Search Results (742)

BK and JC Polyomaviruses (BKPyV and JCPyV) are ubiquitous human pathogens capable of establishing lifelong, asymptomatic persistence in the majority of the global population. While decades of research have focused on their lytic replication cycles and the development of severe diseases, such as polyomavirus-associated nephropathy (PVAN) caused by BKPyV and progressive multifocal leukoencephalopathy (PML) caused by JCPyV, their primary evolutionary strategy is one of persistence rather than pathogenesis. This review shifts the perspective from a replication-centric framework towards an evolutionary persistence model, detailing the multi-layered host and viral determinants that maintain the homeostatic balance. At the cellular level, viral genomes are restricted by chromatinization into minichromosomes and host S-phase licensing. These constraints are reinforced by innate immune sensing and adaptive T-cell and antibody responses that curtail systemic dissemination while permitting periodic, low-level urinary shedding, which is essential for horizontal transmission. In addition to these host barriers, the viruses utilize intrinsic regulatory mechanisms to prevent excessive replication and immune detection, including the stable archetype non-coding control region (NCCR), viral microRNAs that downregulate early gene expression, and the small t antigen (STAg). Finally, we address unresolved questions regarding the full spectrum of cellular reservoirs, the molecular triggers of reactivation, and the ecological factors shaping their transmission routes. Understanding these maintenance mechanisms is crucial for refining clinical interventions and managing the rare, devastating transitions from silent persistence to lytic disease. Full article

Currently, gold nanoparticles are increasingly used in targeted drug delivery nanostructures. However, their intrinsic catalytic activity is often overlooked when using them as a carrier. In this study, the interaction between the sotalol drug from the beta-blocker family and gold nanoparticles was investigated using capillary electrophoresis and high-performance liquid chromatography. Both methods showed that sotalol undergoes catalytic oxidation on the surface of citrate-stabilized gold nanoparticles into three products. Together with a cleavage of the isopropyl group from the nitrogen atom, the oxidation at the hydroxyl group occurs with the formation of a ketone. Analysis of electropherograms showed 100% conversion of sotalol after 48 h of incubation at a surface coverage of 1.2 × 10¹⁹ molecules per m². To examine the role of reactive oxygen species, the experiments were performed in oxygen-saturated and oxygen-deficient gold nanoparticle dispersions. The effects of radical scavenger additives and pH of nanoparticle dispersion were also assessed. The influence of surface ligands on sotalol conversion was studied using gold nanoparticles coated with thiols, surfactants, and polyelectrolytes. Based on comprehensive data, the mechanism of gold-nanoparticle-assisted multicenter oxidation of sotalol is proposed. Full article

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention. Full article

Glioblastoma multiforme (GBM) remains the most aggressive and therapeutically intractable primary brain tumor, with many patients experiencing rapid relapse despite maximal surgical resection followed by standard chemoradiation. This persistent failure reflects the convergence of profound tumor-intrinsic genetic heterogeneity and a highly dynamic, spatially structured, and immunosuppressive tumor microenvironment (TME). Together, these forces create strong selective pressures that fuel tumor evolution, intratumoral diversity, phenotype plasticity, diffuse invasion, and robust resistance to therapy. The TME of GBM is orchestrated through a complex interplay between diverse cellular constituents, including tumor-associated macrophages, reactive astrocytes, endothelial cells, pericytes, and GBM stem cells, and non-cellular components such as extracellular matrix remodeling, hypoxia, metabolic and nutrient gradients, and spatially patterned cytokine and chemokine signaling networks. Additionally, heterogeneity in blood–brain barrier (BBB) and blood–tumor barrier (BTB) complicates drug delivery and immune surveillance, reinforcing therapeutic resistance and regional tumor adaptation. Conventional two-dimensional cell cultures and animal models fail to sufficiently capture these multiscale, patient-specific interactions, limiting their translational predictive power. In this narrative review, we synthesize recent advances in GBM organoid technologies as physiologically relevant, three-dimensional platforms that more faithfully recapitulate TME for driving tumor evolution and treatment resistance. We compare complementary organoid strategies, including patient-derived GBM organoids that preserve native cytoarchitecture, cerebral organoid co-culture systems that reconstruct tumor–brain interactions, and advanced platforms incorporating immune and vascular features such as air–liquid interface cultures, microglia-enriched systems, and BBB/BTB-integrated models. Finally, we highlight emerging innovations such as spatial transcriptomics, organoid-on-a-chip systems, live imaging coupled with lineage tracing, genome engineering, and artificial intelligence integration that collectively position GBM organoids at the forefront of precision neuro-oncology, reproducing TME, enabling dynamic mapping of tumor evolution, and accelerating patient-specific therapeutic discovery. Full article

Volatile organic compounds can aggravate the atmospheric pollution and health risks due to their high toxicity and photochemical reactivity. Herein, a series of cobalt aluminate spinel catalysts with high efficiency was fabricated via a cost-efficient solvothermal method. Plentiful oxygen vacancies with negative charge were introduced adjacent to the octahedrally coordinated Co³⁺ species in CoAl₂O₄ catalysts, thereby generating the synergetic Co³⁺-oxygen vacancy (Ov) sites, which facilitated the rapid activation and migration of oxygen species. Accordingly, the superior catalytic activity was observed for 1Al-1Co even with lower cobalt due to the presence of abundant Co³⁺-Ov sites, revealing the predominant roles of synergetic sites in the toluene oxidation. Moreover, the 1Al-1Co catalyst exhibited the optimal intrinsic catalytic performance with the lowest activation energy of 161.2 kJ·mol⁻¹ and the highest specific toluene reaction rate of 3.18 × 10⁻⁵ mmol·h⁻¹·m⁻². In situ DRIFTS results further verified that oxygen vacancies and active Co³⁺ species could synergistically boost highly reactive oxygen species, which rapidly oxidize benzoate into maleic anhydride, achieving the efficient complete oxidation of toluene. Full article

This review explores the biological properties and application potential of native, technical, and modified lignins, with a focus on their antioxidant, antimicrobial, and anti-inflammatory activities. Native lignin generally preserves more of its original phenolic architecture and thus shows stronger intrinsic biological activity. This is likely due to its more homogeneous structure, which makes its physicochemical behavior more predictable compared with highly processed technical lignins. Among technical lignins, organosolv and soda lignin appear the most promising due to their sulfur-free nature, lower condensation, and higher reactivity. At the monomer level, catechol-type phenolics show the highest antioxidant potential, while vanillin remains the most attractive lignin-derived monomer because it combines bioactivity with direct application potential in food, pharmaceutical, and cosmetic systems. Comparison of modification strategies indicates that phenolic grafting, esterification, and carboxylation are more practical for scale-up than complex multistep polymer grafting. In particular, gallic acid grafting produced some of the strongest results, including near-complete 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging, 98.7% 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition, and a fourfold increase in phenolic hydroxyl content, whereas other modified lignins also showed improved antimicrobial and anti-inflammatory effects. Overall, mild and green lignin modification, especially with food-safe phenolic compounds, appears to be the most promising strategy for future food and human health applications. Full article

Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target. Full article

Daylight Saving Time (DST) creates abrupt, externally imposed circadian disruptions that can impair sleep regulation, hormonal balance, cognitive performance, and emotional stability. Although these effects are known in the general population, individuals with chronic mental illness, whose circadian systems are often intrinsically dysregulated, may face increased neuropsychological consequences. This comprehensive review synthesizes evidence from chronobiology, psychiatry, neuroscience, and population health to examine how DST-related circadian misalignment impacts cognitive functioning, mood regulation, suicidality risk, and symptom exacerbation across psychological disorders such as depression, anxiety disorders, bipolar disorder, post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and psychotic disorders. Following the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, a search of PubMed, PsycINFO, Scopus, and Google Scholar was conducted to identify studies published from 2000–2026 examining DST, circadian rhythm disruption, neuropsychological outcomes, and chronic mental illness. Empirical, theoretical, and mechanistic studies were included to ensure comprehensive synthesis. Across conditions, DST, particularly spring forward transitions, is associated with increased sleep disturbance, impaired executive functioning, reduced attention and working memory, heightened emotional reactivity, increased depressive symptoms, elevated risk of manic episodes, and short-term increases in suicidality. Neurobiological mechanisms include altered melatonin secretion, cortisol dysregulation, Hypothalamus Pituitary Axis (HPA-axis) activation, and clock-gene desynchrony. DST may function as a modifiable negative environmental influence capable of affecting neuropsychological functioning in vulnerable populations. These findings underscore the need for clinical awareness, preventive strategies, and policy reconsiderations, including calls to eliminate seasonal time changes. Standardizing DST-related research outcomes and expanding longitudinal, multi-site studies will be essential for advancing this emerging field. Full article

The output voltage harmonics of electric vehicle (EV) charging converters directly affect grid power quality. This paper proposes a harmonic analysis method based on geometric algebra (GA), which employs a multivector representation of signals and least squares estimation to accurately extract fundamental, integer-order, and inter-harmonics. A coupling coefficient is defined to quantify the phase correlation between frequency components. Based on measured data, harmonic characteristics under four typical operating conditions are analyzed, and an adaptive PID controller is designed to dynamically adjust the virtual resistance for harmonic suppression. The results show that the GA method significantly reduces spectral leakage under non-integer-period sampling conditions, with amplitude estimation errors below ±2%. The total harmonic distortion (THD) decreases with increasing active power and increases with reactive power injection. The droop coefficient exhibits a non-monotonic effect, while reducing the proportional gain raises the THD. Adaptive control reduces the average THD by 14.0–28.5% with a total response time of less than 0.05 s. The coupling coefficient C₁₃ is strongly positively correlated with THD and negatively correlated with the maximum Lyapunov exponent computed using the Rosenstein small-data method (correlation coefficient −0.85), confirming the intrinsic relationship between coupling and stability. Compared with fast Fourier transform (FFT) and other methods, GA achieves higher accuracy under short data records and non-integer-period sampling. This paper provides a complete theoretical framework and engineering solution for harmonic suppression in charging converters. Full article

Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brain tumor. Radiotherapy remains the standard of care, but tumors recur due to radioresistance. Tumor hypoxia contributes to radioresistance, and evidence of oxidative metabolism and hypoxia-associated transcriptomic programs suggests that hypoxia may be relevant in DIPG. We therefore investigated the FDA-approved mitochondrial inhibitor atovaquone as a strategy to target oxidative metabolism and enhance radiation response in DIPG. Methods: Patient-derived DIPG cell lines were used to evaluate atovaquone by extracellular flux analysis, hypoxia and reactive oxygen species assays, clonogenic survival assays, metabolomics, and RNA sequencing. To improve brain exposure, an amorphous solid dispersion (ASD) atovaquone formulation was evaluated and tested in an orthotopic DIPG model. Results: In patient-derived DIPG cultures, atovaquone suppressed mitochondrial respiration, reduced hypoxia-associated readouts, decreased HIF-1α expression in 3D models, and enhanced radiation response. At higher concentrations, atovaquone also increased oxidative stress and enhanced the radiosensitivity of DIPG monolayers. Transcriptomics analysis revealed disruption of cell-cycle and mitotic pathways, supporting additional treatment-associated effects beyond hypoxia reduction alone. Commercial and ASD formulations showed comparable in vitro activity. In vivo, ASD atovaquone combined with radiation prolonged survival in an orthotopic DIPG model. Conclusions: Targeting mitochondrial metabolism enhances radiosensitivity in DIPG and supports mitochondrial metabolism as a potential therapeutic weakness in this disease. Its effects are associated with reduced hypoxia-related signaling and broader metabolic and transcriptional changes. Full article

The transition to renewable carbon resources has positioned lignocellulosic biomass as a key feedstock for sustainable fuel and chemical production; however, its intrinsic recalcitrance limits efficient conversion. Dilute acid pretreatment functions as a homogeneous Brønsted acid catalytic system that selectively depolymerizes hemicellulose and disrupts lignin–carbohydrate complexes, while competing with consecutive sugar dehydration reactions, thereby enhancing downstream processing. This review presents a feedstock-specific analysis of acid catalyzed biomass deconstruction across agricultural residues, woody biomass, and energy crops, with xylose yield employed as a kinetically and mechanistically relevant descriptor of catalytic performance. By correlating proton activity, reaction severity, diffusion constraints, lignin chemistry, and mineral interference with observed conversion behavior, the work establishes a structure–reactivity–performance framework for biomass dependent hydrolysis. Particular attention is given to competing dehydration and condensation pathways that reduce pentose selectivity and generate fermentation inhibitors. The analysis identifies optimal severity windows for maximizing catalytic efficiency while suppressing degradation reactions and provides guidance for feedstock-tailored pretreatment and next-generation acid catalytic systems and reactor configurations in integrated biorefineries. Full article

The Fenton reaction remains one of the most widely investigated advanced oxidation processes for wastewater treatment due to its ability to generate highly reactive oxygen species capable of degrading persistent organic pollutants. However, classical homogeneous Fenton systems suffer from significant limitations, including narrow pH applicability, iron sludge generation, and poor catalyst reusability. In response, extensive research has focused on the development of heterogeneous and advanced Fenton-like catalysts aimed at overcoming these challenges while enhancing catalytic efficiency and operational stability. This review provides a comprehensive and critical analysis of the evolution of Fenton catalysis, from classical homogeneous systems to advanced materials, including nanostructured catalysts, carbon-based Fe–N–C systems, metal–organic frameworks, and single-atom catalysts. A unified evaluation framework is proposed, integrating key performance parameters such as catalytic activity, manufacturability, stability, and catalyst lifespan. Comparative analysis reveals that improvements in activity are often accompanied by trade-offs in cost and scalability, indicating that the most advanced materials do not necessarily provide the best practical performance. A life cycle-oriented perspective is incorporated, emphasizing catalyst reuse, lifespan, and iron leaching, and providing quantitative insight into cumulative catalytic performance. The results demonstrate that long-term efficiency is governed not only by intrinsic activity but also by durability and operational stability under realistic conditions. Finally, current challenges and future directions are discussed, including scalable synthesis, improved mechanistic understanding, and integration into hybrid treatment systems. This review bridges the gap between fundamental research and practical application by highlighting the importance of balancing performance, stability, and sustainability in the design of next-generation Fenton catalysts. Full article

Skin aging is driven by both intrinsic and extrinsic factors, including ultraviolet (UV) radiation and environmental stressors. Tumor necrosis factor-alpha (TNF-α) is a key pro-aging cytokine that promotes reactive oxygen species (ROS) production, leading to collagen degradation and inflammatory responses in skin cells. In this study, we investigated the protective effects of Prunus persica flower extract and its major constituents (1–4) against TNF-α–induced oxidative and inflammatory responses in human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs). In HDFs, the extract and isolated compounds significantly suppressed TNF-α–induced ROS generation and matrix metalloproteinase-1 (MMP-1) secretion while enhancing collagen synthesis. Notably, mandelamide (4) markedly reduced MMP-1 secretion (from 7.53 ± 0.28 to 2.97 ± 0.12, p < 0.001) and restored collagen levels (from 3.3 ± 0.03 to 19.1 ± 0.58, p < 0.001). In HEKs, mandelamide attenuated the production of inflammatory mediators under TNF-α stimulation and further suppressed MMP expression while restoring the mRNA expression of hyaluronan synthase genes under TNF-α/ interferon-γ (IFN-γ) co-stimulation. Importantly, mandelamide exhibited selective activity under inflammatory conditions without affecting basal cellular states. Collectively, these findings demonstrate that mandelamide is a key bioactive constituent of Prunus persica (P. persica) flowers and exerts protective effects against inflammation-associated skin aging through the modulation of oxidative stress and extracellular matrix homeostasis. Full article

The cathodic oxygen reduction reaction (ORR) remains a major kinetic barrier to high-efficiency proton exchange membrane fuel cells (PEMFCs), motivating the search for electrocatalysts that combine high activity, low metal usage, and long-term durability. This review examines single-atom catalysts (SACs) as an emerging platform for fuel-cell cathodes with particular emphasis on how atomic-level design, ORR mechanism, and practical deployment barriers are interrelated. The review discusses the key ORR pathways, intermediate binding principles, and scaling constraints that govern cathodic performance, and examines how metal-center selection, coordination-environment engineering, support regulation, synergistic multi-site construction, and morphology-controlled synthesis can be used to tune intrinsic activity and stabilize isolated active sites. It further highlights mechanistic insights from theoretical and operando studies, with emphasis on structure–activity relationships, dynamic active-site evolution, and approaches to mitigate scaling limitations. Major barriers to practical deployment, including carbon corrosion, demetalization, agglomeration, peroxide/reactive oxygen species attack, and the persistent gap between half-cell metrics and membrane electrode assembly performance, are also critically assessed. Rather than treating these topics separately, this review discusses them as connected factors that together determine the viability of SAC-based fuel-cell cathodes. Full article

Phenolic acids and flavonoids remain attractive redox-active scaffolds in medicinal chemistry, where they are widely used for early-stage prioritization and intrinsic reactivity ranking. However, direct comparisons under harmonized conditions remain scarce, limiting structure-based assessment. Here, a structurally diverse panel of hydroxybenzoic acids, hydroxycinnamic acids, flavonoids, a flavanone, and synthetic comparators was profiled using Folin–Ciocalteu response, ABTS radical cation scavenging, DPPH radical scavenging, and reducing power assays. The data reveal pronounced assay dependence alongside clear structure–activity trends. Gallic acid showed the strongest DPPH scavenging (half-maximal inhibitory concentration, IC₅₀ = 4.45 µmol/L) and reducing power (17.26 µmol TE/mg), while quercetin was consistently active across all four endpoints. Eriocitrin (IC₅₀ = 2.47 µmol/L) and rutin (IC₅₀ = 2.66 µmol/L) were particularly effective in the ABTS assay, showing that glycosylation does not abolish cation-radical scavenging. Lipinski’s Rule of Five and Veber oral-bioavailability criteria place these findings within a drug-likeness context. The results also highlight the limitations of the Folin–Ciocalteu assay as a standalone measure of total phenolic content, since its response depends strongly on hydroxylation density. Rather than asserting therapeutic efficacy, this work provides a harmonized comparative dataset identifying phenolic substructures with the strongest and most consistent redox activity, together with the structural drivers underlying these patterns. Full article