Search Results (11,957)

In Central Europe, the fawning season of roe deer (Capreolus capreolus) directly overlaps with meadow and alfalfa harvest, typically from late May to early June. During these operations, tens or more likely hundreds of thousands of fawns are mutilated by agricultural machinery. To mitigate this unethical mortality, wildlife managers often deploy odor repellents to drive roe deer individuals from high-risk fields before mowing. Therefore, we evaluated repellent efficacy in a paired design. The abundance of roe deer was quantified by drones equipped with thermal cameras before and after repellent application and then compared with untreated control meadows. Results showed high adult abundance that did not differ significantly among treatments. The highest median was paradoxically observed on meadows “after application” (8.25 ind./10 ha), followed by “not treated” meadows (7.92 ind./10 ha), and “before application” (5.72 ind./10 ha). For fawns, differences between treated and untreated plots were likewise non-significant. Their numbers increased over time after application, consistent with the peak of parturition in the second half of May. Overall, the study confirms that the tested odor repellent, when applied according to the manufacturer’s protocol, did not reduce roe deer presence on meadows. This underscores the need to consider alternative approaches, such as the use of thermal-imaging drones combined with the subsequent translocation of detected fawns to safe locations. Full article

Background: Most immunologically “cold” tumors do not respond durably to checkpoint blockade because tumor antigen (TA) release and presentation are insufficient to prime effective T-cell immunity. While prior work demonstrated synergy between cisplatin and a TLR7/8/9 agonist (CR108) in 4T1 tumors, the underlying mechanism—particularly whether chemotherapy functions as a broad antigen-releasing agent enabling TLR-driven immune amplification—remained undefined. Methods: Using murine models of breast (4T1), melanoma (B16-F10), and colorectal cancer (CT26), we tested multiple chemotherapeutic classes combined with CR108. We quantified intratumoral and systemic soluble TAs, antigen presentation and cross-priming by antigen-presenting cells, tumor-infiltrating lymphocytes, and cytokine production by flow cytometry/ICS. T-cell receptor β (TCRβ) repertoire dynamics in tumor-draining lymph nodes were profiled to assess amplitude and breadth. Tumor microenvironment remodeling was analyzed, and public datasets (e.g., TCGA basal-like breast cancer) were interrogated for expression of genes linked to TA generation/processing and peptide loading. Results: Using cisplatin + CR108 in 4T1 as a benchmark, we demonstrate that diverse chemotherapies—especially platinum agents—broadly increase the repertoire of soluble tumor antigens available for immune recognition. Across regimens, chemotherapy combined with CR108 increased T-cell recognition of candidate TAs and enhanced IFN-γ⁺ CD8⁺ responses, with platinum agents producing the largest expansions in soluble TAs. TCRβ sequencing revealed increased clonal amplitude without loss of repertoire breadth, indicating focused yet diverse antitumor T-cell expansion. Notably, therapeutic efficacy was not predicted by canonical damage-associated molecular pattern (DAMP) signatures but instead correlated with antigen availability and processing capacity. In human basal-like breast cancer, higher expression of genes involved in TA generation and antigen processing/presentation correlated with improved survival. Conclusions: Our findings establish an antigen-centric mechanism underlying chemo–TLR agonist synergy: chemotherapy liberates a broadened repertoire of tumor antigens, which CR108 then leverages via innate immune activation to drive potent, T-cell-mediated antitumor immunity. This framework for rational selection of chemotherapy partners for TLR7/8/9 agonism and support clinical evaluation to convert “cold” tumors into immunologically responsive disease. Full article

FVPB1, a novel heteropolysaccharide, was extracted from the Flammulina velutipes fruiting body, and its structure was determined by methylation analysis, nuclear magnetic resonance (NMR) spectroscopy. FVPB1 demonstrated efficacy in inhibiting lipid accumulation in Raw264.7 cells and zebrafish, as well as in reducing weight gain and ameliorating liver injury in high-fat diet-induced mice. High concentration of FVPB1 significantly increased serum ApoA1 levels, while all tested doses (low, medium, and high) reduced serum ApoB levels in mice. Intervention with FVPB1 significantly increased the mRNA expression of Lcat and Cyp7a1 enzymes while markedly reducing the transcriptional level of Hmgcr reductase. Additionally, low concentration of FVPB1 enhanced CYP7A1 protein expression, whereas medium and high concentrations of FVPB1 promoted LCAT protein expression. Medium and high concentrations of FVPB1 significantly enhanced bile acid excretion in mice, with the high dose additionally promoting fecal sterol output. Alpha and beta diversity analyses demonstrated that a high-fat diet induced substantial dysbiosis in the gut microbiota of mice, characterized by reduced microbial diversity and richness. Intervention with FVPB1 significantly modulated the structural composition of the intestinal microbiota in high-fat diet-fed mice. Therefore, FVPB1 exerts lipid-lowering effect in high-fat diet-fed mice by modulating cholesterol metabolism and ameliorating gut microbiota dysbiosis. Full article

Diterpenoid diester alkaloids (DDAs) are the primary toxic constituents in aconite herbs, while also being the key pharmacologically active components. Consequently, establishing rapid enrichment and highly sensitive analytical methods for DDAs is of critical importance. Herein, we developed and constructed a gas–liquid microextraction (GLME) device, which enables the rapid and selective enrichment of DDAs from complex matrices. The enriched extract can be directly analyzed by high-resolution Orbitrap mass spectrometry without requiring any further pretreatment. A comparative analysis of six commonly used Aconitum herbs medicines and their processed derivatives was conducted. Notably, GLME enhanced the mass spectrometric signals of DDAs by 3–4 orders of magnitude, facilitating the identification of 27 alkaloids, including 3 potential new compounds (15-Ethyl-13-deoxyanhydroaconitine, 13-Hydroxy-15-ethylanhydroaconitine and 8-eicosapentaenoic-benzoylmesaconine). It was found that among the tested samples, the DDAs response intensity of raw Caowu was the highest, and the DDA signals decreased significantly after processing. This result chemically validates the detoxification efficacy of traditional methods. The proposed GLME-MS strategy has the advantages of being green, economical, easy to operate, and highly selective (>1000-fold), which provides a technical reference for the rapid detection, safety assessment, and quality control of Aconitum herbs. Full article

Spatially selective nerve stimulation is an active area of research, with the capability to reduce side effects and increase the clinical efficacy of nerve stimulation technologies. Several research groups have demonstrated proof-of-concept devices capable of performing spatially selective stimulation with multi-contact cuff electrodes in vivo; however, optimizing the technique is difficult due to the large possibility space granted by a multi-electrode cuff. Our work attempts to elucidate the most valuable stimulation montages (current ratios between stimulating electrodes) provided by a multi-contact cuff. We characterized the performance of five different montage types when stimulating fibers in different “electrode configurations”, with configurations including up to three rings of electrode contacts, 13 different counts of electrodes per ring, and five electrode arc lengths per electrode count (for 195 unique configurations). Selected montages included several methods from prior art, as well as our own. Among montage types, the most spatially selective stimulation was one we refer to as “X-Adjacent” stimulation, in which three adjacent electrodes are active per ring. Optimized X-adjacent montages achieved an average fiber specificity of 71.9% for single-ring electrode configurations when stimulating fibers located at a depth of two-thirds of the nerve radius, and an average fiber specificity of 77.2% for two-ring configurations. These values were the highest among montages tested, and in combination with our other metrics, led these montages to perform best in the majority of cost functions investigated. This success leads us to recommend X-Adjacent montages to researchers exploring spatially selective stimulation. Full article

Objectives: Chronic pain corresponds to hypersensitivity to painful stimuli; however, its relation to acute pain sensitivity in children is poorly understood. We explored this relationship by comparing acute and chronic pain measures, along with related factors, in children with chronic pain syndromes versus controls, before and after therapeutic intervention. Methods: This prospective controlled cohort study involved 57 children with chronic pain undergoing intensive interdisciplinary pain treatment in a hospital-based pain rehabilitation program and 50 controls. Participants, aged 7–18, were tested using a cold pressor task (CPT) at admission, discharge, and first follow-up visit. Data on sleep, anxiety, psychological distress, functional impairment, and pain were collected. Results: Significant differences were found between control and treatment groups in average pain threshold (p < 0.001), pain tolerance (p = 0.035), sleep visual analog scale (VAS) (p < 0.001), functional disability inventory (p < 0.001), patient reported outcomes information system anxiety assessment tool (p < 0.001), general anxiety disorder 7-item scale (p < 0.001), pain VAS (p < 0.001) and total brief symptom inventory (BSI) (p < 0.001) scores at admission with children with chronic pain scoring worse on all measures save the pain VAS during the CPT. After treatment and at follow-up, function and mental health measures improved but not acute pain threshold. Conclusions: At treatment completion, function and mental health significantly improved but acute pain threshold and sleep quality were unchanged. These findings suggest that while chronic pain treatment improves overall function and mental health, acute pain thresholds may not be a suitable indicator for evaluating the efficacy of interventions. Full article

Shrimp farming often suffers due to high mortalities and poor growth. Mycotoxins can be one of the causes but often underestimated. BIŌNTE^® QUIMITŌX^® AQUA PLUS, an anti-mycotoxin additive (AMA) was tested to assess its efficacy and determine the best dose for Pacific white shrimp (Litopenaeus vannamei). Four treatments (0, 1, 2, and 3 g/kg of diet) were randomly allocated in 12 aquaria during larval rearing (day 1–20) and 12 fiberglass tanks during subsequent grow-out (day 21–111). Results showed positive impacts on feed conversion, protein efficiency, survival, and growth. A decreasing trend in FCR and increasing trend in PER with the increase in AMA dose. The higher the dose, the better was the immunity as indicated by the survival of shrimp against bacterial challenge. However, the survival and growth showed significant quadratic relationships indicating that the dose of 1.4 g/kg can have the highest daily weight gain (66.7 mg) and the dose of 2.5 g/kg results in the highest survival (60.3%) which is more than double the survival of the control group (27.3%). Therefore, the doses between 1.4 and 2.5 g/kg of feed are recommended for the grow-out phase to enhance growth and survival of shrimp. However, further studies should be conducted in outdoor pond conditions for varying feeding regimes, contamination levels and stocking densities. Full article

Background: This exploratory, non-randomized pre–post study compares three school-based stress interventions—Yoga, Climbing, and Social–Emotional Learning—in primary school children. Methods: We compared three low-threshold interventions delivered during regular lessons: (1) a six-week video-guided Yoga sequence (n = 64; grade 3), (2) a 2.5-week social–emotional learning (SEL) module focused on emotion recognition and regulation (n = 60; grade 3), and (3) a two-week Climbing program implemented with a small special-education sample (n = 12). Parallel class-matched controls were included for Yoga and SEL (n = 64 and n = 60, respectively). A quasi-experimental pre–post design was used. Primary outcomes were overall stress and the emotion subdomains of anger, anxiety, and sadness (SSKJ 3–8); the secondary outcome for the Climbing pilot was general self-efficacy (SWE). Non-parametric statistics (Wilcoxon signed-rank, Mann–Whitney U) and rank-biserial effect sizes (r) were reported with Holm-adjusted α = 0.05. Results: Yoga and SEL produced significant within-group reductions in overall stress and all emotional subdomains (all p < 0.001; r = 0.59–0.75) and outperformed their respective controls at post-test (p ≤ 0.038; r = 0.22–0.48). Change-score comparisons between Yoga and SEL were not statistically different (p ≥ 0.44). In the exploratory Climbing group, self-efficacy increased significantly (V = 64.5, p = 0.006, r = 0.80); stress outcomes mirrored Yoga/SEL trends but were under-powered. Conclusions: A brief classroom Yoga routine and a condensed SEL module each yielded clinically meaningful reductions in stress among primary-school pupils, offering flexible options for post-pandemic recovery. Preliminary evidence suggests that Climbing may enhance self-efficacy in older students with psychological challenges; however, larger samples are required. Integrating cost-effective physical and emotional strategies can help schools promote resilience and well-being amid ongoing educational disruptions. Full article

Objective: Morphine is a widely used analgesic for severe pain, but tolerance is a major challenge in long-term pain management. This study examined the potential of Daflon^® to enhance morphine’s pain-relieving effects and to reduce tolerance in a rat model with neuropathic pain induced by partial sciatic nerve transection (PSNT). Methods: Male Wistar rats were divided into five groups: (1) Sham + Saline, (2) PSNT + Saline, (3) PSNT + morphine, (4) PSNT + Daflon, and (5) PSNT + morphine + Daflon. Morphine tolerance was induced through continuous intrathecal infusion (15 µg/µL/h, i.t.) for 7 days, starting on day 7 post-PSNT, while Daflon was administered orally (50 mg/kg/day, oral) for 7 days. Pain relief was assessed using tail-flick and paw withdrawal on days 1, 4, and 7 after osmotic pump implantation. Spinal cords were collected for immunohistochemistry to analyze glial expression, and serum biomarkers (TNF-α, IL-1β, IL-6, and IL-10) were measured to evaluate neuroinflammation. Results: The results showed that oral Daflon significantly enhanced morphine’s analgesic effects, evidenced by improved pain thresholds in all behavioral tests. Moreover, Daflon reduced morphine tolerance. Mechanistically, Daflon upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and activated heme oxygenase-1 (HO-1), reducing oxidative stress and modulating neuroinflammation through glial regulation. Combining morphine and Daflon reduces pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhances anti-inflammatory IL-10 serum level, showing a synergistic effect in managing neuropathic pain with greater efficacy and lower drug dependence. Histology and immunohistochemistry evaluations further confirmed that morphine and Daflon co-treatment substantially reduced mononuclear cell infiltration, astrocyte activation (as indicated by GFAP expression), and microglial activation (as indicated by Iba-1 expression) compared to single treatment. Conclusions: Our findings suggest that dual therapy synergistically targets both oxidative stress and inflammatory pathways, leading to stronger neuroprotection and pain relief. Importantly, the combination approach may allow for lower opioid dosages, minimizing the risks of opioid-related side effects. Overall, morphine and Daflon co-administration offers a promising and safer strategy for managing neuropathic pain and preserving spinal cord integrity. Full article

The aim of our study is to determine the changes in the biomarkers CXCL-16, CCL-20, GDF-15, and CD8a, which play an immunological role in CHB patients according to viral load to determine their diagnostic potential and to investigate their relationships with hematological parameters and non-invasive fibrosis indices. Our study included 96 chronic hepatitis B patients and 30 healthy individuals as a control group. The patients were divided into three groups based on their serum HBV DNA levels: mild (0–10² IU/mL), moderate (10³–10⁵ IU/mL), and severe viral load (10⁶–10⁸ IU/mL). HBV DNA levels were determined by the real-time PCR (Anatolia, Istanbul, Turkey) method. CXCL-16, GDF-15, and CD8a levels in patient serum were quantitatively determined by the ELISA method (Elabscience, Wuhan, China), and CCL-20 levels were determined by the ELISA method BT LAB, Shanghai, China). ROC (Receiver Operating Characteristics) and HUM (Hypervolume Under Manifold) analyses were used to determine the diagnostic efficacy of the biomarkers. ROC analyses showed that GDF-15 (AUC = 0.920) and CCL-20 (AUC = 0.751) had “very good” and “good” diagnostic values, respectively, in predicting hepatitis B disease. HUM analyses revealed that all biomarkers have good potential when it comes to distinguishing the severity of the disease. This study has shown that the biomarkers GDF-15 and CCL-20 may be potential diagnostic biomarkers in detecting the presence of chronic hepatitis B, and the biomarkers CXCL-16, CCL-20, GDF-15, and CD8a may be potential diagnostic biomarkers in determining the severity of the disease. These findings suggest that these biomarkers, which can be measured by the simpler and more economical ELISA method, could be a supportive tool for the HBV DNA test. The clinical use of these biomarkers can be expanded with future prospective studies. Full article

This study focuses on enhancing the comprehensive utilisation of rice straw by proposing a vibration-assisted compression technology, with the aim of resolving inherent issues in traditional baling, such as uneven compression and low density. This study designed a multi-point vibration-assisted compression test rig and established a vibration-enhanced compression mechanical model based on the physical properties of rice straw. By integrating discrete element method (DEM) simulations with bench testing, the optimal length-to-width ratio of 1:1 was identified for achieving superior compaction quality. A systematic analysis was conducted to evaluate the effects of vibration point configuration, frequency, and amplitude control on straw bale integrity. The results of the DEM simulations demonstrated that vibration-assisted compression significantly enhanced the compaction uniformity and stability of rice straw. The dimensional stability coefficient and pressure transmission rates of the straw bales reached 88.25% and 58.04%, respectively, validating the efficacy of the vibration-assisted compression technique. This study provides innovative concepts and theoretical foundations for optimising the design of straw baling and in-field collection equipment. It holds critical significance for advancing the resource-efficient utilisation of agricultural residues and promoting sustainable agricultural practices. Full article

Small molecule inhibitors targeting BRAF mutations at V600 and downstream MEK represent a significant advancement in treating BRAF-mutant melanoma. However, resistance mechanisms, often involving reactivation of the MAPK pathway via ERK1/2, limit their efficacy. The ERK1/2 inhibitor ravoxertinib (GDC0994) was tested on melanoma cell lines with and without resistance to BRAFi or BRAFi + MEKi. Short-term assays evaluated cell viability, apoptosis induction, and pathway modulation via Western Blot, while long-term effects were assessed using a colony formation assay. Resistant and parental melanoma cells responded to long-term ERKi treatment with reduced growth, independent of sensitivity to BRAF or MEK inhibitors. Adding ERKi to BRAFi/MEKi significantly enhanced apoptosis and growth inhibition, particularly in resistant lines. Although ravoxertinib alone showed limited antitumor activity, its combination with BRAFi/MEKi yielded substantial benefits, especially in chronic settings. These findings suggest that combinatorial regimens incorporating ERK inhibitors represent a promising therapeutic strategy for BRAF-mutant melanoma. Full article

The reaction of 4′–bromo-fenamic acid, a bromo-derivative of fenamic acid (the scaffold of the fenamate non-steroidal anti-inflammatory drugs), with Co(II) in the absence or presence of various nitrogen-donor ligands yielded nine novel, neutral mononuclear Co(II) complexes. These complexes were characterized by physicochemical and spectroscopic techniques and single-crystal X-ray crystallography. The biological evaluation of the compounds focused on their antioxidant and antimicrobial efficacy, as well as their interaction with calf-thymus DNA, pBR322 plasmid DNA (in the absence or presence of diverse irradiations) and serum albumins. The complexes have shown significant antioxidant activity since they can scavenge 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals (up to 96.48 ± 0.07%) and reduce H₂O₂ (up to 96.93 ± 0.53%). Antimicrobial testing revealed that the complexes were more active than free 4′-bromo-fenamic acid with four of them classified as bactericidal agents against selected bacterial strains. The compounds can interact with calf-thymus DNA via intercalation, and the calculated DNA-binding constants are on the 10⁶ M⁻¹ order. The plasmid DNA-cleavage ability of the compounds is strongly enhanced under UVA irradiation (photocleavage > 90%). In addition, the compounds can bind tightly and reversibly to serum albumins with binding constants in the 10⁵ M⁻¹ range. Full article

Palm-leaf manuscripts (PLMs) represent a significant component of cultural heritage as a medium for information recording. However, the inherent fragility of these organic materials presents a major challenge for their long-term preservation. Therefore, enhancing the durability of PLMs to ensure longevity has become a critical issue in conservation research. This study includes an examination of the potential of two polymers, cationic polyacrylamide (CPAM) and chitosan quaternary ammonium salt (CQAS), for PLM encapsulation. The encapsulation effects of these materials were assessed through artificial moist heat-accelerated aging tests, enabling a comprehensive evaluation of structural and mechanical properties at both the macroscopic and microscopic levels. The results indicated that CPAM provided superior performance in terms of gloss, color stability, hydrophobicity, pH value, and tensile properties, whereas CQAS demonstrated notable antifungal efficacy. Both CPAM and CQAS possess distinct advantages and can significantly contribute to the preservation of PLMs. This work offers valuable insights for developing effective conservation strategies, emphasizing the potential of CPAM and CQAS as viable encapsulation materials in the face of conservation requirements. Full article

The growing accumulation of non-biodegradable petrochemical plastics and increasing food waste present urgent environmental and public health challenges. This study addresses both issues by developing biodegradable food packaging films from agar and starch, enhanced with antimicrobial properties by incorporating silver nanoparticles. The innovation of this work is the synthesis of novel agar–starch–silver nanoparticle coatings, where the contained nanoparticles were produced via green methods using two agro-industrial by-products of Greek olive oil production—olive stone extract and olive mill wastewater—as reducing agents. The morphology of the novel coatings was confirmed using transmission electron microscopy combined with energy-dispersive X-ray spectroscopy, revealing nanoscale particles with variable sizes. Additional film characterization was performed through Fourier-transform infrared spectroscopy, scanning electron microscopy coupled with energy-dispersive spectroscopy, and surface profilometry. Infrared spectroscopy analysis suggested the presence of functional groups responsible for nanoparticle stabilization, while energy-dispersive X-ray spectroscopy revealed silver aggregation in both olive stone extract and olive mill wastewater-derived films. Profilometry showed that films with olive mill wastewater-based nanoparticles had a rougher surface than those synthesized from olive stone extract. Antibacterial efficacy was tested against Escherichia coli (Gram-negative) and Staphylococcus epidermidis (Gram-positive) using a spot-on-film assay with high (10⁶ CFU/film) and low (10³ CFU/film) bacterial loads. After 72 h of incubation at 4 °C, both film types showed strong antibacterial activity at high bacterial concentrations, demonstrating their potential for active food packaging. These findings highlight a promising approach to sustainable food packaging within the circular economy, utilizing agricultural waste to create biodegradable materials with effective antimicrobial functionality. Full article