Search Results (3,184)

Dietary habits are pivotal in preventing chronic noncommunicable diseases, as vegetable-rich diets provide over 25,000 bioactive phytochemicals that modulate cell-signaling and metabolic pathways. Consequently, nutraceuticals and functional foods are increasingly recognized for their potential to prevent chronic pathologies. Among functional foods, Phaseolus vulgaris L. (common bean) stands out as a critical resource for global nutrition and disease prevention. Beyond its role in food security and environmental sustainability, the common bean offers extraordinary nutrient density, providing a unique “protein plus fiber” package and a source of health-promoting active ingredients. In this review, special emphasis is placed on the bean’s role in preventing or mitigating cardiovascular diseases and cancer, driven by bioactive molecules that modulate metabolic and cell-signaling pathways. Practical evidence of this growing interest is demonstrated by the surge in scientific literature over the last 50 years, as shown by PubMed and Scopus data. By synthesizing data from original research and existing reviews, this work highlights how incorporating common beans into the diet represents a strategic, health-conscious choice with potential therapeutic benefits for human health. Full article

The actinobacterial strain DEC002 was isolated recently from volcanic soils of Deception Island. Its taxonomic identity was resolved through a polyphasic strategy integrating morphology, physiological profiling, multilocus phylogeny, and genome-wide comparisons to resolve its identity. Concatenated core gene trees together with average nucleotide identity and digital DNA–DNA hybridization values place DEC002 within Actinacidiphila fildesensis with robust support. This is the first molecular confirmation of the species beyond King George Island and secures a second verified locality within the South Shetland Archipelago. Growth at low temperature with tolerance to moderate salinity indicates a psychrotolerant lifestyle. Cell-free supernatants inhibited representatives of foodborne Gram-negative and Gram-positive bacteria, including representatives of Enterobacteriaceae, Vibrio, Staphylococcus and Streptococcus. Genome analysis revealed enrichment in multiple biosynthetic gene clusters for nonribosomal peptides, polyketides, terpenes, and ribosomally synthesized and post-translationally modified peptides (RiPPs), supporting the biosynthetic potential of the strain. Functional annotations emphasize replication and repair modules, mobile element-associated proteins, helix–turn–helix regulators, and versatile transport systems, features coherent with cold stress and oligotrophic soils. Antibiotic susceptibility assays indicate a broad resistance phenotype under the experimental conditions tested, together with extracellular antimicrobial activity. These data refine the biogeography of A. fildesensis and indicate DEC002 as a credible Antarctic source of specialized metabolites with antimicrobial promise. Full article

C. burnetii (Cb) is an obligate intracellular bacterial pathogen that replicates within alveolar macrophages following aerosol infection. Unlike most intracellular bacteria, Cb establishes a lysosome-derived replicative niche (Coxiella-containing vacuole or CCV) through the action of its Type IVB secretion system (T4BSS). This system translocates a large repertoire of effector proteins into the host cytoplasm after phagosome acidification. These effectors interfere with diverse signaling pathways to co-opt host processes, such as vesicle trafficking, ubiquitylation, gene expression and lipid metabolism, promoting pathogen survival without triggering robust proinflammatory signaling or host cell death pathways. This effector-triggered immune silencing is particularly unique given the central role of macrophages as innate immune sentinels. In this review, we examine Cb T4BSS effectors that have been characterized as central determinants of innate immunity modulation. We discuss innate immune sensing pathways potentially engaged during infection, including Toll-like receptors, NOD-like receptors, RIG-I-like receptors, inflammasomes, and interferon signaling pathways, and highlight evidence indicating that these pathways are actively suppressed. Emphasis is placed on effector-mediated regulation of NF-κB signaling, type I interferon responses, and inflammasome activation. Finally, we address unresolved questions related to effector-triggered immunity, redundancy in immune suppression, and discrepancies between in vitro and in vivo infection models. Full article

Canine atopic dermatitis is a hereditary chronic inflammatory and pruritic skin disease, which is mediated by T cells and requires long-term, individualized management. In recent years, numerous studies have described a wide range of therapeutic approaches for canine atopic dermatitis, including fast-acting symptomatic treatments, long-term immune-modulating interventions, and strategies to support skin barrier function and microbial balance. This review summarizes the principal treatment modalities currently available, including glucocorticoids, cyclosporine A, mycophenolate, Janus kinase inhibitors, lokivetmab, and allergen-specific immunotherapy, as well as complementary strategies aimed at restoring skin barrier integrity. Emphasis is placed on the importance of a multimodal and personalized approach to optimize long-term disease control and improve quality of life in affected dogs. Providing an integrated overview of current evidence, this article aims to guide clinicians in making informed, evidence-based decisions and to support the safe and effective management of canine atopic dermatitis. Full article

Nano–bio hybrid catalysts have emerged as a promising platform for sustainable energy conversion by integrating the high selectivity of enzymes with the structural robustness and conductivity of nanomaterials. In recent years, the growing demand for clean energy technologies has driven the development of biohybrid systems capable of efficient electron transfer, enhanced catalytic activity, and improved operational stability. This review comprehensively discusses the design principles, mechanistic foundations, and performance metrics of enzyme–nanomaterial interfaces for energy-related applications. We first outline the fundamentals of enzymatic redox catalysis and the limitations of free enzymes in practical systems. Subsequently, we examine the functional roles of nanomaterials including carbon-based materials, metal and metal oxide nanoparticles, and two-dimensional platforms such as MXenes in facilitating enzyme immobilization and promoting direct or mediated electron transfer. Special emphasis is placed on engineering strategies at the bio–nano interface, including immobilization techniques, surface functionalization, and structural tuning to optimize catalytic efficiency. The review further highlights representative hybrid systems based on laccase, glucose oxidase, peroxidase, and hydrogenase enzymes, and evaluates their applications in biofuel cells, solar–bio hybrid systems, green oxidation reactions, and self-powered biosystems. Stability challenges, deactivation mechanisms, and enhancement strategies such as polymer coatings, cross-linking, and nanoconfinement are critically analyzed. Finally, emerging directions including artificial enzymes, AI-guided catalyst design, and self-healing bioelectrodes are discussed to provide a forward-looking perspective on next-generation sustainable bioelectrocatalytic systems. Full article

Various neuromodulatory benefits of the ketogenic diet (KD) have been demonstrated, yet its influence on reward learning and underlying mechanisms remain poorly defined. This study combined proteomics and metabolomics to identify key molecular changes in the hippocampus of KD-fed mice. Our analysis revealed significant upregulation of the “dopaminergic synapse” pathway, with CAMK2A emerging as a central regulator. In vitro, treatment of the hippocampal neuronal cell line HT22 with β-hydroxybutyrate (BHB), a primary KD metabolite, increased the protein expression of CAMK2A and increased the phosphorylation of its downstream target, GluA1. Crucially, Camk2a knockdown completely blocked BHB-induced p-GluA1 enhancement. To determine the behavioral relevance, we stereotaxically delivered AAV-shCamk2a into the hippocampus of KD-fed mice. Knockdown of Camk2a reversed the pro-reward effects of KD, as measured by the sucrose preference test and conditioned place preference test, without impairing general locomotor activity in the open field test. Together, these results suggest a novel BHB–CAMK2A–dopaminergic signaling axis through which KD enhances reward learning, thus bridging systemic metabolism with cognitive function and expanding our understanding of KD-mediated neuromodulation. Full article

In the era of highly integrated circuits, continuous miniaturization has significantly increased routing complexity, thereby directly impacting circuit performance. As process scaling advances and the number of on-chip metal layers increases, conventional standard cell libraries face limitations that cause severe routing bottlenecks. To overcome these limitations, this paper proposes a dual-component approach. First, we introduce a novel standard cell structure that improves routing flexibility by expanding the degrees of freedom for pin access, particularly in highly congested regions. Second, we present a physical design methodology specifically designed to ensure seamless integration with existing electronic design automation (EDA) tools, allowing new cells to be effectively placed and routed without major modifications to current flows. The proposed approach was validated using the open-source ASAP7 process design kit (PDK). Experimental results confirm significant reductions in via count and total wirelength, leading to improved routability, reduced power consumption, and enhanced performance. These findings demonstrate that combining the new cell architecture with a tailored design methodology provides a practical alternative to conventional solutions, enabling more efficient and scalable circuit designs for future technology nodes. Full article

Traumatic brain injury (TBI) represents a significant global health challenge with limited effective treatments. The secondary injury phase, characterized by persistent neuroinflammation, is a major contributor to long-term neurological deficits. Conventional therapies face substantial hurdles, including the blood–brain barrier (BBB), short therapeutic windows, and poor neuroregenerative capacity. Innovative biomaterials offer a promising platform to overcome these limitations by providing localized Drug Deliv., immunomodulation, and structural support for neural regeneration. This review outlines the pathological mechanisms of neuroinflammation and repair obstacles following TBI. It then systematically categorizes and discusses the mechanisms of various biomaterials—including natural, synthetic, nano-scale, composite, and intelligent materials—in modulating neuroinflammation. Furthermore, we elaborate on strategies for promoting neural repair, such as constructing regenerative scaffolds, delivering therapeutic agents (e.g., neurotrophic factors, stem cells, and exosomes), and remodeling the regenerative microenvironment. Special emphasis is placed on the emerging application of exosome delivery systems. Finally, we address the challenges in clinical translation and present future perspectives on smart materials, multi-modal systems, and personalized therapies, highlighting the transformative potential of biomaterials in TBI management. Full article

Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and cellular homeostasis, and their dysregulation is now recognized as a hallmark of cancer. Over the past decades, extensive research has demonstrated that diverse ncRNA classes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other small ncRNA species, participate in complex regulatory networks that influence tumor initiation, progression, metastasis, and therapy response. Through mechanisms such as transcriptional regulation, post-transcriptional gene silencing, epigenetic modulation, and competitive endogenous RNA interactions, ncRNAs shape the molecular circuitry underlying cancer development. In addition to their functional roles in tumor biology, many ncRNAs are released into biological fluids and can be detected as circulating molecules in blood, urine, saliva, and other biofluids. Their remarkable stability in extracellular environments has generated considerable interest in their use as minimally invasive biomarkers in liquid biopsy applications. Emerging evidence has shown that circulating ncRNAs (c-ncRNAs) can support cancer detection, disease stratification, and treatment monitoring. This narrative review provides an integrated view that links ncRNA-mediated regulatory networks with their application as liquid biopsy biomarkers, positioning ncRNAs as comprehensive indicators of tumor conditions. Particular emphasis is placed on c-ncRNA biomarkers, the integration of multiple ncRNA classes, and multi-analyte biomarker strategies that combine ncRNAs with complementary circulating molecules such as cell-free DNA and protein markers. Finally, we discuss the technical and clinical challenges that currently limit the translation of ncRNA-based diagnostics into clinical practice and highlight future directions for advancing ncRNA-guided liquid biopsy approaches in precision oncology. Full article

This study aimed to investigate the effects of resveratrol (RES) and carboplatin (CPT), alone and in combination, on cell viability, apoptosis, cell cycle progression, mitochondrial function, and oxidative stress in Y79 retinoblastoma (RB) cells. Particular emphasis was placed on evaluating the synergistic potential of the combination and elucidating the interconnected molecular mechanisms underlying its anticancer effects. Y79 cells were treated with RES, CPT, and their combinations. Cell viability and synergy were assessed using the MTT assay and combination index (CI) analysis. Apoptosis (annexin V/PI), cell cycle distribution (propidium iodide (PI) staining), intracellular ROS production (DCFH-DA), and mitochondrial membrane potential (JC-1) were evaluated by flow cytometry. ROS dependency was further examined using N-acetylcysteine (NAC) pretreatment. Expression levels of apoptosis- and cell cycle-related genes (BAX, BCL-2, CASP3, CASP9, CCNB1, and CDK1) were analyzed by RT-qPCR. Cytoskeletal alterations were assessed by immunocytochemistry. In addition, the antitumor effects of the combination were validated in a three-dimensional (3D) tumor spheroid model. RES and CPT reduced cell viability in a dose- and time-dependent manner and demonstrated synergistic effects (CI < 1) at selected concentrations. Combination treatment significantly increased apoptosis, induced G2/M phase arrest, enhanced ROS accumulation, and promoted mitochondrial depolarization compared with single-agent treatments. NAC pretreatment attenuated ROS generation and partially restored cell viability, supporting a contributory role of oxidative stress in combination-induced cytotoxicity. At the transcriptional level, the RES + CPT combination significantly increased the BAX/BCL-2 ratio and upregulated CASP3 and CASP9 expression, while downregulating CCNB1 and CDK1, consistent with mitochondrial apoptotic activation and G2/M arrest. Immunocytochemical analysis revealed pronounced cytoskeletal disruption and apoptotic morphology in the combination group. Importantly, in the 3D spheroid model, co-treatment markedly reduced spheroid size and viability and enhanced cell death compared with monotherapies. The combination of RES and CPT exerts a synergistic anticancer effect in Y79 RB cells through coordinated mechanisms involving ROS accumulation, mitochondrial dysfunction, caspase activation, and G2/M phase arrest. The attenuation of cytotoxicity by NAC and the validation of efficacy in a 3D tumor spheroid model strengthen the mechanistic relevance of these findings. These results support further preclinical investigation of this combination strategy in in vivo models and normal retinal cell systems. Full article

To reduce the impact of aviation on the environment, a multitude of concepts must be evaluated to enable subsequent targeted developments. The reduction of on-board energy requirements through the aero-propulsive coupling of a box-wing configuration can represent one possible approach. It enables a decreased environmental impact by cutting the energy required and—in the configuration under consideration—by using hydrogen fuel cells as power generators. To fully exploit the advantages of such a concept, different propulsion system architectures were analyzed. Decision criteria were developed to select the most sensible powertrain architecture for the box-wing regional aircraft considering component and aircraft-level effects in a two-phased approach; following a qualitative preselection, a multi-criteria decision analysis was employed. Fuselage, fairing and nacelle-bound architecture options for the 70-passenger aircraft with a projection of its powertrain characteristics into the year 2045 are shown and compared. The placement of propulsion system components as well as their characteristics play a major role in the downselection of propulsion architecture options, especially considering the requirements placed by the liquid hydrogen energy storage. Due to low aerodynamic interference with the specific aero-propulsive arrangement, its high safety characteristics, synergistic potential with other systems, and not least, ease of integration, a compact propulsion system placement forward of the front hydrogen tank is considered most beneficial on aircraft level. Full article

Nitrate-rich vegetables are increasingly recognised as a key subgroup of phytochemical-dense foods that have significant potential for preventing and managing chronic diseases. Although dietary nitrates were historically approached with caution due to concerns about nitrosamine formation, contemporary evidence highlights their beneficial effects on vascular, metabolic and cognitive functions. Ageing is characterised by endothelial dysfunction, impaired nitric oxide (NO) synthesis and increased oxidative stress, which elevates cardiovascular risk. In this context, nitrate-rich vegetables offer a natural way to restore NO bioavailability and support cardiometabolic health. This narrative review provides an integrative overview of nitrate-rich vegetables as sources of bioactive phytochemicals with therapeutic relevance. We summarise the biochemical pathways of nitrate and nitrite metabolism, including the enterosalivary nitrate–nitrite–NO cycle, the role of oral microbiota, and red blood cell-mediated nitrite reduction. Particular emphasis is placed on NOS-independent NO production, which becomes increasingly important with age, and on the synergistic interactions between dietary nitrates and other phytochemicals such as polyphenols, vitamin C, flavonoids and betalains. These compounds enhance NO stability, reduce oxidative stress, modulate inflammatory signalling and support mitochondrial function, thereby amplifying the health benefits of nitrate-rich vegetables. Beetroot, with its high nitrate content and distinctive antioxidant profile, is highlighted as a prime example. Clinical and mechanistic studies suggest that nitrate-rich vegetables may lower blood pressure, improve endothelial function and cerebral perfusion, enhance cognitive performance and muscle oxygenation, and increase exercise efficiency, particularly in older adults. Additional benefits include anti-inflammatory effects, modulation of platelet function and improvements in metabolic parameters, all of which are relevant to the prevention of chronic diseases such as hypertension, type 2 diabetes and atherosclerosis. While dietary nitrate is generally considered low-risk for healthy adults, caution is warranted in susceptible populations, such as infants and individuals with impaired renal function. Finally, significant research gaps remain, including the need for long-term, well-controlled trials and personalised strategies that account for variability in microbiota composition and nitrate metabolism between individuals. Full article

Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) play a pivotal role in promoting osteogenesis and angiogenesis that concurrently take place during bone regeneration. The rapid degradation and diffusion of these growth factors, combined with the potential side effects associated with their exogenous insertion, limit their applications. To overcome these shortcomings, we developed a controlled release system for BMP-2 and VEGF on microspheres comprising gelatin (Gel) and polyvinyl alcohol (PVA). We fabricated Gel–PVA microspheres using a constant Gel concentration of 10% w/v and a varied PVA concentration of 0, 5, and 10% w/v (Gel–PVA0%, Gel–PVA5%, and Gel–PVA10%, respectively). The microspheres were loaded with the model protein bovine serum albumin (BSA) first. The Gel–PVA10% microspheres demonstrated significantly higher loading capacity and encapsulation efficiency, as well as lower cumulative release rate, compared to the Gel–PVA5% ones when loaded with BSA. Thus, the microspheres with the Gel–PVA10% composition were selected for loading with BMP-2 and VEGF. Kinetic studies of BMP-2 and VEGF loaded into Gel–PVA10% microspheres indicated similar results to those with BSA. The microsphere concentration with the optimal cytocompatibility was 0.5 mg/mL, and it was applied for the assessment of the osteogenic differentiation using bone marrow-derived mesenchymal stem cells (MSCs), and for the angiogenic differentiation in Wharton jelly and adipose-derived MSCs. Alkaline phosphatase activity, collagen secretion, and calcium mineralization were significantly upregulated in the presence of BMP-2-loaded microspheres, while tubular formation and PECAM-1 secretion were significantly higher in VEGF-loaded microspheres compared to the unloaded control, demonstrating their effectiveness as drug delivery carriers. Full article

Antimicrobial peptides (AMPs) have re-emerged as promising anti-infective agents, particularly against multidrug-resistant bacteria; however, their therapeutic development remains constrained by proteolytic degradation, host cell toxicity, and rapid systemic clearance. Rather than focusing solely on sequence discovery, recent efforts have shifted toward structural and supramolecular modification strategies aimed at improving stability, selectivity, and pharmacological performance. This review critically analyzes intramolecular modifications—including phosphorylation, glycosylation, acetylation, methylation, and backbone cyclization—that modulate peptide conformation and resistance to enzymatic degradation. In parallel, extramolecular approaches such as PEGylation, lipidation, and conjugation to antibiotics, siderophores, or antibodies are examined in the context of enhanced targeting and prolonged bioavailability. Particular emphasis is placed on localized delivery systems, including hydrogels, polymeric films, and nanofibrous scaffolds, which enable spatially controlled administration and mitigate systemic exposure. By integrating evidence from ex vivo and in vivo infection models, this work delineates the translational potential and remaining bottlenecks of chemically engineered AMP platforms for skin and soft tissue infections. Full article

In October 2025, an outbreak occurred among farmed Chinese rice-field eels (Monopterus albus) in Jiangxi, China. A Nocardia seriolae strain designated JXMa251025, which has not been previously documented in Chinese rice-field eels, was isolated from moribund fish exhibiting multiple white nodules of various sizes in visceral tissues. Histopathological examination revealed multi-organ damage, including necrosis of liver cells, granulomatous inflammation with hemorrhage in visceral organs, and necrosis of renal glomeruli and tubules accompanied by vascular congestion. Artificial infection trials confirmed that strain JXMa251025 reproduced clinical signs consistent with those observed in the natural outbreak. Infection experiments resulted in 100% mortality in high-concentration challenge groups, with a median lethal dose (LD₅₀) of 9.76 × 10⁵ CFU/mL, indicating high virulence. Whole-genome sequencing revealed a circular chromosome of 8,295,032 bp with a GC content of 68.10%. The genome contains 66 tRNA genes and four copies each of the 23S, 16S, and 5S rRNA genes. Phylogenomic analysis placed strain JXMa251025 within a clade of Nocardia seriolae strains with approximately 99% bootstrap support, confirming its identification as Nocardia seriolae. Further genomic screening identified 253 potential virulence genes associated with nutrient metabolism, regulatory systems, immune modulation, effector delivery, and exotoxin production. Antibiotic susceptibility testing showed that strain JXMa251025 was sensitive to seven antibiotics: ciprofloxacin, neomycin, enrofloxacin, florfenicol, gentamicin, amikacin, and doxycycline. This study represents the first report of Nocardia seriolae infecting Chinesse rice-field eels, providing useful descriptive information for disease diagnosis and reference. Full article