Search Results (10,555)

The continuous emergence of SARS-CoV-2 variants highlights the need for novel antiviral agents with favorable safety profiles. Marine microalgae constitute a valuable source of bioactive compounds, including antiviral peptides. Building on previous in silico identification of peptides derived from the marine microalga Phaeodactylum tricornutum with predicted activity against SARS-CoV-2, this study evaluated the antiviral capacity of peptide fractions generated by enzymatic hydrolysis and separated by molecular weight (10–30, 5–10, 3–5, and <3 kDa) in human alveolar epithelial A549 cells infected with the SARS-CoV-2. Cytotoxicity analyses, assessed using MTT and resazurin assays, revealed a moderate, concentration-dependent reduction in metabolic activity while maintaining overall cell viability within an acceptable range for antiviral evaluation, with higher-molecular-weight fractions (10–30 and 5–10 kDa) displaying the most stable profiles. Antiviral activity was assessed by flow cytometry following post-infection treatment. Lower-molecular-weight fractions (3–5 and <3 kDa) showed early reductions in infection at low concentrations but exhibited variable responses. In contrast, the 10–30 and 5–10 kDa fractions showed more robust, dose-dependent inhibition at medium and high concentrations, reducing infection levels to levels close to those observed in uninfected controls. Comparative analysis with the reference antiviral drug lopinavir demonstrated that peptide fractions exhibit lower cytotoxicity while retaining antiviral activity under equivalent experimental conditions. Overall, these results indicate that antiviral efficacy is strongly influenced by peptide molecular weight and consistency of response. This work provides experimental in vitro validation of P. tricornutum–derived peptide fractions as marine antiviral candidates and supports the integration of in silico and functional approaches for marine drug discovery. Full article

Antimicrobial resistance has renewed interest in bacteriophage therapy, yet bacterial evolution frequently undermines treatment efficacy. Combination phage therapy is commonly implemented as simultaneous phage cocktails, but whether this is optimal remains in question. Here, we experimentally compared simultaneous versus sequential administration of two phages, an evolved λ called ‘λtrn’ and T2, on Escherichia coli K-12 under controlled laboratory conditions. Across replicated experiments, treatment outcome depended strongly on delivery strategy, dosing order, and timing. Contrary to expectations, sequential delivery consistently achieved greater and more sustained bacterial suppression than simultaneous cocktails, although only when T2 initiated the sequence. Phenotypic assays revealed that treatment differences were driven by the accessibility and timing of cross-resistance evolution. λ-first treatments rapidly selected for cross-resistant bacteria prior to exposure to the second phage, rendering subsequent treatment ineffective. In contrast, T2-first sequential treatments delayed or limited cross-resistance and frequently produced single-phage resistance or collateral sensitivity. Cocktail treatments showed intermediate dynamics, with cross-resistance evolving more slowly but consistently. Whole genome sequencing identified distinct genetic routes to cross-resistance, including regulatory mutations in envZ affecting expression of the phage receptor OmpF, as well as envelope-modifying, mucoidy-associated mutations. Engineering envZ mutations into unevolved backgrounds confirmed the mutation’s sufficiency to confer low-cost cross-resistance. Together, these results demonstrated that phage therapy efficacy depended not only on phage composition but on how selection pressures were ordered in time, highlighting evolutionary steering as a powerful principle for multi-phage therapy design. Full article

Post-weaning diarrhea (PWD) in piglets is a common multifactorial disease in global swine production. Traditional prevention and control strategies relying on high-dose zinc oxide and antibiotics face limitations due to antimicrobial resistance and environmental concerns. This review systematically elucidates the mechanisms of action of plant extracts as alternative interventions against PWD, focusing primarily on categories such as polysaccharides, polyphenols, essential oils, and alkaloids. This review discusses how plant extracts exert their effects through various mechanisms, including improving feed intake, enhancing antioxidant and immune capacities, modulating gut microbiota, repairing intestinal barrier function, and inhibiting pathogens—to alleviate diarrhea induced by weaning stress and pathogenic infections. The findings indicate that plant extracts offer advantages such as multi-target effects, natural origin, and a low propensity for inducing resistance, highlighting their promising potential as alternatives to conventional additives. However, challenges related to compositional complexity, stability, and bioavailability require further investigation and optimization. Full article

This study evaluates the effects of Al₂O₃ and CeO₂ nanoparticles as additives to standard diesel and biodiesel fuels on the combustion and emissions characteristics of a CR diesel engine with split injection (pilot and main injections). Three nanoparticle dosing levels (50 ppm, 100 ppm, and 150 ppm) were compared with undoped standard diesel and biodiesel fuels. The results showed that the presence of both Al₂O₃ and CeO₂ in biodiesel increased the ignition delay of the pilot fuel by about 8.0% at low load and about 3.5% at high load. The addition of both nanoparticles to diesel and biodiesel fuels had an insignificant effect on the main injection fuel’s ignition delay, MBF50 position and combustion duration. The thermal efficiency was up to 1.0% lower. Al₂O₃ additive in diesel had no significant effect on NO_x emissions. CO emissions were higher by 4.4–7.5% in most cases. The Al₂O₃ additive in biodiesel reduced NO_x emissions by an average of 38%, 17.1%, and 9.4% at low, medium, and high engine loads, respectively. The reduction in CO emissions averaged 15%. The addition of CeO₂ nanoparticles to diesel fuel reduced NO_x emissions by 22.5%, 8.5%, and 3.1% on average across the corresponding load ranges. When the engine was operated on CeO₂-doped biodiesel, NO_x emissions were lower by an average of 25.7%, 9.6%, and 2.5% at low, medium, and high loads, respectively. Adding CeO₂ nanoparticles to diesel fuel increased CO emissions, whereas adding them to biodiesel significantly reduced CO emissions. Full article

Background/Objectives: Biosecurity and stamping out are key control measures against H5 high-pathogenicity avian influenza (HPAI) outbreaks. Vaccination in poultry is an additional tool to reduce disease risk and facilitate timely containment. This study aimed to establish a candidate vaccine strain against H5 HPAI in Asia and validate its protective efficacy. Methods: Based on genetic and antigenic analyses, a representative HPAI virus, A/duck/Vietnam/HU16-DD3/2023 (H5N1), collected in northern Vietnam, was selected to generate a candidate vaccine strain, rgPR8/VN23HA∆KRRK-NA (rgPR8/VN23; H5N1), using reverse genetics, followed by formulation of an inactivated oil-adjuvanted vaccine. Vaccine efficacy was evaluated by measuring humoral antibody responses after intramuscular vaccination and by assessing mortality and virus recovery following intranasal challenge with a clade 2.3.4.4b virus, A/Ezo red fox/Hokkaido/1/2022 (H5N1). Results were compared with those obtained using an antigenically homologous vaccine to the challenge strain and a Japanese stockpiled vaccine. Results: All vaccinated juvenile chickens developed sufficient immunity to survive the challenge at 21 days post-vaccination. The rgPR8/VN23 (H5N1) and homologous vaccines markedly reduced virus recovery, suggesting near-sterile protection, whereas low-titer viruses were transiently detected in chickens vaccinated with the stockpiled vaccine. The rgPR8/VN23 (H5N1) vaccine conferred clinical protection in juvenile chickens as early as 8 days post-vaccination. A single dose of the rgPR8/VN23 (H5N1) vaccine provided incomplete protection in laying hens, whereas a double-volume regimen improved protective efficacy. Conclusions: The rgPR8/VN23 (H5N1) vaccine conferred strong immunity to juvenile chickens; however, a refined vaccination strategy may be required to achieve complete protection in laying hens. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Background/Objectives: Liver fat represents an early metabolic lesion in the development of diabetes and its cardiometabolic complications. Diets high in free sugars, particularly from sugar-sweetened beverages (SSBs), are associated with abdominal obesity and increased cardiometabolic risk, prompting global guidelines to limit SSBs as a major public health strategy. Low-fat cow’s milk is promoted as the preferred caloric replacement strategy for SSBs due to its high nutritional value and cardiometabolic advantages. Fortified soymilk is a plant-based alternative with approved health claims for cholesterol and coronary heart disease risk reduction that offers an equivalent nutritional value to cow’s milk. However, given concerns about its classification as an ultra-processed food (UPF), it is unclear whether soymilk offers comparable metabolic health benefits to milk as part of clinical and public health strategies to reduce SSB intake. The Soy Treatment Evaluation for Metabolic (STEM) health trial seeks to evaluate the impact of replacing SSBs with either 2% soymilk or 2% cow’s milk on liver fat and other cardiometabolic risk factors in habitual adult consumers of SSBs with obesity. Methods: The STEM trial is a 24-week, pragmatic, 3-arm, parallel, randomized trial. We recruited adults with obesity (high BMI plus high waist circumference based on ethnic specific cut-offs) consuming ≥1 SSB/day. Participants were randomized to one of three groups based on their usual SSB intake at baseline (servings/day): continued SSB (355 mL can) intake; replacement with fortified, sweetened 2% soymilk (250 mL); or replacement with 2% cow’s milk (250 mL). The primary outcome is the change in intrahepatocellular lipid (IHCL) measured by ¹H-MRS at 24 weeks. Hierarchical testing will be done to reduce the familywise error rate. The superiority of cow’s milk to SSBs will be assessed first to establish assay sensitivity. If superiority is established, then the non-inferiority of soymilk to cow’s milk will be assessed using a pre-specified non-inferiority margin of 1.5% IHCL units (assessed by difference of means using a 90% confidence interval [CI]). Analyses will be conducted according to the intention-to-treat (ITT) principle using inverse probability weighting (IPW) for superiority testing and per-protocol analyses for non-inferiority testing, using ANCOVA adjusted for age, sex, metabolic dysfunction-associated steatotic liver disease (MASLD) status, medication use, intervention dose, and baseline levels. We hypothesize that soymilk will be non-inferior to cow’s milk (Clinicaltrials.gov NCT05191160). Results: Recruitment began in November 2021. A total of 3050 individuals were screened. We randomized 186 participants (62 per group) between 19 April 2022 and 16 April 2024. Participants are 57% male; with a mean [SD] age of 39.9 [11.8] years; BMI of 34.6 [6.1] kg/m², waist circumference of 112.6 [13.8] cm; IHCL of 10.0 [8.2] % with 64.1% meeting the criteria for MASLD; and SSBs intake of 2.3 [1.3] servings/day. Conclusions: Baseline characteristics were balanced across the study arms, with participants representing adults with a high-risk metabolic phenotype, and 64.1% meeting the criteria for MASLD. Findings will contribute to evidence on the cardiometabolic benefits of soymilk, informing clinical practice guidelines and public health policy. Full article

Volumetric additive manufacturing (VAM) enables layerless and fast printing within seconds. However, print quality remains highly sensitive to the delivered energy. In this study, the effects of visible (460 nm) and ultraviolet (385 nm) projector power were evaluated in a dual-color VAM setup with a CQ/EDAB initiated TEGDMA/BisGMA resin with an o-Cl-HABI inhibitor. Cubes ($6\times 6\times 6.7 {\mathrm{mm}}^3$) were printed under controlled visible and ultraviolet power and exposure times, then evaluated using in situ shadowgraphy, three-dimensional metrology, and confocal microscopy. Higher visible power reduced the polymerization initiation time, but increasing the visible dose rapidly led to over-polymerization, resulting in dimensional growth, corner rounding, and increased surface roughness ($R_a$). The lowest lateral variation was observed at the shortest exposure times, with a maximum error of 1.8%. Ultraviolet illumination did not significantly change initiation time or reduce over-polymerization within the tested intensities and inhibitor concentration ranges. Surface evaluations revealed a periodic line texture with a pattern pitch of approximately 25 μm. By shifting the focal plane and using a low-resolution projector, the pattern pitch increased to about 150 μm. These values were aligned with the ${\mathrm{MTF}}_{50}$ spatial frequencies of each projector at different defocus positions. This study provides useful guidelines for adjusting intensity to achieve high-fidelity VAM printed parts. Full article

Low-dose ionizing radiation exposure remains a major challenge for long-term health risk assessment, particularly in retrospective cohorts with heterogeneous exposure scenarios and limited biological material. Although next-generation sequencing (NGS) technologies dominate contemporary molecular research, DNA microarrays remain relevant in radiation biology due to their standardization, reproducibility, cost-effectiveness, and compatibility with archived biospecimens. This narrative review examines the contribution of microarray-based transcriptomic and epigenomic profiling to the study of low-dose radiation effects (≤100 mSv, millisievert), with emphasis on human observational studies, radiation epidemiology, and biodosimetric applications. The literature was identified through targeted searches in PubMed and Web of Science (2000–2025). Evidence from experimental models and exposed populations is synthesized to identify recurrent molecular pathways, major sources of variability, and challenges affecting reproducibility and cross-cohort comparability. Based on this evidence, a conceptual framework is proposed to define conditions under which microarray-based analyses remain interpretable and translationally informative. Machine learning approaches are discussed in a supportive role, with emphasis on interpretability and biological plausibility. Overall, DNA microarrays are positioned as a mature, niche technology that complements next-generation sequencing platforms and remains particularly suited for retrospective cohort studies and long-term molecular monitoring in radiation research. Full article

The Asian citrus psyllid Diaphorina citri Kuwayama (Hemiptera: Liviidae) is the vector of the devastating citrus disease Huanglongbing, posing a significant threat to the global citrus industry and necessitating environmentally sound management strategies. This study aimed to evaluate Australian tea tree oil (TTO) and its primary constituents as potential botanical insecticides. Gas chromatography-mass spectrometry (GC-MS) was performed to analyze the chemical profile of commercial TTO, and behavioral effects on D. citri adults were assessed using a Y-tube olfactometer. Direct spray bioassays were conducted to determine contact toxicity. A total of 12 compounds were identified, with TTO being a Terpinen-4-ol chemotype, dominated by Terpinen-4-ol (40.62%), γ-Terpinene (21.46%), and α-Terpinene (10.45%). TTO demonstrated potent, concentration-dependent repellency, achieving 100% repellency at 10 g/L. In contrast, Terpinen-4-ol alone was attractive to psyllids at low concentrations, suggesting synergistic or masking effects within the complex oil blend. TTO and its major constituents also exhibited significant dose- and time-dependent contact toxicity. Although the 72 h LC₅₀ of TTO (19.18 g/L) indicates lower potency compared to conventional insecticides (0.59–1.23 g/L), its combined repellent and toxic properties make it a promising candidate for integrated pest management (IPM) programs aimed at controlling D. citri and mitigating insecticide resistance. Full article

Adsorption is a method widely used to remove low-molecular-weight organics from wastewaters, and phenolic compounds from olive mill wastewater are a persistent class of bioactive pollutants of environmental concern. We screened eleven microalgal candidates at 0.10 g·L⁻¹ using batch kinetics fitted with the Lagergren pseudo-first-order model to obtain rate constants (k) and fitted equilibrium capacities (q_e). Cyanobacteria, particularly Anabaena spp. and Limnospira platensis, exhibited the highest adsorptive potential in the screening; wall-less species (e.g., Dunaliella salina, Isochrysis galbana) showed negligible surface adsorption, indicating that the presence and type of cell wall highly influence biosorption. L. platensis was selected for detailed study because of its established industrial cultivation and valorisation potential. Equilibrium experiments with HCl-functionalized L. platensis at four biomass loadings (0.10–1.00 g·L⁻¹; initial phenolic mix 30 mg·L⁻¹) showed that increasing dose reduced equilibrium concentration (C_e) but decreased specific uptake from ≈77 mg·g⁻¹ to ≈18 mg·g⁻¹ while removal rose from ~26% to ~61%. Nonlinear isotherm fitting favoured the Freundlich model (1/n < 1), consistent with heterogeneous, multi-site adsorption. Targeted macromolecular extractions abolished phenol uptake, demonstrating that the intact protein–polysaccharide matrix is essential for binding. L. platensis route delivered higher single-cycle removal (≈61%) compared to the maize-derived activated carbon reference (≈49%) while also incurring a 1.3-fold lower GWP (approximately 3 kg CO₂-eq per treatment) than the activated carbon route (approximately 4 kg CO₂-eq per treatment) in our model. Overall, L. platensis represents a lower-impact alternative for natural phenols remediation, especially when integrated into valorisation pathways that recover algal co-products. Full article

PET scans have long been used in oncology imaging to provide molecular and metabolic information about diseases. The use of artificial intelligence (AI) in PET scans in oncology theranostics has the potential to optimise PET modality and overcome the constraints that PET scans have, such as semi-quantitative metrics, reader subjectivity, and variability across scanners/institutions. Advances in AI and radiomics are overcoming those limitations by deep learning lesion detection, enhancing image reconstruction, and improving noise resolution, which allows ultra-low dose acquisitions, while physics-informed models integrate with PET systems to strengthen interpretability and quantitative accuracy. There are also predictive AI frameworks that link PET imaging biomarkers to therapy response and outcomes, create individualised care and are even able to simulate treatment response and help with treatment planning. However, challenges do exist. Most AI PET studies are retrospective, single-centre, and underpowered (small sample), with limited external validation and inconsistent standardisation (in acquisition, segmentation, and extraction), leading to poor reproducibility and higher performance estimates. Furthermore, ethical considerations, including data protection and transparency, need to be considered before implementation. Federated learning, physics-informed frameworks, and adherence to standardised protocols offer steps towards regulated AI systems. In summary, PET is evolving from an imaging modality to a platform with the integration of deep learning, radiomics and reconstruction capable of predicting treatment response and guiding treatment. With rigorous prospective validation, cross-institutional collaboration, and regulatory standardisation, AI in PET would create an advancement in nuclear medicine imaging in oncology. Full article

Background/Objectives: This study aimed to investigate the phytochemical composition, antioxidant capacity, and anticancer potential of methanol and ethanol extracts of Lactarius deliciosus (L.) Gray in MCF-7 breast cancer cells, focusing on their effects on energy metabolism and related molecular mechanisms. Methods: In L. deliciosus samples, total antioxidant activity and total phenolic content were determined spectrophotometrically, while individual phenolics were classified by HPLC and volatile aromatic compounds (VOCs) were determined by GC-MS. The anticancer effects of L. deliciosus in MCF-7 breast cancer were determined using RT-qPCR with 46 different genes. Results: Phytochemical profiling via HPLC and GC–MS revealed a rich diversity of bioactive compounds, including significant levels of gallic acid (298.89 µg/g), vanillic acid (191.98 µg/g), and succinic acid (724.73 µg/g). The extracts exhibited robust antioxidant activity and dose-dependent cytotoxicity, reducing cell viability to as low as 5.60% after 72 h. Molecular analysis through Reactome pathway enrichment and expression profiling of 46 genes demonstrated that L. deliciosus drives cancer cells into a metabolic impasse by reversing the Warburg effect. Key findings include the significant downregulation of glycolytic genes like SLC2A1/GLUT1 (−12.34) and HK2 (−1.71), alongside the repression of mitochondrial TCA cycle regulators such as IDH1 (−17.81) and OGDH (−2.54). This metabolic collapse triggered G0/G1 phase cell cycle arrest and induced apoptosis. Conlusions: These results align with international benchmarks for Lactarius species while providing novel insights into the metabolic reprogramming mechanism. The results obtained in this study highlight that L. deliciosus emerges as a promising natural agent for therapeutic strategies targeting cancer bioenergetics. Full article

Background: Active surveillance of small renal masses is challenged by cumulative radiation exposure from repeated CT imaging, raising long-term health concerns. Low-dose CT protocols offer a strategy to mitigate this risk but are limited by uncertainty regarding measurement accuracy and potential effects on clinical decision-making. Methods: We propose an uncertainty-aware analytical framework using a multi-observer dataset of 40 paired CT cases (low-dose vs. standard-dose). The methodology combines statistical agreement assessment (concordance correlation coefficient, intraclass correlation coefficient), multi-algorithm machine learning prediction (linear regression, random forest, gradient boosting, and SVR), and integrated uncertainty quantification to evaluate equivalence across imaging protocols. Results: Comparative analysis demonstrates near-perfect concordance between protocols (concordance correlation coefficient = 0.9930). Linear regression achieved the highest predictive performance (R² = 0.9933, MAE = 0.4239 mm, MAPE = 2.07%), outperforming more complex ensemble models, highlighting that interpretable models can achieve superior accuracy without compromising reliability. Conclusions: Clinically, the framework supports the safe adoption of low-dose CT for longitudinal tumor assessment, preserving measurement fidelity and diagnostic confidence essential for timely intervention or continued surveillance. Radiologically, it ensures robust lesion characterization across protocols while minimizing cumulative radiation exposure, particularly in younger patients. By integrating uncertainty quantification, this approach enhances transparency, informs clinical decision-making, and facilitates personalized, evidence-based surveillance strategies, promoting safer, dose-optimized imaging in the management of small renal masses. Full article

Background: The integration of anti-disialoganglioside GD2 (anti-GD2) immunotherapy during induction chemotherapy has emerged as a promising strategy to improve outcomes in high-risk neuroblastoma (HR-NB). This study evaluated the end-of-induction (EOI) response and tolerability of a modified N7 induction regimen combined with dinutuximab beta in a Hong Kong paediatric cohort. Methods: A retrospective territory-wide analysis was conducted on nine HR-NB patients treated from 2022 to 2025. They received a modified N7 chemotherapy backbone with dinutuximab beta (17.5 mg/m²/day for 4 days per cycle), alongside granulocyte–macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin-2. Response was assessed using the Revised International Neuroblastoma Response Criteria (INRC), and toxicity was graded according to the Common Terminology Criteria for adverse events (CTCAE). Results: The EOI objective response rate was 78% (7/9 patients) for the primary tumour site and 100% at metastatic sites. No patient exhibited progressive disease. A modified Curie score of ≤2 on MIBG scan was achieved in 78% of patients. Grade 3 or higher toxicities, including neutropenic fever, enterocolitis, and capillary leak syndrome, were observed in eight patients but were manageable. Conclusions: The incorporation of dinutuximab beta into a modified N7 induction regimen demonstrates a satisfactory EOI response rate and a manageable safety profile in children with HR-NB. These preliminary results support the feasibility of this chemoimmunotherapy approach and warrant further investigation in larger cohorts to confirm its efficacy in long-term survival outcomes. Full article