Search Results (5,606)

The objective of this study was to investigate the adsorption of 11 azoles (tebuconazole, ketoconazole, econazole, miconazole, fluconazole, clotrimazole, climbazole, flutriafol, epoxiconazole, tiabendazole, and imazalil) on natural and waste-derived sorbents such as ceramsite, perlite, pumice, sawdust, coconut fibers, heavy oil fly ash (HOFA), activated carbon, and silica gel. The results of adsorption efficiency for most sorbents varied depending on the azole compounds and their concentration. The highest adsorption for all tested compounds was obtained for activated carbon and heavy oil fly ash, reaching about 100% in both tested concentrations (0.2 mg L⁻¹ and 0.02 mg L⁻¹). The HOFA material was characterized in terms of elemental analysis (CHNS), confirming the elemental contents of 52% C, 0.65% H, 0.4% N, and 2.3% S. The specific surface area of HOFA was 11.2 m² g⁻¹, and scanning electron microscopy (SEM) results showed the spherical yet porous nature of the particles. Furthermore, the calculated adsorption isotherms demonstrated that for most tested azoles, the Dubinin–Radushkevich (D-R) isotherm best fits the data, with R² = 0.93 or more, which is characteristic of porous carbon materials. The results highlight the significant potential of the tested HOFA sorbent for effectively removing azoles, as the tests performed showed that it was possible to remove these compounds with a concentration of up to 0.2 mg L⁻¹ within an hour. This is particularly important because HOFA is an easily accessible waste material. Furthermore, the adsorption of azoles will not increase the cost of HOFA disposal when using the standard procedures currently applied to this waste. Full article

Soybean inoculation with nitrogen (N) fixing bacteria can be highly promising for enhancing biological nitrogen fixation (BNF) and improving crop productivity. It helps to reduce dependency on chemical fertilizers, promotes sustainable agricultural practices, and minimizes environmental impacts. Therefore, understanding the specific aspects and conditions is essential for establishing the BNF process in particular environments. In this study, we investigated whether soybean inoculation is an effective strategy in cool-climate regions beyond their typical northern distribution, and which soybean varieties and microbial strains are the most effective for optimizing soybean productivity and performance in relatively cool environments. To address these questions, a natural abundance nitrogen stable isotope ratio analysis was conducted on two soybean varieties of different maturity groups, which were inoculated with three Bradyrhizobium japonicum strains, along with organic fertilizer and new promising endophyte treatments. This approach aimed to determine the differences in biological and chemical parameters of soybean, as well as the origin of N sources, its uptake, and the isotopic distribution within the plants. It was demonstrated that inoculation with Bradyrhizobium japonicum was more effective than fertilization, as the strains had a significant effect on nitrogen derived from the atmosphere (Ndfa), produced stable nitrogen isotope ratios close to 0‰, and substantially increased nitrogen content, particularly in beans. Soybean varieties Laulema and Merlin, representing different maturity groups, exhibited distinct nitrogen uptake patterns. Bradyrhizobium japonicum strain AGF78 consistently produced the greatest effect on biological parameters in both varieties, particularly in seed yield and grain weight, with the later-maturing Merlin achieving the highest average yield of 3066.89 kg ha⁻¹. Notably, the Merlin inoculated with AGF78 resulted in the highest nitrogen fixation in beans, with 66.8%NDFA and 134.0 kg/ha of fixed nitrogen. Similarly, Laulema inoculated with AGF78 resulted in 88.2%NDFA and 123.2 kg/ha of fixed nitrogen. Inoculation with selected bacterial strains significantly increased protein content from 30% to 41%, with the effects being both strain- and variety-specific. Our study showed that establishing effective soybean–microbe interactions by choosing soybean variety and microbial strain is crucial for optimizing agricultural practices and improving crop performance, especially in sustainable and environmentally conscious farming systems under cool climatic conditions of Europe. Full article

Purpose: This study aimed to evaluate the effect of different coronal restoration methods on stresses in immature central incisors with regenerative endodontic treatment and excessive loss of coronal structure. Methods: A three-dimensional (3D) Finite Element Analysis (FEA) model of a maxillary central incisor treated with a 3 mm MTA coronal plug after regenerative endodontic treatment was created. Six different models were simulated: (1) intact immature tooth (control), (2) direct composite resin build-up, (3) fibre-reinforced composite build-up, (4) hybrid ceramic endocrown, (5) LiSi ceramic endocrown, and (6) endocore and ceramic crown restoration. Analyses were performed with SolidWorks/CosmosWorks, and a 150 N load was applied at a 135° angle. Results: Maximum tensile stresses were concentrated in the cervical region (4.577 MPa). Direct composite and fibre-reinforced restorations showed high stress in root dentin (3.891 and 3.841 MPa, respectively). The endocore/ceramic crown restoration (1.578 MPa) provided the closest stress distribution to the natural tooth (1.322 MPa). Conclusions: The biomechanical performance of the restoration–tooth complex depends on both the restorative material and the restoration design. In immature teeth undergoing regenerative endodontic treatment, the most biomechanically favourable restoration option was an endocore/ceramic crown. Full article

The novel data show that the Hsp70 protein is a potent activator of the immune system. Using limited trypsinolisis, we have identified the epitopes of Hsp70 responsible for TREM-1-dependent and TREM-1-independent cytotoxicity. The 11aa N9 peptide (AMTKDNNLLGR) contains nine amino acids that correspond to the amino acid sequence of the known TKD peptide. Also, like TKD, this peptide does not interact with the TREM-1 receptor but activates CD94+ NK cells that kill tumor cells by secreting granzymes and inducing apoptosis. The 16aa peptide N7 (SDNQPGVLIQVYEGEK) interacts with the TREM-1 receptor and induces the activation of NK cells and cytotoxic T lymphocytes at different time points. T-lymphocytes activated by this peptide induce two alternative processes of cell death in HLA-negative tumor cells, apoptosis and necroptosis, through the interaction of the FasL lymphocyte with the Fas receptor of the tumor cell. A shortened fragment of this peptide, N7.1 (SDNQPGVL), has been identified that inhibits the interaction of TREM-1 with its ligands. This peptide has shown protective effects in the development of sepsis in mice. The results obtained can be used in antitumor and anti-inflammation therapy. Full article

Background/Objective: Understanding the training effect in high-level running is important for performance optimization and injury prevention. This includes awareness of how different running surface types (e.g., hard versus soft) may modify biomechanics. Recent studies have demonstrated that deep learning algorithms, such as convolutional neural networks (CNNs), can accurately classify human activity collected via body-worn sensors. To date, no study has assessed optimal signal type, sensor location, and model architecture to classify running surfaces. This study aimed to determine which combination of signal type, sensor location, and CNN architecture would yield the highest accuracy in classifying grass and asphalt surfaces using inertial measurement unit (IMU) sensors. Methods: Running data were collected from forty participants (27.4 years + 7.8 SD, 10.5 ± 7.3 SD years of running) with a full-body IMU system (head, sternum, pelvis, upper legs, lower legs, feet, and arms) on grass and asphalt outdoor surfaces. Performance (accuracy) for signal type (acceleration and angular velocity), sensor configuration (full body, lower body, pelvis, and feet), and CNN model architecture was tested for this specific task. Moreover, the effect of preprocessing steps (separating into running cycles and amplitude normalization) and two different data splitting protocols (leave-n-subject-out and subject-dependent split) was evaluated. Results: In general, acceleration signals improved classification results compared to angular velocity (3.8%). Moreover, the foot sensor configuration had the best performance-to-number of sensor ratio (95.5% accuracy). Finally, separating trials into gait cycles and not normalizing the raw signals improved accuracy by approximately 28%. Conclusion: This analysis sheds light on the important parameters to consider when developing machine learning classifiers in the human activity recognition field. A surface classification tool could provide useful quantitative feedback to athletes and coaches in terms of running technique effort on varied terrain surfaces, improve training personalization, prevent injuries, and improve performance. Full article

A modified Johnson–Mehl–Avrami–Kolmogorov (JMAK) model, including the heating rates, was proposed in this study to improve the accuracy of isothermal austenite formation kinetics prediction. Since the ultrafast heating process affects the behavior of ferrite recrystallization and austenite formation before the isothermal process, which in turn influences the subsequent isothermal austenite formation kinetics, the effects of varying austenitization temperatures and heating rates on isothermal austenite formation in cold-rolled quenching and partitioning (Q&P) steel, which remain insufficiently understood, were systematically investigated. Under a constant heating rate, the austenite formation rate initially increases and subsequently decreases as the austenitization temperature rises from formation start temperature A_c1 to finish temperature A_c3, and complete austenitization is achieved more quickly at elevated temperatures. At a given austenitization temperature, an increased heating rate was found to accelerate the isothermal transformation kinetics and significantly reduce the duration required to achieve complete austenitization. The experimental results revealed that both the transformation activation energy ($Q$) and material constant ($k_0$) decreased with increasing heating rates, while the Avrami exponent ($n$) showed a progressive increase, leading to the development of the heating-rate-dependent modified JMAK model. The model accurately characterizes the effect of varying heating rates on isothermal austenite formation kinetics, enabling kinetic curves prediction under multiple heating rates and austenitization temperatures and overcoming the limitation of single heating rate prediction in existing models, with significantly broadened applicability. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Spinal cord injury (SCI) often results in long-term locomotor impairments, and strategies to enhance functional recovery remain limited. While epidural electrical stimulation (EES) has shown clinical promise, our understanding of the mechanisms by which it improves function remains incomplete. Here, we use genetic tools in an animal model to perform neuromodulation and treadmill rehabilitation in a manner similar to EES, but with the benefit of the genetic tools and animal model allowing for targeted manipulation, precise quantification of the cells and circuits that were manipulated, and the gathering of extensive kinematic data. We used a viral construct that selectively transduces large diameter afferent fibers (LDAFs) with a designer receptor exclusively activated by a designer drug (hM3Dq DREADD; a chemogenetic construct) to increase the excitability of large fibers specifically, in the rat contusion SCI model. As changes in locomotion with afferent stimulation can be subtle, we carried out a detailed characterization of the kinematics of locomotor recovery over time. Adult Long-Evans rats received contusion injuries and direct intraganglionic injections containing AAV2-hSyn-hM3Dq-mCherry, a viral vector that has been shown to preferentially transduce LDAFs, or a control with tracer only (AAV2-hSyn-mCherry). These neurons then had their activity increased by application of the designer drug Clozapine-N-oxide (CNO), inducing tonic excitation during treadmill training in the recovery phase. Kinematic data were collected during treadmill locomotion across a range of speeds over nine weeks post-injury. Data were analyzed using a mixed effects model chosen from amongst several models using information criteria. That model included fixed effects for treatment (DREADDs vs. control injection), time (weeks post injury), and speed, with random intercepts for rat and time point nested within rat. Significant effects of treatment and treatment interactions were found in many parameters, with a sometimes complicated dependence on speed. Generally, DREADDs activation resulted in shorter stance duration, but less reduction in swing duration with speed, yielding lower duty factors. Interestingly, our finding of shorter stance durations with DREADDs activation mimics a past study in the hemi-section injury model, but other changes, including the variability of anterior superior iliac spine (ASIS) height, showed an opposite trend. These may reflect differences in injury severity and laterality (i.e., in the hemi-section injury the contralateral limb is expected to be largely functional). Furthermore, as with that study, withdrawal of DREADDs activation in week seven did not cause significant changes in kinematics, suggesting that activation may have dwindling effects at this later stage. This study highlights the utility of high-resolution kinematics for detecting subtle changes during recovery, and will enable the refinement of neuromechanical models that predict how locomotion changes with afferent neuromodulation, injury, and recovery, suggesting new directions for treatment of SCI. Full article

We synthesized the current evidence from the literature and conducted a 2 × 3 factorial experiment to quantify the impact of thermocycling on the Vickers microhardness (HV) of dental CAD/CAM materials: VITA ENAMIC (VE, polymer-infiltrated ceramic network) and CERASMART (CS, nanofilled resin-matrix). Sixty polished specimens (n = 10 per Material × Cycles cell; 12 × 2 × 2 mm) were thermocycled at 5–55 °C (0, 10,000, 20,000 cycles; 30 s dwell, ≈10 s transfer) and tested as HV0.3/10 (300 gf, 10 s; five indentations/specimen with standard spacing). Assumptions regarding the model residuals were met (Shapiro–Wilk W ≈ 0.98, p ≈ 0.36; Levene F(5,54) ≈ 1.12, p ≈ 0.36), so a two-way ANOVA (Type II) with Tukey’s HSD post hoc (α = 0.05) was applied. VE maintained consistently higher HV than CS at all cycle levels and showed a smaller drop from baseline: VE (mean ± SD): 200.2 ± 10.8 (0), 192.4 ± 13.9 (10,000), and 196.7 ± 9.3 (20,000); CS: 60.8 ± 6.1 (0), 53.4 ± 4.7 (10,000), and 62.1 ± 3.8 (20,000). ANOVA revealed significant main effects from the material (η²p = 0.972) and cycles (η²p = 0.316), plus a Material × Cycles interaction (η²p = 0.201). Results: Thermocycling produced material-dependent changes in microhardness. Relative to baseline, VE varied by −3.9% (10,000) and −1.7% (20,000), while CS varied by −12.2% (10,000) and +2.1% (20,000); from 10,000→20,000 cycles, microhardness recovered by +2.2% (VE) and +16.3% (CS). Pairwise comparisons were consistent with these trends (CS decreased at 10,000 vs. 0 and recovered at 20,000; VE only showed a modest change). Conclusions: Thermocycling effects were material-dependent, with smaller losses and better retention in VE (PICN) than in CS. These results align with the literature (resin-matrix/hybrids are more sensitive to thermal aging; polished finishes mitigate losses). While HV is only one facet of performance, the superior retention observed in PICN under thermal challenge suggests the improved preservation of superficial integrity; standardized reporting of aging parameters and integration with wear, fatigue, and adhesion outcomes are recommended to inform indications and longevity. Full article

At non-professional levels of rugby league, run-based tests are commonly performed on outdoor turfed fields and on indoor multipurpose sport surfaces, and results are monitored to gauge player performance and progression. However, test–retest reliability has not been conducted on indoor surfaces in adolescent rugby league players, and no research has examined if results obtained on outdoor and indoor surfaces are comparable for practitioners. Adolescent, male, rugby league players (N = 15; age = 17.1 ± 0.7 years) completed a 20 m linear sprint test (10- and 20 m splits), 505-Agility Test, and Multistage Fitness Test (MSFT) weekly for three consecutive weeks. Absolute (coefficient of variation (CV)) and relative (intraclass correlation coefficient (ICC)) reliability of each run-based test performed on the indoor surface was quantified. Dependent t-tests, Hedges g, and 95% confidence intervals were used to examine if differences in performance occurred between indoor and outdoor surfaces. Effect size magnitudes were determined as Trivial: <0.20, Small: 0.20–0.49, Medium: 0.50–0.79, and Large: ≥0.80. All tests were considered reliable on the indoor surface (CV < 5.0%; ICCs = moderate-good) except for the 505-Agility Test (CV = 4.6–5.1%; ICCs = poor). Non-significant (p > 0.05), trivial differences were revealed between surface types for 10 (g = 0.15, 95% CI = −0.41 to 0.70) and 20 m (g = 0.06, 95% CI = −0.49 to 0.61) sprint tests, the 505-Agility Test (Right: g = −0.53, 95% CI = −1.12 to 0.06; Left: g = −0.40, 95% CI = −0.97 to 0.17), and the MSFT (g = 0.25, 95% CI = −0.31 to 0.81). The 10 and 20 m linear sprint test and MSFT have acceptable test–retest reliability on an indoor multipurpose sport surface, and practitioners may compare results of run-based tests obtained on an outdoor and indoor surface. Full article

The glyoxalase pathway intermediate S-d-lactoylglutathione was recently implicated in protein post-translational modifications in animal systems. Here, we examined the spontaneous modification of the Arabidopsis thaliana cytosolic glyceraldehyde-3-phosphate dehydrogenase C1 (GAPC1) by this compound. Incubation of GAPC1 with S-d-lactoylglutathione resulted in the inhibition of enzyme activity. The inhibitory effect was concentration dependent and increased at alkaline pHs. Furthermore, the inhibition of GAPC1 by S-d-lactoylglutathione was favored by oxidative conditions and reversed by reduction with dithiothreitol. Analyses of the S-d-lactoylglutathione-treated protein by nanoLC-MS/MS revealed S-glutathionylation of its two Cys residues and N-lactoylation of six Lys residues. Protein structure predictions showed that the double S-glutathionylation is accommodated by the GAPC1 catalytic pocket, which likely explains enzyme inhibition. N-lactoylated sites overlap partially with previously reported N-acetylated sites at the surface of the GAPC1 tetramer. The efficiency of cytosolic glutaredoxin and thioredoxin isoforms was tested for reversing the S-d-lactoylglutathione-induced modification. In these assays, recovery of GAPC1 activity after inhibition by S-d-lactoylglutathione treatment was used as indicator of efficiency. The results show that both types of redoxins were able to reverse inhibition. We propose a model describing the mechanisms involved in the two types of post-translational modifications found on GAPC1 following exposure to S-d-lactoylglutathione. The possible involvement of these findings for the control over glycolytic metabolism is discussed. Full article

Coccidiosis represents a major constraint to sheep productivity worldwide, with increasing concerns regarding anticoccidial resistance and growing interest in reducing dependency on conventional synthetic anticoccidials. This investigation evaluated the anticoccidial properties of faveira pods (Parkia platycephala pod—PpP) and their influence on productive performance in naturally infected lambs. Eighteen uncastrated Dorper × Santa Inês crossbred males (20.0 ± 2.5 kg, 5 months) were randomly allocated to three groups: G1 (0% PpP; n = 6), G2 (100% PpP replacing roughage, 30.0% of total diet; n = 6), and the control group (0% PpP plus 20 mg/kg toltrazuril; n = 5). Parasitological assessments, productive performance, and behavioral parameters were monitored over 45 days using oocyst counts, morphometric analysis, digestibility trials, and biometric measurements. Nine Eimeria species were identified, with E. crandallis, E. parva, and E. bakuensis representing 53.5% of total oocyst shedding. Group G2 demonstrated a numerical 8.5% reduction in parasite load compared to G1 (p = 0.42), while toltrazuril achieved 36.6% efficacy (p < 0.05). Species-specific effects were significant for E. crandallis, E. parva, and E. ovinoidalis (p < 0.01). A robust correlation emerged between parasite load and water consumption (r = 0.652, p = 0.0045), establishing a novel behavioral biomarker for coccidiosis monitoring. Environmental oocyst elimination decreased by 43.4% in the P. platycephala group. These findings demonstrate that PpPs possess moderate anticoccidial properties, offering a sustainable complementary strategy for integrated coccidiosis management while contributing to environmental sustainability. Full article

The present study examines the effect of viruses on forest insects depending on the virus dose. Two model approaches are used to quantify the effect of viruses on insect survival. Both approaches describe the processes of virus exposure to insects within the framework of the second-order phase transition model, which is well known in theoretical physics. The first approach examines the temporal dynamics of larval survival at a given dose of virus exposure. This dependence is characterized by the time–effect curve. In this case, the lethal time of exposure LT100 is the time required for the death of all larvae in the experiment at a given dose D of exposure. The second approach describes the relationship between the proportion q_r of larvae that survived a fixed time T_c after the start of the experiment and the dose D of virus exposure. This dependence is characterized by the dose–effect curve. The experiments tested the effect of two different viruses—nucleopolyhedrovirus (NPV) and cypovirus (CPV)—on such insect species as Lymantria dispar L., Manduca sexta L. and Loxostege sticticalis L. It was shown that the proposed models of second-order phase transitions very accurately (with coefficients of determination of the models close to R² = 0.95) describe experiments on studying the effect of different virus strains on insect survival. The proposed models turned out to be useful for assessing the effectiveness of different virus strains against insect pests. Since the parameters of the second-order “dose–time” and “dose–effect” phase transition models are related to each other, it is possible to reduce the number of measurements of virus–insect interaction due to the relationship between these parameters, and instead of n observations of insect dynamics over time depending on the dose of exposure, the basic parameters characterizing the “virus–insect” interactions can be accurately estimated using only one measurement. It appears that the proposed model can be used to calculate the effect of toxic agents on the population of victims for a wide variety of toxicant species and populations. A sharp reduction in the labor intensity of experiments to assess the toxicity of certain toxicants on animal populations will simplify and reduce the cost of testing the response of living objects to toxicants. Full article

Background: Adherence to tyrosine kinase inhibitors (TKIs), the first-line treatment for renal cell carcinoma (RCC), is critical to ensure intended treatment outcomes. However, 75% of patients with RCC have persistency gaps (>7 days) within the first 90 days after initiating TKIs. This study explored factors affecting TKI adherence in RCC patients to inform future interventions. Methods: A retrospective cohort study was conducted at a specialist oncology hospital in Northwest England from October 2020 to October 2022 on patients with RCC treated with TKIs. TKI prescriptions and persistence gaps (>7 days) were identified from electronic dispensing records. Factors associated with persistence gaps were retrieved by reviewing patients’ clinical records. We used descriptive statistics to summarise the results and Kaplan–Meier analysis to assess the probability and the time to the first gap, stratified by adverse drug effect (ADE)-related and non-ADE-related gaps. Results: Among 165 included patients, 611 persistence gaps were identified. ADEs accounted for 59% (n = 464) of 787 recorded factors, with diarrhoea being the most frequent ADE (9.5%). Patients holding leftover TKIs were the primary (15.1%) non-ADE factor for persistency gaps. At least one gap was observed with 82% of patients (n = 135); 19% had ≥5 ADE-related gaps, and 25% had ≥5 non-ADE-related gaps. ADE-related gaps typically occurred within the first three months (50%), while non-ADE-related gaps were not time-dependent. Conclusions: ADEs, including diarrhoea and pain-related reactions, were the most frequently reported issues affecting TKI persistency in patients with RCC. These ADEs are likely to impact patients’ quality of life and adherence. Future qualitative research is warranted to explore patients’ care needs and additional factors such as health literacy and self-efficacy. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article