Search Results (19,199)

As global demand grows for natural health-promoting food ingredients, the agri-food industry’s organic wastes are emerging as promising alternatives thanks to attributes such as biocompatibility, nutritional value and nutraceutical effect. During saffron (Crocus sativus L.) production, approximately 53 kg of petals are obtained as a by-product for every 1 kg of saffron spice. The use of saffron petals and petal extracts in bakery products improves products’ shelf life due to the petals’ high content of nutraceuticals and minerals acting as natural preservatives. Petal-enriched bakery products contain high levels of fiber, minerals and antioxidants. Addition of saffron petals into bread dough reduces gluten network strength, increases crumb hardness, enhances acidity, improves water retention, alters color profiles and increases the duration of the shelf life. The formulation for incorporating saffron petals or petal extracts into food products must address three primary criteria: the maximum concentration of bioactive compounds per 100 g of the finished matrix, the thermal stability of these compounds during the baking process, and their bioavailability (in the food matrix) within the human gastrointestinal tract. Nutraceuticals with pharmacological potential are also influenced by the compositional profile: the proximate composition, minerals, phenolic content, flavonols, and antioxidant capacity of saffron petals and bakery products containing saffron petals. Saffron petals exhibit diverse therapeutic potentials, acting as antidepressants, anxiolytics, anticonvulsants, and neuroprotective agents. They also offer metabolic, cardiovascular, hepatoprotective, and renoprotective benefits, along with anti-inflammatory, antimicrobial, and antitumor activities. This article proposes a roadmap for developing bakery products enriched with saffron petals or petal extracts, targeting both pharmacological applications and consumer goods focused on disease prevention and general wellness. This study investigates the biochemical composition of saffron petals and their integration into bakery products. It evaluates the influence of petal-derived additives on rheological properties, shelf stability, and organoleptic characteristics, alongside an assessment of their bioactivity and toxicological profiles. Furthermore, the analytical methodologies employed for ingredient and biological sample characterization are discussed, emphasizing their role in verifying the authenticity, safety, and nutritional functionality of both raw materials and finished formulations. Full article

Cellulose-derived gel films are promising matrices for the immobilization and delivery of beneficial microorganisms in sustainable plant protection. This study evaluated the effects of polymer molecular weight and chemical structure on the physicochemical properties and biocontrol performance of hydroxyethyl cellulose (HEC) films of low, medium, and high molecular weight, as well as sodium carboxymethyl cellulose (CMC-Na), loaded with Bacillus subtilis. The films were characterized in terms of morphology, swelling behavior, mechanical properties, microbial viability, and antifungal activity against Fusarium avenaceum and Alternaria solani. Increasing HEC molecular weight produced progressively denser and more homogeneous gel networks, resulting in improved structural integrity, whereas CMC-Na formed dense but less stable networks. Swelling studies at pH 4, 7, and 9 showed high water uptake for all HEC systems, with enhanced structural stability observed in high-molecular-weight films, whereas CMC-Na dissolved rapidly under all conditions. Mechanical testing further confirmed that increasing molecular weight enhanced stiffness and tensile strength but reduced flexibility. Immobilized in gel matrices, B. subtilis remained viable after 12 months of storage and rapidly reactivated after rehydration. All biohybrid films inhibited fungal growth, with stronger formulation-dependent responses against F. avenaceum than against A. solani. In general, polymer molecular weight and structure were identified as key parameters controlling network organization, hydration behavior, mechanical performance, and biological functionality. These findings highlight the potential of cellulose-derived gel matrices as tunable carriers for microbial biocontrol applications. Full article

Background: Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with distinct clinical and biological features compared to rarer entities such as primary cutaneous CD8⁺ aggressive epidermotropic cytotoxic T-cell lymphoma (PCAECTCL). Although recurrent genomic alterations in CTCL have been described, comparative analyses at the pathway level across biologically divergent subtypes remain limited. Here, we leveraged a conversational artificial intelligence (AI) platform for precision oncology to enable rapid, integrative, and hypothesis-driven interrogation of publicly available genomic datasets. Methods: We conducted a secondary analysis of somatic mutation and clinical data from the Columbia University CTCL cohort accessed via cBioPortal. Cases were stratified into SS (n = 26) and PCAECTCL (n = 13). High-confidence coding variants were curated and mapped to biologically relevant signaling pathways and functional gene categories implicated in CTCL pathogenesis. Pathway-level mutation frequencies were compared using Fisher’s exact tests, with effect sizes quantified as odds ratios. Tumor mutational burden (TMB) was compared using the Wilcoxon rank-sum test. Subtype-specific co-mutation patterns were evaluated using pairwise association analyses and visualized through oncoplots and network heatmaps. A conversational AI agent, AI-HOPE, was used to iteratively refine cohort definitions, prioritize pathway-level signals, and contextualize findings. Results: TMB was comparable between SS and PCAECTCL (p = 0.96), indicating no significant difference in global mutational load. In contrast, pathway-centric analyses revealed marked qualitative differences. SS demonstrated enrichment of alterations in epigenetic regulators, tumor suppressor and cell-cycle control pathways, NFAT signaling, and DNA damage response mechanisms, consistent with transcriptional dysregulation and immune modulation. PCAECTCL exhibited relatively higher frequencies of alterations involving epigenetic regulators and MAPK pathway signaling, suggesting distinct oncogenic dependencies. Co-mutation analysis revealed a more constrained and focused interaction landscape in SS, whereas PCAECTCL displayed broader and more heterogeneous co-mutation networks, indicative of divergent evolutionary trajectories. Notably, ERBB2 mutations were significantly enriched between subtypes (p = 0.031), highlighting a potential subtype-specific therapeutic vulnerability. Conclusions: This study demonstrates that SS is distinguished from PCAECTCL not by increased mutational burden but by distinct pathway-level architectures, particularly involving epigenetic regulation, immune signaling, and transcriptional control. These findings generate biologically grounded, testable hypotheses for subtype-specific therapeutic targeting and underscore the value of conversational AI as a scalable framework for accelerating discovery in translational cancer genomics. Full article

Background: The risk stratification of unruptured intracranial aneurysms (UIAs) relies largely on static clinical and morphological parameters, which may not fully capture aneurysm-specific wall behavior. ECG-gated four-dimensional computed tomography angiography (4D-CTA) enables the time-resolved assessment of aneurysm wall motion, but reliable interpretation requires the differentiation of biological motion from measurement uncertainty. Methods: In this prospective exploratory pilot study, ECG-gated 4D-CTA was used to evaluate the longitudinal aneurysm size change, global volumetric pulsation (GVP), spatial wall pulsation (SWP), intrinsic wall deformability and variability. Size change and pulsation were defined using predefined resolution- and noise-based thresholds. Spatial wall motion was assessed using phase-resolved three-dimensional displacement maps. Harmonic modeling isolated periodic pulsation, and residual variability exceeding empirically derived uncertainty limits was conservatively interpreted as deformability. Associations with aneurysm growth and ELAPSS scores were analyzed using exploratory statistics. Results: Eleven UIAs in ten patients were followed for 4.3 ± 1.1 years. A longitudinal size change occurred in six aneurysms (54.5%). Baseline GVP was present in eight aneurysms (73%) and SWP in nine (82%). GVP was not associated with a size change (p = 1.00). All aneurysms with a size change exhibited baseline SWP, whereas no size change was observed in aneurysms without SWP; however, this association did not reach statistical significance in this small exploratory cohort (p = 0.18). Conservative variability metrics were not associated with growth but correlated with baseline shape irregularity, particularly the undulation index (Spearman’s ρ up to ~0.90). Conclusions: In this small exploratory pilot cohort, spatial wall pulsation showed a descriptive directional pattern with longitudinal aneurysm size changes, whereas global volumetric pulsation did not. These findings are preliminary, should be interpreted cautiously, and require confirmation in larger, adequately powered longitudinal studies before clinical application. Full article

Background/Objectives: Despite substantial progress in the management of psoriasis, evidence on as-needed dosing strategies for biologic therapies remains scarce. In this context, the present study aimed to assess the effectiveness of a previously defined as-needed bimekizumab (BKZ) dosing regimen in a larger cohort of patients with psoriasis, as well as to identify clinical factors associated with treatment response. Methods: In this retrospective study, medical records of 64 patients with moderate-to-severe psoriasis treated with BKZ between May 2023 and November 2025 at a specialized psoriasis unit in Madrid, Spain, were reviewed. Patients followed an off-label, as-needed dosing regimen, consisting of two initial 320 mg doses at Weeks 0 and 4, with subsequent administrations only upon loss of a PASI 90 response. The primary outcome was the proportion of patients achieving and maintaining optimal disease control (PASI 90) over time. The duration of treatment effect was defined as the interval between the second dose and loss of PASI90 in the absence of further treatment. Safety outcomes were also evaluated. Results: A total of 59 out of 64 patients achieved a PASI 90 response after the initial two BKZ doses, and all maintained disease control with the as-needed dosing strategy over time. On average, patients received approximately one-third of the doses expected under the standard dosing regimen. The mean duration of treatment effect following the second dose was approximately 24 weeks. Systemic and bio-naïve patients presented the longest treatment effect duration under the as-needed dosing regimen. Oral candidiasis was reported in two patients and resolved without complications. Conclusions: This study reinforces previous evidence supporting the effectiveness of an as-needed BKZ dosing strategy, particularly in patients naïve to systemic and biologic therapies for psoriasis. Nevertheless, larger prospective studies are required to confirm these findings. Full article

Vegetatively propagated crops, including cassava, sweet potato, banana, and potato, are susceptible to mixed-pathogen infections resulting from the continuous use of clonal planting material and infrequent seed replacement. A diverse array of viruses, bacteria, and fungi can accumulate within these materials over successive cultivation cycles, precipitating seed degeneration and complex disease syndromes that complicate diagnosis and management. Mixed infections frequently trigger synergistic interactions that exacerbate disease severity and yield losses. This review synthesizes data on mixed-pathogen complexes in vegetatively propagated crops, with particular focus on vascular and systemically colonizing pathogens and analyzing starch crops to highlight the epidemiological, biological, and ecological drivers of synergism and antagonism. Furthermore, the review examines host defense responses during coinfection, including the modulation of plant immune pathways, and evaluates how interpathogen dynamics influence pathological outcomes. Although advancements in molecular diagnostics—notably next-generation sequencing and metagenomics—have revolutionized the detection of mixed infections, they have also introduced challenges in differentiating causal agents from commensal microorganisms. Finally, we discuss the implications for integrated disease management, emphasizing clean seed systems, resistance breeding, and phenotyping strategies tailored to multipathogen environments. The dynamics of mixed infections is critical for resilient and sustainable management strategies amidst increasingly complex agricultural and climatic shifts. Full article

Objectives: To evaluate the influence of two surface finishing procedures—mechanical polishing and glaze firing—on the color stability and wear behavior of lithium aluminium disilicate (LAD) hybrid abutment crowns over a three-year clinical observation period. Methods: Twenty-four patients requiring 34 implant-supported single crowns were included in this prospective clinical study. LAD abutment crowns were fabricated using n!ce ceramic and a CAD/CAM workflow and finished either by mechanical polishing (P, n = 17) or glaze firing (G, n = 17). After insertion as well as after one and three years (P: n = 9, G: n = 9) of clinical use color measurements were performed using spectrophotometry, and color differences (ΔE00) were calculated. Wear was assessed by digital surface comparison of baseline and the two follow-up scans using three-dimensional analysis software. Reference teeth (R) were defined and evaluated comparable to the P and F groups. Biological and technical complications were recorded throughout the observation period. Results: Color deviations increased over time in all groups (P, G, R). After three years, G showed lower mean color differences (ΔE00 ≈ 2.77) compared with F (ΔE00 ≈ 5.40), although the difference was not statistically significant. No significant differences in vertical height loss were observed between P and G. One adhesive fracture occurred both in the P and G group, five crowns (P: n = 3, G: n = 2) developed periimplantitis. Conclusions: Both polishing and glazing resulted in comparable clinical outcomes regarding color stability, wear behavior, and complication rates. Clinical Significance: Both finishing protocols might be a reliable option for LAD hybrid abutment crowns. Full article

Gene regulatory networks differ substantially across individual cell lines, and population-level network inferences often fail to capture the underlying biological heterogeneity. To better capture this heterogeneity, cell line-specific gene network analysis is required. However, interpreting such high-dimensional cell line-specific networks remains a major challenge in the field of network biology. One interpretative approach is to identify differentially regulated gene networks (DGNs) between phenotypes because these networks can highlight phenotype-specific regulatory mechanisms. Although several methods have been proposed for DGN analysis, they are not suitable for cell line-specific gene network analysis, which is characterized by pronounced heterogeneity across individual networks. To address this problem, we proposed a novel statistical method for identifying DGNs in a cell line-specific scenario. The proposed framework integrates cell line-specific network estimation, a Kullback–Leibler divergence-based comparison of multivariate distributions, and a DKL-ratio statistic to quantify between-phenotype heterogeneity relative to within-phenotype homogeneity. Our method evaluates both between-phenotype heterogeneity and within-phenotype homogeneity, ensuring the robust detection of phenotype-specific network structures. Through Monte Carlo simulation studies, we systematically evaluated the performance of the proposed method and demonstrated that our strategy consistently outperformed existing methods in terms of accuracy, precision, true positive rate (TPR), true negative rate (TNR), and F-measure across diverse network structures and mean shift scenarios. Statistical significance was assessed using a permutation-based framework, confirming that the identified networks are unlikely to arise from random variation. We further applied our strategy to Quizartinib sensitivity-specific gene network analysis and identified immune-related subnetworks enriched in antigen processing and presentation pathways. These subnetworks included hub genes such as IFIT1, PSMB9, and HLA-B, which are known to be associated with immune evasion and drug resistance in acute myeloid leukemia. Our findings demonstrate that the proposed method enables statistically reliable and biologically interpretable identification of phenotype-specific gene regulatory mechanisms, providing insights into potential therapeutic targets. Full article

Soft tissue reconstruction often requires biomaterials that provide temporary mechanical support while permitting vascular integration and tissue remodeling. In reconstructive breast surgery, these demands converge within a uniquely challenging environment characterized by large surface areas, variable perfusion, frequent exposure to radiation, and reliance on prosthetic implants. Consequently, breast reconstruction serves as a clinically relevant model for evaluating the performance and limitations of soft tissue scaffolds. Acellular dermal matrices (ADMs) were introduced to provide biologically derived reinforcement capable of host integration and neovascularization. Although ADM has transformed implant-based reconstruction, clinical experience has revealed important limitations, including variability in mechanical properties, inconsistent vascularization, susceptibility to fibrosis, and suboptimal performance in compromised tissue beds. These challenges have driven increasing interest in synthetic polymer scaffolds engineered for reproducible mechanics, controlled degradation, and scalable manufacturing. This narrative review examines the evolution from ADM to synthetic and hybrid scaffold systems in breast reconstruction. We discuss how scaffold architecture, thickness, porosity, and degradation kinetics influence angiogenesis, immune response, and mechanical load transfer during healing. Hybrid strategies that incorporate selective bioactivity within synthetic frameworks are also explored, highlighting their translational promise and current limitations. These principles are particularly relevant in implant-based breast reconstruction, where scaffold performance directly influences complication rates, implant stability, and long-term outcomes. Collectively, breast reconstruction serves as a rigorous translational model demonstrating that optimal soft tissue scaffolds must balance vascular permissiveness, mechanical reliability, and predictable resorption to optimize reconstructive success and guide future biomaterial innovation. Full article

Propolis is a natural product of honey bees whose chemical composition is influenced by different plant species and environmental factors, resulting in diverse biological activities. A new propolis type, the greenish-brown propolis (GBPUP), was identified in the northeast of Brazil. This study aimed to evaluate the influence of seasonal variation in the chemical composition of GBPUP extracts over a 12-month period. LC–ESI–Orbitrap–FTMS and UFLC–DAD–UV–Vis revealed a chemical composition with some differences to that of Brazilian green propolis, with pinocembrin as the major compound, followed by galangin, pinostrobin, chrysin, artepillin C, and pinobanksin. The extracts exhibited high levels of total phenolic, flavonoid, and flavanone contents and moderate to high antioxidant activity. Circos plot analysis showed that specific metabolites were responsible for the high activity against S. aureus (artepillin C, kaempferol, and ferulic acid) and C. albicans (galangin, pinobanksin, chrysin, and pinocembrin) and for moderate antibacterial activity against E. faecalis (rutin) and E. coli (luteolin, rutin, quercetin, and caffeic acid). ANOVA simultaneous component analysis (ASCA) showed a strong correlation between the metabolites (p-coumaric acid, artepillin C, luteolin) and leishmanicidal activity. Thus, seasonal evaluation allowed the identification of bioactive molecules, the months with greater bioactivity of the GBPUP extracts representing the first comprehensive study of the seasonality of this new and promising propolis variety. Full article

Background/Objectives: Photodynamic therapy (PDT) relies on light activation of photosensitizers to generate reactive oxygen species for tumor ablation; however, limited tumor selectivity and systemic toxicity of free photosensitizers remain challenges. This study aimed to develop polymer-based nanotheranostics carrying tetraphenylporphyrin (TPPc) derivatives and to evaluate how linker structure impacts their performance. Methods: TPPc derivatives were covalently conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymers via either pH-sensitive hydrazone linkages (using aliphatic 5-hydroxy-2-pentanone or aromatic 1-(4-hydroxymethyl)phenyl)ethanone spacer) or stable amide bonds, forming amphiphilic polymer conjugates. The conjugates were characterized based on their physicochemical and in vitro and in vivo biological behavior. Results: Polymer conjugation reduced dark toxicity while preserving photodynamic activity. Linker structure influenced intracellular behavior and singlet oxygen production, with hydrazone systems showing faster activation-related responses under acidic conditions in vitro. All conjugates accumulated in tumors and induced significant tumor growth inhibition after irradiation at low doses (2.5 mg kg⁻¹ TPPc equivalent), while the amide-linked conjugate showed the strongest overall in vivo therapeutic effect, likely due to more favorable biodistribution and sustained delivery. Conclusions: The developed HPMA-based polymer–TPPc conjugates improve the therapeutic profile of photosensitizers by reducing toxicity and enabling effective PDT. These findings highlight the importance of linker design in balancing photosensitizer activation, circulation stability, and biodistribution, which together determine the overall therapeutic outcome. Full article

Seed aging is a critical biological process that leads to progressive loss of seed vigor, thereby constraining germplasm conservation and agricultural productivity. To elucidate the molecular mechanisms underlying this process in grass species, we performed transcriptomic analyses to characterize regulatory networks underlying seed aging in Elymus sibiricus, a dominant forage species on the Qinghai–Tibet Plateau. Seeds were subjected to artificial accelerated aging (45 °C, 80% relative humidity, 1–6 days), followed by physiological evaluation and RNA sequencing. Seed vigor and germination percentage declined markedly with aging, accompanied by extensive transcriptional reprogramming. Integrative analyses identified pyruvate metabolism, MAPK signaling, and peroxisome function as key processes associated with vigor loss during late-stage aging. WGCNA further revealed that genes encoding heat shock proteins and glutathione metabolism-related enzymes were co-localized within the same module, suggesting a possible synergistic role in preserving seed viability during aging. In addition, WRKY24, ARF9, and ARF19 were identified as candidate hub transcription factors. WRKY24 may contribute to aging by modulating antioxidant defense-related genes (e.g., TRX1 and NRPC1), while ARF9 and ARF19 may regulate ROS homeostasis through predicted downstream targets, including FQR1, PER2, MAO1B, ANN5, and MT2B. Together, these findings support a hypothetical regulatory model in which WRKY and ARF transcription factors coordinate redox homeostasis and hormone signaling to regulate seed longevity in E. sibiricus. This study provides a systems-level framework for understanding seed aging in perennial grasses and identifies potential genetic targets for improving seed storability, with implications for germplasm conservation and alpine grassland sustainability. Full article

Since MDCK cells are inherently tumorigenic, their safety in vaccine production has long been a concern; thus, establishing a screening method for low-tumorigenic cells is of great significance for influenza vaccine development. This study successfully obtained a low-tumorigenic MDCK cell line through monoclonal screening and systematically evaluated its potential as a cellular substrate for influenza vaccines using male nude mice (BALB/c nu/nu, 4–7 weeks old) for tumorigenicity assessment. Comprehensive analysis of the biological characteristics of the screened cells—including growth curves and transcriptomic features—showed that the cell line exhibits stable growth and consistent traits. Transcriptomic comparison was performed between two defined biological states: parental MDCK cells (SQ group) and the low-tumorigenic clone MDCK-20B9 (SH group). Transcriptomic analysis revealed good dispersion among samples and an overall consistent gene expression distribution. Differential expression analysis identified a total of 2198 differentially expressed genes, including 902 upregulated and 1296 downregulated genes. GO functional enrichment analysis indicated that these genes are mainly involved in biological processes such as acute-phase response, retinol metabolism, mitotic chromosome condensation, and cell migration; are enriched in cellular components such as kinetochores and the extracellular matrix; and are associated with molecular functions including calcium ion binding and the Wnt signaling pathway. KEGG pathway analysis further revealed that the differentially expressed genes are significantly enriched in key pathways such as cancer pathways, cell cycle, and cell adhesion molecules. The expression trends of five key differentially expressed genes were validated by RT-qPCR. In summary, this study successfully screened a stable and consistent low-tumorigenic MDCK cell line, providing a theoretical basis and practical foundation for its use as a cellular substrate in influenza vaccine development. Full article

This study presents the first bioarcheological analysis of the Mnogovalikovaia culture (Middle Bronze Age) from the North Pontic region, evaluating six human skeletons (six adult males) discovered in tumuli at Novosiolovca, Burlăceni, and Ordășei (Republic of Moldova). Dental analysis reveals moderate-to-advanced occlusal wear, chipping on posterior teeth, and anterior teeth modifications indicating both dietary practices and extramasticatory activities. The characteristics of the dental morphology, including non-metric dental traits (i.e., degree of cusp expression, presence of supernumerary cusps, bilateral asymmetry and the occlusal surface shape of maxillary and mandibular second molars (M2) highlight population-specific features influenced by genetic and environmental factors. Traces of ochre on skeletons suggest specific funerary practices. The study fills a significant gap in the understanding of Mnogovalikovaia communities, providing important data on their biological and cultural characteristics, lifestyle, and funerary practices. These findings also represent a basis for future research on this population, requiring larger samples and biomolecular analysis. Full article

Background/Objectives: Propolis is well recognized for its antioxidant, anti-inflammatory, and wound-healing properties, supporting its cutaneous application in phytopharmaceuticals for the management of ultraviolet B (UVB)-induced skin damage. However, the application of propolis is limited by its intense coloration, stickiness, and poor user convenience. In situ film-forming systems (FFS) represent a novel dosage form designed to overcome these challenges, although efficacy data for using FFS remains limited. Consequently, this study aimed to develop a propolis-based FFS and evaluate its efficacy in mitigating UVB-irradiated HaCaT keratinocytes. Methods: Apis mellifera propolis was macerated and analyzed for total phenolic content (TPC) and total flavonoid content (TFC), radical scavenging activity (DPPH assay), and nitric oxide scavenging capability. Bioactive compounds were identified using high-performance liquid chromatography analysis (HPLC). The propolis extract was formulated into FFS and investigated on UVB-damaged HaCaT keratinocytes. An MTT viability assay, propidium iodide flow cytometry for cell cycle analysis, and a scratch wound healing assay were used to evaluate the therapeutic effects of the FFS. Results: The 72 h macerated propolis extract contained high levels of TPC, TFC, and targeted phytochemicals. The propolis extract exhibited free radical scavenging and nitric oxide inhibitory activities. Seven formulations exhibited suitable performance, with formulation F7 (FFS-F7) demonstrating superior drying time and dose-dependent free radical scavenging. Notably, FFS-F7 (≥12.5 µg/mL) significantly enhanced HaCaT proliferation, mitigated UVB-induced cell cycle arrest, reduced cellular damage, and accelerated wound closure. Conclusions: This study successfully developed an FFS that not only overcomes these physical drawbacks but also preserves the biological activity of the extract. The significant protective and restorative effects against UVB-induced HaCaT damage demonstrate the therapeutic potential of Thai Apis mellifera propolis and establish the FFS as a versatile base with the potential for delivering other bioactive compounds. Full article