Search Results (754)

Background: Colorectal cancer (CRC) is characterized by pronounced genetic and phenotypic heterogeneity, which substantially influences therapeutic response and limits the efficacy of uniform treatment strategies. Cannabinoid-derived phytochemicals and boron-based compounds have independently been reported to modulate cancer cell proliferation, survival, and redox balance. However, the extent to which these agents interact at the cellular level and whether such interactions are dependent on tumor-specific molecular contexts remains poorly defined. Methods: Sodium pentaborate (NaB) was combined with non-cytotoxic concentrations of cannabidiol (CBD) or cannabigerol (CBG) and evaluated in HCT-116 and HT-29 colorectal cancer cell lines. Cell viability and drug interactions were assessed by MTS and combination index analyses. Apoptotic responses were examined by Annexin V/PI staining, caspase-3/7 activity assays, and transcriptional profiling of apoptosis-related genes. Cell cycle dynamics and proliferation-associated markers were analyzed by flow cytometry and quantitative PCR. In parallel, ferroptosis-associated gene expression patterns were investigated to evaluate alterations in redox and iron metabolism pathways. Results: NaB–cannabinoid combinations produced divergent biological outcomes depending on cellular background. HT-29 cells exhibited dose-dependent antiproliferative responses to NaB + CBD and NaB + CBG, with synergistic interactions observed only at selected dose combinations accompanied by increased early apoptosis. In contrast, HCT-116 cells primarily responded with cell cycle arrest and transcriptional stress signaling rather than enhanced cytotoxicity. Modulation of ferroptosis-related gene expression further indicated differential redox adaptation between the two cell models. Conclusions: NaB–cannabinoid combinations elicit distinct biological outcomes in colorectal cancer cells that are strongly determined by cellular context. While HT-29 cells are selectively sensitized to combination dose level, HCT-116 cells predominantly respond through cell cycle arrest and adaptive stress-response pathway activation. These findings emphasize the necessity of context-aware combination strategies and provide a mechanistic framework for the further development of boron–cannabinoid-based therapeutic approaches in colorectal cancer. Full article

MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p < 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax/Bcl-2 ratio and reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V/propidium iodide (Annexin V/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid–drug bioactivity. Full article

Long-term degradation of vanadium redox flow batteries (VRFBs) is strongly coupled with the evolution of discharge direct current internal resistance (DCIR). This work employs 213 constant-current cycles on a 4 cm² single cell to examine the associations between discharge DCIR and capacity, discharge voltage and efficiencies. The average values of the initial 10 cycles were used as the baseline. Multiple statistical approaches, including detrending, differencing, moving-block bootstrap, and internal chronological holdout evaluation were used to assess the influence of shared temporal trends and serial dependence. Self-calculated DCIR matches test records closely with merely 1.03% average relative error. After trend correction, normalized DCIR maintains a strong negative correlation with normalized capacity. The established free-intercept quadratic model achieved the best full-data fitting performance, with an R² of 0.99593 and a root mean square error (RMSE) of 0.00524. The fitted empirical relationship indicates that equal increments in normalized DCIR are associated with larger concurrent capacity-state reductions in the higher-resistance region. During the internal chronological holdout evaluation, the DCIR-based model yielded an RMSE of 0.00854. These results establish a statistically robust DCIR–capacity relationship over long-term cycling and demonstrate the potential of routinely recorded discharge DCIR as a low-cost concurrent capacity-state indicator, providing a quantitative foundation for its future extension to broader VRFB operating scenarios. Full article

Commercial carbon-based electrodes such as graphite felt and carbon felt in all-vanadium redox flow batteries suffer from inherent drawbacks, including slow vanadium ion redox kinetics, insufficient intrinsic catalytic activity, fiber corrosion, and functional group loss under strong acidic oxidative conditions, significantly limiting battery energy efficiency and long-term operational reliability. Rare-earth elements, with their unique 4f electron shell structure, tunable electronic levels, abundant surface oxygen vacancy defects, and strong coordination ability, offer a dual pathway—electronic and microstructural modulation—to optimize the interfacial electrocatalytic behavior of carbon electrodes, providing a novel materials system to overcome electrode performance bottlenecks in vanadium batteries. This review systematically summarizes recent advances in rare-earth-functionalized carbon electrodes and electrocatalysts for vanadium redox flow batteries, elaborating on core modification strategies, performance enhancement trends, and synergistic catalytic mechanisms. It also presents quantitative experimental results from the literature to clearly demonstrate the benefits: CeO₂-modified graphite felt at 0.2 wt% shows a 10.8% increase in energy efficiency compared to pristine graphite felt at a current density of 200 mA·cm⁻², while multi-rare-earth co-doped carbon electrodes achieve a 65% reduction in charge transfer resistance relative to unmodified electrodes. The review systematically categorizes two dominant modification routes—surface nano-decoration with rare-earth oxides and lattice bulk doping with rare-earth elements—and summarizes design principles and enhancement mechanisms of diverse composite catalytic systems, including rare-earth–carbon nanocomposites, rare-earth-based heterojunctions, and porous rare-earth catalysts. It further analyzes critical challenges in current research, such as unclear long-term stability mechanisms, high costs of high-purity rare-earth raw materials, immature large-scale fabrication processes, and limited in situ dynamic characterization techniques. Compared with existing reviews, this work clearly distinguishes between surface loading and lattice doping as two distinct rare-earth modification approaches, clarifying their differences in active site formation, electronic regulation logic, and cycling stability. It establishes a comprehensive theoretical framework for the coupled electronic–geometric effects in rare-earth-modified carbon electrodes, linking the intrinsic physicochemical properties of rare earths, material microstructure design, and battery electrochemical performance. Moreover, it innovatively proposes a pathway toward full-lifecycle recycling and reuse of rare-earth-based catalytic electrodes for industrial implementation. This review provides a complete theoretical foundation for developing high-performance, long-cycle, low-cost vanadium redox flow battery electrode materials and supports their engineering scale-up, contributing to the development of large-scale, long-duration energy storage technologies. Full article

Although biochar has been widely applied for chromium (Cr)-contaminated soil remediation, its direct mixing with soil is limited by poor recoverability and insufficient long-term stability, while the role of groundwater table fluctuation (GTF) is often overlooked. In this study, we developed a biochar tubule-based strategy using Fe, Mg, and Al dual-modified sludge biochar (SBC) for Cr immobilization, and evaluated its performance, mechanisms, and engineering potential under GTF conditions. The demonstrated that modification substantially improved the microstructure and surface chemical properties of biochar. Experiments showed that Fe-SBC exhibited optimal immobilization performance, followed by Mg-SBC, Al-SBC, and SBC. Compared with the controls, Fe-SBC reduced Cr release by 97.66% (slightly contaminated) and 71.40% (heavily contaminated), while the corresponding Cr-retained amounts (predominantly in stable fractions) increased by 155.68% and 257.42%; meanwhile, 7.05% and 9.05% of the total amounts were removed by the biochar tubule, respectively. Mechanistic analysis revealed that Cr(VI) was transported into the biochar tubules via tubule-induced preferential flow and subsequently immobilized through synergistic adsorption, reduction, complexation, and precipitation processes, with redox reactions playing a predominant role (67.37–98.87%). Additionally, the environmental risks, application cost and prospects of biochar were evaluated. This study provides new insights into sludge resource utilization and soil immobilization techniques. Full article

Redox flow batteries (RFBs) are an interesting option for long-term energy storage. A well-performing membrane sits at the heart of the electrochemical battery cell and should effectively mitigate crossover of active species while minimizing resistance. However, current commercial membranes are rather expensive and demonstrate sub-optimal performance, leading to an extensive search for alternatives. Research on membranes for RFBs has long been dominated by dense ion-exchange membranes and porous membranes, both potentially with fillers. In recent years, increased interest in alternative morphologies such as thin-film composites (TFCs) has ignited new research directions. TFCs consist of a thin dense layer on top of a porous support, aiming to merge the advantages of both. Traditionally, TFCs are made using polyamide top layers. In this paper, a novel chemistry is developed with increased chemical stability for RFBs. Poly(vinylbenzyl chloride) is crosslinked interfacially with a diamine, demonstrating for the first time the potential of support-mediated interfacial crosslinking with two immiscible solvents. Optimization of the support, amine crosslinker, reaction time and synthesis procedure allowed a shift of the trade-off between vanadium crossover and proton transport, highlighting the opportunities for this promising TFC chemistry. Full article

Background/Objectives: Dietary nitrate, long framed through food-safety concerns about N-nitroso compound formation, is now also recognised as a substrate of the nitrate–nitrite–nitric oxide pathway. This review aims to define the mechanistic, dietary and host conditions under which nitrate bioactivation becomes functionally relevant, with particular attention to its microbial determinants and to the level of inference the evidence actually supports. Methods: We conducted a narrative review supported by a structured literature search (PubMed, Scopus and Web of Science; 1 January 1976 to 14 February 2026; full-text, peer-reviewed, English-language, human-relevant sources; 148 sources retained, of which 93 contributed to the evidence synthesis), with narrative synthesis of mechanistic, interventional, observational and regulatory sources addressing dietary source and food matrix, enterosalivary metabolism, oral and gut microbial function, and health-related outcomes. A PRISMA-style flow diagram summarises the documented screening and inclusion process, and the complete database-specific search strategies are provided in Supplementary Table S1; no meta-analysis was performed because of substantial heterogeneity in designs and outcomes. Results: Within the canonical enterosalivary pathway, nitrate-to-nitrite bioactivation is predominantly microbiota-dependent and downstream conversion is chemically conditional: within the enterosalivary cycle, nitrate-reducing bacteria on the tongue dorsum generate the nitrite required for downstream nitric oxide formation, and its conversion in the stomach depends on pH and on matrix constituents. Dietary source and food matrix therefore govern both the delivered dose and the chemistry that follows, so vegetables, beetroot products, inorganic salts, drinking water and processed meat are not interchangeable exposure models. The oral microbiota is the principal microbial determinant of the response, whereas the gut microbiota acts as a context-dependent modifier of intestinal redox tone, barrier function and microbial ecology, supported by markedly weaker human evidence. Nitrate-rich sources reproducibly raise nitrate and nitrite biomarkers, with variable effects on blood pressure, vascular function and exercise efficiency, limited or inconsistent effects on cognition, cerebral blood flow and metabolic endpoints, and a safety profile whose interpretation depends on food matrix, dose, exposure pattern and host context rather than concentration alone. Conclusions: We propose the Source–Matrix–Microbiota–Host (SMMH) framework, in which biological impact depends on the interaction between dietary source and dose, food matrix, microbial nitrate-reducing capacity and host susceptibility, rather than on nitrate dose alone, and in which pathway-level, physiological and clinical evidence are kept explicitly distinct. The evidence base is mechanistically robust for the oral microbiota, considerably less defined for the gut microbiota, and variable at the level of validated clinical endpoints; it does not yet support source-independent guidelines or population-level recommendations. Full article

Neurologic manifestations of long COVID, also called neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC: NP) include persistent alteration of cognitive functions. We investigated whether these could be driven by immune perturbations. We combined flow cytometry (FC), sleep profiling, and single-cell RNA sequencing of peripheral blood immune cells from older adult (>55 years) individuals with and without NP to evaluate relationships with objective cognitive performance. NP participants showed reduced numbers of blood monocytes with increased mitochondrial superoxide, indicating an altered monocyte mitochondrial redox state. Higher peripheral capillary oxygen saturation (SpO₂) was associated with better processing speed in NP participants. Monocyte transcriptional analyses identified mitochondrial adenosine triphosphate (ATP) synthase/Complex V (Complex V) pathway associated with cognitive performance in people without NP; this coupling was abrogated in NP patients, in whom cognitive performance instead showed an opposite relationship with Complex V. Shared leading-edge genes defined a 13-gene monocyte anchor representing this cognition-associated NP phenotype. Higher anchor scores were associated with coordinated oxidative phosphorylation and cytotoxic programs across CD3⁺ T-cell subsets in individuals without NP, but not in NP participants. T-cell receptor stratified analyses showed that this altered relationship occurred in both expanded and unexpanded T-cell populations. FC correlations also supported reduced monocyte-to-lymphocyte mitochondrial coordination in NP. These exploratory findings identify a sleep and cognition-linked monocyte mitochondrial phenotype characterized by altered myeloid–lymphoid immune coordination in NP. Full article

Electron upconversion, the promotion of a single electron into a higher-energy orbital as the direct consequence of an exergonic chemical step, has been studied mainly as a way to generate transient “super-reductants” that hand off a high-energy electron to an external acceptor. Here, we explore a different application of this phenomenon. Using density functional theory calculations in combination with a survey of enzyme-catalyzed processes, we show that the same upconverted radical anions can act intramolecularly to expel otherwise recalcitrant leaving groups, accomplishing transformations that are formally two-electron, heterolytic eliminations. Taking redox dehydratases as the starting inspiration, we compare the energetics of hydroxide elimination from a ketyl radical anion against the classical, stereoelectronically favorable enolate route. Elimination through the upconverted ketyl is thermodynamically preferred by ~10 kcal/mol, and although this preference diminishes, it does not disappear even for a remote, non-activated γ-hydroxyl group. The orbital picture is simple: occupation of a high-energy antibonding orbital is relieved when electron density flows into the σ* orbital of the scissile bond, so that bond cleavage demotes the electron into a lower-energy, non-bonding orbital. Thus, upconversion is not only a route to strong reductants; it is a general activation mode for bond cleavage. The same logic applies to the C–O, C–N, and C–S eliminations carried out by diol dehydratases, 4-hydroxybutyryl-CoA dehydratase, certain glycyl radical enzymes, and ribonucleotide reductase under mild, metal-sparing, anaerobic conditions, and it suggests design principles for synthetic eliminations that avoid strong acids, strong bases, and pre-activated substrates. Full article

MOF-derived catalysts have considerable potential for aqueous contaminant control, but their practical application is often constrained by the aggregation and difficult recovery of powder catalysts. In this study, a self-supporting N-doped Fe/Ni-based monolithic catalyst, denoted N-101-NFF, was fabricated through the in situ growth of an Fe-based MOF precursor on nickel–iron foam followed by pyrolysis. Under the conditions of 50 mg/L chlortetracycline (CTC), 0.08 mmol/L peroxymonosulfate (PMS), and an effective catalyst area of 1 cm², N-101-NFF degraded 90.3% of CTC within 60 min and maintained a degradation efficiency of 88.6% after five consecutive cycles. Quenching experiments and EPR analysis indicated the involvement of •OH, SO₄•⁻, O₂•⁻, and ¹O₂ in CTC degradation. Electrochemical measurements indicated improved interfacial charge-transfer characteristics, while post-reaction XPS analysis revealed changes in the Fe and Ni valence states and surface N- and O-containing groups, supporting the involvement of Fe and Ni redox cycling and these surface functionalities in PMS activation. In a fixed-bed reactor, the system maintained more than 86% CTC removal over 24 h of continuous-flow operation at a CTC feed rate of 200 mL/h. These results highlight the potential of N-101-NFF as a recoverable monolithic catalyst for PMS-based treatment of antibiotic-contaminated water. Full article

Testicular torsion is a time-critical urological emergency in which surgical detorsion, the only accepted treatment, simultaneously rescues and injures the gonad. Restoration of blood flow triggers a burst of reactive oxygen and nitrogen species, neutrophil recruitment, inflammasome activation, and regulated germ cell death, so that a substantial proportion of anatomically salvaged testes still undergo atrophy and functional loss. A large experimental literature, running to several hundred reports, has shown that antioxidants of almost every chemical class attenuate this injury in rodent models, yet no antioxidant has entered routine clinical use as an adjunct to detorsion in humans, and we are not aware of any adequately powered randomized trial in this setting. This narrative review integrates the redox pathophysiology of testicular ischemia–reperfusion injury with an appraisal of the agents tested against it, and then asks why the translational gap has proved so durable. We examine model heterogeneity, the dominance of pretreatment designs that cannot be reproduced in an emergency department, the reliance on short-term surrogate biochemistry rather than fertility endpoints, and the sobering precedents of neuroprotection and cardioprotection. We close with a roadmap for first-in-human evaluation, covering candidate prioritization, route and timing of administration, biomarker selection, and a feasible trial architecture. Full article

Deep eutectic solvents (DESs) are promising electrolyte media for solar redox flow batteries, but their high viscosity and sluggish ion transport can limit redox-species diffusion, interfacial charge transfer, and photocharging performance. This study aimed to regulate a TEMPO/VCl₃-based DES electrolyte by controlled water addition for a Yb,Er-doped TiO₂–g-C₃N₄ photoanode solar redox flow battery. DES electrolytes containing 0, 5, 10, and 15 wt% added water were evaluated by physicochemical, electrochemical, and photoelectrochemical measurements, while full-cell tests compared pristine DES with the half-cell-selected 10 wt% electrolyte. While water incorporation systematically enhanced bulk redox-species transport, the optimal photoelectrochemical performance was achieved at 10 wt% water, rather than 15 wt%. Although the 15 wt% electrolyte exhibited the highest bulk diffusivity, the 10 wt% composition provided the most favorable balance between mass transport and interfacial charge transfer kinetics. The Raman spectra supported water-induced reorganization of the bulk DES hydrogen-bonding network. Full-cell tests confirmed that the 10 wt% water-containing electrolyte delivered higher and more stable photocharging responses than pristine DES over 20 cycles. These results indicate that moderate water regulation is an effective strategy for improving DES-based solar redox flow batteries. Full article

Polyploidization can generate morphological and physiological variation in plants, but the molecular basis underlying leaf trait changes after genome doubling in grapevine remains insufficiently understood. This study aimed to characterize phenotypic, physiological, transcriptomic, and metabolomic differences between diploid and induced autotetraploid plants of ‘Thompson Seedless’ and to identify biological processes potentially associated with the observed leaf trait variation. In this study, autotetraploid plants were induced from axillary buds of ‘Thompson Seedless’ using colchicine treatment, and ploidy levels were confirmed by flow cytometry and chromosome counting. Phenotypic, physiological, transcriptomic, and metabolomic analyses were performed to compare diploid and tetraploid plants. Compared with diploids, tetraploids exhibited enlarged leaves, reduced plant stature, larger but less dense stomata, increased chloroplast number in guard cells, and higher total chlorophyll and carotenoid contents. Fv/Fm remained unchanged, whereas increased Vj and decreased ψEo and φEo suggested differences in electron transport-related characteristics beyond QA. Transcriptomic analysis identified 1564 differentially expressed genes, and metabolomic profiling detected 618 differentially accumulated metabolites. Integrated analyses highlighted coordinated molecular differences associated mainly with cell-wall processes, secondary metabolism, redox-related functions, and carbon-related pathways. These findings identify candidate biological processes for future functional validation and provide a basis for evaluating the potential value of autotetraploid germplasm in grapevine breeding. Full article

Background and Objectives: Arterial hypertension is a major cause of systemic microvascular damage involving target organs such as the kidneys and retina. Because the retinal and renal microcirculations share common pathogenic mechanisms, retinal imaging may provide non-invasive biomarkers of hypertensive microvascular injury. This study investigated the association between the renal resistive index (RRI), systemic oxidative stress biomarkers, and retinal abnormalities in patients with essential hypertension. Retinal structural and microvascular parameters were evaluated using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Materials and Methods: In this cross-sectional exploratory study, 32 patients with essential hypertension (64 eyes) underwent comprehensive ophthalmic examination, OCT/OCTA imaging, renal Doppler ultrasonography for RRI assessment, and evaluation of systemic oxidative stress biomarkers. Associations between renal, ocular, and biochemical parameters were analyzed. Results: No significant differences were observed in most global OCT/OCTA parameters. However, higher RRI values were associated with localized macular thinning and reduced optic nerve head perfusion metrics. Patients with RRI values ≥ the 75th percentile showed significantly increased hydrogen peroxide levels (p = 0.004) and reduced nitric oxide bioavailability (p = 0.033), together with thinning of selected inner macular sectors. A trend toward reduced optic nerve head flow index was also observed, suggesting early microvascular impairment that may not be detected by conventional global OCT measurements. Conclusions: These exploratory findings suggest a possible association among increased renal vascular resistance, oxidative stress, and localized retinal structural alterations in patients with essential hypertension. The coexistence of systemic redox imbalance and sectorial retinal changes supports the hypothesis of an eye–kidney–redox interplay and indicates that advanced retinal imaging, particularly detailed sectorial OCT analysis, may represent a complementary non-invasive tool for the early detection of subclinical microvascular damage. Larger prospective studies are warranted to validate these findings. Full article

Background/Objectives: Advanced prostate cancer remains difficult to treat because docetaxel, although clinically important, is limited by systemic toxicity, poor tumor selectivity, and acquired resistance. Camptothecin is a potent anticancer agent, but its clinical application is restricted by poor solubility and instability. This study investigated the synergy between docetaxel and camptothecin and developed transferrin-conjugated, camptothecin-bearing dendrimersomes entrapping docetaxel as a targeted nanocarrier for prostate cancer therapy. Methods: Drug synergy was evaluated in PC3-Luc cells using an MTT assay and combination index analysis. Transferrin-conjugated, disulfide-linked camptothecin-bearing PEGylated DAB dendrimers were synthesized and characterized by ¹H-NMR, critical aggregation concentration analysis, transmission electron microscopy, and entrapment efficiency measurements. pH- and redox-dependent drug release was assessed by dialysis. Cellular uptake and uptake mechanisms were investigated by confocal microscopy, flow cytometry, and inhibitor studies in PC3-Luc, DU145, and LNCaP cells. Anti-proliferative efficacy was determined by an MTT assay. Results: Docetaxel and camptothecin showed marked synergy in PC3-Luc cells, with a minimum combination index of 0.20 ± 0.01 and 88.10 ± 0.41% growth inhibition at low nanomolar concentrations. Transferrin-conjugated dendrimersomes self-assembled into spherical vesicles with a critical aggregation concentration of approximately 250 µg/mL. They had high docetaxel entrapment efficiency (89.10 ± 0.08%) and enhanced drug release under acidic and reductive conditions. They significantly increased cellular uptake of docetaxel relative to non-targeted dendrimersomes (by up to 3-fold) and free drugs (by up to 20-fold), mainly through transferrin receptor-mediated endocytosis, and improved anti-proliferative activity in all three cell lines. Tf-conjugated DPSSC produced the lowest IC₅₀ values among the tested formulations: 11.72 ± 1.02 nM in PC3-Luc, 9.88 ± 1.22 nM in DU145, and 7.88 ± 1.35 nM in LNCaP cells. Conclusions: Transferrin-conjugated camptothecin-based dendrimersomes entrapping docetaxel represent a promising multifunctional nanocarrier for prostate cancer that combines synergistic dual-drug therapy, active targeting, and stimulus-responsive release, supporting further evaluation as a selective delivery strategy in advanced prostate cancer using preclinical models and in vivo studies. Full article