Search Results (5,386)

Background and Objectives: Very preterm infants are vulnerable to late-onset infection and prolonged NICU exposure, with potential downstream effects on caregiver health. We evaluated neonatal outcomes and caregiver psychosocial status across culture-confirmed infection phenotypes. Methods: We investigated a single-center prospective cohort (March 2023–December 2025) of 87 preterm infants assigned to one of three groups: no proven infection (n = 44), bacterial sepsis (n = 31), or candidemia (n = 12). Neonatal outcomes included a composite adverse endpoint (death or major morbidity) and resource utilization. Caregivers completed the SF-36, WHOQOL-BREF, HADS, PHQ-9, GAD-7, and Body Image Scale near discharge. Results: Candidemia occurred later than bacterial sepsis (day of life 17.8 ± 4.8 vs. 10.1 ± 3.9; p < 0.001) and had a longer time to effective therapy (23.3 ± 9.5 vs. 13.3 ± 5.3 h; p = 0.004). The composite adverse outcome was 27.3% in the no-infection group versus 54.8% in the bacterial group and 58.3% in the candidemia group (p = 0.025); ROP requiring treatment increased from 4.5% to 29.0% and 25.0% (p = 0.012). Length of stay rose from 39.7 ± 10.2 to 50.1 ± 11.9 and 60.9 ± 13.1 days (p < 0.001), and ventilation days from 15.7 ± 7.6 to 23.3 ± 7.5 and 34.2 ± 10.4 (p < 0.001). Caregiver SF-36 mental health (MCS) scores decreased from 44.7 ± 7.5 to 38.5 ± 6.0 and 36.7 ± 6.4 (p < 0.001), while PHQ-9 scores increased from 9.4 ± 3.9 to 11.6 ± 3.3 and 15.5 ± 4.6 (p < 0.001); NICU burden correlated with PHQ-9 scores (r = 0.52, p < 0.001). Conclusions: Culture-confirmed infection, particularly candidemia, was associated with higher neonatal morbidity, markedly greater resource use, and substantial caregiver distress at discharge. Full article

Purpose: Hearing loss (HL) is a prevalent condition significantly impairing quality of life, with genetic mutations accounting for a substantial proportion of congenital cases, notably those involving the GJB2 gene encoding connexin 26. This study aims to analyze the current knowledge, feasibility, and challenges of gene therapy targeting GJB2-related HL, emphasizing both embryonic and postnatal interventions. Methods: A comprehensive scoping review was conducted across electronic databases up to October 2025, including studies focusing on GJB2-associated HL, gene therapy approaches, and the timing of interventions. Data extraction encompassed mutation types, animal models, delivery strategies, outcomes, and ethical considerations. Results: The results indicated over 467 GJB2 variants which could impair cochlear ion homeostasis and development. Animal models, mainly murine, demonstrated early-onset degeneration with limited recovery following delayed gene therapy, while early postnatal intervention showed greater efficacy. Viral vectors like AAV have been employed for targeted gene delivery via cochlear injections, achieving partial restoration of connexin expression and cochlear function, yet they have faced limitations including transduction efficiency, immune responses, and long-term stability. Challenges in translating these findings to humans have been compounded by anatomical, immunological, ethical, and safety issues, particularly regarding embryonic gene therapy and germline modifications. Ethical frameworks can vary internationally, highlighting the necessity for careful regulation. Conclusions: While promising advances in gene therapy for GJB2-related HL have been achieved in preclinical studies, significant scientific, technical, and ethical barriers must be addressed before clinical application, especially during embryogenesis. A multidisciplinary, cautious approach is essential to realize the potential of gene therapy in restoring natural hearing while safeguarding individual and societal interests. Full article

The ‘Mollar de Elche’ pomegranate cultivar is highly valued for its organoleptic properties, yet it often suffers from inadequate fruit pigmentation, reducing its commercial competitiveness. This study, carried out in a mature commercial orchard located in Spain (Alicante), evaluated the impact of preharvest applications of sorbitol at different concentrations (0, 0.1, 0.5, and 1% in 2023, and 2.5 and 5% in 2024) and three application periods: S1 (nine applications from fruit set), S2 (six applications from seed hardening), and S3 (three applications at the onset of colour change) over two consecutive growing seasons (2023 and 2024). Treatments were applied via foliar spraying from the time of fruit set until the onset of external colour change. The results showed that sorbitol acted as an effective metabolic ‘vector’, significantly increasing fruit weight and total yield, particularly at concentrations of 1 and 5%. Furthermore, sorbitol treatments enhanced fruit firmness by stabilizing cell wall structures and significantly improved exocarp red pigmentation by reducing the hue angle. While the highest doses (1, 2.5, and 5%) enhanced biomass accumulation, they also triggered a potential negative feedback loop in sugar sensing that could interfere with secondary metabolism at excessive thresholds. These findings suggest that preharvest sorbitol applications, particularly at concentrations between 1 and 5% starting from early application period (S1), serve as an effective strategy for improving yield and external pigmentation in ‘Mollar de Elche’ pomegranate fruit. Full article

Bisphenol A (BPA) is a widespread endocrine disruptor that interferes with metabolism in humans and animals by inducing oxidative stress, lipid peroxidation, and cell death. Probiotics, conversely, have shown potential in promoting host health and reducing the toxicity of endocrine-disrupting chemicals (EDCs). This study examined whether sub-chronic BPA exposure disrupts hepatic lipid metabolism in female zebrafish (Danio rerio), and whether co-administration of probiotics mitigates these effects. Adult females were exposed for 28 days to the following treatments: 10 µg/L BPA via water (BPA); 10⁹ CFU/g body weight/day of probiotic formulation (P); and both treatments (BPA+P). An untreated group served as a control (CTRL). Hepatic lipid composition was analyzed using UHPLC-QTOF-MS, while liver sections were investigated by Fourier Transform Infrared Imaging (FTIRI) spectroscopy. BPA exposure decreased 14 unsaturated triacylglycerols and lysophosphatidylcholine 18:0, suggesting steatosis onset and inflammation, while in the group exposed to BPA+P, the decrease was limited to 8 triacylglycerols and the reduction in lysophosphatidylcholine 18:0 was prevented. Analyses of pooled liver samples precluded modeling tank-level effects; thus, the results are interpreted as semi-quantitative. Partial least square discriminant analysis built on the comparison of all groups together confirmed an intermediate phenotype for BPA+P fish between BPA and P groups. The observed beneficial role of probiotics in counteracting BPA-related metabolic disturbances was also supported by FTIRI, evidencing the ability to mitigate the effects of BPA on lipid and glycosylated compound metabolism. These findings highlight the potential of probiotic supplementation as a practical and accessible strategy to mitigate BPA-induced metabolic disturbances, contributing to the development of mitigating approaches against environmental contaminant-related liver dysfunction. Full article

Sorghum is recognized as a potential functional ingredient with high resistance to digestion. Therefore, this study investigates the anti-digestive properties of eight different types of sorghum cultivars with distinct compositional differences. The results confirmed that the whole sorghum flours exhibit stronger anti-digestive properties compared to its isolated starch, indicating that non-starch components play a role in inhibiting starch digestion. However, there was no significant correlation between the differences in individual components among sorghum varieties and their resistance to digestion. Analysis of sorghum starch structure demonstrated that relative crystallinity and double-helix degree in the long-range ordered architecture show a significant positive correlation with resistant starch (RS). Small-angle X-ray scattering (SAXS) revealed that the relatively thick and dense layered structure of sorghum starch is associated with a lower degree of enzymatic hydrolysis. Gel permeation chromatography (GPC) analysis showed that higher weight-average molecular weight is associated with a higher RS content to a certain extent, while a higher PDI is unfavorable for the formation of digestion-RS structures due to its association with a reduction in the onset gelatinization temperature. Cultivars AH-3, AH-5, and AH-2 with higher molecular weight, narrower molecular weight distribution and denser nanoscale lamellar structures exhibit superior digestion resistance. This research provides a reference for the screening of low-glycemic-index sorghum varieties and their application in functional foods. Full article

Type 1 diabetes (T1D) is an autoimmune disease with a strong genetic component (~70% heritability). Early identification of individuals at risk is crucial for early intervention or risk assessment. Although polygenic risk scores (PRS) have shown promise in risk assessment, most current approaches remain constrained by linear assumptions and limited generalizability. We aimed to develop a neural network-driven classifier using T1D-associated single nucleotide polymorphisms (SNPs). In addition, we explored the inclusion of an entropy-derived feature as a complementary variable, representing the degree of genetic variability within an individual’s genotype profile across the 67 T1D-associated SNPs, to evaluate its potential additive contribution to the model performance. We analyzed genotype data from 11,909 individuals in the UK BioBank (546 T1D cases and 11,363 controls). Sixty-seven well-known SNPs associated with T1D were utilized as inputs to the model, using two distinct allele-encoding strategies. A feed-forward neural network was evaluated under varying case–control ratios through five-fold cross-validation. Performance was assessed using the area under the receiver operating characteristic curve (AUC) on a held-out test set and on an external European cohort as a validation cohort. Across five-fold cross-validation, the best configuration achieved a median AUC of 0.903. On the held-out UK Biobank test set, the model generalized well, with an AUC of 0.8889 (95% CI: 0.8516–0.9262). A probability-based risk framework, constructed using five risk groups (“very low”, “low”, “intermediate”, “high”, and “very high” risk), yielded a negative predictive value (NPV) of 98.9% for the “very low” risk group and a Positive Predicted Value (PPV) of 61.9% with a specificity of 97.3% for the “very high” risk group, assuming a 10% T1D prevalence. External validation in the German Diabetes Study reproduced clear case–control separation; for individuals with recent onset diabetes and glutamic acid decarboxylase antibodies (GADA+) vs. controls, specificity reached 91.9% in the “high” risk group (PPV of 94.3%) and 97.6% in the “very high” risk group (PPV of 95.7%). The proposed neural network reliably predicts T1D genetic risk using a compact SNP panel of 67 SNPs and maintains accuracy in both internal and external European cohorts. Its probabilistic output enables clinically interpretable risk thresholds, while entropy features contributed modestly to performance. These results demonstrate that a neural network-based approach achieves discriminative performance that is comparable to established T1D genetic risk models, while offering flexible probability-based risk stratification and architectural extensibility for future integration of additional features. Full article

Dental implants are a popular clinical procedure for the rehabilitation of fully and partially ede ntulous patients. There is long-term evidence that implant-supported dental prostheses represent a predictable treatment for replacing missing teeth. However, several types of complications may arise, which can compromise implant treatment outcome. Peri-implant disease is a growing biological complication, consisting of a progressive loss of supporting bone, associated with microbial biofilm and clinical inflammation. It represents a concern for clinicians and patients, having a negative impact on quality of life. This narrative review aimed at summarize the current knowledge on etiology, epidemiology, risk factors, and pathogenesis of peri-implant disease. It also focused on the diagnostic potential of active matrix metalloproteinase-8 (aMMP-8) in peri-implant sulcular fluid for assessing the status of peri-implant tissues and the risk of developing peri-implantitis. A literature search was conducted in PubMed and Scopus databases using search terms like: peri-implantitis, peri-implant biomarkers, aMMP-8, implant maintenance, risk assessment. Clinical studies, systematic reviews, meta-analysis and consensus papers published up to June 2025 were considered. Finally, based on the main factors involved in the onset and progression of peri-implant disease, a new protocol was conceived for determining the optimal implant maintenance scheduling for individual patients. The Biomarker-Guided Implant Maintenance (BGIM) protocol considers a few key parameters, among which aMMP-8 level, and proposes three categories associated with different levels of risk for peri-implantitis. The higher the risk, the more frequently a patient should undergo professional maintenance, to prevent peri-implant disease, with potential favorable effects on implant longevity. The proposed BGIM protocol, that requires prospective validation, represents a structured and clinically applicable biomarker-driven framework for individualizing implant maintenance scheduling by integrating real-time chairside quantification of aMMP-8 with established patient-related risk factors. Full article

Cadmium (Cd) is an environmental toxicant originating from both natural processes and human activities. Cd has been strongly associated with multiple diseases, including breast cancer (BC). Background/Objective: Environmental Cd exposure represents a significant contributor to BC onset and progression. Cd-induced breast carcinogenesis is driven by a constellation of molecular events, including DNA damage, oxidative stress (OS), and the dysregulation of key signaling pathways. These include the ERK/JNK/p38 MAPK cascade, the PI3K/AKT/mTOR axis, NF κB activation, and Wnt signaling, all of which collectively promote tumor initiation, survival, and metastasis. This review underscores the complex interplay between Cd exposure and its effects on cancer-triggering factors. Methods: The complexity of the mechanisms Cd-induced BC, underlying Cd-induced BC makes it challenging to treat, highlighting the need for novel therapeutic strategies that complement or enhance conventional chemotherapy. Therefore, this review was developed by reviewing the literature and presenting the different aspects of the challenge associated with Cd exposure and BC therapy. Results: Phytochemicals, especially phenolics, alkaloids, carotenoids, terpenoids, and related plant-derived compounds, have emerged as promising candidates for mitigating Cd-induced BC. Their antioxidants, anti-estrogenic, and anti-inflammatory properties position them as potential chemopreventive and therapeutic agents capable of counteracting Cd’s molecular toxicity. Conclusions: The review presents current evidence linking Cd exposure to BC development and highlights the protective potential of selected phytochemicals in preventing or attenuating Cd-induced BC. Understanding these interactions reinforces the importance of phytochemical-based interventions as a strategy to reduce Cd-related cancer risk and support breast health. Full article

Background: While immune checkpoint inhibitor (ICI)-related pneumonitis (CIP) may relapse during or after steroid treatment, clinical factors associated with CIP relapse are unclear. This study explored risk factors potentially associated with CIP relapse. Methods: This single-center retrospective study included 1099 patients who received ICIs at our institution between April 2015 and March 2022. Among them, 39 patients who developed CIP and were treated with systemic steroids and tapered to prednisolone (PSL) ≤ 20 mg/day were analyzed. Patients were classified into relapse and non-relapse groups based on whether CIP recurred during or after steroid treatment. Patient characteristics, clinical features at onset, and treatment strategies were compared between the two groups. Results: Thirteen patients (33.3%) experienced relapse. Compared with the non-relapse group, the relapse group had a significantly higher proportion of non-smokers (30.8 vs. 3.3%, p = 0.035), a greater frequency of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 pneumonitis (92.3 vs. 53.8%, p = 0.029), and lower serum KL-6 levels (288 vs. 704 U/mL, p = 0.014). The relapse group also had a shorter duration of steroid therapy at the initial dose, ≥0.5 mg/kg/day, ≥15 mg/day, and ≥20 mg/day (p < 0.05) and lower cumulative steroid doses (1140 vs. 1902 mg, p = 0.015). Relapse tended to occur in patients with relatively mild pneumonitis who received lower steroid doses and shorter treatment durations. Conclusions: Non-smoking status, CTCAE Grade 2 pneumonitis, lower serum KL-6 levels, shorter duration of steroid therapy, and lower cumulative steroid dose were potentially associated with CIP relapse. Adequate steroid dosing and tapering may help prevent relapse. Full article

Epilepsy is a progressive network disorder in which recurrent seizures drive maladaptive neurodevelopmental remodeling, cognitive decline, and pharmacoresistance, particularly in developmental epileptic encephalopathies. Cannabidiol (CBD) has emerged as an evidence-based adjunctive therapy for selected childhood-onset epilepsies; however, its broader clinical utility remains limited by heterogeneous responsiveness, restricted indications, and an incomplete understanding of developmental stage–specific efficacy and safety. Here, we synthesize molecular, preclinical and clinical evidence supporting the pleiotropic antiseizure and neuroprotective actions of CBD, including modulation of endocannabinoid-related G protein–coupled receptors, adenosine signaling, transient receptor potential channels, GABAergic maturation, and neuroinflammatory cascades. We highlight critical neurodevelopmental windows during which timely CBD intervention may exert disease-modifying effects by preventing pathological consolidation of hyperexcitable networks. Furthermore, we position human brain organoids as transformative translational platforms that recapitulate early human cortical development and epileptic network dynamics, enabling functional stratification of CBD-responsive phenotypes, developmental safety profiling, and precision therapeutic discovery within human-relevant neural circuits. Collectively, organoid-guided frameworks provide a mechanistic foundation for personalized, developmentally informed CBD therapy and advance precision medicine strategies aimed at modifying epileptogenic trajectories rather than solely suppressing seizures. Full article

Osteoarthritis (OA) is the main degenerative joint disease affecting nearly 7% of world population. OA is a multifactorial pathology due to environmental, inflammatory and genetic causes. Recently, the diet and consumption of specific foods have been associated to onset and progression of OA. Dietary patterns, macronutrients, micronutrients, and bioactive compounds can influence inflammatory pathways, oxidative stress, and cartilage metabolism. These effects are mediated not only by structural support but also through the modulation of gene expression and cellular signaling pathways. The emerging fields of nutrigenomics and nutrigenetics provide a mechanistic framework to explain interindividual variability in dietary responses. Nutrigenomics investigates how nutrients influence gene expression and molecular pathways involved in OA pathophysiology, whereas nutrigenetics examines how genetic polymorphisms affect nutrient metabolism, bioavailability, and biological efficacy. This narrative review critically examines current evidence on the interaction between diet, nutraceuticals, and common non-pathological genetic variants in OA. We discuss whether specific dietary patterns exert genotype-independent effects or require personalized approaches to optimize outcomes. By integrating genetic, metabolic, and nutritional perspectives, this review aims to clarify inconsistent findings in the literature and to outline the potential of precision nutrition as a complementary strategy for OA prevention and management. The integration of these approaches enables the development of personalized nutritional strategies tailored to an individual’s genetic background, metabolic profile, and comorbid conditions such as obesity, cardiovascular disease, and diabetes. Full article

Background/Objectives: Racial and ethnic disparities in cesarean birth and labor management persist in the United States, including among individuals considered low risk. Understanding variation in labor progression and cesarean indications within low-risk nulliparous, term, singleton, vertex (NTSV) births may help clarify potential contributors to inequities. This study examined differences in cesarean rates, cesarean indications, and labor duration by race and ethnicity in a low-risk NTSV cohort. Methods: We conducted a retrospective secondary analysis of electronic medical record data from 13,231 low-risk NTSV births within a Midwestern academic health system. Multivariable logistic regression models were used to evaluate the likelihood of cesarean birth and cesarean indications by race and ethnicity, adjusting for maternal age, gestational age, body mass index, insurance type, and labor onset. Linear regression models examined differences in first-stage, second-stage, and total labor duration. Interaction terms assessed whether associations varied by labor onset. Results: The overall cesarean rate was 29%. Absolute cesarean rates were higher among non-Hispanic Black and Hispanic individuals compared with non-Hispanic White individuals; however, these differences were not statistically significant after adjustment. Labor duration differed significantly by race and ethnicity. Non-Hispanic Black and Hispanic individuals experienced longer median first-stage and total labor durations compared with non-Hispanic White individuals; however, second-stage duration was markedly shorter among non-Hispanic Black individuals. Among induced labors resulting in cesarean birth, non-Hispanic Black and Hispanic individuals had increased odds of cesarean for early arrest of dilation, although these findings should be interpreted as hypothesis-generating, given data limitations in labor onset documentation. Body mass index was positively associated with likelihood of cesarean. Conclusions: In this low-risk NTSV cohort, adjusted cesarean rates did not differ significantly by race or ethnicity; however, differences in labor duration and cesarean indication were observed. These findings underscore the importance of continued investigation into labor management practices and structural contributors to obstetric inequities. Full article

Background: Circulating cytokines and their soluble receptors in body fluids have been implicated in the pathogenesis of multiple sclerosis (MS). Alterations in serum levels of pro- and anti-inflammatory cytokines and/or their soluble receptors can dysregulate central nervous system (CNS) signaling pathways and, therefore, may serve as potential biomarkers for the diagnosis of MS. Therefore, the primary end-point of this study is to investigate the utility of various cytokines and their soluble receptors as diagnostic biomarkers in MS. The secondary outcome is also to assess whether these cytokines are useful in differentiating the severity of MS. Methods: In this case–control study, we compared a panel of pro-inflammatory interleukins (ILs), including IL18 and tumor necrosis factor-alpha (TNFα), soluble IL receptors (sIL7Rα and sIL2Rα), and insulin-like growth factor-1 (IGF-1) in 45 MS patients and in 45 healthy control individuals matched for sex and age. Associations of these biomarkers with age, disease severity (Expanded Disability Status Scale [EDSS]), disease duration, and age at first MS symptom onset were also assessed. Results: Serum levels of cytokines and soluble IL receptors were elevated in MS patients compared to healthy controls. IGF-1 was lower (p < 0.001) in the MS patients than in the healthy individuals. The serum level of IGF-1 was higher (p < 0.01) in the remitting-relapsing phase compared to the primary progression and secondary progression stages. Similarly, only IGF-1 was more elevated (p < 0.01) in the mild stage compared to the moderate stage based on the EDSS score. Receiver operating characteristic (ROC) curve analysis demonstrated that IL18 had excellent discriminatory power for the diagnosis of MS (p < 0.001), with an area under the curve (AUC) of 0.96 ± 0.017, followed by IGF-1 (p < 0.001), which showed strong diagnostic performance (AUC = 0.873 ± 0.037). Soluble (s) IL2Rα exhibited fair diagnostic accuracy (p < 0.001; AUC = 0.717 ± 0.054). In contrast, sIL7Rα and TNFα showed poor discriminatory power despite statistical significance (p < 0.01), with AUC values of 0.675 ± 0.057 and 0.687 ± 0.056, respectively. Results of regression analysis revealed that EDSS, duration of disease, and use of any treatment had no impact on the cytokines. Similarly, no significant correlations were noted between these confounders and cytokines, except a moderate negative correlation (−0.418) between IGF-1 and EDSS. Conclusions: IL18 and IGF-1 have the potential to be used as biomarkers in distinguishing MS from healthy individuals. However, both biomarkers failed to demonstrate the discrimination between various phenotypic patterns of disease, limiting their utility for disease stratification. Future studies with larger, longitudinal cohorts and multi-marker panels are warranted to validate these results and to explore whether combining cytokines with imaging or genetic markers can improve prognostic precision. Full article

Background/Objectives: The global incidence of diabetes in childhood is increasing, raising concern about its long-term effects on the developing brain. Although paediatric diabetes research has traditionally focused on microvascular and macrovascular complications, accumulating evidence indicates that the brain is also a vulnerable target. Methods: This narrative review synthesizes current knowledge on the impact of diabetes on brain health in children and adolescents, with emphasis on epidemiology, neuroimaging and cognitive outcomes, underlying mechanisms, risk and protective factors, and clinical implications. Results: In type 1 diabetes (T1D), studies consistently demonstrate subtle but measurable alterations in brain structure, including reduced growth of total, grey, and white matter volumes, alongside functional and microstructural changes. These neurobiological differences are associated with mild deficits in cognition, particularly in attention, executive function, memory, and processing speed. While clinically significant impairment affects a minority, subclinical alterations are common and may accumulate over time. Key risk factors include chronic hyperglycaemia, glycaemic variability, severe hypoglycaemia, diabetic ketoacidosis, and younger age at onset, whereas good glycaemic stability, diabetes technologies, supportive psychosocial environments, and adequate sleep appear protective. Proposed mechanisms involve oxidative stress, neuroinflammation, disrupted insulin signalling, altered cerebral metabolism, and vulnerability of the immature brain during critical developmental windows. Type 2 diabetes (T2D), increasingly diagnosed in youth, is also associated with adverse brain outcomes. Emerging data link early-onset T2D to alterations in brain structure and connectivity, poorer cognitive performance, and increased mental health burden, mediated by hyperglycaemia, insulin resistance, inflammation, and psychosocial stressors. Conclusions: Overall, childhood diabetes—both T1D and T2D—is associated with meaningful effects on brain development and function. Longitudinal and interventional studies are needed to establish causality and determine whether optimizing glycaemic control and psychosocial support can mitigate neurocognitive risk. Recognizing brain health as a potential complication of paediatric diabetes has important implications for monitoring, prevention, and clinical care. Full article

L-glutamate (L-Glu) is the primary excitatory neurotransmitter in the mammalian central nervous system. Developing a real-time monitoring system is essential to understanding the onset and progression of related conditions. However, the absence of an L-Glu dehydrogenase that is insensitive to oxygen limits the development of oxygen-independent electrochemical enzymatic sensors. Additionally, the most commonly used L-Glu-specific oxidase requires site-specific proteolytic post-translational modifications in specific host microorganisms, which makes protein engineering difficult. To address these issues, L-Glu oxidase derived from Streptomyces mobaraensis (SmEOx), which does not require post-translational modifications, was engineered to function as a dehydrogenase. Residues crucial for the oxidative half reaction with oxygen in SmEOx were identified, and mutagenesis studies were conducted. Mutant SmEOx variants with suppressed oxidase activity and improved dye-mediated dehydrogenase activity compared to the wild-type enzyme were successfully obtained. The ratio of dehydrogenase activity to oxidase activity (Dh/Ox) increased ~2900-fold in mutant M117I and ~6700-fold in mutant M117F/K400N compared to wild-type recombinant SmEOx. The resulting virtually L-Glu dehydrogenases (vEDHs) were modified with a redox mediator and evaluated using transient open-circuit potential (OCP)-based L-Glu measurements. As a result, the vEDH (M117F/K400N mutant)-immobilized electrode enabled electrochemical L-Glu detection under ambient oxygen without the need for an external electron mediator, unlike the wild-type enzyme. The created vEDH, together with the OCP sensor developed using it, paves the way for future development of miniaturized, real-time L-Glu monitoring systems with high temporal and spatial resolution. Full article