Search Results (81,647)

Regenerative endodontics seeks to restore the vascularized pulp–dentin complex following conventional root canal therapy, yet reliable neovascularization within the constrained root canal remains a key challenge. This study investigates the development of an injectable, dual-curing hydrogel based on methacrylated decellularized amniotic membrane (dAM-MA) and compares its performance to a conventional gelatin methacryloyl (GelMA). The dAM-MA platform was designed for biphasic release, incorporating both free vascular endothelial growth factor (VEGF) for an initial burst and matrix-metalloproteinase-cleavable VEGF conjugates for sustained delivery. The dAM-MA hydrogel achieved shape-fidelity via thermal gelation at 37 °C and possessed tunable stiffness (0.5–7.8 kPa) after visible-light irradiation. While showing high cytocompatibility comparable to GelMA (>125% hDPSC viability), the dAM-MA platform markedly outperformed the control in promoting endothelial tube formation (up to 800 µm total length; 42 branch points at 96 h). The biphasic VEGF release from dAM-MA matched physiological injury kinetics, driving both early chemotaxis and late vessel maturation. These results demonstrate that dAM-MA hydrogels combine native extracellular matrix complexity with practical, dual-curing injectability and programmable VEGF kinetics, offering a promising scaffold for minimally invasive pulp–dentin regeneration. Full article

Nitrogen (N) and potassium (K) are essential macronutrients for plants whose functions and interactions profoundly influence plant physiological metabolism, environmental adaptation, and agricultural production efficiency. This review summarizes research advances in plant N and K nutrition and their interaction mechanisms, elucidating the key physiological functions of N and K individually and their respective absorption and transport mechanisms involving transporters such as NRTs and HAKs/KUPs. The review discusses the types of nutrient interactions (synergism and antagonism), with a primary focus on the physiological basis of N–K interactions and their interplay in root absorption and transport (e.g., K⁺-NO₃⁻ co-transport; NH₄⁺ inhibition of K⁺ uptake), photosynthesis (jointly optimizing CO₂ conductance, mesophyll conductance, and N allocation within photosynthetic machinery to enhance photosynthetic N use efficiency, PNUE), as well as sensing, signaling, co-regulation, and metabolism. This review emphasizes that N–K balance is crucial for improving crop yield and quality, enhancing fertilizer use efficiency (NUE/KUE), and reducing environmental pollution. Consequently, developing effective N–K management strategies based on these interaction mechanisms and implementing Balanced Fertilization Techniques (BFT) to optimize N–K ratios and application strategies in agricultural production represent vital pathways for ensuring food security, addressing resource constraints, and advancing green, low-carbon agriculture, including through coordinated management of greenhouse gas emissions. Full article

Coffee cherry pulp (CCP), a coffee by-product rich in pectin and phenolic compounds, serves as a valuable substrate for microbial enzyme production, improving the nutritional and antioxidant properties of poultry feed. This study evaluated the potential of Kluyveromyces marxianus ST5 to produce pectin-degrading enzymes using CCP. Under unoptimized conditions, the pectin lyase (PL) and polygalacturonase (PG) activities were 3.29 ± 0.22 and 6.32 ± 0.13 U/mL, respectively. Optimization using a central composite design (CCD) identified optimal conditions at 16.81% (w/v) CCP, 5.87% (v/v) inoculum size, pH 5.24, and 30 °C for 48 h, resulting in PL and PG activities of 9.17 ± 0.20 and 15.78 ± 0.14 U/mL, representing increases of 178.7% and 149.7% over unoptimized conditions. Fermented CCP was further evaluated using an in vitro chicken gastrointestinal digestion model. Peptide release increased by 66.2% compared with unfermented CCP. Antioxidant capacity also improved, with significant increases observed in DPPH (32.4%), ABTS (45.0%), and FRAP (42.3%) assays, along with an 11.1% increase in total phenolic content. These results demonstrate that CCP bioconversion by K. marxianus ST5 enhances digestibility and antioxidant properties, supporting its potential as a sustainable poultry feed additive and contributing to the valorization of agro-industrial waste. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K⁺) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K⁺ channel may be a potential target for the resolution of the acute phase of ARDS. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

Flexible sensors have emerged as essential components in next-generation technologies such as wearable electronics, smart healthcare, soft robotics, and human–machine interfaces, owing to their outstanding mechanical flexibility and multifunctional sensing capabilities. Despite significant advancements, challenges such as the trade-off between sensitivity and detection range, and poor signal stability under cyclic deformation remain unresolved. To overcome the aforementioned limitations, this work introduces a high-performance soft sensor featuring a dual-layered electrode system, comprising silver nanoparticles (AgNPs) and a composite of multi-walled carbon nanotubes (MWCNTs) with carbon black (CB), coupled with a laser-engraved crack-gradient microstructure. This structural strategy facilitates progressive crack formation under applied strain, thereby achieving enhanced sensitivity (1.56 kPa⁻¹), broad operational bandwidth (50–600 Hz), fine frequency resolution (0.5 Hz), and a rapid signal response. The synergistic structure also improves signal repeatability, durability, and noise immunity. The sensor demonstrates strong applicability in health monitoring, motion tracking, and intelligent interfaces, offering a promising pathway for reliable, multifunctional sensing in wearable health monitoring, motion tracking, and soft robotic systems. Full article

In the sciences of the deep past, it is taken for granted that the hypothesis that offers the best explanation is the best confirmed. I examine in detail the debate over the K/Pg mass extinctions that began in 1980 with the publication of the paper by Alvarez et al. that proposed the impact extinction hypothesis. I summarize this debate and show how the impact hypothesis eventually achieved consensus as the best explanation. I then consider the relevance of that case study to an evaluation of the employment of inference to the best explanation (IBE) in the earth sciences. I first reject a number of the standard objections to IBE and then strongly endorse John Norton’s claim that no form of ampliative inference can receive a priori justification. Nevertheless, drawing on the case study and other instances, we may identify four “abductive virtues” that characterize many of the most successful instances of IBE, making them attractive and even compelling. Full article

Hydrogen offers an effective pathway for the large-scale storage of renewable energy. For a tourist city located in a plateau region rich in renewable energy, hydrogen shows great potential for reducing carbon emissions and utilizing uncertain renewable energy. Herein, the wind–solar–hydrogen stand-alone and grid-connected systems in the plateau tourist city of Lijiang City in Yunnan Province are modeled and techno-economically evaluated by using the HOMER Pro software (version 3.14.2) with the multi-criteria decision analysis models. The system is composed of 5588 kW solar photovoltaic panels, an 800 kW wind turbine, a 1600 kW electrolyzer, a 421 kWh battery, and a 50 kW fuel cell. In addition to meeting the power requirements for system operation, the system has the capacity to provide daily electricity for 200 households in a neighborhood and supply 240 kg of hydrogen per day to local hydrogen-fueled buses. The stand-alone system can produce 10.15 × 10⁶ kWh of electricity and 93.44 t of hydrogen per year, with an NPC of USD 8.15 million, an LCOE of USD 0.43/kWh, and an LCOH of USD 5.26/kg. The grid-connected system can generate 10.10 × 10⁶ kWh of electricity and 103.01 ton of hydrogen annually. Its NPC is USD 7.34 million, its LCOE is USD 0.11/kWh, and its LCOH is USD 3.42/kg. This study provides a new solution for optimizing the configuration of hybrid renewable energy systems, which will develop the hydrogen economy and create low-carbon-emission energy systems. Full article

Background: Growing disparities in development, governance, and logistics performance across countries pose challenges for global policymaking and Sustainable Development Goal (SDG) monitoring. This study proposes a classification of 137 countries based on multiple structural dimensions. The dataset for 2023 includes six components of the Logistics Performance Index (LPI), six dimensions of the Worldwide Governance Indicators (WGIs), and four proxies of the Human Development Index (HDI). Methods: The Uniform Manifold Approximation and Projection (UMAP) technique was used to reduce dimensionality and allow for meaningful clustering. Based on the reduced space, the K-means algorithm was employed to group countries with similar development characteristics. Results: The classification process allowed the identification of three distinct groups of countries, supported by a Hopkins statistic of 0.984 and an explained variance ratio of 87.3%. These groups exhibit structural differences in the quality of governance, logistics capacity, and social development conditions. Internal consistency checks and multivariate statistical analyses (ANOVA and MANOVA) confirmed the robustness and statistical significance of the clustering. Conclusions: The resulting classification offers a practical analytical tool for policymakers to design differentiated strategies aligned with national contexts. Furthermore, it provides a data-driven approach for comparative monitoring of the SDGs from an integrated and empirical perspective. Full article

Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein primarily found in milk, saliva, tears, and nasal secretions. LF is well known for its antibacterial and immunomodulatory effects. However, the extraction of LF from milk is inadequate for large-scale therapeutic applications, presenting a challenge for economic mass production. Recombinant protein expression systems offer a solution to overcome this challenge and efficient production of LF. This review discusses recent progress in the translational research of LF gene transfer and biopharming, focusing on different expression systems such as bacteria, yeast, filamentous fungi, transgenic crops, and animals as well as purification methods. The optimization of expression yields, prospects for genetic engineering, and biotechnology to enhance LF production for biomedical applications are emphasized. This review systematically sourced the literature from 1987 to 2025 from leading scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. Despite ongoing debates, progress in this field indicates a viable path towards the effective use of LF in therapeutic settings. Full article

The rising demand for energy resources and industrial goods presents significant challenges to sustainable development. Sunflower oil, commonly utilized in the food sector, biofuels, and various industrial applications, is notably affected by this demand. In Bulgaria, it serves as a primary source of vegetable fats, ranking second to butter in daily consumption. The aim of this study is to evaluate and propose methods to improve energy and resource efficiency in sunflower oil production in Bulgaria. The analysis is based on data from an energy audit conducted in 2023 at an industrial sunflower oil production facility. Reconstruction and modernization initiatives, which included the installation of high-performance, energy-efficient equipment, led to a 34% increase in energy efficiency. The findings highlight the importance of adjusting the technological parameters such as temperature, pressure, grinding level, and pressing time to reduce energy use and operational costs. Additionally, resource efficiency is improved through more effective raw material utilization and waste reduction. These strategies not only enhance the economic and environmental performance of sunflower oil production but also support sustainable development and competitiveness within the industry. The improvement reduces hexane use by approximately 2%, resulting in energy savings of 12–15 kWh/t of processed seeds and a reduction in CO₂ emissions by 3–4 kg/t, thereby improving the environmental profile of sunflower oil production. Full article

2,5-bis(hydroxymethy)lfuran (BHMF), a renewable compound with extensive industrial applications, can be obtained by selective hydrogenation of the C=O group of 5-hydroxymethylfurfural (HMF), a platform molecule derived from lignocellulosic biomass. In this work, we perform kinetic modeling of the selective liquid-phase hydrogenation of HMF to BHMF over a Cu/SiO₂ catalyst prepared by precipitation–deposition (PD) at a constant pH. Physicochemical characterization, using different techniques, confirms that the Cu/SiO₂–PD catalyst is formed by copper metallic nanoparticles of 3–5 nm in size highly dispersed on the SiO₂ surface. Before the kinetic study, the Cu/SiO₂-PD catalyst was evaluated in three solvents: tetrahydrofuran (THF), 2-propanol (2-POH), and water. The pattern of catalytic activity and BHMF yield for the different solvents was THF > 2-POH > H₂O. In addition, selectivity to BHF was the highest in THF. Thus, THF was chosen for further kinetic study. Several experiments were carried out by varying the initial HMF concentration (C⁰_HMF) between 0.02 and 0.26 M and the hydrogen pressure (P_H2) between 200 and 1500 kPa. In all experiments, BHMF selectivity was 97–99%. By pseudo-homogeneous modeling, an apparent reaction order with respect to HFM close to 1 was estimated for a C⁰_HMF between 0.02 M and 0.065 M, while when higher than 0.065 M, the apparent reaction order changed to 0. The apparent reaction order with respect to H₂ was nearly 0 when C⁰_HMF = 0.13 M, while for C⁰_HMF = 0.04 M, it was close to 1. The reaction orders estimated suggest that HMF is strongly absorbed on the catalyst surface, and thus total active site coverage is reached when the C⁰_HMF is higher than 0.065 M. Several Langmuir–Hinshelwood–Hougen–Watson (LHHW) kinetic models were proposed, tested against experimental data, and statistically compared. The best fitting of the experimental data was obtained with an LHHW model that considered non-competitive H₂ and HMF chemisorption and strong chemisorption of reactant and product molecules on copper metallic active sites. This model predicts both the catalytic performance of Cu/SiO₂-PD and its deactivation during liquid-phase HMF hydrogenation. Full article

Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. Methods: We reviewed a patient-reported outcomes dataset from “Tikun Olam,” a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). Conclusions: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief. Full article

Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article