Search Results (11,299)

In pancreatic cancer, cancer stem-like cells (CSCs) contribute to tumor initiation, reduced drug sensitivity, and recurrence. Limited strategies are currently available to target this cell population. Here we used a proteasome-low CSC enrichment system to identify microRNAs that negatively regulate CSC-like properties. From PANC-1 cells expressing a ZsGreen–ODC degron reporter, a proteasome-low population was isolated through sequential fluorescence-activated cell sorting of ZsGreen-positive cells. Molecular and functional analyses confirmed the CSC-like phenotype of this cell population. Integrated in silico analysis was used to select 31 microRNAs predicted to target CSC-related molecules, which were then evaluated by in vitro viability-based screening to identify candidates that selectively suppressed the viability of CSC-like cells, relative to non-CSCs. Moreover, comprehensive miRNA expression profiling revealed that miR-136-5p was downregulated in the CSC-like population and was therefore selected for further analysis. Mechanistically, miR-136-5p directly targets the 3′ untranslated region of DCLK1 and reduces its expression, with a greater reduction in the short isoform. Finally, in a CSC-derived xenograft mouse model, systemic delivery of miR-136-5p using super carbonate apatite nanoparticles significantly suppressed tumor growth. Taken together, these findings suggest that miR-136-5p restoration may provide a therapeutic approach for targeting CSC-driven tumor growth in pancreatic cancer. Full article

Aluminum (Al) toxicity constrains plant performance in acidic volcanic soils, yet nitrogen (N) fertilization may influence Al availability and plant responses. This study evaluated the effects of N source and rate under contrasting soil liming conditions on vegetative growth, mineral nutrition, and physiological performance of non-bearing northern highbush blueberry (Vaccinium corymbosum L. cv. Blue Ribbon^®) plants. A split–split-plot experiment was conducted in southern Chile using urea or potassium nitrate applied at 0, 20, or 40 kg N ha⁻¹ to plants grown in unlimed soil or soil amended with calcium carbonate or magnesium oxide. Vegetative growth, tissue mineral composition, stomatal conductance, chlorophyll fluorescence, and leaf chlorophyll were monitored during the first season. Growth responded primarily to soil liming rather than N supply, indicating low N demand and substantial soil N mineralization under the experimental conditions. Foliar N increased from 1.36 to 1.70% with increasing N rates. Urea nutrition reduced foliar Al concentration by 12% compared with nitrate. Under unlimed conditions, representing maximal soil Al availability, urea fertilization was associated with 70% higher Al retention in roots relative to nitrate. Chlorophyll content was consistently higher under urea supply, while the maximum photochemical efficiency of photosystem II remained unaffected. These findings indicate that N form influences plant Al partitioning independently of growth responses. Although the underlying mechanisms were not directly assessed, the observed patterns suggest that urea fertilization may reduce Al translocation to shoots under conditions of high Al availability. Full article

The preventive maintenance (PM) of asphalt pavements reduces life-cycle costs and minimizes resource consumption compared with reactive rehabilitation, yet its cost-effectiveness is highly sensitive to application timing. This study develops a data-driven framework for determining optimal PM timing on Korean expressways by integrating network-level pavement management system (PMS) deterioration modeling with life-cycle cost analysis (LCCA). Using 10-year PMS time-series data from approximately 2200 asphalt pavement sections (2012–2021), a nonlinear regression of the Highway Pavement Condition Index (HPCI) yielded an exponential deterioration model with exponent β = 1.87 (R² = 0.996), confirming accelerating deterioration beyond a critical service age. The HPCI inflection coincides with the Grade-2 boundary (3.5–4.0), where surface distress growth—dominated by linear cracking (91.3% of total SD)—also peaks. A LCCA across 44 scenarios demonstrated that PM applied immediately before this acceleration onset minimizes the 40-year net present value (NPV; discount rate 4.5%). The optimal first PM application time was estimated at 10.8 years (≈56% of the 19.3-year average service life), reducing the 40-year NPV by up to 7 million KRW per section relative to the milling and overlay baseline (up to 16 million KRW in absolute NPV terms for concrete overlay sections). These findings provide a quantitative, reproducible basis for PM timing decisions applicable to the approximately 4000 km of expressway pavement managed by Korea Expressway Corporation. Full article

Efficient cultivation is essential for the rose industry. Both substrate formulation and plant growth-promoting rhizobacteria (PGPR) application both critical, yet their synergistic effects remain limited. This study investigated the synergistic effects of Bacillus subtilis (Bs) and Priestia megaterium (Pm) combined with five substrate formulations on the growth physiology, photosynthetic characteristics, and soil properties of Rosa × hybrida ‘Ruby’. Two-way ANOVA revealed significant interactions between substrate and PGPR treatments for most growth and physiological indicators. Orthogonal experiments demonstrated that specific PGPR–substrate combinations significantly enhanced plant growth and photosynthetic performance of the studied cultivar, as well as soil quality. Principal component analysis and membership function analysis identified four substrate–PGPR combinations as optimal, with the T4 substrate (humus/perlite/vermiculite/coconut coir/peat/biochar = 5:1.5:1:1:1:0.5) showing the most pronounced effects. In this T4 substrate, PGPR inoculation significantly altered the rhizobacterial community structure. LEfSe analysis revealed 67 enriched microbial biomarkers—substantially more than single-strain treatments. The relative abundance of beneficial genera such as Acidibacter and Chryseotalea increased, and the combined bacterial treatment enhanced functional pathways associated with signal transduction, cell motility, and RNA processing. Compared to single-strain treatments, the combined bacterial application demonstrated superior regulatory effects on plant growth. The optimal combined treatments increased plant height by up to 42.7%, root activity by 103.0%, soluble protein content by 302.8%, and soil ammonium nitrogen by 168.8%. These findings demonstrated that tailored combinations of PGPR and cultivation substrates highlight the potential for optimizing rose cultivation and improving the rhizosphere microecological environment. Full article

Capsicum annuum is a Solanaceae crop that is sensitive to cold, which affects its growth and development upon prolonged exposure and ultimately reduces yield. In response, a complex regulatory network of cold-responsive genes is activated. Earlier studies have shown that SnRKs play a positive role in enhancing cold tolerance in different crops, including peppers; however, the underlying molecular mechanisms and downstream targets have yet to be fully elucidated. In this study, yeast hybrid screening using CaSnRK2.4 identified a potential interacting partner CaPDX1. The interaction between CaPDX1 and CaSnRK2.4 was further confirmed through Y2H, luciferase complementation, and bimolecular fluorescence complementation assays. Subcellular localization showed that CaPDX1 and CaSnRK2.4 are localized in the nucleus as well as in the cell membrane. Silencing of CaPDX1 through VIGS showed increased susceptibility of peppers to cold stress, negatively influenced antioxidant enzymatic activities, and increased relative electrolyte leakage and malondialdehyde levels. Conversely, transient overexpression of CaPDX1 in peppers enhanced cold tolerance by reducing the accumulation of REL and MDA. Ectopic expression of CaPDX1 in Arabidopsis thaliana significantly improved its cold tolerance, accompanied by enhanced activity of antioxidant enzymes and increased chlorophyll content. In summary, these results indicate that CaPDX1 is a positive regulator of cold tolerance in pepper, and its mechanism of action involves interaction with CaSnRK2.4 and the regulation of physiological and molecular responses in pepper under cold stress. Full article

Sulfate-reducing ammonium oxidation (SRAO) is an emerging anaerobic autotrophic nitrogen removal process that combines ammonium oxidation with sulfate reduction. However, it faces some challenges, such as the slow growth of autotrophic microorganisms, weak synergistic interaction between different microorganisms, and poor substrate transfer capability. Herein, graphene oxide (GO) was added to a lab-scale bioreactor to promote SRAO reaction, and its effect on nitrogen removal was systematically investigated. The results demonstrated that GO served not only microbial carriers but also electron shuttles, which were conducive to microbial spatial distribution and better electron transfer, improving the sulfur cycle-driven multi-pathway nitrogen removal performance. The addition of 50 mg/L GO not only enhanced the SRAO activity and increased the ammonium removal efficiency by 24.7%, but also reduced the effluent nitrite concentration and promoted nitrogen production. After reaction, the main functional groups on the surface of GO had been changed, and the composite aggregates of microorganisms were formed. Mass balance analysis revealed that SRAO was the dominant pathway, while Anammox and sulfur-autotrophic denitrification (SADN) played complementary roles. Moreover, after adding GO, the relative abundances of Desulfosarcinaceae and Bacillus, which were functional microorganisms in the SRAO reaction, were increased by 35.7% and 58.5%, respectively. This study will provide an in-depth understanding of the mechanisms for nitrogen removal in the SRAO bioreactor. Full article

The escalating challenge of solid waste disposal necessitates innovative recycling strategies. This study aims to constructed technosols from bulk solid wastes (fly ash, straw and sewage sludge) for the dual purpose of sustainable waste management and the rehabilitation of degraded land. Following a 150-day incubation period, six resulting technosols were systematically evaluated for aggregate stability, bacterial community structure, and biological safety to assess their viability as functional soil materials. All constructed technosols had a pH of 7.44–7.71 and were enriched in soil organic matter, nitrogen, and phosphorus. Aggregate stability (R_0.25: 46.6–64.0%) surpassed that of typical Chinese soils. Bacterial analysis revealed a stable consortium of 165 core genera, accounting for 92.93–98.11% of the total relative abundance, and were dominated by six phyla (Proteobacteria, Bacteroidota, Planctomycetota, Gemmatimonadota, Firmicutes, Actinobacteriota). The addition of straw modulated phylum structure, elevating Bacteroidota and reducing Proteobacteria. The bacterial communities exhibited clear functional hierarchy at class and order levels, with dominant groups forming a complementary carbon–nitrogen–phosphorus cycling network. Functional prediction further indicated distinct differentiation in carbon and nitrogen metabolic pathways. The technosols were non-phytotoxic and significantly enhanced the growth of Portulaca oleracea, increasing plant height (4.9–86.7%), dry weight per plant (67.3–605.4%), and SPAD values (8.1–15.9%), respectively. This study provides a sustainable strategy for repurposing solid wastes into functional technosols, aligning with circular economy principles and offering a viable solution for the ecological restoration of degraded lands such as mining areas. Full article

Microplastics (MPs), particularly low-density polyethylene (LDPE), are widespread pollutants in aquatic environments and may affect cyanobacterial physiology. This study investigated the concentration-dependent effects of LDPE-MPs on the physiology and transcriptomic responses of Arthrospira platensis. Cultures were exposed to 10–5000 mg/L LDPE-MPs (nominal size ≤ 500 µm) for 16 days. Low to moderate concentrations (10–1000 mg/L) produced minimal effects on growth, biomass accumulation, or pigment contents. In contrast, higher concentrations (3000–5000 mg/L) were associated with reduced growth and biomass, accompanied by declines in chlorophyll a (Chl a) and phycobiliproteins over time. By day 16 at 5000 mg/L, biomass and Chl a decreased to 1.47 ± 0.03 g/L and 8.39 ± 0.24 µg/mL, respectively, compared with 1.64 ± 0.04 g/L and 10.81 ± 0.52 µg/mL in the control (p < 0.05). Accordingly, Chl a yield decreased by 13%. Field-emission scanning electron microscopy revealed adhesion of LDPE particles to filament surfaces and the formation of extracellular polymeric substance (EPS)-rich aggregates, which may influence light availability and nutrient exchange. Transcriptomic analysis indicated changes in several metabolic pathways, including nitrogen assimilation, photosynthetic electron transport, carbon metabolism, and metal homeostasis, together with differential expression of genes related to stress responses and EPS biosynthesis. Overall, these findings suggest that relatively high concentrations of LDPE microplastics may influence physiological and metabolic processes in A. platensis. Full article

This experiment evaluated the effects of pellet diameter on growth performance and intestinal health of piglets during the creep feeding stage. A total of 144 7-day-old suckling piglets (body weight of 2.2 ± 0.3 kg) were randomly assigned to four groups and fed the same formula as meal feed and pellets of 2 mm, 4 mm, and 8 mm in diameter, respectively. Each treatment consisted of six replicates of six piglets. The trial was divided into two phases by weaning time: 7–21 days (breast milk + creep feed) and 21–35 days (creep feed only). After the feeding trial, piglets from the meal feed group and the 8 mm pellet group were selected for slaughter and sampling. The results showed that before weaning, average daily feed intake (ADFI) increased significantly with increasing pellet diameter (p < 0.001). Post-weaning, piglets fed 8 mm pellets presented significantly higher final body weight (FBW) and average daily gain (ADG) than those in the meal group (p < 0.05). Apparent nutrient digestibility (ATTD) in pellet groups was significantly higher than that in the meal feed group and rose with increasing pellet diameter (p < 0.001). The organ indices of the stomach and large intestine in the 8 mm group of piglets were significantly lower than those of the meal group. The jejunal villus height (VH) in the 8 mm group showed a trend toward an increase (p = 0.066), and the ileal crypt depth (CD) was significantly lower (p = 0.004), with significantly higher digestive enzyme activities in the jejunum and ileum (p < 0.05). In the 8 mm group, the relative abundances of Bacteroidetes in the jejunum and Actinobacteriota in the cecum and colon increased, while those of Pseudomonadota decreased; jejunal microbial relative richness increased significantly, while the ileal microbial operational taxonomic unit (OTU) richness decreased obviously. In conclusion, pellets improved the growth performance of creep feeding piglets. Compared with meal, 8 mm pellets can significantly enhance intestinal health level and nutrient digestion and absorption capacity by optimizing intestinal morphology, boosting digestive enzyme activities, and improving flora structure. Full article

Background: Human wellbeing consists of dynamic interactions and feedback loops across multiple life domains, a perspective increasingly emphasised within positive psychology’s systemic and strengths-based approach to flourishing. This study develops a systemic framework to model these interdependencies and examines how cross-domain investment can optimise both domain-specific and integrated wellbeing across the lifespan. Methods: Using a Cobb–Douglas functional form with associated growth and resource constraints, we formalise the interaction between physical and financial wellbeing as an example and analyse their joint contribution to overall wellbeing. Results: The model demonstrates that improvements in one domain of wellbeing can enhance wellbeing in another, thereby shifting the optimisation frontier. While narrow domain-specific wellbeing strategies are subject to larger diminishing marginal returns, cross-domain investment generates reinforcing effects that elevate both domains simultaneously and increase integrated wellbeing. Conclusions: In line with positive psychology’s focus on leveraging strengths to support areas of relative weakness, the findings show how developing one domain of wellbeing can mitigate constraints in another. These findings align with positive psychology’s emphasis on multidimensional flourishing and resource-building processes, highlighting the importance of systemic resource allocation and suggesting that wellbeing optimisation requires coordinated, contextualised multi-domain strategies rather than siloed approaches. Full article

This paper examines economic and institutional convergence between EU Core, EU New, and Western Balkan countries over the period 2004–2023 using a comprehensive panel dataset and multiple convergence frameworks. Evidence of absolute β-convergence is found, although at a slow pace, while conditional specifications show that structural and institutional factors explain growth differences; institutional quality appears to affect growth primarily through direct effects rather than through significant interaction-based β-convergence. A Principal Component Analysis-based Institutional Index (PC1) explains 90% of the variance in institutional quality, highlighting its role in shaping cross-country growth differentials rather than directly influencing convergence speed. Group-specific models reveal heterogeneous convergence paths across European regions. EU Core economies exhibit relatively stable convergence patterns, reflecting their proximity to steady-state income levels. In contrast, EU New and Cohesion Economies do not display statistically significant β-convergence, suggesting that catch-up processes are uneven and not uniformly driven by initial income differences. Western Balkan economies show weak and limited convergence patterns, reflecting persistent structural and institutional constraints. Robustness tests (FE/RE, Hausman, VIF, Breusch–Pagan, residual diagnostics) confirm the validity of the results. Findings suggest an important role of institutional quality in supporting long-term growth and the accession process of the Western Balkans. Policy implications highlight the importance of governance reforms, human capital development, and EU integration mechanisms in accelerating convergence. Full article

Drought stress critically impacts plant growth and productivity. The bZIP transcription factor family is crucial for abiotic stress responses, yet its role in larch drought tolerance remains unclear. This study identified 19 bZIP genes in Larix kaempferi (Lamb.) Carr. and characterized LkbZIP4. Bioinformatics analysis classified it into the A subgroup. Subcellular localization and yeast two-hybrid assays confirmed that it is a nucleus-localized transactivator. Expression pattern analysis revealed that LkbZIP4 was highly specifically expressed in roots and was significantly induced by drought stress. A series of transgenic overexpression lines was successfully established through Agrobacterium tumefaciens-mediated method, using embryogenic callus of hybrid larch (L. kaempferi × L. gmelinii). Under 7% PEG-induced drought stress, LkbZIP4-overexpressing transgenic calli displayed enhanced drought tolerance relative to wild-type. This was evidenced by better growth, higher biomass, and reduced membrane damage, indicated by lower malondialdehyde content and relative electrolyte leakage. Meanwhile, these transgenic calli accumulated higher levels of osmoregulatory substances, including proline and soluble sugars, along with enhanced activities of antioxidant enzymes including superoxide dismutase and peroxidase. Our results indicate that LkbZIP4 functions to promote drought tolerance in larch, likely through the enhancement of osmotic adjustment and oxidative defense mechanisms. Full article

Climate change poses an escalating threat to food security in the Near East, a region characterized by water scarcity, rapid population growth, and heavy dependence on rainfed agriculture. Despite extensive research on climate change impacts on crop yields, the effects on rainfed crop suitability—the fundamental capacity of a region’s climate to support crop growth—remain insufficiently explored, particularly across transboundary river basins. This study assesses the impact of climate change on the suitability of seven rainfed crops in the Near East, specifically the Nile, Levant, and Tigris-Euphrates River basins. Using the EcoCrop model and climate projections for 2041–2060 under RCP 4.5 and 8.5 scenarios, we analyzed changes in crop suitability relative to a 1970–2000 baseline. Results project significant temperature increases (2.1–3.8 °C) and precipitation reductions (8–20%) in the Levant by mid-century, leading to alarming declines in crop suitability. While the Nile Basin is projected to gain substantial rainfall (+214 billion m³ under RCP 8.5 by 2050), the Fertile Crescent faces a significant rainfall decrease (−24 billion m³ under RCP 8.5 by 2050). Contrary to the negative impacts predicted for the Levant and parts of the Fertile Crescent, the Tigris-Euphrates basin shows potential suitability gains for maize and olives (up to +30% under RCP 4.5 for maize), with olives also showing increased suitability in other basins. However, the suitability of the remaining five rainfed crops is projected to decline across all basins under both emission scenarios. These findings highlight the complex and regionally diverse impacts of climate change on agricultural productivity in the Near East and provide critical information for cross-border food and water security policies. Full article

Accurate prediction of corrosion-fatigue crack growth rate in aluminum alloys is critical for the safety assessment of aerospace structures. Conventional empirical fracture-mechanic models often struggle to capture multiphysics coupling effects, whereas purely data-driven machine-learning models may lack physical interpretability and generalize poorly beyond the training distribution. To address this challenge, this study proposes a physics-guided knowledge-based XGBoost (KBXGB) model. Based on a comprehensive dataset comprising 2786 experimental records, Permutation Feature Importance was utilized to identify 11 key features, including the stress intensity factor range, stress ratio, frequency, and environmental parameters. The KBXGB framework learns the residual between physics-based empirical models (e.g., the Paris and Walker laws) and measured experimental data, recasting the complex nonlinear mapping into a correction of the systematic deviations of the physical models, thereby achieving deep integration of domain knowledge and data-driven learning. Test results demonstrate that the KBXGB model achieves a coefficient of determination (R²) of 0.9545 and a reduced Mean Relative Error (MRE) of 1.61% on the test set, outperforming standard XGBoost and traditional regression models. Crucially, in independent extrapolation validation, the standard XGBoost model failed (R² = 0.2858) with non-physical staircase artifacts, whereas the KBXGB model maintained high predictive fidelity (R² = 0.8646) and successfully reproduced physical crack growth trends. The proposed approach effectively mitigates the “black-box” limitations of machine learning in sparse data regions, offering a high-precision and physically robust tool for corrosion fatigue-life prediction under complex service conditions. Full article

Optimizing nitrogen form under drip fertigation may improve wheat productivity by regulating the root-zone inorganic N environment during early vegetative growth. A two-year field experiment evaluated nitrate-dominant (N1), balanced ammonium–nitrate (N2), and ammonium-enriched nitrogen strategies (N3) during GS13–GS31, with conventional farmer practice (CK) and a zero-N control (N0) for comparison. Nitrogen-form regulation markedly altered the soil NH₄⁺-N ratios, especially in the 0–20 cm soil layer, with N3 highest, N1 lowest, and N2 intermediate. Compared with the nitrate- or ammonium-dominant strategy, the balanced treatment N2 improved spike formation rate and maintained relatively higher N accumulation at GS31 and GS65, and showed greater N translocation and contribution of translocated N to grain N than N1. Correlation analyses indicated that spike formation rate was closely related to spike number (R² = 0.764) and N accumulation at GS31 was positively related to Ntrans (R² = 0.588). N2 showed the most favorable overall performance, with the highest numerical values for grain yield, nitrogen recovery efficiency, irrigation water use efficiency, and net profit among the fertigation treatments. However, the advantages of N2 over N3 in grain yield and SPAD-AUC were modest and not consistently significant. These results indicate that balancing ammonium and nitrate supply during GS13–GS31 under drip fertigation can improve root-zone N conditions and support better overall agronomic performance in winter wheat under the alkaline soil conditions of the North China Plain. Full article