Search Results (254,703)

Background: The management of resected stage III colorectal cancer (CRC) has long been reliant on fluoropyrimidine-based adjuvant chemotherapy. However, the 10–15% of patients with mismatch repair-deficient (dMMR) tumors derive limited benefit from this approach. While immunotherapy has revolutionized the treatment of metastatic dMMR CRC, its role in the early-stage setting is rapidly evolving, creating a paradigm shift. Methods: A systematic literature review was conducted to identify pivotal clinical trials evaluating therapeutic strategies for non-metastatic dMMR CRC. Databases including PubMed/MEDLINE and conference proceedings from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched up to June 2025. The review focused on phase II and III trials reporting on disease-free survival (DFS), pathological complete response (pCR), and safety. Study selection followed PRISMA guidelines. Results: The systematic review identified 14 key studies that were included for narrative synthesis. The evidence base encompassed three areas: (1) Foundational adjuvant chemotherapy trials (e.g., MOSAIC, IDEA); (2) Pivotal metastatic trials (e.g., KEYNOTE-177) validating immunotherapy efficacy in dMMR CRC; and (3) Modern trials in non-metastatic disease. The phase III ATOMIC trial demonstrated that adding atezolizumab to mFOLFOX significantly improved 3-year DFS versus chemotherapy alone (86.4% vs. 76.6%; Hazard Ratio [HR] 0.50, 95% Confidence Interval [CI] 0.34–0.72; p < 0.001). Concurrently, phase II neoadjuvant immunotherapy trials (e.g., NICHE-2) reported remarkable pCR rates of 68% and a 3-year DFS of 100%, with a more favorable safety profile compared to chemoimmunotherapy. Conclusions: The landscape for non-metastatic dMMR CRC is shifting from a chemotherapy-based model to an immunotherapy paradigm. The ATOMIC trial establishes adjuvant chemoimmunotherapy as a new standard, while robust neoadjuvant data suggest a potential future where short-course, chemotherapy-free immunotherapy could become a preferred strategy. Ongoing trials directly comparing these approaches are awaited. Full article

Waterfront wilderness landscapes in mountainous cities, such as Chongqing, play a vital role in sustaining urban biodiversity and human well-being amid steep topography and hydrological variations that create unique habitats. However, public recognition of their ecological values and potential ecological–aesthetic conflicts remain underexplored. This study investigated biodiversity features and public preferences in Chongqing’s central urban waterfront wilderness through field surveys of 218 quadrats for biodiversity assessment (e.g., Shannon–Wiener and Simpson indices, cluster analysis identifying 12 typical communities) and two questionnaire surveys (N = 260 and 306) evaluating spatial features and plant attributes, with correlation and regression analyses examining relationships between ecological indices and preference scores. Results recorded 116 plant species from 41 families, dominated by herbaceous plants (77.6%), with herbaceous, shrub-herbaceous, and tree-herbaceous communities prevalent. No significant correlations existed between objective diversity indices and preference scores; instead, structure (β = 0.444, p < 0.001) and color (β = 0.447, p < 0.001) drove preferences (explaining 96.7% variance), favoring accessible mid-successional shrub-herbaceous structures over dense, low-diversity evergreen types. These findings reveal ecological–aesthetic conflicts in mountainous settings where aesthetic dominance limits biodiversity recognition. Implications include user-centered zoning: restrict access in low-preference steep areas with buffers for conservation, while enhancing high-preference flat zones via selective pruning and native colorful species introduction, supplemented by educational signage. This research provides a mountainous city archetype, enriching global urban wilderness studies and informing sustainable management in rapidly urbanizing regions. Full article

Coronaviruses include various strains that reside in natural animal reservoirs, with zoonotic transmission posing risks to both domesticated animals and human health. Recent efforts to address coronavirus infections have focused on developing inhibitors targeting the main protease (M^pro), some of which exhibit potential broad-spectrum efficacy. This study presents crystal structures of four clinically relevant inhibitors—GC376, PF-00835231, nirmatrelvir, and ibuzatrelvir—bound to M^pro from the feline coronavirus strain FECV-UU23. Structural analysis identified distinct FECV-specific features within the active site where these inhibitors bind and revealed S4 loop as a susceptible structural region essential for the enhanced binding of inhibitors in UU23 M^pro. We therefore propose to incorporate sterically constrained, functionally tailored heterocyclic moieties at the P3 site of known inhibitors which can optimally engage Q187, P188, and S189 residues of the S4 loop. The findings presented enhance understanding of inhibitor specificity and reinforce the promise of these inhibitor scaffolds for developing antivirals against feline coronavirus strains, with possible applications in broad-spectrum coronavirus therapy. Full article

The community structure and ecological niche of benthic macroinvertebrates in the upper Yarlung Zangbo River were analyzed in April and September 2023. The benthic macroinvertebrate community largely comprises aquatic insects, with Diptera accounting for approximately half. Commonly observed were Chironomus anthracinus, Tadamus sp.1, Piscicola geometra, species of the family Corixidae spp. and the genera Monodiamesa sp., Apatania sp., and Valvata sp. in April, and Orthocladius sp.1, Gammarus sp., Isoperla sp., Nais sp., Baetis sp., Monodiamesa sp., Tanytarsus sp., Ilisia sp., Nebrioporus sp. and species of the family Corixidae spp. in September. The α-diversity analysis showed significant seasonal differences (p < 0.05) in Shannon–Wiener diversity variable and Margalef richness variable. The Pielou evenness variable did not show seasonal effects (p > 0.05). The β-diversity April/September differences can be attributed to species turnover rather than to nestedness, indicating that benthic macroinvertebrate diversity protection strategies are critical to all areas of the river. In April, Chironomus anthracinus exhibited the broadest ecological niche, and, in September, the widest niche was observed in Gammarus sp. The largest observed ecological niche overlap values were between Chironomus anthracinus and Valvata sp. in April and Gammarus sp. and Ilisia sp. in September, indicating interspecific competition. The study clarifies the diversity status of benthic macroinvertebrates in the upper Yarlung Zangbo River and provides data for related research to facilitate formulation of biodiversity conservation policies. Full article

Background: Metabolically Associated Fatty Liver Disease (MAFLD) is a prevalent liver disorder closely tied to metabolic dysfunction, insulin resistance, and chronic low-grade inflammation. Vascular Endothelial Growth Factor (VEGF) may have a dual interesting role in MAFLD pathophysiology—supporting vascular repair in early stages, but potentially contributing to fibrosis in later stages. In this study, berberine (BBR), a plant-derived isoquinoline alkaloid, exhibits multiple beneficial properties, including anti-inflammatory, antioxidant, and endothelial-protective effects, on the study group, perhaps by influencing VEGF concentration. Objective: This study aimed to investigate the effectiveness of BBR in addressing vascular function parameters linked to MAFLD, particularly its impact on serum VEGF levels and arterial stiffness. Methods: This randomized, double-blind, placebo-controlled clinical trial enrolled seventy individuals with MAFLD who were overweight or obese. Participants were randomly assigned in a 1:1 ratio to receive either BBR (1500 mg/day) or a placebo orally for 12 weeks. The following parameters were assessed pre- and post-intervention: VEGF, brachial SBP (Systolic Blood Pressure)/DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), AIx (Augmentation Index), AP (Aortic Pressure), number of waveforms, Pulse Pressure (PP), PWV (Pulse Wave Velocity), and PWA-SP/PWA-DP (Pulse Wave Analysis Systolic/Diastolic Pressure). The results for the metabolic parameters—FLI (Fatty Liver Index)—and anthropometric parameters—BMI (Body Mass Index), fat mass corp—and laboratory parameters, among them, hsCRP (high-sensitivity C-reactive protein), were published by us earlier. Results: In the BBR-treated cohort, VEGF concentrations demonstrated a statistically significant increase following the intervention, rising from a baseline mean of 456.23 ± 307.61 pg/mL to 561.22 ± 389.77 pg/mL (p < 0.0001). In the BBR group, a significant reduction in PWA-SP was observed after 12 weeks of supplementation (134.85 ± 16.26 vs. 124.46 ± 13.47 mmHg, p < 0.0001). No statistically significant differences were observed in the parameters determining arterial stiffness in the BBR and placebo groups. In the BBR group, delta VEGF correlated negatively with delta FLI; no such associations were observed in the placebo group. Changes in PWV were consistent and significantly correlated with changes in brachial SBP/DBP, PWA-SP, PWA-DP, and MAP. No serious adverse events were reported, and BBR was well tolerated. Conclusions: BBR appears to be a safe and promising adjunct in MAFLD therapy, potentially exerting reparative effects through VEGF modulation and vascular support. Further research is warranted to confirm its long-term impact and elucidate underlying protective mechanisms. Full article

Corticosterone (CORT) is the primary avian stress hormone and regulates key physiological processes, but chronically elevated levels can be detrimental. This study simulated chronic stress by exogenously increasing CORT to assess effects on gait score, bone morphometry, immune indicators, and fluctuating asymmetry (FA) in broiler chickens. A total of 60 one-day-old male Ross 308 broiler chickens were allocated to six treatment groups (T0–T5; n = 10 per group). T0 received a placebo and served as the control group, while T1–T5 were gavaged daily with increasing corticosterone doses (1–5 mg/kg body weight). Treatments were administered from day 1 to day 42. CORT did not affect gait score on day 11 (p = 0.232) or day 42 (p = 0.112), but gait score was significantly correlated with body weight (day 11: p < 0.001; day 42: p = 0.004). Elevated CORT reduced bursa diameter (p < 0.001) and increased bursa follicle scores (p < 0.001), while heterophil-to-lymphocyte ratios remained unaffected (p = 0.349). Carcass and bone dimensions decreased consistently with higher doses (p < 0.001), and body weight correlated positively with all bone traits (p < 0.001). Length-to-width ratios increased with CORT dose (p < 0.001). Composite carcass FA showed dose-related variation in carcass asymmetry, with highest in T4, intermediate in T2, T3, and T5, and lowest in T0–T1 (p = 0.026). Trait-specific FA effects were detected for metatarsus length (p = 0.005) and wattle (p = 0.018), while bone FA remained unaffected (p = 0.272). Overall, exogenously increasing CORT impaired growth, suppressed immune function, and increased fluctuating asymmetry, indicating reduced developmental stability. Full article

The heterogeneous Fenton-like catalysts TiO₂/Fe₃O₄ were fabricated using maize straw as template (MST-TiO₂/Fe₃O₄) by calcination followed by the hydrothermal method. The characterization showed that higher Fe₃O₄ particle dispersion, closer interaction between TiO₂ and Fe₃O₄, stronger electron transfer ability, and lower leaching of Fe ions of MST-TiO₂/Fe₃O₄ catalyst resulted in higher catalytic activity towards the degradation of tetracycline (TC) compared to pure Fe₃O₄. The best conditions for TC degradation were initial pH = 6.74, 11.52 mmol/L of H₂O₂, 0.38 g/L of MST-TiO₂/Fe₃O₄, and a reaction time of 56.63 min according to the response surface methodology (RSM) result based on the Box–Behnken design (BBD). The quadratic model was well-fitted to the experimental data with R2 (0.9843) and adj-R2 (0.9660) by the analysis of variance (ANOVA). Under the optimum reaction conditions, a maximum removal rate of 98.67% was achieved. The findings of the present study revealed that heterogeneous UV–Fenton process catalyzed by MST-TiO₂/Fe₃O₄ was a suitable way for the degradation of TC from aqueous environment. Full article

The purpose of this study was to examine the convergent validity and reliability of the session rating of perceived exertion (sRPE) in complete CrossFit^® sessions by comparing it with a weighted RPE measure (RPE_W) obtained from different session phases. Twenty-four recreational practitioners (13 men and 11 women; age 34.5 ± 8.3 years; height 172.9 ± 11.2 cm; body mass 76.2 ± 15.2 kg) completed 28 standardized sessions (~60 min) consisting of warm-up, strength/skill, Workout of the Day (WOD), and cooldown phases. Phase-specific RPE values were collected after each session component, and a global sRPE was recorded ~30 min post-session. Results showed that RPE_W (5.8 ± 1.5) was significantly lower than sRPE (6.8 ± 1.4; p < 0.001, d = 0.69), resulting in a higher training load estimated by sRPE (+15.5%). Bland–Altman analysis revealed a positive bias and wide limits of agreement, while relative reliability was moderate to good (ICC = 0.73–0.77). Multiple regression analysis indicated that WOD RPE explained 70% of the variance in sRPE (R² = 0.70, p < 0.001), confirming its role as the primary perceptual determinant. In conclusion, sRPE represents a valid, simple, and cost-effective tool for monitoring internal load in CrossFit^®. However, it tends to overestimate RPE_W and shows substantial interindividual variability, limiting its precision for individualized monitoring. Coaches and practitioners should therefore interpret sRPE values with caution, especially considering the strong influence of the final session phase. Full article

To address the limitations of traditional groundwater quality assessment and prediction methods, this study integrates game theory and machine learning to investigate the drinking quality of groundwater in the southwestern Qinghai–Tibet Plateau. The results showed that the groundwater in the study area is generally weakly alkaline (mean pH: 8.08) and dominated by freshwater (mean TDS: 302.58 mg/L), with hardness levels mostly ranging from soft to medium. Major cations follow the concentration order: Ca²⁺ > Na⁺ > Mg²⁺ > K⁺; anions are in the sequence of HCO₃⁻ > SO₄²⁻ > Cl⁻. The hydrochemical type is mainly Ca-HCO₃. A few samples exceed the limit values specified in the Groundwater Quality Standard. Through multivariate statistical analysis, ion ratio analysis, and saturation index calculations, water-rock interaction is identified as the primary factor influencing groundwater chemistry. It consists of carbonate dissolution and silicate weathering, accompanied by cation exchange. The water quality index improved based on game theory, integrated subjective weights (from analytic hierarchy process) and objective weights (from entropy-weighted method), shows that the overall groundwater quality in the study area is good: 95.97% of the samples are high-quality water (WQI ≤ 50), more than 99% of the samples have a WQI < 150, which is suitable as drinking water sources; only 0.81% of the samples are of extremely poor quality, presumably related to local pollution. Linear regression achieved the best performance (R² = 0.99, RMSE≈0.00) with strong stability, followed by support vector machines (test R² = 0.98), while the extreme gradient boosting model showed overfitting. This study provides a scientific basis for groundwater management in river basins. Full article

Purpose: Post-stroke spasticity (PSS) substantially affects functional recovery and quality of life in stroke survivors. However, the current clinical assessment methods exhibit certain subjectivity and equipment limitations. Human pose estimation presents a promising alternative for objective and user-friendly spasticity assessment. Materials and Methods: A total of 20 stroke survivors with PSS underwent pendulum tests with smartphones from multiple angles to quantitatively assess knee muscle spasticity. Pose estimation was conducted using the AlphaPose and STCFormer algorithms, with simultaneous measurements using an electronic goniometer as a reference. Three pendulum parameters were evaluated: normalized relaxation index (P1), first maximum of oscillation (P2), and relaxation index at half swing (P3). Bland–Altman analyses were used to analyze the consistency between pose estimation and electronic goniometer measurements. Intraclass correlation coefficient (ICC) and Spearman’s correlation analyses were conducted to evaluate agreement and reliability between electronic goniometer measurements and clinical evaluation. Results: P1 demonstrated the highest consistency between pose estimation and electronic goniometer measurements, with the highest ICC values (0.931 for AlphaPose and 0.911–0.94 for STCFormer). P1 and P3 differentiated between affected and unaffected limbs (p < 0.01) and demonstrated significant negative correlations with Modified Ashworth Scale scores, particularly for knee extensors (P1: ρ = −0.747 for AlphaPose and −0.781 for STCFormer; p < 0.01). P2 demonstrated low consistency and differential performance across all analyses. Conclusions: Video-based human pose estimation, particularly using P1, offers a reliable and objective method for evaluating PSS, demonstrating strong agreement with electronic goniometer measurements. This approach is clinically feasible for evaluating spasticity. Full article

Different sources of nanomaterials on the adsorption of selenium (Se) in aqueous solutions were evaluated, including nanoscale municipal drinking water treatment residues (nWTRs) and agricultural waste pomegranate peels (PNPs), in comparison with commercial carbon nanoparticles (CNPs). Different Se(IV) treatments and application doses of each nanomaterial were evaluated. The Se adsorption kinetics were determined at different time intervals. The results showed that the Se sorption capacity of different nanomaterials and their mixtures varied significantly (p < 0.05). Se concentration, the application dosage of nanoparticles, and the interaction time of Se and nanoparticles in Se solutions significantly affect the efficiency of Se adsorption at pH 3.51. The sorption isotherm of Se varied amongst different nanomaterials. Se adsorption on CNPs, nWTRs-CNPs, nWTRs, PNPs-CNPs, nWTRs-PNPs, and PNPs at the 800 mg Se/L treatment was 79.93, 77.48, 76.00, 72.97, 70.49, and 68.16 mg Se/g sorbent, respectively. The H-type isotherm became dominant, indicating intensive interaction between Se and nanoparticles. With the Se treatment of 50 mg/L, the Se removal efficiency of CNPs, nWTRs-CNPs, nWTRs, PNPs-CNPs, nWTRs-PNPs, and PNPs was 100, 96, 93, 87, 85, and 80%, respectively, but became 100, 97, 95, 91, 88, and 85%, respectively, at a higher Se concentration of 800 mg/L. Increasing the application dosage of nanomaterials resulted in a significant increase in Se mass sorbed by the nanoparticles. Se adsorption was best predicted by the Langmuir isotherm model. The desorption rate of the Se mass sorbed by nanoparticles at 800 mg Se/L was 0.4% of the total Se adsorbed by CNPs, with 0.88% by nWTRs-CNPs and 1.69% by PNPs-CNPs, while higher Se desorption rates of 4.2, 7.3, and 17.6% were observed with nWTRs, nWTRs-PNPs, and PNPs, respectively. This study demonstrates that nanoscale municipal and agricultural solid waste materials can be effective in removing Se from contaminated water. Full article

Aniline aerofloat (AAF) is a typical refractory organic regent residual in mineral processing wastewater (MPW). Microbial fuel cells (MFCs) have been proven highly effective in degrading organic contaminants and resource recovering in wastewater treatment processes. However, AAF biodegradation potential and the related mechanisms in MFC systems remain poorly understood. In this study, the degradation of AAF, electricity generation performance and microbial mechanisms in the single-chamber MFC (sMFC) were confirmed. Affecting factors including AAF concentration, operation resistor, and pH were analyzed. The results indicated that under initial sodium acetate/AAF concentration of 300/100 mg/L, pH 7.0 and an operation resistor of 200 Ω, the AAF removal efficiency achieved 72.7 ± 1.6% with an output voltage of approximately 232 mV. The existence of AAF increased the relative abundance of electroactive bacteria, especially Comamonas and Geobacter. Functional prediction analysis showed that carbohydrate metabolism pathways was the dominant process. The relative abundance of N-respiration and S-respiration functional groups significantly increased, thereby improving COD and AAF removal. This study demonstrated that the MFC anode was beneficial to AAF degradation and provided an alternative route for the biodegradation of organic mineral processing reagents. To our knowledge, this is the first study evaluating AAF biodegradation performance in the MFC system. Full article

Climate change poses increasing challenges to Reclamation Consortia, which must ensure equitable and sustainable water distribution under conditions of growing scarcity. This study evaluates supplemental irrigation management strategies adopted by three Reclamation Consortia in the Venetian Plain (Northeast Italy): Piave, Veneto Orientale and Acque Risorgive. The Consortia were selected based on their territorial and structural characteristics, as well as their different approach to managing water resources. This study fills a critical gap by integrating FAO AquaCrop-based estimates of irrigation needs for the 2022 and 2023 irrigation seasons in maize, grapevine and radicchio with an institutional analysis of Reclamation Consortia, offering an innovative framework that links technical and governance aspects of sustainable water management. Results reveal considerable variability among Consortia in terms of organizational structure, technological adoption, and resilience to drought. The 2022 season, characterized by extreme drought, required substantially higher irrigation volumes across all crops and soil types with significant differences compared to 2023 (p < 0.001), particularly for maize and grapevine (73% more irrigation water in maize). Well-drained soils and sprinkler irrigated crops showed the highest water demand (+45 mm compared to drip irrigation, p = 0.058), while loamy soils and drip systems proved more efficient. The Piave Consortium demonstrated the most advanced management system, supported by digital tools and structured rotation schedules. Nevertheless, structural factors, such as geographic location and infrastructure capacity, play a critical role in shaping resilience, leading to higher vulnerability in Consortia like Veneto Orientale and robustness in Acque Risorgive during drought conditions (i.e., 2022). Overall, the findings highlight the need to strengthen the main pillars of adaptation in irrigated agriculture, i.e., technology (decision support systems), governance (inter-Consortium coordination), and infrastructure (storage facilities), to promote flexible irrigation planning, enhance adaptive capacity, and ensure long-term sustainability under changing climatic conditions. These strategies also contribute directly to the achievement of Sustainable Development Goals 2, 6, and 13 (Zero Hunger, Clean Water and Sanitation, and Climate Action) by improving water use efficiency, securing crop production, and enhancing resilience to climate change. Full article

Background: Very few case reports have explored a potential link between ankylosing spondylitis (AS), an autoimmune disorder, and amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative condition. We aimed to investigate whether genetic liability to AS causally influences the risk of ALS, and vice versa, using a bidirectional two-sample Mendelian randomization (MR) framework. Methods: We performed a two-sample MR study to evaluate the bidirectional causal relationship between genetic liability to ankylosing spondylitis and ALS risk. We used 6 valid single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data (AS: 1462 cases and 164,682 controls; ALS: 27,205 cases and 110,881 controls). We used the inverse-variance weighted (IVW) approach as the primary statistical method for causal estimation, with sensitivity analyses (including MR-Egger, weighted median, weighted mode, Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO), leave-one-out, and single SNP analysis) to assess pleiotropy and heterogeneity. Results: There was no evidence of a causal association between genetic predispositions to ankylosing spondylitis (AS) and amyotrophic lateral sclerosis (ALS) (IVW OR = 1.01; 95% CI: 0.99–1.02; p = 0.10). The results from the weighted median, weighted mode, MR-Egger, and simple mode methods were consistent and nonsignificant. In the reverse analysis, genetic liability to ALS showed no causal effect on AS (IVW OR = 0.88; 95% CI: 0.70–1.12; p = 0.33), with similar null findings across all sensitivity methods. Conclusions: Overall, our bidirectional two-sample MR analyses provided no evidence supporting a causal relationship between AS and ALS. Full article

This paper presents an optimized control strategy based on a Doubly Fed Induction Generator (DFIG) and Gravity Energy Storage System (GESS) for AC voltage support in unbalanced grid conditions. The presented control aims to achieve precise rotational speed control, voltage stabilization, and harmonic component suppression. The optimization strategy responds to voltage and frequency fluctuations in an unbalanced grid. Based on Grid-Forming (GFM) control, it adjusts the DFIG’s operating state in real time. This ensures stable voltage support and mitigates harmonic distortion caused by the unbalanced grid. Simulation results, under a weak grid (SCR = 3) and unbalanced (0.9 p.u. voltage sag) conditions, validate the strategy, which reduces rotor current THD from 12.57% to 1.71% and maintains precise speed tracking during a 0.8 p.u. to 0.7 p.u. load change. The results demonstrate that the presented control method effectively improves grid power quality. It also enhances system stability and reliability. This approach provides strong support for integrating renewable energy into unbalanced grids. Full article