Search Results (11,460)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disorder linked to obesity, insulin resistance, and dyslipidemia. Nutrition plays a central role in modulating hepatic lipid metabolism, oxidative stress, and inflammation, yet practical, evidence-based dietary strategies remain limited. This study aimed to develop Mediterranean diet-based meal plans with varying macronutrient compositions and to characterize their nutritional profiles, as well as to evaluate them using established nutritional indices and diet score calculations, such as the Dietary Inflammatory Index, Dietary Antioxidant Index, and dietary lipid indices. Methods: Clinical practice guidelines (CPGs) from various academic and professional organizations were reviewed to assess current non-pharmacological treatments for MASLD, with a focus on determining whether the Mediterranean diet is the most recommended dietary pattern. Traditional, low-carbohydrate, and low-fat MedDiet patterns were translated into food-based meal plans. A 7-day meal plan was developed and analyzed for nutrient composition, then evaluated using the Dietary Inflammatory Index (DII), Dietary Antioxidant Index (DAI), Dietary Lipophilic Index (DLI), and Dietary Lipophilic Load (DLL). A Western diet (WD) that is characterized by ultra-processed food (UPF) was included as a comparative reference. Results: The validated dietary score calculations showed that all MedDiet patterns demonstrated consistently low DII scores (−2.00 to −2.81) and high DAI scores (3 to 20.03), whereas the WD showed high DII scores (5.0 to 6.09) and low DAI scores (−12.47 to −17.99). Despite these variations in macronutrients, the menu developed in the study on three MedDiet patterns showed negative DII and positive DAI scores. When comparing the traditional MedDiet with the WD, which have similar macronutrient distributions, the WD was characterized by less favorable DII and DAI scores. Conclusions: This study provides a descriptive, guideline-informed framework for Mediterranean diet-based meal plans with varying macronutrient compositions. Utilizing DII, DAI, DLI, and DLL offers a potential framework for designing dietary interventions. Further validation through clinical studies is needed to justify the potential for practical and digital translation. Nevertheless, the study provides initial insights that may inform future research on nutritional approaches for MASLD integrating dietary indices. Full article

Breast cancer (BRCA) is the most common cancer worldwide, with an incidence exceeding that of lung cancer. Protein lactylation, a newly identified post-translational modification involving the binding of lactic acid to lysine residues, plays an important role in BRCA. However, its role in BRCA progression remains largely unexplored. This study aims to identify and characterize the lactylation-related genes involved in BRCA biology. Transcriptomic and clinical data of BRCA and normal breast tissues were obtained from TCGA and GEO. Lactylation-related genes were curated from literature and intersected with BRCA datasets to identify candidates. A prognostic risk model was constructed using LASSO and Cox regression. Functional enrichment was performed using KEGG, GSVA, and GSEA. Immune correlations were evaluated by ESTIMATE, CIBERSORT. Single-cell RNA-seq data were integrated to assess gene expression heterogeneity across tumor and immune compartments. In vitro, MDA-MB-231 cells were treated with sodium L-lactate and lactylation-inducing agents, and gene expression was validated by Western blot and RT-qPCR, while EdU and wound healing assays evaluated proliferation and migration. We identified six hub genes associated with the immune microenvironment. Notably, S100A4 is significantly underexpressed, suggesting their potential regulatory roles in BRCA. Further analysis demonstrated that lactylation-related genes are closely linked to immune regulation in BRCA, indicating a possible crosstalk between metabolic modification and tumor immunity. Additionally, we found that lactylation significantly influences gene expression patterns and immune infiltration in BRCA. Importantly, lactic acid ions were shown to upregulate lactylation levels in BRCA cells, underscoring the functional impact of metabolic signals on post-translational modifications in tumorigenesis. Our findings indicate a potential mechanism wherein lactylation affects BRCA progression via lactic acid-driven regulation of the immune microenvironment; they also highlight the possible involvement of S100A4 in this process and offer new insights that could contribute to the diagnosis and treatment of BRCA. Full article

Ischemic stroke and its chronic cerebrovascular complications represent significant public health challenges with considerable societal impact. Consequently, healthcare initiatives worldwide are placing greater emphasis on preventing and lowering cerebrovascular risk. Alongside medical therapies, it is now widely recognized that modifying risk factors—many of which are controllable—can substantially reduce the probability of acute cerebrovascular events, up to 33% according to data from trials such as PREDIMED. This modification is often achievable through dietary interventions such as the Mediterranean diet (MedDiet), which positively influences vascular health. The MedDiet, long established as the traditional eating pattern in Mediterranean regions, is an effective means of counteracting factors that jeopardize vascular health and elevate the risk of acute events. To date, there are no narrative reviews that have addressed the impact of the Mediterranean diet on cerebrovascular risk and the consequences of acute cerebrovascular events in terms of disability and neurological functional recovery, focusing on how individual components of the MedDiet, at the molecular level, contribute to the prevention of acute vascular episodes, paving the way for new approaches in the treatment of cerebrovascular patients. Full article

Background/Objectives: The growth status of children and adolescents with discrepancies of maxilla/mandible during the growing period should be closely monitored to determine the appropriate time to begin growth modification in orthodontic treatment. Skeletal growth assessment using the cervical vertebral maturation (CVM) method is widely used and accepted; however, monitoring requires additional doses of radiation. Thus, this study aimed to evaluate tooth development from routine panoramic radiographs to represent the growth status rather than using the CVM method. Methods: Three hundred and sixty pairs of lateral cephalometric and panoramic radiographs (180 males and 180 females) aged 7–15 years were included. Teeth 31–37 of each panoramic radiograph were identified as A to H according to the Demirjian method, and the stages of skeletal growth were indicated from lateral cephalometric radiographs using the CVM method. The relationship between tooth development and CVM was analyzed using Spearman’s rank correlation coefficients. Results: The correlation coefficients ranged from 0.487 to 0.768 for male subjects and from 0.503 to 0.759 for female subjects. Tooth 33 was found to have the highest correlation in males (r = 0.768) and tooth 37 was revealed to have the highest correlation in females (r = 0.759) (p < 0.01). Conclusions: Teeth 33–37 showed correlation coefficients close to 0.7 or above, which indicated a moderate-to-high correlation between tooth development and CVM. Thus, the pattern of tooth development from teeth 33–37 may serve as a supplementary indicator of skeletal maturation timing which was similar in both males and females, and may serve as a supplementary indicator of skeletal maturation timing. Full article

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

Background: Unhoused individuals face disproportionately high rates of preventable chronic disease due to fragmented access to care and prolonged exposure to environmental stressors. Street medicine programs offer a mobile, low-barrier model to assess and address these unmet needs. Despite well-documented disparities, no publications in the current literature provide numerically specific screening recommendation guidelines tailored to unhoused populations. This study fills that gap using clinical data from Street Medicine Phoenix (SMP), a mobile healthcare initiative serving urban Arizona. Methods: We retrospectively reviewed 1322 clinical encounters recorded by SMP between August 2023 and October 2024. Diagnoses and treatments were manually categorized. Blood pressure (BP) and glucose values were analyzed using descriptive statistics and compared against national norms (CDC 50th percentile and ADA guidelines). Kruskal–Wallis and Dunn’s tests assessed age-based differences, while chi-square and Mann–Whitney U tests examined glucose patterns. Results: The mean patient age was 51.4 years; 34.5% identified as female. Cardiovascular issues (39.4%) and routine screenings (39.6%) were most frequently documented. Systolic and diastolic BP values were significantly elevated across all age groups except those 60+, with even the 18–39 group showing median systolic BP above CDC norms (124.0 mmHg). Among 60 patients with fasting glucose data, 41.4% met ADA criteria for diabetes, and 10.7% of those without a known diagnosis had diabetic-range values. Conclusions: Our findings suggest that cardiometabolic disease may emerge earlier and more aggressively among unhoused individuals than in the general U.S. population, reflecting patterns of accelerated biological aging. The elevation of cohort-based BP percentiles suggests that current national benchmarks may underrepresent clinical risk in this group. We propose initiating blood pressure screening at age 18 and fasting glucose screening by age 35 in unhoused individuals—adaptations of existing USPSTF recommendations based on cohort-specific trends. These screening thresholds can be feasibly implemented in street medicine settings to promote earlier detection and improve long-term health outcomes. Full article

Additive manufacturing (AM) represents a quite interesting technology for manufacturing components of nuclear reactors. This work investigated the microstructural stability of 316 L steel fabricated via Laser Powder Bed Fusion (L-PBF) from room temperature to 650 °C. Despite the reduced susceptibility of the material to sensitization owing to its low carbon content, temperature variations may induce deleterious effects in nuclear safety-critical components. In as-printed condition, the microstructure is not stable and undergoes significant changes induced by thermal cycling up to 650 °C in Mechanical Spectroscopy (MS) tests: the typical melt-pool pattern disappears, a population of equiaxed grains substitutes the original ones elongated in the build direction, the average size of the cells forming a finer sub-structure inside the grains increases, texture changes, and the excess of vacancies induced by the rapid cooling is recovered. Although the current literature reports that the microstructure is stable up to 500 °C, MS results indicate that the aforesaid irreversible phenomena start at a lower temperature (~230 °C). The present results suggest that the microstructure of the printed material must be stabilized through suitable heat treatments before its application in structural components for nuclear reactors. Full article

Background: Depression is highly prevalent among individuals with chronic pain and strongly impacts pain intensity, psychological functioning, and health-related quality of life. Self-efficacy has emerged as a potentially modifiable resilience factor within this interplay, yet large-scale real-world evidence integrating self-efficacy into multidimensional pain–depression models remains limited. Methods: This cross-sectional registry-based analysis evaluated standardized patient-reported measures from chronic pain patients enrolled in the German Pain e-Registry. All variables were directionally harmonized and transformed into standardized deviation scores (hSDSs) relative to patients without depression. Group-level hSDS profiles for five DASS-21 depression severity strata (none, mild, moderate, severe, extreme) were compared across pain intensity, disability, psychological well-being, affective pain processing, quality of life, neuropathic pain features, and pain-related self-efficacy (PSEQ). Correlations and exploratory principal component analysis (PCA) were used to assess multivariate structure. PCA-informed path models were estimated to evaluate directional relationships between pain, function, depression, and self-efficacy. All directional and mediation models represent exploratory, theory-informed statistical frameworks and do not imply causal or mechanistic relationships. Results: Across all domains, hSDS values increased monotonically with depression severity, while self-efficacy showed the strongest inverse gradient. Exploratory PCA revealed a dominant severity component explaining most variance and a secondary affective–self-efficacy axis, supporting the conceptual separation between functional–physical and psychological–affective symptom clusters. In the bottom-up path model (pain → function → self-efficacy → depression), self-efficacy showed the largest indirect statistical contribution within the proposed path models, and the model explained 55% of depression variance (R² = 0.55). In the top-down model (depression → affective pain → self-efficacy → pain), 45% of pain intensity variance was explained (R² = 0.45), again with self-efficacy as a central mediating construct. Associations remained robust after adjustment for age, sex, and BMI, as well as during sensitivity analyses. Conclusions: This large real-world cohort demonstrates a highly coherent pattern of associations across biopsychosocial domains and highlights pain-related self-efficacy as a central statistical construct linking pain, functional impairment, and depressive symptom burden within the applied exploratory models. The findings suggest that self-efficacy occupies a key position in the interplay between pain and mood, and that pharmacological and non-pharmacological treatments traditionally used in chronic pain management may be associated with changes in this construct. Importantly, all directional and mediation analyses are exploratory and do not imply causal or mechanistic relationships. Therapeutic strategies aimed at enhancing self-efficacy may therefore represent promising targets for future research within multimodal pain management frameworks. Full article

This study systematically compared the induction and resuscitation characteristics of the viable but non-culturable (VBNC) state in Klebsiella pneumoniae FY170-1 following sublethal exposure to sodium hypochlorite (NaClO) or glutaraldehyde (GA). Treatment with 30 mg/L NaClO or 60 mg/L GA for 60 min reduced culturability to below the detection limit (<1 CFU/mL). However, CTC staining showed that 50.80% and 63.44% of cells, respectively, retained respiratory activity, while SYTO 9/PI staining indicated that membrane integrity was largely preserved, consistent with induction of the VBNC state. Scanning electron microscopy revealed distinct morphological alterations in the two groups. NaClO-induced VBNC cells showed surface depressions and wrinkling, consistent with oxidative damage, whereas GA-induced cells exhibited filamentous and net-like surface structures, consistent with aldehyde-mediated cross-linking. Among the tested additives, sodium succinate showed the strongest resuscitation-promoting effect under the experimental conditions, with OD600 increasing after approximately 2 h of incubation. Post-resuscitation analysis further revealed marked differences between the two VBNC states. In resuscitated NaClO-induced VBNC cells, ATP partially recovered, but reactive oxygen species remained elevated and catalase activity showed little recovery. In contrast, resuscitated GA-induced VBNC cells exhibited lower ATP recovery but more rapid normalization of ROS and better recovery of oxidative stress-related parameters. Total protein analysis and SDS-PAGE further supported distinct patterns of protein-level alteration between the two treatments. Overall, these findings suggest that NaClO and GA induce phenotypically distinct VBNC states in K. pneumoniae, with different recovery behaviors and stress response profiles. Sodium succinate was identified as the most effective recovery-promoting additive under the tested conditions. These results highlight the risk of underestimating bacterial survival when culturability is used as the sole indicator of disinfection efficacy and support the need for more comprehensive viability assessment. Full article

Background: Conventional Herbst appliances are effective for the correction of skeletal Class II malocclusion, but they are frequently associated with dentoalveolar side effects, particularly lower incisor proclination. Skeletal anchorage systems may improve orthopedic outcomes; however, submucosal miniplates require invasive surgical procedures that may reduce patient acceptance. This pilot clinical study evaluated the feasibility, safety, and skeletal effects of a minimally invasive digitally guided protocol using supragingival miniplates for bone-supported Herbst therapy in late adolescents. Methods: Eleven late-adolescent patients (14–17 years; cervical vertebral maturation stages CS4–CS5) with skeletal Class II malocclusion due to mandibular retrusion were prospectively treated using a bone-supported Herbst appliance anchored to digitally planned supragingival stainless-steel miniplates fixed with bicortical miniscrews. Miniscrew placement was planned by merging CBCT and intraoral scan data and performed using 3D-printed surgical guides. Cephalometric variables, including SNA, SNB, Wits appraisal, mandibular plane angle, and incisor inclinations, were assessed before treatment and after a 10-month Herbst phase. Mandibular advancement was additionally explored using a complementary linear measurement (SeMndb-line). Results: All patients completed treatment without anchorage loss, appliance failure, or surgical complications. Significant skeletal improvements were observed, including an increase in SNB (+3.36°, p < 0.001) and a reduction in Wits appraisal (−2.65 mm, p < 0.001). The SeMndb-line increased by +3.49 mm (p < 0.001), supporting effective mandibular advancement. Lower incisor inclination remained stable (Δ = −0.18°, p = 0.909), indicating effective dentoalveolar control. No clinically relevant changes in vertical skeletal pattern were observed. Conclusions: Digitally guided supragingival miniplates for bone-supported Herbst therapy appear to be a feasible and minimally invasive approach for the treatment of skeletal Class II malocclusion in late adolescents. This protocol achieved clinically meaningful mandibular advancement while minimizing dentoalveolar side effects. Given the pilot design, small sample size, and lack of a control group, further controlled studies with larger samples and long-term follow-up are required. Full article

With the continuous expansion of Pleurotus ostreatus cultivation, substantial quantities of post-harvest spent mushroom substrate (SMS) are generated. Improper disposal of this organic waste poses potential threats to soil health, including contamination and ecological imbalance. Consequently, a rigorous safety assessment is indispensable to support the sustainable and agronomically viable utilization of SMS as a soil amendment. In this study, P. ostreatus SMS was subjected to sterilized and non-sterilized treatments, and a controlled co-culture system integrating P. ostreatus mycelium with wheat was established. This system facilitated a comprehensive evaluation of residual mycelium impacts on wheat growth and development at phenotypic, cytological, and non-targeted metabolomics (LC-MS) levels. Results demonstrated that direct field application of non-sterilized SMS severely compromised wheat performance, inducing root necrosis and significantly reducing grain set. Comparative experiments confirmed that non-sterilized SMS—not its sterilized counterpart—exerted pronounced phytotoxic effects, markedly inhibiting seedling growth and triggering wilting symptoms. To elucidate the temporal dynamics of mycelial interaction, wheat seedlings were inoculated with viable P. ostreatus mycelium and co-cultured for seven days. Under these conditions, the mean root length of the control group (10.82 cm) was approximately threefold that of the treatment group. Histopathological analysis revealed a progressive infection pattern initiating at the root apex and extending basipetally; prolonged exposure ultimately caused complete root system collapse. Scanning electron microscopy further showed extensive mycelial colonization on infected root surfaces, accompanied by characteristic cellular damage—including severe cell wall wrinkling and widespread cell death. LC-MS profiling identified 1867 annotated compounds. Comparative analysis revealed significant dysregulation of secondary metabolism, with 495 metabolites upregulated and 419 metabolites downregulated in the treatment group. Collectively, these findings provide robust evidence that unprocessed P. ostreatus SMS poses tangible agronomic risks upon direct soil application. This study establishes a critical scientific foundation for developing safe, evidence-based protocols for the valorization and integrated management of SMS. Full article

Digital economy and agricultural technological innovation are key drivers of agricultural economic resilience and sustainable development. However, existing research has yet to clarify how they jointly affect agricultural economic resilience, particularly through potential nonlinear patterns and spatial spillover effects. Using panel data from 30 Chinese provinces, this study measures digital economy development and agricultural economic resilience via the entropy weight method. It systematically examines the direct impact, transmission mechanisms, threshold effects, and spatial spillover effects using two-way fixed effects, mediation, threshold regression, and spatial Durbin models. The findings are as follows. First, the digital economy significantly improves agricultural economic resilience, a result robust to various tests and endogeneity treatments. Second, agricultural technological innovation plays a partial mediating role, accounting for 19.37% of the total effect. Third, the resilience-enhancing effect of agricultural technological innovation exhibits a double-threshold pattern: its positive impact gradually strengthens as the digital economy develops to a higher level. Fourth, the digital economy generates a positive spatial spillover effect on agricultural economic resilience. Fifth, although the digital economy and agricultural technological innovation show synergistic development, their coupling coordination degree remains relatively low, indicating substantial untapped potential for synergy. From a sustainable development perspective, this study reveals the mechanisms through which the digital economy and agricultural technological innovation enhance agricultural economic resilience, providing empirical evidence and policy insights for strengthening agricultural risk resistance and achieving agricultural sustainability via digital transformation and technological progress. Full article

Background: Esophageal cancer (EC) is an aggressive malignancy with low survival rates, making accurate prognosis critical for guiding treatment decisions. Traditional prognostic methods, while essential, often lack precision and comprehensive data insights. This study aims to apply machine learning (ML) approaches to investigate EC prognosis by identifying key factors associated with 5-year survival. Methods: Multiple ML algorithms—Random Forest (RF), Artificial Neural Networks (ANN), K-Nearest Neighbors (KNN), AdaBoost, and Naïve Bayes—were applied to a dataset from the SEER database. Model development included exploratory data analysis, internal validation, and 5-fold cross-validation. Traditional survival analysis methods, such as Cox regression and Kaplan–Meier (KM) analysis, were integrated to further explore relationships between key predictor and outcome variables. Additionally, time-series analysis was conducted to examine survival trends over time and identify influencing factors. Results: RF demonstrated the highest predictive performance among the models tested. Key prognostic factors identified included surgery, summary stage, tumor size, metastasis, AJCC M stage, and age. An exploratory analysis of temporal trends further showed changes in survival outcomes across diagnosis years. Conclusions: The findings highlight the potential of ML approaches to analyze prognostic patterns in EC. Integrating ML models with traditional statistical analyses helped identify key prognostic factors such as surgery, summary stage, and metastasis, while the exploratory temporal analysis provided additional context regarding survival trends over time. While promising, further external validation and addressing time-series challenges are necessary. Overall, this study demonstrates the potential of ML to support the identification of prognostic factors in EC and may contribute to more informed clinical decision-making. Full article

Kidney Injury Molecule-1 (KIM-1), a type I transmembrane glycoprotein, is emerging as a promising biomarker in the landscape of genitourinary malignancies. Initially it was described for its role in renal tubular injury, but it is currently being studied for its expression in various neoplasms, particularly renal cell carcinoma, where it correlates with tumor grade, stage and prognosis. Recent studies have demonstrated its potential usefulness as a non-invasive diagnostic tool through urinary and plasma/serum studies, offering a valuable adjunct to imaging and pathology studies. KIM-1 may also play a role in urothelial cancer, although its specificity and relevance in this context are not clearly established yet. The following review presents our current knowledge on the biology of KIM-1, its expression patterns across various genitourinary tumors and its clinical implications in early detection, prognosis and treatment monitoring. We also explore the limitations and future directions regarding the integration of KIM-1 into precision oncology approaches. Full article

C3H-type zinc finger proteins play essential roles in plant responses to abiotic stresses, as well as in the regulation of growth, development, and signal transduction. Birch (Betula platyphylla Suk.), an ecologically adaptable tree species widely distributed in northern regions, has not yet been systematically characterized for its C3H gene family. In this study, a total of 15 BpC3Hs were identified from a genome-wide analysis of birch. Their physiochemical properties, gene structures, conserved motifs and domains were systematically analyzed. Promoter analysis identified cis-acting elements associated with stress responses, hormone signaling, and developmental regulation. Transcriptome data further showed that most BpC3Hs were responsive to salt, drought, high/low-temperature stresses, and light/dark treatment, and showed differential expression patterns in tension wood and opposite wood. Additionally, they displayed stage-specific expression patterns during male inflorescence development. This study lays a foundation for future functional characterization of the C3H gene family in birch and its application in molecular breeding for stress resistance. Full article