI [-5.85, -2.66]; P < 0.01). Furthermore, oral l-arginine significantly lowered nSBP (WMD = -5.70 mmHg, 95% CI [-7.81, -3.58]; P < 0.01) and nDBP (WMD = -4.18 mmHg, 95% CI [-6.27, -2.09]; P < 0.01). CONCLUSION: Oral l-arginine supplementation significantly reduces ABP. However, the number of included studies was limited, and further validation through additional relevant research is warranted.

Arginine↗

PubMed2026

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress↗

PubMed2026

Protein persulfidation emerges as a conserved component of the redox response to DNA damage.

Genotoxic stress is frequently accompanied by alterations in cellular redox homeostasis; however, the mechanisms linking redox regulation to the DNA damage response (DDR) remain incompletely understood. Here, we investigated the early redox response to DNA damage induced by methyl methanesulfonate (MMS) in Saccharomyces cerevisiae, focusing on cysteine oxidative post-translational modifications (PTM). We show that activation of the DNA damage response is accompanied by rapid redox changes that occur in the absence of a generalized oxidative stress response. MMS exposure promotes selective remodeling of cysteine oxidative modifications, characterized by decreased free thiols, robust induction of protein persulfidation, and comparatively modest changes in sulfenylation. These alterations are accompanied by increased intracellular hydrogen sulfide levels, supporting the involvement of reactive sulfur species in the cellular response to DNA damage. Proteome-wide analyses revealed that cysteine oxidative modifications preferentially target proteins involved in central metabolism, nucleotide biosynthesis, and genome maintenance. Consistent with these observations, MMS-induced genotoxic stress promotes metabolic adaptation characterized by increased mitochondrial respiration, elevated ATP production, and mitochondrial morphological remodeling, linking bioenergetic adaptation to redox regulation. Importantly, perturbation of intracellular redox balance using N-acetylcysteine compromises survival under DNA-damaging conditions, supporting a functional role for redox signaling during the DDR. Finally, MMS treatment also induces protein persulfidation in mammalian cells. Moreover, exposure to etoposide, a mechanistically distinct genotoxic agent that induces DNA double-strand breaks through topoisomerase II inhibition, showed a similar trend, suggesting that protein persulfidation may not be restricted to alkylation-induced DNA damage. Together our findings identify protein persulfidation as a prominent component of the redox response to DNA damage and provide new insight into the functional interplay between mitochondrial metabolism, cysteine-based redox regulation, and genome maintenance.

Oxidation-Reduction↗

PubMed2026

Meta-PseU: A meta-classifier for robust prediction of RNA pseudouridine modification sites from long sequences.

BACKGROUND AND OBJECTIVES: Pseudouridine (Ψ) represents one of the most abundant and conserved RNA modifications. Ψ provides an additional hydrogen-bond donor that enhances RNA structural stability and modulates translation. It participates in diverse biological processes, including RNA-protein interactions, splicing, translational control, and stress responses. Aberrant pseudouridylation is implicated in cancer, neurodegenerative disorders, and autoimmune diseases. Despite its biological importance, experimental identification of Ψ sites remains time-consuming and costly, limiting the feasibility of transcriptome-wide profiling. Computational approaches have therefore become essential complements to experimental techniques. However, state-of-the-art machine-learning and deep-learning predictors often suffer from limited generalizability due to small training datasets. To overcome these issues, we aim at constructing new long-sequence datasets and developing a novel Ψ site predictor. METHODS: New long-sequence datasets were constructed as benchmarks for RNA Ψ-site prediction. The Ψ modification sites in RMBase 3.0 were mapped to the reference genomes across three species of human, mouse, and yeast, and the RNA sequences with a length of 201 were generated by extending the upstream and downstream from the mapped, central sites. To eliminate sequence redundancy, the sequences were clustered using CD-HIT with a 70% sequence identity threshold. We developed Meta-PseU, a logistic regression-based meta-classifier that considered 118 machine learning and deep learning classifiers. The datasets and programs are freely accessible at https://github.com/kuratahiroyuki/MetaPseU. RESULTS: By optimizing model configuration, we proposed the Meta-PseU model stacking 32 machine learning and deep learning classifiers out of 118 classifiers. Meta-PseU substantially improved model generalizability, overcoming a key limitation of existing approaches. It greatly outperformed state-of-the-art predictors and achieved increasing accuracy with increasing sequence length. CONCLUSIONS: Long-sequence datasets were newly constructed as benchmarks for RNA Ψ-site prediction. Meta-PseU offers a new framework for robust Ψ-site identification by using long sequences.

Pseudouridine↗

PubMed2026

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans↗

PubMed2026

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105 kg P₂O₅ ha⁻¹) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B‑type starch granule formation. Starch granule‑associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch‑synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation‑related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain‑filling intensity and duration, and were associated with the highest theoretical grain weight (50.70 mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210 kg P₂O₅ ha⁻¹) was associated with disrupted inter‑tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C‑type starch granules (0∼5 µm) at 7 DPA, yet by maturity achieved the highest proportion of large A‑type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome‑related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue‑specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗

PubMed2026

A Conserved 3'UTR Stem-loop Directs UPF1/eIF4AIII-Dependent Regulation of GABARAPL1 mRNA.

RNA-binding proteins (RBP) interact with mRNA untranslated regions containing cis-regulatory elements to govern mRNA localization, stability, and translational efficiency. Among these trans-regulatory factors, RNA helicase UPF1 is a central factor which play a role in multiple mRNA decay pathways, including nonsense-mediated mRNA decay (NMD). NMD is triggered when an exon-junction complex (EJC) is located downstream of a premature termination codon. However, in some cases, NMD can be activated in an EJC-independent manner through mechanisms involving the 3'UTR. In the present study, we focused on the GABARAPL1 3'UTR, as previous studies had shown that this region plays a key role in NMD targeting, although the underlying molecular mechanism had not yet been elucidated. Unlike canonical NMD targets such as SC35, we found that the chemical inhibition of eIF4AIII helicase activity did not affect GABARAPL1 transcript levels, indicating that this transcript is regulated through its 3'UTR via an EJC-independent mechanism. We therefore investigated the potential presence of cis-regulatory element within the 3'UTR of GABARAPL1 which can regulate mRNA and protein levels in a UPF1-dependent manner. Furthermore, we identified a conserved RNA region spanning nucleotides 364-421 involved in GABARAPL1 targeting and used biochemical analysis to demonstrate the direct binding of UPF1 and eIF4AIII to this RNA region, to analyse its secondary structure in solution, and to map the protein-binding sites. By complementing these approaches with molecular modelling, we showed that this stem-loop adopts a stable global fold but a local flexibility and dynamic behaviour properties. Together, our results support the role of UPF1 and eIF4AIII as specific regulators of GABARAPL1 transcript and reveal a novel RNA regulatory element within its 3'UTR, which provides a completely unexpected binding site for these factors.

3' Untranslated Regions↗

PubMed2026

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 ≥1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans↗

PubMed2026

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27 ± 7 y) and 24 older adults (12M/12F, age 67 ± 8 y) were randomized to receive either placebo or PB125 (200 mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8 ± 1.5 to 3.8 ± 1.3%, p < 0.0001) and popliteal FMD (PB125: 1.5 ± 1.5 to 2.3 ± 1.4%, p = 0.033) in older, but not younger adults (both, p > 0.27). During bed rest, PB125 preserved brachial (3.8 ± 1.3 to 3.6 ± 1.4%, p = 0.543) and popliteal FMD (2.3 ± 1.4 to 2.7 ± 1.4%, p = 0.269), LVC (1.1 ± 0.8 to 1.1 ± 1.5 AUC, p = 0.530) and circulating SOD concentrations (28.3 ± 7.2 to 28.6 ± 8.6 U/mL, p = 0.888) in older adults compared to placebo (all, p < 0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4 ± 2.8 to 3.4 ± 1.8%, p = 0.302) in younger adults compared to placebo (p < 0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans↗

PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗

PubMed2026

Beyond antigen matching: compatibility intelligence theory for transfusion as an emergent biological system.

BACKGROUND: Despite major advances in serologic testing, extended phenotyping, and blood group genomics, clinically similar transfusion exposures may result in markedly different immune and clinical outcomes. Existing compatibility strategies do not fully explain this biological variability. OBJECTIVES: To examine transfusion compatibility as an emergent donor-recipient biological state and propose a systems-level conceptual framework that integrates established biological determinants into a testable model for future precision transfusion medicine. METHODS: This narrative review critically synthesizes current evidence from blood group genomics, recipient immunobiology, inflammation, disease-specific biology, transfusion medicine, and computational prediction. The proposed framework distinguishes Compatibility Intelligence Theory (CIT) as a biological interpretation from Precision Transfusion Intelligence (PTI) as its potential clinician-supervised translational application. RESULTS: The review argues that transfusion compatibility is shaped by interactions among donor genetics, recipient immune biology, inflammatory physiology, disease context, transfusion history, and longitudinal adaptation rather than by antigen matching alone. CIT provides an organizational framework for integrating these determinants, whereas PTI describes a possible clinician-supervised translation. To address current feasibility, the revised framework separates variables into routinely measurable, contextually available but incompletely standardized, and research-stage domains, and proposes a staged strategy for deriving rather than assuming their quantitative weights. Any clinical implementation would require comparative validation against current serologic, phenotypic, and genotype-based practice. CONCLUSIONS: Compatibility Intelligence Theory offers a testable systems-level framework for understanding transfusion compatibility without replacing established transfusion practices. The framework is not presented as a ready-to-use score: currently measurable variables can be organized for structured risk review, whereas inflammatory, immunogenetic, and multi-omic inputs require prospective standardization and validation. If future studies demonstrate incremental predictive and patient-centered benefit, CIT-informed PTI could support an adaptive, evidence-based extension of current precision transfusion practice.

Humans↗

PubMed2026

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗