Abstract: Inferring demographic history from whole-genome data is a fundamental objective in evolutionary and conservation genomics. However, the Pairwise Sequentially Markovian Coalescent (PSMC) framework, the most widely used demographic inference method for whole-genome sequence data, is highly sensitive to sequencing coverage, with low coverage producing systematic underestimation of heterozygosity and biased effective population size trajectories. Here, we present PSMC-FAC, an automated method designed to optimize false-negative rate correction in low-coverage genomes by minimizing geometric distances between corrected and high-coverage demographic trajectories. Whole-genome datasets from humans, gray wolves, and cattle were downsampled across multiple coverage levels and processed through standard demographic inference pipelines. Corrected trajectories were compared using Hausdorff and discrete Fréchet distance metrics projected onto a common temporal grid, and optimal correction factors were modeled as a function of sequencing depth using polynomial regression. Across species and demographic contexts, PSMC-FAC markedly improved concordance between low- and high-coverage trajectories and revealed highly predictable coverage-dependent correction patterns. Overall, PSMC-FAC provides a reproducible and mathematically grounded alternative to subjective correction approaches, enabling reliable demographic inference from moderate-coverage genomes and facilitating broader population-scale genomic analyses.

Abstract: Background: Vitamin D (25(OH)D) deficiency affects over one billion people globally and is associated with type 2 diabetes (T2D) and cardiometabolic diseases. However, causal relationships remain unclear, as vitamin D supplementation have shown limited benefit in reducing T2D risk. Genetic studies have identified variants influencing circulating 25(OH)D levels, but whether genetically determined vitamin D status predicts cardiometabolic outcomes is still uncertain. We therefore used bidirectional Mendelian randomization with genome-wide polygenic scores to evaluate the causal relationship and directionality between vitamin D status and T2D. Methods and Results: We analyzed multi-ethnic populations from the UK Biobank (N = 471,861), and 3,486 participants from the Asian Indian Diabetic Heart Study/Sikh Diabetes Study with serum 25(OH)D measures and genome-wide genotype data. A global polygenic score of vitamin D–raising alleles did not significantly reduce the risk of T2D, coronary artery disease, stroke, or other cardiometabolic risk factors. In contrast, a higher T2D polygenic risk score (PRS) was strongly associated with increased risk for 25(OH)D deficiency (<50 nmol/L). Genetically instrumented analyses showed per SD increase in T2D PRS significantly reduced circulating 25(OH)D levels (β = −8.9 nmol/L; 95% CI: −9.3 to −8.5; p = 3.6 × 10⁻²⁸). Conclusions: Our findings suggest low circulating vitamin D levels are unlikely to causally predict T2D risk but may serve as a marker for secondary prevention in endocrine and cardiovascular health. Instead, genetic susceptibility to T2D appears to contribute to reduced vitamin D levels. Further studies are needed to clarify the mechanisms underlying vitamin D deficiency in diabetes.

Abstract: Chronic muscle unloading, following denervation, aging, long-term bedrest as either spaceflight analog or actual spaceflight missions, results in a decline of neuromuscular junction (NMJ) structure and function, resulting in muscle mass decline and impaired fine motor control. Similar changes are also observed in several neuromuscular diseases and myopathies with signs and symptoms related to impaired movement control. Here, we report on a powerful 3D co-culture experimental model developing NMJ-like structures, as a novel in vitro platform for functional/regulatory studies during time (4D co-culture) for basic and translational research purpose. Murine NErve (NSC-34 motor neuron) and MUscle (C2C12 myoblast) cell CO-cultures (NEMUCO) were grown on either synthetic or biological three-dimensional (3D) scaffolds. The co-cultures were analyzed using a significant array of molecular and cellular biology tools, based on NMJ-specific molecular marker expression combined with muscle- and nerve-cells specific differentiation biomarkers. Specialized cell-cell contacts were present starting at day 2 of co-culture. Triple immunostaining indicated neurofilament-positive axonal nerve terminals approaching clustered α-bungarotoxin-positive nicotinic acetylcholine receptors (nAChRs) in desmin-positive developing myotubes, representing the first signs of NMJ-like structure assembly in vitro. 3D reconstruction morphometry revealed a 50-nm-wide distance similar to the in vivo native synaptic cleft dimension. It is noteworthy that co-cultured motor neurons showed a trend of increase of SNAP-25 transcription, one of the most important SNARE proteins, whereas co-cultured myotubes showed a slight increase of junctophilin and ryanodine receptor type 1 transcription, both critical proteins of the triadic junction of differentiated muscle fibers. In most respects, neuronal-myotube cell-cell communication contacts in our 3D co-cultures mimicked native NMJ microdomains. Neuronal-myotube co-cultures grown in 3D scaffolds represent a powerful tool for investigating the molecular mechanisms underlying NMJ adaptation and plasticity in muscle myopathies. Moreover, this approach could be adapted for customized miniaturized platforms designed for cellular neurobiology research during spaceflight conditions.

Abstract: Neutrophils, once viewed as short-lived and functionally uniform antimicrobial cells, are now recognized as highly plastic immune regulators with context-dependent roles in cancer. Among circulating neutrophil subsets, low-density neutrophils (LDNs) have emerged as a clinically relevant population in oncology due to their distinct phenotypic, potent immunosuppressive activity, and strong association with disease progression. LDNs are rare in healthy individuals but markedly expanded in patients with solid tumors.LDNs display enhanced activation, increased expression of immunoregulatory molecules such as programmed death‑ligand 1, elevated reactive oxygen species production, and a heightened propensity for neutrophil extracellular trap formation, collectively impairing cytotoxic T cell function and promoting tumor immune evasion.Although LDNs have been described across multiple malignancies, their biological and clinical relevance has been most characterized in breast and lung cancers. This review synthesizes current knowledge on neutrophil biology, emphasizing the clinical and mechanistic features of LDNs, with a focus on these two tumor types.In breast cancer, increased LDNs abundance correlates with metastatic disease, poor response to neoadjuvant chemotherapy, immunosuppression, accelerated progression, and reduced survival. In lung cancer, elevated LDNs frequencies similarly associate with advanced disease stage, unfavorable clinical outcomes, and distinct surface marker profiles distinguishing them from high-density neutrophils.Mechanistic studies indicate that tumor-derived cytokines and chronic inflammation drive LDNs expansion, functional reprogramming, and tissue trafficking, linking systemic neutrophil dysregulation to tumor progression.Finally, we highlight emerging biomarkers, unresolved challenges, and therapeutic strategies targeting neutrophil plasticity and LDN-mediated immunosuppression, underscoring their potential as actionable components in precision oncology.

Abstract: Muscle size and architecture contribution to force and power production in young fe-male acrobatic gymnasts (ACRO) remains unclear. This study examined the associa-tions between quadriceps muscle size and architecture and strength–power perfor-mance in young elite female ACRO. Twenty athletes (12–18 years) underwent ultra-sound assessment of rectus femoris (RF) and vastus lateralis (VL) cross-sectional area (CSA), muscle VL volume, VL fascicle length, and VL pennation angle. Performance testing included one-repetition maximum (1RM) squat and hang power clean (HHPC), squat power (Pmax), and countermovement jump (CMJ). In adjusted (Tanner stage and height) linear regression models, VL CSA at 35% (β = 2.38 kg per cm², 95% CI 0.24–4.51; p = 0.031) and 50% femur length (β = 2.31 kg per cm², 95% CI 0.60–4.01; p = 0.011) were associated with 1RM squat (R² = 0.46). Similarly, VL CSA at 35% (β = 45.75 W per cm², 95% CI 21.74–69.77; p < 0.001) and 50% (β = 38.43 W per cm², 95% CI 17.93–58.94; p < 0.001) were associated with Pmax (R² = 0.50). No associations were observed for CMJ, HHPC or RF. Mid-thigh VL size appears to be an independent predictor of squat strength and power in ACRO.

Abstract: What if cotton could grow already colored — eliminating the need for dyes altogether? Today nearly all cotton is harvested white and later dyed using chemical processes that account for roughly 17–20% of global industrial water pollution. Billions of liters of water and large quantities of synthetic chemicals are used each year simply to give fabrics their color. This work explores a transformative alternative: cotton that produces its own colors while growing. We present a unified biological design framework for cotton fibers capable of naturally producing six shades — the existing brown and green, along with engineered pink, blue, and, for the first time, black cotton. Instead of dyeing fabric after harvest, the plant itself is programmed to create pigments directly inside the fiber. A key innovation is a dual-pigment strategy that enables the production of black cotton by combining two natural pigment systems commonly found in plants and biological materials. By carefully activating these pathways only in the developing fiber, the plant can generate stable coloration without affecting normal growth. Beyond proposing the concept, this study provides a practical roadmap for turning naturally colored cotton into a real agricultural technology. The framework outlines the full journey from laboratory design to field deployment, including gene construction, plant transformation, greenhouse testing, field trials, regulatory approval, and large-scale seed production. Methods for combining color traits with existing pest-resistant cotton varieties are also discussed to ensure compatibility with modern farming. If successfully implemented, naturally colored cotton could dramatically reduce the environmental footprint of the textile industry by eliminating large portions of the dyeing process. In the long term, this approach points toward a future where the colors of clothing are not manufactured in factories but grown directly in the field.

Abstract: Pyrethroids, widely used insecticides, have raised concerns regarding their adverse effects on non-target organisms, particularly molluscs, which play vital roles in aquatic ecosystems. Pyrethroids disrupt immune responses in molluscs, impairing their ability to combat pathogens and environmental stressors. Behavioural changes, including altered feeding, locomotion, and mating patterns, are observed, which can affect population dynamics and ecosystem functioning. Additionally, pyrethroids influence molluscan metabolism by altering enzymatic pathways involved in detoxification, leading to potential metabolic overload and toxicity. These disruptions threaten molluscan biodiversity and ecological balance. This review summarize the impact of pyrethroid exposure on molluscan diversity, focusing on immunological, behavioural, and metabolic alterations. This review also explores potential mitigation strategies, including the use of environmentally safer alternatives, bioremediation techniques, and the development of resistance management approaches. Understanding the multifaceted impacts of pyrethroids on molluscs is crucial for safeguarding aquatic ecosystems and developing effective pest management strategies.

Abstract: The starch and moisture content of saffron corms are critical indicators of their flowering potential and yield. This study investigated the use of rapid, non-destructive vis-NIR reflectance spectroscopy measurement to assess these parameters. The measurements were used to develop predictive models through four machine learning algorithms (PLSR, RF, SVR, and GPR). Spectral data were obtained from 130 fresh corm samples. Wavelength analysis identified key starch-sensitive intervals (~930–1000 nm and ~1150–1220 nm) and a broad moisture-sensitive region (~900–1350 nm). Among the evaluated models, the partial least squares regression (PLSR) model demonstrated the optimal predictive performance for moisture (R² = 0.89, RMSE = 0.91%, RPD = 3.67, RPIQ = 4.91) and moderate performance for starch (R² = 0.68, RMSE = 26.29 mg g⁻¹, RPD = 1.87, RPIQ = 2.37, dry weight). These results demonstrated the viability of VIS-NIR spectroscopy as a viable, non-destructive tool for the pre-planting assessment of saffron corm quality. The method provides a practical foundation for corm screening and selection, with potential for further improvement in starch prediction through expanded calibrations and advanced modeling techniques.

Abstract: Glucose transporter type 4 (GLUT4), encoded by the SLC2A4 gene, is the final effector of insulin-stimulated glucose uptake in insulin-sensitive tissues: skeletal muscle, adipose tissue, and cardiac muscle. Its dynamic localization, retained intracellularly under basal conditions and massively translocated to the plasma membrane upon stimulation, makes it a master regulator of glycemic homeostasis. While the canonical insulin pathway (PI3K/Akt/TBC1D4) is the most potent and specific mechanism, its dysfunction is associated with insulin resistance and type 2 diabetes. Crucially, there are robust signaling pathways that are completely independent of insulin and regulate GLUT4 synthesis and translocation. Among these, those activated by muscle contraction are prominent, employing calcium signals (via CaMKII), mechanical/metabolic stress (via p38 MAPK γ/δ), and AMP-activated protein kinase (AMPK) activation. This review critically and comprehensively integrates current knowledge, from the molecular architecture of GLUT4 and its facilitated transport mechanism to the complex signaling networks converging on its regulation. The hierarchy, redundancy, and interdependence of these pathways are emphasized. It discusses how understanding insulin-independent mechanisms offers promising therapeutic opportunities for metabolic diseases, particularly for mimicking the benefits of exercise. Finally, future research directions are proposed to translate this molecular knowledge into novel clinical interventions.

Abstract: Neurofibromatosis type 1 (NF1) patients are predisposed to develop plexiform neurofibromas (PNFs). By cross comparison of RNA sequencing and RUNX1-CHIP sequencing data on mouse PNF, we found that transcript encoding the NF1 interacting p97/valosin-containing protein (VCP) gene is overexpressed in PNF. Co-immunoprecipitation confirmed that VCP bounded to neurofibromin. Western blot and immunostaining confirmed VCP protein overexpression in both mouse and human PNFs. Treatment of primary mouse PNF Schwann cells with CB-5083, a p97/VCP inhibitor, led to accumulation of poly-ubiquitinated proteins and generation of irresolvable proteotoxic stress. Pharmacological or genetic inhibition of VCP reduced mouse PNF cell derived sphere number, and genetic inhibition of Vcp in Schwann cell precursors decreased tumor-like lesion numbers in a cell transplantation model. In vivo treatment with CB-5083 on the Nf1fl/fl;DhhCre PNF mouse significantly inhibited cell proliferation, increased cell apoptosis and reduced PNF volume. The combination with a MEK inhibitor did not increase efficacy compared to the single agent, supporting the hypothesis that VCP functions in parallel to, and may be modulated by, RAS–MAPK signaling under stress or oncogenic conditions. The significant effects of VCP inhibition in this pre-clinical study suggest a potential novel therapy for patients with PNFs.

Abstract: Background/Objectives: Motor competence is a multidimensional indicator of developmental health, yet most studies treat it as a single composite outcome and ignore the contextual class-level structure of school-based data. This cross-sectional study examined motor competence across three domains, manual dexterity, aiming-catching, and balance, in 312 Greek primary school children aged 6–12 years (156 girls) using the Movement Assessment Battery for Children–Second Edition (MABC-2). Methods: Standard scores were analyzed using a linear mixed-effects model with correlated domain-specific random slopes at both the class and student levels, partitioning inter-individual variability in overall motor level, intra-individual variability in domain profiles, and contextual class-level contributions. Post-hoc power analysis via parametric bootstrap confirmed adequate power for the primary outcome and indicated that non-significant age and sex main effects were negligibly small rather than undetected. Results: Balance yielded the highest standard scores, followed by aiming-catching and manual dexterity, with all three domains differing significantly. Neither age nor sex produced significant main effects. A significant component × sex interaction revealed domain-specific sex differences: boys outperformed girls on aiming-catching, while balance exceeded aiming-catching among girls but not boys. However, the observed interaction effect fell below the minimum detectable effect size threshold, suggesting potential upward bias and warranting cautious interpretation pending replication in larger samples. Approximately 13% of children were classified as at risk and 9% showed scores consistent with severe coordination difficulties. Contextual class-level sources accounted for 23.4% of total variance, with 52% of classes deviating significantly from the population mean. Conclusions: These findings highlight manual dexterity as a curricular priority in Greek primary physical education and underscore the importance of contextually sensitive, domain-specific approaches to motor competence monitoring and intervention.

Abstract: Bacterial panicle blight (BPB) of rice, a disease caused by Burkholderia glumae and B. gladioli, threatens global rice yields and has recently emerged in Bangladesh. Three hundred BPB-infected samples from 20 Bangladesh districts were analyzed using S-PG medium and gyrB PCR amplification, identifying 46 B. gladioli and 5 B. glumae potential isolates. Twenty of these isolates were chosen for in-depth characterization. Pathogenicity tests identified BD_21g (B. glumae) as the most virulent strain, followed by BDBgla132A (B. gladioli). Disease severity on rice strongly correlated with onion bulb assays, validating the assay as a rapid virulence-screening tool. Phenotypic characterization of the 20 isolates revealed substantial variation in toxoflavin production, lipase activity, polygalacturonase activity, motility, and type III secretion system. Comparative genomic analysis of virulence-associated genes between BDBgla132A and BD_21g showed high protein sequence identity, particularly in toxoflavin biosynthesis and transport genes, while genes encoding lipase (lipA/lipB), polygalacturonase (pehA/pehB), and those involved in motility, displayed moderate to high identity. Both strains retained virulence-related genes that are homologous to those of B. cepacia but displayed differential virulence strategies. Retrotranscribed-qPCR revealed significantly higher expression of toxoflavin and lipase-encoding genes in BD_21g compared with BDBgla132A, consistent with its elevated enzymatic activities. Conversely, BD_21g showed reduced expression of pectinolytic and flagellar genes over BDBgla132A, consistent with the enhanced pectinolytic activity and motility observed in BDBgla132A. These findings reveal that BD_21g (B. glumae) and BDBgla132A (B. gladioli) rely on different virulence strategies to infect rice, providing critical insights for developing targeted BPB management approaches in Bangladesh.

Abstract: Oxidative stress disrupts protein function through direct oxidation and triggers adaptive post-translational modifications. Among these, small ubiquitinlike modifier (SUMO)-ylation mediates fast and reversible remodeling of nuclear and cytoplasmic proteins. Redox regulation of the SUMO E1–E2 conjugation complex and specific SUMO proteases, such as SENP1 and SENP3, allows ROS to influence SUMO turnover and substrate selectivity. This defines SUMOylation as a versatile stressresponse module under oxidative stress. In this review, we describe oxidative stress-induced remodeling of SUMO conjugation and deconjugation, with a focus on SUMO2/3 responses that transiently adjust transcription, DNA damage repair, and nuclear body dynamics. We discuss disease-relevant SUMO targets and pathological alterations in SUMO regulation across four major disease categories: neurodegenerative diseases, cardiovascular disease, cancer, and diabetes/metabolic diseases. In addition, we summarize emerging evidence connecting redox-sensitive SUMO remodeling to germ-cell function and reproductive health. Together, these perspectives highlight the dual role of SUMOylation as both a driver of stress adaptation and a tractable target for informing therapeutic strategies targeting the SUMO pathway.

Abstract: Insect trap records are widely used for monitoring stored-product pests but are less frequently applied in predictive decision-support systems. The present study aimed to evaluate whether biweekly trap data could support the development of a temperature-driven population dynamics model for stored-product pest management. A facility-level time series of aggregated biweekly insect counts was analyzed using a discrete negative binomial regression model, with mean temperature during the preceding 14 days and the number of insecticidal spraying applications within each monitoring interval as predictors. The fitted model showed that recent temperature was positively associated with expected insect counts, whereas spraying applications were negatively associated with expected counts. Specifically, each 1°C increase in 14-day mean temperature was associated with a 17.5% increase in expected biweekly insect counts, while each additional spraying application was associated with a 39.6% reduction. Scenario analysis was used to compare alternative temperature-triggered spray policies. A standard threshold policy produced outcomes very similar to those of the observed historical schedule, suggesting that the original intervention timing was already broadly aligned with a biologically plausible temperature-based rule. In contrast, a preventive intensified policy substantially reduced predicted insect counts but required a markedly higher number of spraying applications. Overall, the results indicate that routine biweekly trap data can support a practical, facility-level population dynamics model and can be used to quantify trade-offs between expected pest suppression and intervention effort. The proposed framework provides a proof of concept for transforming routine monitoring records into an operational tool for pest-management decision support.

Abstract: Objective: To investigate the effects of yeast extract on colonic damage in sheep caused by high-concentrate diets, providing a theoretical basis for developing more precise probiotic formulations.Methods:This study selected 45 three-month-old Du Han F1 sheep of similar body condition and randomly divided them into three groups: a control group (CON) fed a standard diet, a high-concentrate diet (HC) group, and a yeast culture treatment group. A 15-day pretrial period was followed by a 60-day main trial. Following the feeding trial, colonic contents and colonic tissue samples were collected.Results: Indicate that feeding a high-concentrate diet caused damage to both the colonic mucosa and muscularis layers. Compared with the control group (CON), the high-concentrate diet (HC) group presented 29 DEGs. Following the addition of yeast culture (YC), the number of differentially expressed genes increased to 683, among which 6 were YC-specific genes. Eight differentially abundant bacterial genera were identified: increased abundance of [Eubacterium]-xylanophilum-group, Alistipes, Gastranaerophilales, Lachnospiraceae-UCG-010, and Cyanobacteria; decreased abundance of Ruminococcaceae;uncultured, Akkermansia, and Verrucomicrobiota. Concurrently, VFA levels decreased while ammonia nitrogen levels increased, accompanied by abnormal expression of host immune barrier-related genes (e.g., CLDN1, CXCL8). In the HCY group, colonic mucosal integrity improved, microbial composition underwent significant changes, VFA levels rebounded, and ammonia nitrogen levels decreased.Conclusions: This indicates that YC modulates the “microbiota-VFA-host” axis network to a certain extent.

Abstract: Soils represent a critical leverage point for mitigating global warming, acting simultane-ously as major carbon reservoirs and active sources of greenhouse gas emissions under unsustainable management. This review synthesizes current evidence on soil steward-ship practices aimed at reducing carbon emissions and enhancing carbon sequestration. Comparative insights are provided across conventional mineral fertilization, organic amendments, and circular fertilization approaches based on agro-industrial by-products. The review integrates findings from field experiments, long-term trials, and life cycle as-sessment studies to evaluate the effects of different management practices on soil organic carbon dynamics, greenhouse gas fluxes, nutrient use efficiency, and soil biological func-tioning. Special emphasis is placed on the role of waste-derived fertilizers—such as com-posts, digestates, vermicompost—in promoting soil carbon stabilization while reducing the environmental burden associated with synthetic inputs. Evidence consistently indi-cates that soil stewardship strategies grounded in circular economy principles can lower net carbon footprints, improve soil resilience, and mitigate trade-offs between productivity and climate mitigation. By framing soil management within the context of global warm-ing mitigation, this review highlights the multifunctional role of soils as climate regula-tors and underscores the potential of agro-industrial waste valorization as a scalable pathway toward climate-smart and low-emission agricultural systems.

Abstract: Foodborne diseases and food poisoning caused by bacterial pathogens is a significant global health as well as economic concern. While synthetic compounds are widely used as preservatives to ensure food safety, growing concerns regarding their potential health risks and the rise of antimicrobial resistance have driven the search for natural alternatives. Essential oils (EOs) and their individual bioactive constituents, known as essential oil components (EOCs), have emerged as promising, eco-friendly candidates for food preservation due to their robust broad-spectrum antibacterial properties. This review provides comprehensive mechanistic insights into how individual EOCs exert their antibacterial effects, detailing the disruption of bacterial cell membranes, inhibition of vital metabolic enzymes and ATP synthesis, modulation of virulence gene expression, and the prevention and eradication of biofilms. Furthermore, the review explores the practical applications and limitations of EOCs in food systems, addressing challenges such as chemical instability, toxicity at high doses, and adverse organoleptic effects. It also highlights advanced formulation strategies, such as micro/nano-encapsulation, nano-emulsions, and chemical derivatization, which significantly enhance EOC stability, bioavailability, and overall preservative efficacy. Ultimately, understanding the multifaceted mechanisms of individual EOCs paves the way for their optimized and sustainable use, ensuring global food safety.

Abstract: Antimicrobial resistance (AMR) is a silently escalating global crisis, presenting a specific challenge for the One Health approach. Landscapes can serve as reservoirs of AMR, while synurban wildlife may act as vectors of bidirectional exchange. However, these species can also be utilised as sentinels of landscape AMR load. Herbivorous avian bioindicators, such as the Common Wood Pigeon (Columba palumbus), continuously sample the landscape during foraging and drinking, providing unbiased data on the state of AMR. This study aimed to investigate the potential of this species for assessing the impact of landscape diversity on bacterial communities and their AMR patterns. Toward this objective, two landscape units of 4-km-diameter located at an upstream and a downstream section of a river, relative to a provincial town, were compared using 16 cloacal samples per site. Heterotrophic plate count techniques resulted in 60 isolates, of which 48 were identified, and 35 were tested for AMR using the VITEK 2 Compact system. Rényi diversity profiles of landscape compositions, bacterial communities, and AMR patterns revealed that higher landscape diversity was associated with lower bacterial but higher AMR pattern diversity. Additionally, the structure of more diverse bacterial communities shifted toward Gram-negative taxa. These findings support the hypothesis that culture-based methods using Common Wood Pigeons, complemented by Rényi diversity analysis and the determination of Gram-positive/Gram-negative ratios, provide valuable data on landscape health, even with small sample sizes.

Abstract: Telmisartan (TEL) is a non-peptide, orally administered antihypertensive agent primarily known as angiotensin II type 1 (AT1) blocker. In this review, we provide a detailed overview of how TEL modulates voltage-gated Na⁺ current (I_Na) and affects action potential (AP) firing behavior. TEL exerts differential stimulatory effects on the peak and late components of I_Na when subjected to brief depolarizing pulses across a range of cell types, such as mHippoE-14 hippocampal neuron, cultured dorsal root ganglion neurons, and HL-1 atrial cardiomyocytes. TEL can augment the inactivating (persistent) I_Na elicited by ascending long ramp pulse in mHippoE-14 cells. By using a parvalbumin-expressing interneuron-based modeled cell combined with bifurcation analysis, it is possible to predict how applied current influences subthreshold oscillations and the generation of somatic spiking in the presence of TEL. According to the Hodgkin-Huxley model, mimicking the action of TEL—characterized by an increased peak amplitude of I_Na and a slowed inactivation time course—leads to the emergence of periodic oscillations in membrane potential. Using a Markovian process, a separate model can also be mathematically constructed, showing that changes in certain rate constants can simulate the effect of TEL on I_Na in cardiac cells. The molecular docking prediction between TEL and the NaV1.7 channel was made by expected formation of hydrophobic interactions as well as hydrogen bonding. Beyond its antagonistic action on AT1 receptor and agonistic activation of peroxisome proliferator-activator-γ, the direct stimulation of I_Na may also contribute to its modulation of AP firing in various excitable cells. Current evidence supports TEL’s modulatory impact on Na_V channel activity and cellular excitability, while also acknowledging that the mechanism—whether direct or indirect—remains under investigation.

Abstract: Inadequate surface sanitization represents a significant risk to sterility assurance and regulatory compliance. Therefore an effective cleaning and disinfection programme is a critical component of contamination control strategies in pharmaceutical facilities manufacturing sterile medicinal products. This study aimed to standardize a carrier-based methodology for evaluating the efficacy of disinfectants against in-house environmental isolates recovered from a pharmaceutical industry facility. Nine representative strains (six bacteria and three fungi), selected based on historical environmental monitoring data (2012–2022), were characterized using matrix-assisted laser desorption/ionization - time-of-flight / mass spectrometry (MALDI-TOF MS) and molecular sequencing (16S rRNA or D2 LSU rDNA). Disinfectant efficacy was assessed on stainless-steel and low-density polyethylene surfaces using NF T 72-281:2014 with adaptations, testing alcohol 70%, sodium hypochlorite 0.5%, quaternary ammonium 0.05%, peracetic acid 0.5%, and accelerated hydrogen peroxide wipes. All agents demonstrated ≥5 log₁₀ reductions against vegetative bacteria and fungi on both surfaces. However, variable sporicidal performance was observed, particularly for one Bacillus cereus group strain (B1342/15), which showed limited reduction on stainless-steel. These findings highlight inter-strain variability and the greater tolerance of surface-associated spores. The study reinforces the importance of carrier-based testing using in-house isolates to ensure realistic validation of disinfectants and to strengthen microbiological risk management within pharmaceutical contamination control strategies.