Search Results (28,787)

The systems in nature are rarely isolated and there are different influences that can perturb their states. Dynamic noise in physiological systems can cause fluctuations and changes on different levels, often leading to qualitative transitions. In this study, we explore how to detect and extract the physiological noise, in terms of dynamic noise, from measurements of biological oscillatory systems. Moreover, because the biological systems can often have deterministic time-varying dynamics, we have considered how to detect the dynamic physiological noise while at the same time following the time-variability of the deterministic part. To achieve this, we use dynamical Bayesian inference for modeling stochastic differential equations that describe the phase dynamics of interacting oscillators. We apply this methodological framework on cardio-respiratory signals in which the breathing of the subjects varies in a predefined manner, including free spontaneous, sine, ramped and aperiodic breathing patterns. The statistical results showed significant difference in the physiological noise for the respiration dynamics in relation to different breathing patterns. The effect from the perturbed breathing was not translated through the interactions on the dynamic noise of the cardiac dynamics. The fruitful cardio-respiratory application demonstrated the potential of the methodological framework for applications to other physiological systems more generally. Full article

Carotid atherosclerosis remains one of the primary etiological factors underlying ischemic stroke, contributing to adult neurological disability and mortality. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, actively modulating molecular pathways involved in atherogenesis. This systematic review, the first to be exclusively focused on carotid atherosclerosis, aimed at synthesizing current findings on the differential expression of ncRNAs throughout the natural history of the disease, thus providing the first comprehensive attempt to delineate a stage-specific ncRNA expression profile in carotid disease. A comprehensive literature search was conducted in PubMed and Scopus databases in January 2025, following PRISMA guidelines. Original studies involving human subjects with carotid atherosclerosis, evaluating the expression of intracellular or circulating ncRNAs, were included and then categorized according to their association with cardiovascular risk factors, carotid intima-media thickness (cIMT), presence of atherosclerotic plaques, plaque vulnerability, clinical symptoms, and ischemic stroke. Out of 148 articles initially identified, 49 met the inclusion criteria and were analyzed in depth. Among the different classes of ncRNAs, microRNAs (miRNAs) were the most frequently reported as dysregulated, followed by circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Notably, the majority of identified ncRNAs were implicated in key pathogenic mechanisms such as inflammatory signaling, vascular smooth muscle cell (VSMC) phenotypic modulation, and ABCA1-mediated cholesterol efflux. Collectively, the evidence underscores the association and possible involvement of ncRNAs in the initiation and progression of carotid atherosclerosis and its cerebrovascular complications. Their relative stability in biological fluids and cell-specific expression profiles highlight their strong potential as minimally invasive biomarkers and—possibly—novel therapeutic targets. Full article

Numerous sectors of the food processing and oleochemical industries require oils with specific physicochemical properties. Fruit processing generates substantial waste potentially containing valuable raw materials for oil extraction. The significant volumes of apples and cherries processed in Poland prompted an assessment of their seeds’ suitability as oil sources. Seed dry matter, protein, and oil content were determined. The extracted oils were analyzed for acid value (AV), peroxide value (PV), oxidative stability, fatty acid composition, and sterol and tocopherol content. The predominant higher fatty acids identified in the sour cherry and sweet cherry kernel oils were linoleic acid (C18:2, n-6), with mean concentrations of 45.82% and 29.23%, respectively, and oleic acid (C18:1, n-9), accounting for 41.54% and 46.59%, respectively. Additional fatty acids detected included palmitic acid C16:0 (6.23% and 5.91%), palmitoleic acid C16:1, n-7 (0.29%), stearic acid C18:0 (1.36% and 3.11%), arachidic acid C20:0 (1.13%), α-eleostearic acid C18:3 (5.07% and 9.48%), and α-linolenic acid C18:3, n-3 (4.09%). Given the substantial proportion of the oil fraction containing numerous potentially biologically active compounds, including nutritionally valuable fatty acids, tocopherols, and phytosterols, apple, sour cherry, and sweet cherry seeds demonstrate considerable potential as raw materials for applications in the food, pharmaceutical, and cosmetics industries. Full article

Dietary bioactive compounds derived from plant-based and fermented foods act as plei-otropic modulators of human health, exerting antioxidant, anti-inflammatory, cardiopro-tective, neuroprotective, and metabolic effects beyond basic nutrition. Whole foods (fruits, vegetables, grains, nuts) provide synergistic mixtures of bioactives, whereas fermented foods generate a wide range of microbial-derived metabolites (peptides, organic acids) as well as probiotics that enhance nutrient bioavailability and support gut health. The gut microbiota plays a central mediating role in the biological effects of dietary bioactives through a dynamic, bidirectional interaction: dietary compounds shape microbial composition by promoting beneficial taxa and suppressing pathogens, while microbial metabolism converts these compounds into bioactive metabolites, including short-chain fatty acids, that profoundly influence host health. Despite their demonstrated health potential, the clinical translation of many dietary bioactives is limited by low bioavailability, which is influenced by digestion processes, food matrix and processing conditions, host genetics, and individual microbiota profile. Overcoming these limitations requires a deeper understanding of the synergistic interactions among dietary bioactives, probiotics, microbial metabolites, and host signaling pathways. This review provides an integrated perspective of the sources, mechanisms of action, and health effects of food-derived bioactive compounds and probiotic mediated effects, while highlighting current translational challenges and future directions for the development of effective functional foods and personalized nutrition strategies. Full article

Traditional plant scouting is often a costly and labor-intensive task that requires experienced specialists to diagnose and manage plant stresses. Artificial intelligence (AI), particularly deep learning and computer vision, offers the potential to transform scouting by enabling rapid, non-intrusive detection and classification of early stress symptoms from plant images. However, deep learning models are often opaque, relying on millions of parameters to extract complex nonlinear features that are not interpretable by growers. Recently, eXplainable AI (XAI) techniques have been used to identify key spatial regions that contribute to model predictions. This project explored the potential of convolutional neural networks (CNNs) for classifying the severity of chilli thrips damage in strawberry plants in Florida and employed XAI techniques to interpret model decisions and identify symptom-relevant canopy features. Four CNN architectures, YOLOv11, EfficientNetV2, Xception, and MobileNetV3, were trained and evaluated using 2353 square RGB canopy images of different sizes (256, 480, 640 and 1024 pixels) to classify symptoms as healthy, moderate, or severe. Trade-offs between image size, model parameter count, inference speed, and accuracy were examined in determining the best-performing model. The models achieved accuracies ranging from 77% to 85% with inference times of 5.7 to 262.3 ms, demonstrating strong potential for real-time pest severity estimation. Gradient-Weighted Class Activation Mapping (Grad-CAM) visualization revealed that model attention focused on biologically relevant regions such as fruits, stems, leaf edges, leaf surfaces, and dying leaves, areas commonly affected by chilli thrips. Subsequent analysis showed that model attention spread from localized regions in healthy plants to wide diffuse regions in severe plants. This alignment between model attention and expert scouting logic suggests that CNNs internalize symptom-specific visual cues and can reliably classify pest-induced plant stress. Full article

Background/Objectives: Resveratrol is a multi-target polyphenolic stilbene widely studied for its antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, neuroprotective, immunomodulatory and anticancer properties. This review summarizes current evidence on its molecular mechanisms, therapeutic potential, metabolic interactions and biological implications, with particular emphasis on bioavailability, signaling pathways and organ-specific actions. Methods: A comprehensive literature review was conducted focusing on recent in vitro, in vivo and clinical studies evaluating resveratrol’s biochemical activity, molecular targets and physiological effects. Special attention was given to oxidative stress regulation, inflammatory signaling, mitochondrial function, metabolic pathways, gut microbiota interactions, and its influence on chronic diseases. Results: Resveratrol modulates several key signaling pathways including NF-κB, SIRT1, AMPK, MAPK, Nrf2 and PI3K/AKT/mTOR. It reduces oxidative stress, inhibits inflammatory cytokines, regulates apoptosis, improves mitochondrial performance, and activates endogenous antioxidant systems. The compound demonstrates protective effects in cardiovascular diseases, hepatic steatosis, neurodegenerative disorders, metabolic dysfunction, and various cancers through anti-inflammatory, anti-proliferative and anti-fibrotic mechanisms. Additionally, resveratrol beneficially alters gut microbiota composition and microbial metabolites, contributing to improved metabolic homeostasis. Despite high intestinal absorption, systemic bioavailability remains low; however, novel nanoformulations significantly enhance its stability and plasma concentrations. Conclusions: Resveratrol exhibits broad therapeutic potential driven by its capacity to regulate oxidative, inflammatory, metabolic and apoptotic pathways at multiple levels. Its pleiotropic activity makes it a promising candidate for prevention and complementary treatment of chronic diseases. Advances in delivery systems and microbiota-derived metabolites may further enhance its clinical applicability. Full article

Steroidal compounds lie at the crossroads of inflammation and cancer, where modulation of common signaling pathways creates opportunities for dual-action therapeutic intervention. Accumulating evidence indicates that their anti-inflammatory and antitumor activities are frequently interconnected, reflecting shared molecular mechanisms that regulate immune signaling, oxidative stress, cell proliferation, and apoptosis. This review provides a critical and comparative analysis of major classes of bioactive steroids—including furanosteroids, neo-steroids, aromatic steroids, α,β-epoxy steroids, peroxy steroids, cyanosteroids, nitro- and epithio steroids, halogenated steroids (fluorinated, chlorinated, brominated, iodinated), and steroid phosphate esters—with emphasis on their dual anti-inflammatory and anticancer potential. More than one thousand steroidal metabolites derived from plants, fungi, marine organisms, bacteria, and synthetic sources are surveyed. While the majority exhibit either anti-inflammatory or antineoplastic activity alone, only a limited subset displays potent activity in both domains. Comparative evaluation highlights the structural features that favor dual functionality, including epoxide, peroxide, nitrile, nitro, halogen, and phosphate ester moieties, as well as rearranged or heteroatom-enriched steroidal frameworks. Where available, biological data from in vitro and in vivo assays (IC₅₀ values, enzyme inhibition, cytokine modulation, and antiproliferative effects) are summarized and critically compared. Special attention is given to rare natural metabolites—such as polyhalogenated marine steroids, phosphorylated sterols, and heteroatom-containing derivatives—as well as synthetic analogues designed to enhance cytotoxic or immunomodulatory efficacy. Mechanistically, steroids exhibiting dual activity commonly modulate convergent signaling pathways, including NF-κB, JAK/STAT, MAPK, PI3K/AKT, redox homeostasis, and apoptosis regulation. Collectively, these findings underscore the potential of structurally optimized steroids as multifunctional therapeutic agents and provide a framework for the rational design of next-generation anti-inflammatory and anticancer drugs. Full article

Marine-derived fungi have become a vital resource for the discovery of novel secondary metabolites with diverse structures and significant biological activities. This study focuses on a systematic chemical investigation of the sponge-associated fungus Talaromyces stipitatus HF05001, leading to the isolation and identification of 20 compounds, including one new marine ketal natural product (Compound 17, Talarobispiral A). These compounds were structurally elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS. All isolates were screened for their anti-inflammatory and anti-adipogenic properties. Among them, compound 4 (Secalonic acid D, SAD), 7 (Sch 725680) and 16 (bacillisporins C) demonstrated significant anti-inflammatory potential by markedly suppressing nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Notably, compound 4 showed superior inhibitory effect, with an IC₅₀ value of 0.22 μM. Additionally, compound 4 exhibited the strongest dose-dependent inhibition of lipid droplet accumulation in 3T3-L1 preadipocytes. These findings highlight the dual therapeutic potential of metabolites from Talaromyces stipitatus, identifying promising lead compounds for the development of novel treatments for inflammatory and metabolic disorders. Full article

Multipotent mesenchymal stromal stem cells have captivated the scientific community in recent years due to their ability to differentiate into multiple adult cell types. Central to this potential are many members of the nuclear hormone receptor superfamily, comprising 48 ligand-modulated transcription factors involved in key biological processes such as metabolism, physiology, embryonic development, and reproduction. These transcription factors influence cellular fate by regulating gene expression networks critical for MSC specification, commitment, and differentiation. This review explores the role of nuclear receptors in MSC development, focusing on interactions with chromatin structure, co-regulatory complexes, and responsiveness to extracellular stimuli such as hormones, metabolic cues, and endocrine-disrupting chemicals. We conclude with a discussion of the dangers posed by exogenous and aberrant signaling through nuclear receptors. Full article

Silica spicules provide a natural transdermal conduit but require a linker that binds strongly under physiological conditions and releases payloads selectively in response to biological cues. Existing silane chemistries or polydopamine coatings lack enzyme responsiveness and show limited control over release. We created a 180-member peptide library with the motif L–X1–X2–[Y–F–Y]–A–L–G–P–H–C and screened for silica binding. Biophysical assays (circular dichroism, ζ-potential, quartz crystal microbalance, atomic force microscopy) and molecular dynamics identified high-affinity binders. The lead, P176, was tested for matrix metalloprotease (MMP)-responsive cleavage. Conjugation and release of Vitamin C and Stigmasterol were analyzed by HPLC and Franz diffusion cells. P176 showed high silica affinity (~55 µg mg⁻¹), robust biophysical signals (Δf −35 to −38 Hz; rupture force ~154 pN; ζ shift −22 to−11.5 mV), and favorable adsorption energy (−48.5 kcal mol⁻¹, contact 4.5 nm², 8.5 H-bonds). The MMP gate displayed efficient kinetics (Vmax 117.9 RFU·min⁻¹, Km 5.0 µM) with >90% cleavage at 60 min, reduced to 26% by inhibitor. Conjugation yields reached 87% (Vitamin C) and 77% (Stigmasterol). Franz diffusion showed MMP-dependent release (24 h: Vitamin C 90–96%, Stigmasterol 80–85%) with minimal basal leakage. Released Vitamin C enhanced collagen I to ~250% in fibroblasts, while Stigmasterol attenuated LPS-induced macrophage morphology; keratinocytes retained normal marker expression. This study demonstrates that a single amphipathic, sequence-programmed peptide can couple strong silica anchoring with protease-responsive release and broad payload compatibility, establishing a versatile platform for spicule-based transdermal and regenerative delivery. Full article

Lipoxygenases are enzymes found in plants, mammals, and other organisms that catalyse the hydroperoxidation of polyunsaturated fatty acids, such as arachidonic, linoleic, and linolenic acids. They have attracted a lot of attention as molecular targets for industrial and biomedical applications, due to their implication in key biological processes, such as plant development and defence, cell growth, as well as immune response and inflammation. Soybean (Glycine max) lipoxygenase (LOX) is a versatile biocatalyst used in biotechnology, pharmaceutical, and food industries. sLOX1, a soybean LOX isoform, is central in various industrial applications; thus, it is of particular interest to develop an efficient sLOX1 isolation process, control its activity, and leverage its potential as an effective industrial biocatalyst, tailoring it to a specific desired outcome. In this study, sLOX1 was extracted and purified from soybean seeds using an optimized protocol that yielded an enzyme preparation with higher activity compared to the commercially available lipoxygenase. Comprehensive biophysical characterization employing dynamic and electrophoretic light scattering, fluorescence, and Fourier-transform infrared spectroscopies revealed that sLOX1 exhibits remarkable structural and functional stability, particularly in sodium borate buffer (pH 9), where it retains activity and integrity up to at least 55 °C and displays minimal aggregation under thermal, ionic, and temporal stress. In contrast, sLOX1 in sodium phosphate buffer (pH 6.8) remained relatively stable against ionic strength and time but showed thermally induced aggregation above 55 °C, while in sodium acetate buffer (pH 4.6), the enzyme exhibited a pronounced aggregation tendency under all tested conditions. Overall, this study provides physicochemical and stability assessments of sLOX1. The combination of enhanced catalytic activity, high purity, and well-defined stability profile across diverse buffer systems highlights sLOX1 as a promising and adaptable biocatalyst for industrial applications, offering valuable insights into optimizing lipoxygenase-based bioprocesses. Full article

Melanocytic Tumors of Uncertain Malignant Potential (MELTUMPs) remain among the most challenging entities in dermatopathology due to overlapping morphologic features and marked inter-observer variability. This comprehensive review critically assesses the diagnostic and potential prognostic significance of combining p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as a practical surrogate for genomic alterations involving the 9p21 (CDKN2A/MTAP) locus. We analyzed the molecular underpinnings of the CDKN2A/MTAP axis and systematically reviewed existing literature to define an integrated IHC strategy for ambiguous melanocytic lesions. The combined use of p16, a sensitive marker of CDKN2A inactivation, and MTAP, a highly specific marker for homozygous 9p21 deletion, was assessed for its diagnostic complementarity and potential clinical utility. p16 IHC demonstrates high sensitivity but limited specificity due to heterogeneous staining in borderline lesions. In contrast, MTAP loss exhibits near-absolute specificity for CDKN2A/MTAP co-deletion, albeit with lower sensitivity. Concordant loss of both markers strongly supports melanoma or high-risk melanocytoma, while MTAP retention may predict responsiveness to adjuvant interferon therapy. Combined p16/MTAP IHC provides a synergistic, biologically grounded approach that refines diagnostic accuracy in MELTUMPs. This dual-marker algorithm promotes a shift from purely morphology-based evaluation toward a reproducible, molecularly informed classification, improving both diagnostic confidence and patient management. Full article

Microbial biological control agents are a sustainable alternative to synthetic pesticides, yet their widespread application is limited by a lack of environmental resilience of commercial products. To address this, we exploited honey—a stringent ecological niche—as a reservoir for stress-tolerant bacteria. In this study, the bioprospection utilizing five types of commercially available honeys yielded a collection of 53 bacteria and 10 fungi. All bacterial isolates were evaluated for antimicrobial activity against a laboratory-standard bacterium and yeast, and six economically relevant phytopathogenic microorganisms. Initial screening with standard laboratory organisms proved to be an efficient method to detect strains with antimicrobial potential, correlating significantly with further phytopathogen inhibition (Spearman’s r = 0.4512, p = 0.0005). Two promising strains, M2.7 and M3.18, were selected for quantitative dual-culture assays along with molecular identification using 16S rDNA and gyrA gene sequencing, classifying them as Bacillus velezensis. These strains exhibited high inhibitory effects against the pathogens (p > 0.001), often with equivalent efficacy to the commercial biocontrol strain, and also induced significant phytopathogen hyphal deformities, such as increased septation and swelling. These findings support honey as a viable source of robust biocontrol agents, offering a sustainable strategy to substitute or complement current agrochemicals. Full article

Pediatric obesity is an increasingly prevalent, chronic, and multifactorial disease. Achieving successful and sustained weight reduction with current interventions remains challenging due to significant heterogeneity in treatment response. This review summarizes current evidence describing variability in outcomes across lifestyle, pharmacologic, and metabolic/bariatric surgery interventions in children and adolescents, and examines key biological, metabolic, behavioral, environmental, and psychosocial factors that influence response. In adults, recent findings on energy balance obesity phenotypes (characterized by abnormal satiation, abnormal postprandial satiety, abnormal hedonic eating, and reduced energy expenditure) have demonstrated promise in predicting weight loss outcomes and guiding tailored interventions. However, data on obesity phenotyping within children and adolescents remain limited. Addressing this gap is essential for advancing precision medicine approaches in pediatric obesity, with the potential to improve treatment selection, enhance effectiveness, and optimize long-term clinical outcomes. Full article

Background: Plant architecture, particularly branching patterns, plays a crucial role in plant growth, photosynthetic performance, and yield. Spur-type apple, characterized by compact growth, early fruiting, high productivity, and manageable canopy structure, represent valuable germplasm for establishing dwarf and high-density apple orchards. While hybrid breeding of spur-type varieties offers significant potential for genetic advancement, severe segregation of traits in hybrid progeny and the difficulty of combining multiple favorable traits still significantly limit breeding efficiency. Moreover, the genetic basis and molecular mechanisms of the spur-type trait remain poorly understood at the genomic level, hindering the development of precise molecular breeding approaches. Methods: To address this, we used the spur-type line ‘0301-13-14’ and the non-spur-type line ‘0301-50-32’ from hybrid progenies of the spur-type cultivars ‘Miyazaki Spur Fuji’ and ‘Starkrimson’ to elucidate the regulatory mechanisms underlying apple branch formation and spur-type trait development by characterizing their branching traits, performing whole-genome resequencing analysis, and identifying candidate genes using bioinformatics analyses. Results: Anatomical observations revealed that the spur-type line ‘0301-13-14’ possessed smaller cells with a more compact spatial arrangement compared to the non-spur-type line ‘0301-50-32’. Whole-genome resequencing generated 5,003,968 high-quality single-nucleotide polymorphisms (SNPs) and 577,886 high-quality insertions/deletions (InDels). We further identified 29,157 candidate genes harboring predicted deleterious mutations (classified as high or moderate impact). Gene Ontology (GO) enrichment analysis indicated that genes associated with the spur-type trait were mainly enriched in molecular function and biological process categories. Specifically, variant genes related to molecular function were enriched in transferase and catalytic activities, while those in biological process were mainly involved in phosphorylation and phosphorus metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that candidate genes were significantly enriched in environmental information processing and metabolic pathways. Conclusions: These results will provide a genomic foundation for identifying genes controlling spur-type branching traits and facilitate the genetic improvement of spur-type apple. Full article