Search Results (4,456)

RNA degradation plays a vital role in post-transcriptional regulation of gene expression. RNA stability is changed in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD), but its role and underlying mechanisms in sleeve gastrectomy (SG) effectively remodeling hepatocytes and improving MASLD is unclear. A high-fat diet-induced MASLD model for SG and a hepatocyte-specific Zfp36 knockdown mouse model were established to evaluate the role of zinc finger protein 36 (ZFP36) in MASLD. The expression of ZFP36 and TEA domain transcription factor 4 (TEAD4) was examined in liver tissue samples from MASLD patients. Hepatic ZFP36 expression is downregulated in MASLD but is restored following SG. Hepatocyte-specific Zfp36 knockdown exacerbates high-fat diet-induced liver injury and impairs the therapeutic effect of SG on hepatic steatosis. Mechanistically, ZFP36 binds to TEAD4 mRNA to promote its degradation, thereby modulating the Hippo pathway. Inhibition of TEAD4 transcriptional activity reverses the aggravated MASLD phenotype caused by Zfp36 knockdown. In liver biopsy samples from MASLD patients, ZFP36 expression correlates negatively with TEAD4 expression. Collectively, these findings identify SG-induced upregulation of ZFP36 as a critical mechanism for alleviating MASLD through suppression of TEAD4. Full article

Leaf blight and fruit rot caused by Phomopsis vexans are critical issues for eggplant crops. Our study evaluated the biochar amendment, alone and in combination with a foliar spray of silicon dioxide nanoparticles (SiO₂-NPs), on plant performance and disease development. Fungal infection reduced plant growth, with a 22% decline in plant height and a marked decrease in chlorophyll and carotenoid levels. Adding biochar plant height mitigated these effects: the highest dose (30 g) increased plant height in infected plants by 17.1% and increased pigment concentrations and POX and PPO activities. At the same time, the blight index declined. When biochar was combined with SiO₂-NPs, the improvements were more pronounced. In infected plants, the 30 g + SiO₂-NPs treatment produced substantial improvement in plant height (+31.3%) and shoot biomass and restored chlorophyll and carotenoid contents by 63% and 28.1%, respectively. This treatment also produced the lowest blight index and the strongest enzymatic responses. Principal component analyses discriminated treated plants from infected ones. These findings indicate that biochar and SiO₂-NPs can jointly enhance plant resilience to P. vexans infection, reducing its negative impact. Full article

In this paper, we utilized sodium titanate as a substrate to fabricate a supported antifungal repair agent capable of inhibiting fungi through the release of silver ions, and applied it to the preservation and restoration of wooden materials. The structural and material properties of sodium titanate were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and adsorption kinetic modeling. Furthermore, its effectiveness in wood restoration as well as its antifungal performance were evaluated. Results indicate that the synthesized sodium titanate exhibits a distinctive tubular structure, with a diameter of approximately 12 nm, a pore size of 7 nm, and a specific surface area as high as 310.91 m²/g. The abundant ion exchange active sites on the material surface provide conditions for the loading of silver ions. At 25 °C, the maximum adsorption capacity for silver ions reaches 515.5 mg/g, with an adsorption amount accounting for 34.0 wt.%. When combined with polyvinyl alcohol (PVA) for reinforcing wooden materials, it significantly increases the packing density of the reinforcing agent, ultimately enhancing the compressive strength of wood from 155.0 MPa to 412.2 MPa. Furthermore, owing to the antifungal effect of silver ions, the treated wood demonstrates effective resistance against the growth of Aspergillus niger. Full article

Extreme low-light image enhancement (ELLIE) targets the restoration of visual quality under ultra-dim environments (<0.1 lux). Conventional image signal processing (ISP) pipelines often fail in such scenarios due to the limitations of heuristic, hand-crafted algorithms. While deep learning has advanced the field via end-to-end mapping, existing models suffer from constrained generalization and suboptimal perceptual fidelity, primarily stemming from the scarcity of large-scale, high-diversity datasets. To bridge this gap, we present the Day and Night (DaN) dataset, a semi-synthetic benchmark synthesized through a rigorous physics-based noise model. This approach effectively captures authentic noise characteristics while enabling the scalable generation of paired samples across multifaceted illumination conditions and scenes. Furthermore, we propose No Longer Vigil (NLV), a fully differentiable AI-ISP framework. By replacing traditional rigid blocks with adaptive non-linear networks, NLV facilitates scene-dependent transformations without requiring manual priors. Comprehensive evaluations demonstrate that our method significantly outshines state-of-the-art approaches, yielding a 4.15 dB gain in PSNR and a 0.026 improvement in SSIM. Full article

Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging. Full article

Continuous greenhouse watermelon cultivation is widely constrained by declining soil function, impaired nutrient cycling, and increasing soil-borne disease pressure. Developing biologically driven strategies to restore soil–crop coupling is therefore critical for sustainable protected horticulture. Here, we conducted a two-year field experiment (2024–2025) using a randomized block design with three treatments (CK, ST, and STE), three replicates per treatment, and a plot area of 22.5 m² to evaluate how straw application alone and in combination with earthworms regulate soil processes and crop performance in a continuous greenhouse watermelon system. Compared with CK and ST, earthworm–straw co-application (STE) exerted stronger effects, particularly during the mid-to-late growth stages. In 2024, STE increased soil organic matter by 25.34% and 30.28% relative to CK at the fruiting and harvest stages, respectively; in 2025, the corresponding increases were 25.22% and 27.62%. STE also significantly increased total nitrogen at nearly all growth stages, with the maximum increase reaching 67.23% relative to CK at harvest. In 2025, total phosphorus under STE was significantly higher than under CK and ST across all growth stages, with increases of 75.82% and 79.63%, respectively, at the fruiting stage. Neutral phosphatase activity was markedly enhanced, increasing by 292.24% at the fruiting stage in 2025. These improvements were accompanied by higher plot yield and lower wilt disease incidence, with yield increasing by 34.00% in 2024 and 21.29% in 2025 relative to CK, while disease incidence decreased by 41.46% and 56.06%, respectively. Integrative Mantel tests showed that total nitrogen was the factor most strongly associated with watermelon yield, with the correlation coefficient increasing from r = 0.490 (p = 0.001) in 2024 to r = 0.662 (p = 0.001) in 2025. Co-occurrence network analysis further revealed a strong positive correlation between yield and total nitrogen (r = 0.848 in 2024; r = 0.673 in 2025) and a negative correlation between disease incidence and total nitrogen (r = −0.661 in 2024; r = −0.822 in 2025), indicating progressively strengthened soil–plant functional coupling over time. Our findings demonstrate that earthworm–straw co-application strengthened soil nutrient transformation capacity and enhanced soil suppressiveness against wilt disease, thereby providing an effective ecology-based strategy for alleviating continuous-cropping constraints in greenhouse watermelon systems. Full article

Conserved lands play a central role in sustaining ecological functions within working agricultural regions, yet their capacity to maintain wetland conditions varies widely depending on hydrologic persistence and seasonal dynamics. This study assesses the hydrologic performance of Nebraska’s major conservation programs using multi-year Sentinel-2 satellite observations spanning from 2018 to 2024. Five land-protection categories were evaluated: the Wetlands Reserve Program (WRP), Wildlife Management Areas (WMAs), Waterfowl Production Areas (WPAs), the Conservation Reserve Program (CRP), and additional protected lands mapped in the Protected Areas Database of the United States (PAD-US). To capture hydrologic dynamics across scales, we quantified parcel-level inundation percentages alongside program-level wetness metrics that represent cumulative surface-water extent. Lands enrolled in WRP and WPA generally exhibited higher inundation levels at the 0% threshold across annual and seasonal periods, with variability across programs, reflecting their role in wetland restoration and habitat provision. WMAs showed greater seasonal variability but retained water under higher persistence thresholds (≥25% and ≥50%), underscoring their importance in maintaining semi-permanent wetland conditions during drier periods. Wetland-associated CRP lands provide essential short-duration wetness that supports regional hydrologic connectivity across working agricultural landscapes. Similar seasonal patterns were observed across other protected lands, which generally contributed to episodic surface water rather than long-term hydrologic storage. Seasonal analyses highlighted strong intra-annual variability driven by snowmelt, precipitation regimes, and evapotranspiration. Collectively, the results demonstrate substantial differences in hydrologic function among conservation programs and provide an empirical basis for prioritizing investments toward lands that most effectively sustain wetland habitats and water-quality benefits. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by interconnected dysregulation of steroidogenesis and insulin signaling. Multi-target therapeutic strategies are increasingly needed to address its heterogeneous pathophysiology. Methods: An integrative approach combining transcriptomic analysis of GSE137684, including stratification of normoandrogenic and hyperandrogenic PCOS subtypes to capture androgen-related heterogeneity, network pharmacology, molecular docking, and in vitro validation was employed. Principal component analysis (PCA), differential expression analysis, and enrichment analyses were used to identify candidate genes and pathways. Molecular docking evaluated interactions between phytochemicals from Cinnamomum burmannii and Myristica fragrans and key PCOS targets. Functional validation was performed in insulin-resistant 3T3-L1 adipocytes and DHEA-induced KGN cells, assessing cell viability, lipid accumulation, glucose uptake, gene expression, and hormone levels. Results: PCA revealed partial separation between PCOS and the control samples, with PC1 and PC2 explaining 44.8% and 12.5% of variance, respectively. No genes remained significant after multiple testing correction; however, nominally significant candidates (p < 0.01) highlighted pathways related to steroidogenesis and metabolic regulation. Network analysis identified key hub genes including CYP17A1, CYP19A1, AKT1, ESR1, and MAPK1. Molecular docking demonstrated strong binding affinities, with top compounds showing binding energies up to −11.4 kcal/mol (CYP17A1) and −10.9 kcal/mol (AKT1). In vitro, cell viability remained above 80% across all tested concentrations, indicating low cytotoxicity. Treatment significantly reduced lipid accumulation and enhanced glucose uptake in insulin-resistant 3T3-L1 cells (p < 0.05). Additionally, expression of AKT1 and MAPK1 was significantly restored (p < 0.05). In KGN cells, testosterone levels were significantly decreased while the estradiol levels increased (p < 0.05), accompanied by the downregulation of CYP17A1 and upregulation of CYP19A1 (p < 0.05). The combination treatment exhibited more consistent effects across metabolic and hormonal endpoints. Conclusions:Cinnamomum burmannii and Myristica fragrans exert multi-target effects on metabolic and steroidogenic pathways relevant to PCOS. This integrative study demonstrates that transcriptomics-guided network pharmacology combined with experimental validation can identify synergistic phytotherapeutic strategies for complex endocrine disorders. Full article

Antibiotic-associated diarrhea (AAD) is primarily driven by disruption of the gut microbiota accompanied by intestinal mucosal injury. Although multiherb formulations are widely used in East Asian medicine, their collective ecological effects and integrated microbiome–host mechanisms have not been systematically synthesized. This systematic review included 17 preclinical studies that investigated multiherbal formulations in AAD models. Given the substantial heterogeneity in the formulation composition, experimental design, and analytical platforms, a descriptive synthesis was performed. The included formulations were categorized into four clusters based on their shared herbal composition: Qiwei Baizhu San (QWBZP), Lizhong Tang (LZT), Gegen Qinlian Tang (GQT), and other supportive multiherbal formulations. The cluster-based synthesis revealed distinct convergent therapeutic strategies. The QWBZP and LZT clusters primarily supported the restoration of host metabolic and digestive functions, whereas the GQT cluster exhibited potent pathogen control effects with the suppression of opportunistic taxa. Across all clusters, a convergent microbiome–host response emerged, characterized by enrichment of commensal bacteria (e.g., Lactobacillus), upregulation of tight junction proteins (e.g., ZO-1, occludin), and attenuation of pro-inflammatory mediators (e.g., TNF-α, myeloperoxidase). Multiherb formulations in AAD models not only act as microbial modulators but also function as host-directed modulators that stabilize the intestinal homeostatic niche. Botanical interventions may facilitate endogenous microbiome recovery by reinforcing mucosal integrity and reducing environmental resistance. This ecological framework provides a rationale for future translational studies evaluating integrated herbal–probiotic strategies and precise microbiome management for patients with AAD, while further clinical validation is warranted. Full article

Background: Intracavernosal platelet-rich plasma (PRP) is increasingly used for erectile dysfunction (ED), despite the absence of standardized biological characterization and clear dose definitions. This systematic review evaluates the clinical efficacy of PRP in ED while integrating emerging immune-centric mechanistic evidence. Methods: Following PRISMA 2020 guidelines, randomized controlled trials (RCTs) and prospective studies (2020–2025) investigating intracavernosal PRP in adult men with ED were identified across major databases. Validated outcomes included International Index of Erectile Function (IIEF-EF or IIEF-5), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP), and penile Doppler parameters. Preclinical data were narratively integrated to contextualize biological plausibility. Results: Fourteen clinical studies met the inclusion criteria (six RCTs, eight prospective cohorts). Across most studies, PRP produced clinically relevant within-patient improvements, and three RCTs demonstrated minimal clinically important difference (MCID) responder rates compared with placebo. However, other trials showed comparable improvements in placebo arms, underscoring substantial contextual effects. Safety was consistently favourable. Marked heterogeneity in blood volume processed (10–120 mL), injected PRP volume (3–12 mL), preparation systems, and session protocols precluded cross-study comparability. Critically, no study reported platelet dose, leukocyte subsets, peripheral blood mononuclear cell (PBMNC) content, or red blood cell contamination. Preclinical models consistently demonstrate that PRP restores erectile function through angiogenic, neuroprotective, and immunomodulatory mechanisms, including CXCL5-mediated monocyte recruitment and M1-to-M2 macrophage polarization. Conclusions: Intracavernosal PRP shows promising short-term efficacy signals and a favourable short-term safety profile in mild-to-moderate vasculogenic ED, but current evidence is limited by profound biological and methodological heterogeneity. PRP should be reconsidered as an immune-regenerative intervention requiring dose-defined, composition-defined, and mechanistically informed randomized trials. Interpretation of these findings is constrained by the absence of formal risk-of-bias assessment for non-randomized studies, substantial clinical and biological heterogeneity across trials, and the lack of standardized PRP characterization. Full article

Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity—particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome–drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes. Full article

Background/Objectives: Malignant distal biliary obstruction (MDBO) is a frequent complication of pancreatic cancer and often leads to obstructive jaundice, impaired liver function, and delayed oncologic treatment. Endoscopic biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the standard minimally invasive approach for restoring biliary flow. However, clinical outcomes and complication rates vary across studies depending on stent design, placement technique, and patient characteristics. The aim of this systematic review was to evaluate the clinical outcomes and complications associated with endoscopic biliary stenting in pancreatic cancer-related MDBO. Methods: A systematic literature search was performed in PubMed/MEDLINE, ScienceDirect, Web of Science, and the Cochrane Library for studies published between January 2016 and January 2026. Studies evaluating ERCP-guided biliary stenting in adult patients with pancreatic cancer-related malignant distal biliary obstruction were included. Study selection followed PRISMA 2020 guidelines, and methodological quality was assessed using the Newcastle–Ottawa Scale. Clinical outcomes including technical success, clinical success, stent patency, recurrent biliary obstruction, and procedure-related complications were analyzed. Results: Eighteen studies involving a total of 3291 patients were included in the qualitative synthesis. Technical success rates were consistently high, reaching up to 100% in several studies, while clinical success rates generally exceeded 90%. Median time to recurrent biliary obstruction ranged from approximately 102 to 541 days depending on stent type and placement technique. Recurrent biliary obstruction was the most frequently reported complication, occurring in 30.7% of patients. Stent migration occurred in 14.9% of cases, while post-ERCP pancreatitis was reported in approximately 4.2% of patients. Several studies demonstrated longer patency with self-expandable metal stents compared with plastic stents. Conclusions: Endoscopic biliary stenting performed during ERCP is an effective and safe strategy for the management of malignant distal biliary obstruction in pancreatic cancer. Self-expandable metal stents provide more durable biliary drainage and reduce the need for repeat interventions. Nevertheless, recurrent biliary obstruction remains a common limitation, highlighting the need for further improvements in stent technology and optimized placement strategies. Full article

Oxidative stress critically affects cellular viability and function under in vitro culture conditions, often compromising physiological integrity of somatic cells used in livestock biotechnology. This study aimed to investigate hydrogen peroxide (H₂O₂)-induced oxidative stress in buffalo fibroblasts and evaluated the cytoprotective effects of melatonin, focusing on redox homeostasis, mitochondrial function, apoptosis, and antioxidant defence. Fibroblasts were exposed to graded concentrations of H₂O₂ (100–1000 µM) for 2 h, followed by treatment for 72 h in culture media with and without melatonin (10⁻⁹ M). Oxidative stress markers, including GSSG/GSH ratio, ROS generation, mitochondrial membrane potential (MMP), and apoptosis, were assessed using flow cytometry and biochemical assays, while antioxidant (GPx, SOD, CAT) and apoptotic (BAX, Caspase 9) gene expression was analyzed by qPCR. H₂O₂ exposure induced a dose-dependent increase in oxidative stress, evidenced by elevated ROS, redox imbalance, mitochondrial depolarization, and enhanced apoptosis. Severe oxidative damage was observed at higher H₂O₂ (500–1000 µM) concentrations. Melatonin (MT) significantly (p ≤ 0.05) alleviated oxidative stress under mild to moderate conditions (100–200 µM H₂O₂) by restoring redox homeostasis, preserving mitochondrial integrity, suppressing ROS accumulation, enhancing antioxidant defence, and reducing apoptosis. However, its protective efficacy was lost under severe oxidative stress, indicating a defined redox threshold beyond which cellular damage becomes irreversible. These findings suggest that melatonin exerts cytoprotective effect against oxidative stress within a limited oxidative window and provide mechanistic insights for improving fibroblasts culture systems in livestock biotechnology and regenerative applications. Full article

Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy. Full article

Background: Screw loosening remains a common mechanical complication in implant-supported restorations; however, the combined effect of sealing and superstructure materials on abutment screw stability warrants further investigation. Methods: This study evaluated the influence of access channel sealing material and superstructure material on abutment–implant screw stability after thermomechanical cyclic loading. Forty-eight Straumann analog–abutment assemblies restored with monolithic zirconia or resin nano-ceramic (Cerasmart) crowns were assigned to two sealing protocols: Polytetrafluoroethylene (PTFE) + composite or polyvinyl siloxane (PVS) putty (n = 12). After 750,000 off-axis cycles, reverse torque values (RTV) were analyzed using two-way analysis of variance (ANOVA) and Tukey’s HSD, with effect sizes calculated (α = 0.05). Results: A significant interaction between restorative material and sealing protocol was observed (p = 0.0170; η² = 0.116). Superstructure material showed no significant influence on RTV (p = 0.8368), whereas sealing protocol had a significant main effect (p = 0.0499). RTVs were highest for zirconia + PVS putty (36.33 ± 4.53 Ncm) and lowest for zirconia + PTFE (29.32 ± 6.30 Ncm), while the Cerasmart groups showed intermediate values. Post hoc analysis confirmed higher RTV for zirconia + PVS compared with zirconia + PTFE (p = 0.0138). Conclusions: Access channel sealing materials showed a material-dependent influence on abutment screw stability. Silicone-based sealing improved torque maintenance in zirconia, indicating that rigid restorative materials may be more sensitive to sealing material selection. In contrast, Cerasmart showed comparable RTV regardless of sealing protocol, suggesting that resilient restorative materials may reduce the influence of sealing on preload maintenance. Full article