Search Results (19,103)

Low temperatures limit the yield and stability of autumn-sown oats; thus, investigating cold resistance physiological responses is essential. In this study, we compared a cold-resistant variety (‘Aiwo’) and a cold-sensitive variety (‘Hewang’). ‘Aiwo’ exhibited a significantly higher overwintering survival rate (96.9%) and superior physiological traits, including elevated levels of soluble proteins, proline, putrescine, unsaturated fatty acids, and glutathione, alongside greater ATPase activity and reduced ROS levels. Exogenous putrescine application suggested a potential role of Put in alleviating lipid peroxidation. Metabolomic analysis showed that the arginine–proline and cysteine–methionine pathways were enriched among DAMs associated with ‘Aiwo’, accompanied by the accumulation of stress-protective metabolites. These metabolic changes may contribute to improved energy balance and membrane stability under low-temperature conditions. Our findings suggest that proline, putrescine, and glutathione are candidate physiological indicators associated with the cold-resistant phenotype, which may facilitate future screening of cold-resistant oat germplasm. Full article

Background: The incremental value of iodine-125 (I-125) seed implantation in advanced refractory lung squamous cell carcinoma (LUSC) with hemoptysis treated with bronchial artery chemoembolization (BACE) and immunotherapy remains unclear. Methods: This retrospective cohort study included 90 patients treated between June 2023 and June 2025. Patients receiving BACE plus immunotherapy were classified according to whether I-125 seed implantation was performed within 7 days after BACE: G1, BACE plus immunotherapy (n = 42), and G2, BACE, I-125 seed implantation, and immunotherapy (n = 48). Inverse probability of treatment weighting (IPTW) served as the primary adjustment method. Results: After IPTW, baseline covariates were well balanced; propensity score matching yielded 26 patients per group. Compared with G1, G2 was associated with longer hemoptysis-free survival (not reached vs. 11 months; HR = 0.34, 95% CI 0.18–0.64, p < 0.05), overall survival (19 vs. 14 months; HR = 0.26, 95% CI 0.15–0.44, p < 0.05), and progression-free survival (12 vs. 9 months; HR = 0.34, 95% CI 0.21–0.56, p < 0.05). The 6-month objective response rate (ORR) and disease control rate (DCR) were higher in G2, whereas no significant difference in 24-h hemostasis or recorded grade 3 or higher adverse events was observed. Conclusions: Adding I-125 seed implantation to BACE plus immunotherapy was associated with improved outcomes in selected patients, and prospective validation is warranted. Full article

Vitamin K is a well-established cofactor for γ-glutamyl carboxylase in vertebrates, yet its physiological functions in insects remain poorly understood. Warfarin, a vitamin K antagonist, inhibits vitamin K epoxide reductase, thereby blocking the vitamin K cycle. We have previously demonstrated that, in Drosophila melanogaster, vitamin K3 (menadione sodium bisulfite, MSB) is converted into endogenous vitamin K2, and that warfarin interferes with this cycle, leading to reduced oxidative stress. In the present study, we investigated the effects of chronic exposure to MSB (3.5 mM) and/or warfarin (1 mM and 10 mM) during larval development on adult survival, lifespan, mitochondrial ATP hydrolysis rate, and the transcriptional expression of target genes. Warfarin at 1 mM did not affect development or egg laying, whereas 10 mM caused significant postembryonic lethality. Transcriptional analysis revealed marked sex-specific effects. In females, warfarin downregulated the levy gene (encoding a complex IV subunit) and the ATPsynB gene (encoding an ATP synthase subunit B), while MSB suppressed cell cycle genes (cmet, sti, mcm2). In contrast, males exhibited upregulation of COQ7 (encoding a key enzyme in ubiquinone biosynthesis) in response to warfarin and increased sti expression in response to MSB, suggesting a more robust compensatory response. Notably, the combined application of MSB and warfarin increased mitochondrial ATP hydrolysis, thereby offsetting the negative physiological effects despite persistent transcriptional suppression. In females, either MSB or warfarin alone significantly reduced median lifespan; however, when applied together, female lifespan was restored to control levels. In males, the effects were considerably weaker. Thus, this study reveals a novel, sex-specific interaction between vitamin K and its antagonist in D. melanogaster, providing new insights into mitochondrial adaptation and sexual dimorphism in metabolic stress responses. Full article

Objectives: Pediatric nasopharyngeal carcinoma (NPC) is rare and often presents at an advanced stage. Although multimodal treatment can achieve favorable survival, long-term survivors may experience substantial treatment-related morbidity. We aimed to evaluate survival outcomes according to stage and metastatic status and to characterize late toxicity in a 20-year single-center pediatric NPC series. Methods. We retrospectively reviewed 24 pediatric patients diagnosed with NPC between 2003 and 2023. Histology was classified according to WHO criteria, and tumors were staged using the AJCC TNM system. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan–Meier method. Survival distributions were compared using the log-rank test. Late treatment-related toxicities documented during follow-up were recorded descriptively. Results: Twenty-four patients with WHO type III NPC were included. Fourteen patients had stage III disease and 10 had stage IV disease; three had distant metastasis at diagnosis. The median follow-up duration was 50.5 months. At last follow-up, 19 patients were alive and five had died. The estimated 5- and 10-year OS rates were both 72.7%, and the corresponding EFS rates were both 63.7%. Stage IV disease and metastatic presentation were associated with inferior OS. Dysphagia, malnutrition, xerostomia, fibrosis, hypothyroidism, and deafness were the most frequently recorded adverse health effects. Conclusions: This 20-year single-center experience shows that AJCC stage and metastatic status remain key determinants of survival in pediatric NPC. The high burden of late treatment-related complications highlights the importance of integrating long-term multidisciplinary survivorship surveillance into the care of pediatric NPC survivors. Full article

Lifetime data arising in engineering reliability, survival analysis, actuarial science, and environmental studies often exhibit substantial right-skewness, extreme observations, and heterogeneous hazard-rate structures. Classical lifetime distributions may not adequately capture these characteristics, thereby affecting risk assessment, reliability evaluation, and predictive performance. In this paper, we introduce the Heavy-Tailed QLindley (HTQL) distribution, a new two-parameter heavy-tailed extension of the QLindley model obtained through the New Family of Heavy-Tailed (NFHT) transformation. The proposed distribution provides greater flexibility for modelling positively skewed and heavy-tailed data while preserving analytical tractability. The HTQL model accommodates increasing, decreasing, bathtub-shaped, unimodal, and nearly constant hazard rate functions, making it suitable for applications in reliability analysis, survival studies, actuarial science, and environmental modelling. Several mathematical and statistical properties of the HTQL distribution are derived, including explicit expressions for the quantile function, ordinary and incomplete moments, order statistics, and reliability measures. Important tail-based risk measures such as Value-at-Risk, Tail Value-at-Risk, Tail Variance, Tail Variance Premium, and Expected Shortfall are also obtained. Parameter estimation is investigated using maximum likelihood, ordinary least squares, Cramér–von Mises, and Bayesian approaches, together with bootstrap confidence intervals. A Monte Carlo simulation study is conducted to evaluate the finite-sample performance of the proposed estimators. The practical usefulness of the HTQL distribution is illustrated using three real-world datasets from pharmacokinetics, engineering reliability, and environmental studies. The empirical results show that the HTQL distribution provides highly competitive fits compared with several classical, Lindley-type, and heavy-tailed distributions. Overall, the proposed model constitutes a flexible and parsimonious alternative for modelling positive heavy-tailed data. Full article

Bumblebees are dominant pollinators threatened by environmental antibiotic residues. This study investigated sublethal chloramphenicol (12 and 120 μg/L) effects on Bombus terrestris after 15 days’ exposure. The results showed that chloramphenicol exposure had no significant effect on the survival rate and cumulative food intake of bumblebees, confirming the sublethal property of the tested concentrations. However, chloramphenicol significantly dysregulated the expression of genes related to learning–memory (DopR2, Oamb, NMDA), immunity (abaecin, defensin) and detoxification (cyp9Q6) in bumblebees. High-dose chloramphenicol significantly increased carboxylesterase activity and reduced malondialdehyde content, while superoxide dismutase activity remained unchanged. In addition, chloramphenicol exposure significantly reshaped the gut microbiota structure of bumblebees, reduced the abundance of core beneficial symbiotic bacteria, and increased the proportion of drug-resistant bacteria. Our findings indicate that sublethal concentrations of chloramphenicol can impair bumblebee health through multiple pathways, including regulating gene expression, altering antioxidant enzyme activity and disrupting gut microbiota homeostasis. This study provides multi-dimensional toxicological data and a scientific basis for the ecological risk assessment of agricultural antibiotic residues to pollinator insects. Full article

Background: Chest X-ray imaging is a widely used diagnostic modality for identifying various lung diseases. Accurate multiclass classification of lung diseases enables timely treatment and improves patient survival. However, disease detection using chest X-ray images remains challenging due to heterogeneous data, overlapping radiographic features, and data privacy concerns. Furthermore, distinguishing among different lung diseases is difficult because of their similar clinical manifestations and imaging characteristics. Method: To address these challenges, a novel chaotic evolution optimization-enabled deep channel-attention broad convolutional neural network (CCEO-DCABNet) is proposed for multiclass lung disease classification within a federated learning (FL) framework. The proposed model ensures enhanced data privacy by allowing multiple client nodes and a central server to collaboratively train the model without sharing raw data. Prior to classification, image preprocessing is performed using Gaussian filter-based denoising followed by multiscale unsharp masking-based image sharpening. Subsequently, multiclass disease classification is carried out using DCABNet, whose parameters are optimized through the proposed CCEO algorithm. In addition, the federated learning process employs an averaging strategy for local model updates and global aggregation. Results: The proposed CCEO-DCABNet achieves an accuracy, true positive rate (TPR), and true negative rate (TNR) of $96.98\%$, $96.41\%$, and $97.45\%$. Conclusions: Experimental results demonstrate that the proposed CCEO-DCABNet framework effectively classifies multiple lung diseases from chest X-ray images while preserving data privacy through federated learning. The model achieves superior classification performance and can support reliable computer-aided diagnosis in clinical settings. Full article

Background/Objectives: Despite improved survival with immune checkpoint inhibitors, the optimal treatment after anti-PD-1 progression in metastatic melanoma remains unclear. This study compared survival outcomes and treatment responses between chemotherapy (CT)- and immunotherapy (IO)-based therapies administered after nivolumab progression in patients with BRAF-negative metastatic melanoma. Methods: This multicenter retrospective study included patients with BRAF-negative metastatic melanoma who developed disease progression during nivolumab treatment. Post-progression systemic therapies were categorized as CT- or IO-based treatments. Treatment responses were assessed according to RECIST version 1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: A total of 141 patients were included. Following nivolumab progression, 107 (75.9%) received CT and 34 (24.1%) received IO. Based on best response to nivolumab, the objective response rate (ORR; CR + PR) was 55.1% in the CT group and 44.1% in the IO group. After post-nivolumab treatment, ORRs were 29.9% and 32.4% in the CT and IO groups, respectively, whereas complete response rates were higher with IO (21.2% vs. 3.0%). Median PFS was 4.17 months in the CT group and 3.9 months in the IO group (p = 0.403). Median OS was 7.83 and 8.17 months, respectively (p = 0.416). Elevated LDH level was identified as an independent adverse prognostic factor. Conclusions: In this multicenter real-world cohort, no statistically significant differences in survival were observed between patients receiving CT or IO after nivolumab progression. Given the retrospective, non-randomized study design, these findings should not be interpreted as evidence of comparative treatment efficacy. The higher CR rate observed with IO should be interpreted cautiously due to potential selection bias. Prospective studies are warranted to define the optimal treatment strategy after anti-PD-1 failure. Full article

Glioblastoma multiforme (GBM), isocitrate dehydrogenase (IDH)-wildtype, is the most aggressive primary malignant tumor of the central nervous system, characterized by poor prognosis and high recurrence rates despite standard multimodal treatment. This study investigates the molecular response of glioblastoma cells to 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT), focusing on gene expression changes associated with apoptosis, ferroptosis, and oxidative stress. Human glioblastoma T98G cells were treated with 5-ALA followed by light irradiation, and gene expression was analyzed using RT-qPCR. PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) alongside increased expression of the anti-apoptotic gene BCL2, indicating simultaneous activation of cell death and survival pathways. Ferroptosis-related genes showed mixed responses, with slight upregulation of ACSL4 and downregulation of GPX4, suggesting increased susceptibility to lipid peroxidation. The most significant change was observed in GCH1 expression, reflecting activation of oxidative stress response mechanisms. However, none of the observed changes reached statistical significance, likely due to the limited sample size. These findings demonstrate that PDT induces a complex and dual biological response in glioblastoma cells, involving both cytotoxic and adaptive mechanisms. This may limit therapeutic efficacy and contribute to treatment resistance. The results support the rationale for combining PDT with targeted molecular therapies aimed at inhibiting antioxidant defenses and anti-apoptotic pathways. Additionally, personalized therapeutic strategies based on tumor molecular profiles may enhance treatment outcomes. Further studies with larger sample sizes and functional validation are required to confirm these preliminary observations. Full article

The interaction between increased dissolved carbon dioxide, rising temperatures, and oxygen loss—the so-called “deadly trio”—is expected to strongly affect marine biota over the coming years, undermining ocean services and uses. Nonetheless, no study has so far scrutinized the cumulative impact of these three stressors on fish embryos and larvae. To fill this knowledge gap, we conducted a fully multi-factorial experiment to investigate the effects of warming (+4 °C: 22 °C), acidification (Δ − 0.4 pH units: 7.7 pH, pCO₂ ~1000 μatm), and deoxygenation (Δ − 60% O₂ saturation: 3 mg O₂ L⁻¹) on physiological and behavioral responses of the commercially important species Sparus aurata. Deoxygenation was the primary factor reducing hatching rates (64.25%), survival (46.71%), and heart rates (31.99%) of recently hatched larvae, being generally further exacerbated when combined with warming and acidification. No larvae exposed to the interaction of the three treatments reacted to the phototactic behavior test. However, acidification alone caused a 50% reduction in phototactic behavior. Our findings demonstrate that the deadly trio is detrimental to early fish development, impacting several key features at this critical life stage, and the need to assess the impacts of stressors’ interaction on marine taxa to better predict future ecosystem responses to ocean changes. Full article

Background/Objectives: Contemporary patient-specific subperiosteal implants have re-emerged as graftless solutions for oral and maxillofacial rehabilitation, driven by advances in digital planning, CAD/CAM workflows, additive manufacturing, and biomaterial engineering. Their indications have progressively expanded from severely atrophic edentulous jaws to segmental defects, single-tooth replacement, congenital craniofacial anomalies, salvage situations, and oncologic reconstruction. This scoping review aimed to map the current evidence on modern patient-specific subperiosteal implants, focusing on indications, workflow, design principles, materials, outcomes, complications, and maintenance. Methods: A scoping review was conducted according to PRISMA-ScR principles to identify clinical studies, case series, case reports, systematic and scoping reviews, technical notes, finite element analyses, in vitro studies, and relevant translational investigations dealing with contemporary custom-made or CAD/CAM subperiosteal implants. The evidence was narratively synthesized according to clinical indication and thematic domains, including full-arch rehabilitation, sectional and single-tooth applications, congenital and post-oncologic defects, rescue indications, biomechanics, material selection, surface response, prosthetic protocols, and complication management. No quantitative meta-analysis was performed because of the scoping design and the substantial heterogeneity of study types, indications, implant systems, outcome definitions, and follow-up durations. Results: The final evidence map included 116 records, of which 56 were unique human clinical records with extractable denominators and 60 were biomechanical, in vitro, surface-biology, review, consensus, historical, or conceptual records. Of the 56 unique clinical records, 49 were mapped within the six indication-level clinical sections, while seven were retained as cross-cutting clinical evidence addressing patient-reported outcomes, design-related complications, bone apposition, anchorage strategy, comparative graftless rehabilitation, or reconstructive/prosthetic principles. The six indication-level sections included 52 clinical-record assignments: 15 for full-arch rehabilitation, 13 for segmental or sectional rehabilitation, one for single-tooth rehabilitation, four for congenital or craniofacial indications, 13 for post-oncologic or post-ablative reconstruction, and six for rescue or salvage indications. Because three records addressed more than one indication, these counts represent indication-level assignments rather than mutually exclusive clinical records. Reported survival in most short- to mid-term clinical series was generally high, commonly ranging from 90% to 100%, although lower values of 70–80% were reported in selected longer-term cohorts and survival clearly overestimated clinical success in some studies. Expanding applications include posterior mandibular and maxillary defects, lateral incisor agenesis, cleft-related or syndromic deformities, maxillectomy reconstruction, obturator support, and hybrid rehabilitation with endosseous implants; however, evidence for the indications at the extremes of this spectrum—single-tooth replacement and primary oncologic reconstruction—remains limited to small, largely single-group case series and reports. Soft-tissue events, including dehiscence, mucositis, recession, and framework exposure, were the dominant complications and showed wide variability, with reported recession/exposure rates ranging from approximately 10% in some sectional and full-arch series to as high as 65% in bilateral maxillary cohorts; their clinical significance varied from asymptomatic stable findings to progressive inflammatory complications requiring revision. Conclusions: Patient-specific subperiosteal implants represent a promising and increasingly versatile reconstructive option; however, the present findings should be interpreted as evidence mapping rather than as definitive comparative evidence. Their clinical use should remain highly selective, prosthetically driven, and supported by meticulous planning, rigid fixation, soft-tissue management, and structured maintenance. Standardized success criteria, longer follow-up, and comparative prospective studies are required. Full article

The practical efficacy of Azadirachtin (AZA)—a botanical insecticide valued for its strong antifeedant activity—is often undermined by its poor environmental stability, arising from rapid photolysis and thermal decomposition. Herein, amino-modified mesoporous silica nanoparticles (MSNs) were employed as nanocarriers to encapsulate AZA, yielding the AZA@MSNs−NH₂ nanoinsecticide. Under UV irradiation (254 nm), the degradation rate of AZA@MSNs−NH₂ was more than 35% lower than that of commercial AZA after 24 h of exposure. In biosafety tests, MSNs at 50–800 mg/L enhanced cotton seed germination and seedling growth, whereas MSNs below 200 mg/L caused no observable harm to zebrafish survival. Free AZA (0.5–10 mg/L) showed limited efficacy in bioassays against Helicoverpa armigera and Apolygus lucorum, reducing larval weight gain only marginally in the former (mortality < 5%) and performing poorly against the latter. In contrast, AZA@MSNs−NH₂ significantly boosted both growth inhibition and lethal effects against both pests, yielding > 80% growth inhibition and 62.65% corrected mortality for H. armigera, as well as strong lethality toward A. lucorum. Overall, this work confirms that nanoformulation of AZA not only circumvents its physicochemical drawbacks but also boosts its insecticidal performance against cotton pests, supporting the advancement of sustainable cotton pest control. Full article

This review summarizes recent studies on the use of nanoparticles (NPs) in plant in vitro clonal micropropagation and secondary metabolite production. The analyzed applications include culture initiation, shoot multiplication, rooting, acclimatization, callus culture, and hairy root culture. Because NPs’ effects are strongly endpoint-dependent, their effectiveness is evaluated separately for micropropagation endpoints, including contamination control, explant survival, multiplication rate, shoot and root development, and plantlet quality, and for metabolite-production endpoints, including biomass accumulation, target metabolite concentration, and total metabolite yield. Based on the quantitative analysis of published data, the most frequently beneficial NP size range was 20–60 nm, whereas effective concentrations, combining a positive effect on plant growth and the synthesis of secondary metabolites, were mainly within 1–120 mg L⁻¹. For the most extensively studied NPs, the corresponding indicative concentration ranges were 15–45 mg L⁻¹ for 25–40 nm Ag-NPs, 75–200 mg L⁻¹ for 15–45 nm ZnO-NPs, 120–150 mg L⁻¹ for 50–80 nm Se-NPs, and 90–145 mg L⁻¹ for 54–55 nm Si-based NPs. Ag- and carbon-based nanomaterials showed relatively strong overall responses in micropropagation datasets, whereas Ag- and Se-NPs were often associated with enhanced target metabolite accumulation. NP responses depend on particle composition, synthesis method, surface properties, dose, culture system, species, genotype, and may involve phytotoxic or residue-related risks. Full article

Background: Early recurrence following curative-intent hepatectomy for colorectal liver metastases (CRLMs) remains a significant clinical challenge. This study investigates risk factors for recurrence within 6 and 12 months and evaluates the impact of salvage surgery on long-term survival. Methods: We conducted a retrospective cohort study of 109 patients who underwent liver resection for CRLMs between 2013 and 2024. The primary outcome was the identification of predictors for early recurrence using Cox proportional-hazards models. The secondary outcomes focused on overall survival (OS) stratified by the timing of recurrence and subsequent treatment. Results: High tumor burden (>4 metastases) was an independent predictor of recurrence at both 6 months (HR 3.526; p = 0.008) and 12 months (HR 3.115; p = 0.004). Intraoperative blood loss >1000 mL was significantly associated with 6-month recurrence (HR 3.356; p = 0.004) and 12-month recurrence (HR 2.171; p = 0.041). For the 12-month window, independent predictors included AJCC T3/T4 stage (HR 6.513; p = 0.011) and RAS mutation (HR 2.740; p = 0.006). Notably, patients with early recurrence who underwent salvage re-hepatectomy achieved 5-year OS rates that did not statistically differ from those without recurrence (p = 0.907 for <6 months; p = 0.433 for <12 months); however, these subgroup analyses are highly underpowered. Conclusions: High tumor burden (>4 metastases), RAS mutations, significant blood loss (>1000 mL), and primary tumor T3/T4 identify patients at high risk for early recurrence. While aggressive salvage re-hepatectomy is associated with prolonged survival in select patients, the non-significant p-values in our small salvage cohorts cannot be interpreted as evidence of survival equivalence. The observed survival benefits in the salvage cohort are heavily confounded by inherent selection biases, and therefore, the true extent of this ‘rescue’ effect must be interpreted with extreme caution and validated in larger, adequately powered multicenter studies. Full article

This study compares the efficacy of ozonated sunflower oil (OSO) and ozonated olive oil (OOO) in terms of antioxidant properties, modulation of high-density lipoprotein (HDL) functionality, and protective effects against carboxymethyllysine (CML)-mediated stress in zebrafish embryos and adults. The spectral and electronic nose (e-nose) analyses revealed that OSO and OOO possessed markedly distinct physicochemical characteristics and volatile and olfactory constituents compared with non-ozonated sunflower (SO) and olive oil (OO). The fluorescence spectrum analysis of HDL treated with OOO and OSO exhibited a red shift (2.6~3.3 nm) in the wavelength maximum fluorescence (WMF), accompanied by pronounced quenching of tryptophan fluorescence. Additionally, a significant increase in HDL-associated paraoxonase (PON) and ferric ion reduction (FRA) activity was observed in the OSO- and OOO-treated HDL. However, compared to OOO, significantly higher PON and FRA activities were observed in HDL treated with OSO. Also, compared to OOO, OSO effectively reverses CML-induced oxidative stress, altered heart rate, and reduced embryo survival. Similarly, in adult zebrafish, CML-compromised survival, swimming impairment, and disturbed antioxidant parameters were prevented by treatment with OOO and OSO. Nonetheless, OSO showed significantly higher efficacy than OOO. Consistently, OSO substantially reduced the CML-elevated blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels with a marked increase in high-density lipoprotein cholesterol (HDL-C) levels. Notably, no significant effect of OOO was observed on the reduction in and augmentation of LDL-C and HDL-C, respectively. Both OOO and OSO significantly protect against CML-triggered liver and kidney damage. However, compared with OOO, OSO significantly reduced neutrophil infiltration, interleukin-6 (IL-6) production, liver steatosis, ROS generation, and cellular senescence in the kidneys. The study concludes that OSO exerts significantly higher beneficial effects than OOO on HDL functionality and antioxidant defense, thereby attenuating CML-induced inflammatory and oxidative damage. Full article