Search Results (876)

Background/Objectives: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Akkermansia muciniphila and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic Lacticaseibacillus paracasei L9 for targeted Amuc_1100 delivery. Methods: We engineered Lc. paracasei L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity, and mucosal repair. Results: The secretory (pUA-L9) and surface-display (pUPA-L9) strains most effectively suppressed pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in macrophages. In mice, both strains alleviated colitis and outperformed native A. muciniphila in improving disease activity. Crucially, they exhibited distinct, specialized functions: pUA-L9 acted as a systemic immunomodulator, reducing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), elevating anti-inflammatory mediators (IL-4 and IL-10), and promoting goblet cell differentiation; notably, the inhibitory effect of pUA-L9 on IL-6 expression was approximately 2-fold greater than that of pUPA-L9. In contrast, pUPA-L9 excelled in local barrier repair, uniquely restoring mucus layer integrity (Muc1, Muc2, and Tff3) and reinforcing tight junctions (ZO-1, Occludin, Claudin1, Claudin3, and Claudin4). In particular, pUPA-L9 increased Muc2 expression by approximately 3.6-fold compared with pUA-L9. Conclusions: We demonstrate that the subcellular localization of Amuc_1100 within an engineered probiotic dictates its therapeutic mode of action. The complementary effects of secretory and surface-displayed Amuc_1100 offer a novel, spatially targeted strategy for precision microbiome therapy in IBD. Full article

Background and Objectives: Urothelial carcinoma (UC) is one of the most prevalent and lethal cancers worldwide. Identifying and understanding the factors that influence treatment outcome is essential for improving therapeutic effectiveness and predicting patient response. The objective of this review is to estimate how clinical, biochemical, molecular and therapeutic factors impact the prognosis of patients with advanced urothelial carcinoma (aUC) and metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). Methods: A review was performed using PubMed, Scopus and Web of Science databases. All articles were published from 2013 to 2025 focusing on prognostic factors in locally advanced and metastatic urothelial carcinoma treated with ICIs. Results: Clinical prognostic factors for patients treated with ICIs include poor Eastern Cooperative Oncology Group (ECOG) performance status and the presence of liver or bone metastases, both associated with poor outcomes. Low hemoglobin levels and several biochemical markers, such as high neutrophil-to-lymphocyte ratio (NLR), elevated systemic immune-inflammation index (SII) and low serum sodium are also associated with reduced survival. Programmed cell death-ligand 1 (PD-L1) expression shows predictive relevance for ICI response. Concomitant use of antibiotics or proton pump inhibitors (PPIs) may diminish immunotherapy effectiveness. Additionally, sarcopenia and high lactate dehydrogenase (LDH) levels correlate with poorer clinical outcomes. Conclusions: Prognostic outcomes in aUC and mUC are influenced by a complex interaction of clinical, biochemical and molecular factors. Integrative prognostic models are essential to the guidance of personalized immunotherapeutic strategies and the improvement of patient outcomes in aUC and mUC. Full article

Background: Amoxicillin, clindamycin and azithromycin are the most frequently prescribed antibiotics for odontogenic infections, but their comparative effects on gut microbiota and intestinal homeostasis remain insufficiently understood. Disruption of gut microbiota, short-chain fatty acid (SCFA) production, and mucosal barrier integrity may contribute to gastrointestinal symptoms. We aimed to compare the impacts of these antibiotics on gut microbiota, SCFA levels, and colonic goblet cells. Methods: C57BL/6N mice were treated with oral amoxicillin, clindamycin, or azithromycin at clinically relevant dosages. Cecal index, fecal water content, and diarrhea index were assessed during treatment and recovery. Gut microbiota composition and absolute bacterial abundance were determined using 16S rRNA amplicon absolute quantification sequencing. SCFAs in cecal contents were quantified by gas chromatography–mass spectrometry. Goblet cell abundance and Muc2 mRNA expression in colon tissues were evaluated using Alcian blue staining and RT-PCR. Results: Amoxicillin caused moderate increases in cecal index, reduced Ligilactobacillus abundance, increased Escherichia-Shigella, lowered SCFA levels, and decreased goblet cells and Muc2 expression, with partial recovery after two weeks. Clindamycin induced more severe dysbiosis, including sustained Proteobacteria expansion, persistent loss of beneficial taxa, 86–90% reduction in SCFA production, and lasting decreases in goblet cells and Muc2 expression without recovery during the observation period. Azithromycin caused mild and reversible changes across all parameters. Conclusions: Among the three antibiotics, azithromycin had the least detrimental effects on gut microbiota, SCFA production, and mucosal barrier function, whereas clindamycin caused profound and persistent intestinal disruption. These findings provide comparative evidence to inform antibiotic selection in clinical practices. Full article

Eurotium cristatum-Fermented White Tea (FWT) significantly alters white tea (WT) composition, increasing caffeine while decreasing polyphenols and amino acids. FWT effectively ameliorated dextran sulfate sodium (DSS)-induced murine colitis symptoms (reducing weight loss, colon shortening). Mechanistically, FWT suppressed TLR4/Myd88/NF-κB signaling and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) while upregulating tight junction proteins (ZO-1, occludin, claudin-1), MUC2, and E-cadherin. Single-cell/spatial transcriptomics revealed that FWT treatments augment enterocyte, goblet cell, and stem cell populations, optimize goblet function, restructure stem cell differentiation, and induce epithelial REG3B (antimicrobial) and LYPD8 (motility inhibitor), plus immunomodulator GM42418 lncRNA across cell types, repairing the barrier. FWT intervention was also associated with an increase in beneficial bacteria (Akkermansia, Lactobacillus, Bifidobacterium), restoration of microbiota balance, and elevated levels of short-chain fatty acids (SCFAs) and was associated with alterations in caffeine-related metabolite profiles. Collectively, these multi-scale changes correlate with the alleviation of UC, suggesting an integrated mechanism involving mucosal barrier repair, immune–stromal modulation, microbiota–metabolism regulation, and cellular reprogramming. Full article

Background/Objectives: Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) remains a major challenge in the treatment of EGFR-mutant lung adenocarcinoma (LUAD). This study aimed to develop and characterize representative models of acquired EGFR-TKI resistance and to identify potential therapeutic targets mediating this process. Methods: Resistant models of PC9 and LUAD-PDCs were generated using a standardized dose-escalation protocol. The resulting models were characterized by drug response assays, morphology, and transcriptomic sequencing. Candidate target genes were validated across all resistant models using siRNA knockdown followed by re-sensitization assays. Clinical relevance was further examined through analysis of publicly available datasets. Results: These generated models displayed stable resistant phenotypes and unique transcriptomic alterations. Cross-model analysis revealed MUC16 as a consistently upregulated gene associated with resistance. Functional validation demonstrated that MUC16 depletion re-sensitized all resistant models to EGFR-TKIs. Furthermore, analysis of clinical data linked high MUC16 expression to poorer patient outcomes. Conclusions: This study establishes stable in vitro models for investigating acquired resistance in EGFR-mutant LUAD and identifies MUC16 as a functionally validated and clinically relevant mediator of EGFR-TKI resistance, providing a potential therapeutic target for overcoming drug resistance. Full article

Mastication trait is an important indicator for evaluating citrus fruit texture and may modulate the biological activity of citrus polysaccharides. This study compared the protective effects of pulp polysaccharides from citrus fruit with different mastication traits, namely Hongmeiren (HMR, superior), Satsuma (WM, moderate), and Nanfeng tangerine (NF, inferior mastication trait) on ulcerative colitis (UC) in mice. All polysaccharides alleviated UC symptoms, with HMR showing the most pronounced effects by more markedly reducing TNF-α levels, while enhancing IL-10, ZO-1, Occludin, and MUC2 expression. NF exhibited a stronger inhibitory effect on IL-6. Microbiota analysis revealed that citrus polysaccharides suppressed Escherichia–Shigella and Helicobacter, enriched Akkermansia and norank_f_Muribaculaceae, and promoted short-chain fatty acid production, particularly of propionate and butyrate. LEfSe analysis further indicated that HMR selectively enriched Dubosiella and norank_o_Clostridia_UCG-014, WM increased the abundance of Lachnospiraceae_NK4A136_group, and NF promoted the growth of Parabacteroides. Overall, HMR with superior mastication trait exhibited the greatest efficacy in attenuating inflammation and maintaining intestinal homeostasis. These findings reveal an intrinsic link between citrus mastication traits and their colitis-alleviating activity, offering a mechanistic basis for dietary intervention in inflammatory bowel disease as well as for functional citrus breeding. Full article

Colorectal cancer (CRC) is one of the most common and fatal malignant tumors globally, and its development is increasingly related to the gut microbiota. Despite its effect on CRC having been extensively researched, the intestinal mucus barrier, which forms a fundamental link between the host tissues and gut microbes, is seldom discussed. A double-layered barrier, mainly formed by MUC2 mucin, isolates the outside world from epithelial cells to maintain intestinal homeostasis. Furthermore, it is subjected to a dynamic impact of microbial activity. Now, increasing evidence shows that mucus barrier disruption driven by certain gut microbes is an early event in the development of CRC. This review first introduces the structure and function of the colonic mucus barrier and then discusses how gut microbiota in different areas promote the development of CRC by disrupting the mucus layer. Finally, we examine translational opportunities for exploiting microbiota–mucus barrier interactions in CRC therapy. Full article

Background/Objectives: Intestinal ultrasound (IUS) is increasingly used to monitor ulcerative colitis (UC), but its predictive value remains unclear. This systematic review evaluated the ability of IUS parameters and scores to predict short- and long-term treatment response, remission, and adverse outcomes in hospitalized and outpatient UC populations. Methods: A systematic review was conducted according to Cochrane and PRISMA guidelines. MEDLINE and Embase were searched for prospective studies assessing IUS as a predictor of clinical or endoscopic response, remission, relapse, or adverse outcomes in adult UC. Two reviewers independently performed screening, data extraction, and QUADAS-2 assessment. Results: Eighteen prospective studies were included: eleven outpatient studies and seven involving hospitalized patients treated with intravenous corticosteroids (IVCS). In hospitalized patients, bowel wall thickness (BWT) was the most consistent predictor of treatment failure, rescue therapy, colectomy, and clinical response. Baseline BWT showed variable performance, but once IVCS was initiated, early BWT change within 48–72 h was the strongest marker of disease trajectory. Non-responders had higher BWT and smaller reductions. A BWT ≥ 4 mm, absolute reduction ≤ 1 mm, or relative reduction ≤ 20% at 48 h reliably identified patients needing rescue therapy (area under the curve (AUC) values of 0.77 (95% confidence interval (CI) 0.71–0.74), 0.71 (95% CI 0.56–0.86), and 0.74 (95% CI 0.60–0.88)). Colectomy risk was similarly predicted: BWT < 3 mm at 48 h was associated with no colectomies, whereas BWT ≥ 4 mm or persistently elevated BWT at day 6 markedly increased risk (Odds ratio (OR) 9.5-fold (95% CI 1.4–64.0) and OR 8.3 (95% CI 1.7–40.0), respectively). Other sonographic features (loss of haustration, increased vascularity) added supplementary but less consistent value. In outpatients, BWT also demonstrated the strongest predictive accuracy. BWT ≤ 3.6 mm at 2 weeks and <3.0 mm at 6 weeks were associated with early endoscopic remission (area under the receiver operating characteristic (AUROC) of 0.87 (95% CI 0.71–1.00) and 0.82 (95% CI 0.63–1.00), respectively). Dynamic changes with ≥23–25% relative reduction predicted clinical or endoscopic response (AUROC of 0.81 (95% CI 0.61–1.00) and OR of 13.9 (95% CI 1.13–1986.85), respectively). Persistent BWT > 3.5 mm or minimal reduction (<20% or <1 mm) indicated a low likelihood of long-term remission. Composite vascularity-based indices, particularly the Milan Ultrasound Criteria (MUC), strengthened prediction: MUC ≤ 4.3 or ≥2-point reduction at 12 weeks predicted long-term remission (AUROC 0.88 (95% CI 0.750–0.952) and 0.82 (95% CI 0.68–0.91), respectively), while MUC ≥ 7.7 indicated high risk of treatment failure or colectomy (AUROC 0.77 (95% CI: 0.73–0.82)). Conclusions: Across clinical settings, BWT consistently emerged as the strongest IUS predictor of UC treatment outcomes. Early BWT change within 48–72 h in hospitalized patients and absolute BWT values at 2–6 weeks in outpatients showed high predictive accuracy for response, remission, and colectomy. Composite indices incorporating vascularity further improved prediction. These findings support the incorporation of IUS into early treatment-response algorithms and underscore the need for standardized cut-offs and multicenter validation. Full article

Background/Objectives: The polypeptide N-acetylgalactosaminyltransferase (GALNT) family initiates mucin-type O-glycosylation, a post-translational modification that plays a pivotal role in cellular signaling, adhesion, and immune evasion. Dysregulated GALNT expression has been increasingly implicated in carcinogenesis. Methods: We reviewed the literature on the expression, function, and clinical relevance of GALNT isoforms across various cancers, with a focus on their mechanistic roles, biomarker potential, and therapeutic implications. Results: Aberrant GALNT expression is observed in numerous malignancies, including breast, colorectal, gastric, lung, ovarian, and hepatocellular carcinomas. Isoforms such as GALNT1, -T2, -T3, and -T14 contribute to tumorigenesis by modulating the glycosylation of mucins such as Mucin-1 (MUC1), epithelial growth factor receptors (EGFR), and other signaling proteins. These alterations promote cancer cell proliferation, metastasis, epithelial–mesenchymal transition (EMT), and chemoresistance. Deranged GALNT expression is frequently associated with poor prognosis, and certain GALNT genotypes predict treatment response. However, functional redundancy among isoforms poses challenges for selective targeting. Conclusions: Despite their strong potential as modulators of cancer progression, GALNTs face substantial limitations in terms of substrate identification, mechanistic clarity, immune relevance, and therapeutic tractability. Overcoming these challenges requires advanced glycoproteomics, development of isoform-specific tools, and integrated studies across cancer and immunology to fully harness GALNT biology for clinical benefit. Full article

Personalized cancer vaccines are a key strategy for training the immune system to recognize and respond to tumor-specific antigens. Our earlier software release, AutoEpiCollect 1.0, was designed to accelerate the vaccine design process, but the identification of tumor-specific genetic variants remains a manual process and is highly burdensome. In this study, we introduce AutoEpiCollect 2.0, an improved version with integrated genetic analysis capabilities that automate the identification and prioritization of tumorigenic variants from individual tumor samples. AutoEpiCollect 2.0 connects with RNA sequencing and cross-references the resulting RNAseq data for efficient determination of cancer-specific and prognostic gene variants. Using AutoEpiCollect 2.0, we conducted two case studies to design personalized peptide vaccines for two distinct cancer types: cervical squamous cell carcinoma and breast carcinoma. Case 1 analyzed five cervical tumor samples from different stages, ranging from CIN1 to cervical cancer stage IIB. CIN3 was selected for detailed analysis due to its pre-invasive status and clinical relevance, as it is the earliest stage where patients typically present symptoms. Case 2 examined five breast tumor samples, including HER2-negative, ER-positive, PR-positive, and triple-negative subtypes. In three of these breast samples, the same epitope was identified and was synthesized by identical gene variants. This finding suggests the presence of shared antigenic targets across subtypes. We identified the top MHC class I and class II epitopes for both cancer types. In cervical carcinoma, the most immunogenic epitopes were found in proteins expressed by HSPG2 and MUC5AC. In breast carcinoma, epitopes with the highest potential were derived from proteins expressed by BRCA2 and AHNAK2. These epitopes were further validated through pMHC-TCR modeling analysis. Despite differences in cancer type and tumor subtype, both case studies successfully identified high-potential epitopes suitable for personalized vaccine design. The integration of AutoEpiCollect 2.0 streamlined the variant analysis workflow and reduced the time required to identify key tumor antigens. This study demonstrates the value of automated data integration in genomic analysis for cancer vaccine development. Furthermore, by applying RNAseq in a standardized workflow, the approach enables both patient-specific and population-level vaccine design, based on statistically frequent gene variants observed across tumor datasets. AutoEpiCollect 2.0 is freely available as a website based tool for user to design vaccine. Full article

Progressive pulmonary fibrosis (PPF) encompasses fibrosing interstitial lung diseases marked by relentless scarring of the lungs, leading to respiratory failure. Although its pathogenesis remains incompletely understood, recent genetic discoveries have shed light on the molecular mechanisms that drive PPF onset and progression. This comprehensive review summarizes current knowledge of PPF genetics, highlighting both rare pathogenic variants and more common susceptibility polymorphisms. Key genetic contributors include telomere maintenance genes, surfactant protein genes, and the MUC5B promoter variant rs35705950, which is the strongest known genetic risk factor for idiopathic pulmonary fibrosis. We also discuss epigenetic factors such as DNA methylation and histone modifications that regulate fibrotic gene expression. Integrating genetic findings with clinical phenotypes reveals distinct disease endotypes with different prognoses and therapeutic responses, laying the groundwork for precision medicine in PPF treatment. Finally, we address the clinical implications of PPF genetics, including advances in genetic testing, biomarker development, and emerging gene-targeted treatment strategies. Full article

Sheep are an economically important livestock species, and reproductive performance is a key trait affecting productivity. The Dorper × Hu hybrid sheep (DHS), widely bred in China, provides a valuable model for studying the genetic basis of prolificacy. This study aimed to investigate the genomic architecture and identify candidate genes associated with high litter size in DHS using whole-genome selective sweep analysis and genome-wide association study (GWAS). A total of 31 DHS individuals with complete reproductive records were sequenced and compared with publicly available genomic data from 20 Hu sheep (HUS) and 10 Dorper sheep (DPS). Population genetic structure and diversity were assessed using phylogenetic trees, principal component analysis (PCA), and ADMIXTURE analysis. To identify key genomic regions associated with litter size, we performed selective sweep analysis between the polytocous and monotocous subpopulations of DHS using multiple methods within a 50 kb sliding window framework, including $F_{ST}$, ${\theta }_{\pi }$ ratio, XP-CLR, and XP-EHH; we also conducted GWAS. DHS exhibited a distinct genetic structure with admixed ancestry and elevated genetic diversity. Genetic diversity analysis showed that DHS retained moderate levels of heterozygosity and polymorphism, comparable to or exceeding those of its parental breeds. Comparative analysis between polytocous and monotocous DHS identified reproduction-associated genes, including MUC1, PLCB4, SIN3A, and ELAVL2, enriched in pathways such as ovarian steroidogenesis, insulin secretion, and circadian entrainment. Furthermore, genome-wide association study (GWAS) identified 140 significant loci (p < 10⁻⁵) associated with reproductive traits. From these, 10 candidate SNPs were selected for validation through single-marker association analysis in 200 DHS individuals, among which two loci—g.88680390 C>A (SLC24A2/MLLT3) and g.18197516 T>C (ABCA1)—showed significant correlations with litter size. These findings enhance our understanding of the genetic basis of prolificacy in DHS and provide valuable molecular markers for genomic selection in sheep-breeding programs. Full article

Background/Objectives: This study aimed to further enhance the properties of paclitaxel (PTX) and honokiol (HNK) through encapsulation in planetary ball-milled nanoparticles (PBM NPs) and specific targeting of breast cancer (BrCa) cells via MUC1 targeting using an aptamer (S2.2) coating. Methods: Tissue microarray (TMA) analysis was utilized to measure MUC1 expression in stages 1, 2, 3, and 4 BrCa tissue samples. Pharmacokinetic simulations were performed to explore the potential advantages of using PTX and HNK in combination while targeting MUC1 for BrCa treatment. To investigate the efficacy of the PBM NPs for MUC1 targeting, we synthesized the aptamer-conjugated PTX and HNK PBM NPs (PTX-S2.2-PBM NPs, HNK-S2.2-PBM NPs) using N-hydroxysuccinimide (NHS) coupling. Dynamic light scattering (DLS), Fourier-transform infrared (FTIR), and high-performance liquid chromatography (HPLC) were utilized to characterize the NPs. MTT and live/dead cell assays were used to evaluate the cytotoxicity of the NPs. Results: TMA sample analysis confirmed the upregulation of MUC1 in BrCa tissues, which increased with the stage of BrCa. DLS analysis revealed that the PTX-S2.2 and HNK-S2.2 NPs have a desirable size (83.4 nm and 163 nm, respectively) and zeta potential (−9.74 mV and −7.16 mV, respectively), which are suitable for systemic circulation and improved therapeutic outcomes. FTIR and HPLC analysis suggest proper conjugation was achieved, and an encapsulation efficiency of PTXS2.2 and HNKS2.2 NPs at 77% and 84%, respectively, was achieved. Cell viability assays demonstrated that PTX-S2.2-PBM and HNK-S2.2-PBM NPs exhibit cytotoxicity comparable to or greater than free PTX and HNK, respectively. Conclusions: These findings support the belief that using PTX-S2.2 and HNK-S2.2 PBM NPs could be a promising treatment option for BrCa. Full article

Aging of the gut involves progressive changes in structure, function, and microbial composition, which impact overall health. The vermiform appendix extends from the apex of the cecum; it contains gut-associated lymphoid tissue and serves as a reservoir of gut microbiota. This study investigates histologic and gene expression changes in 20 morphologically normal appendiceal samples obtained from pediatric (n = 5), adult (n = 8), and geriatric (n = 7) patients. Histologic analysis revealed a higher prevalence of lymphoid follicles reduction and the presence of fibrous obliteration of the appendiceal tip in aged samples. RNA sequencing identified 1004 differentially expressed genes (385 upregulated and 619 downregulated; p < 0.05) between the adult and geriatric population. Upregulated pathways were enriched for oxidative stress response, cholesterol metabolism, and mucosal barrier maintenance, including NRF2 targets (NQO1, MGST1), suggesting enhanced antioxidant activity. Downregulated genes were associated with synaptic signaling, ion channel regulation, and neuronal adhesion (e.g., GRIA2, RET, NOS1, NCAM2, CNTN1), reflecting age-related decline in enteric neuronal integrity. Across all age groups, 25 protein-coding genes showed progressive expression shifts with aging, including upregulation of CLDN2, MUC2, and GDF15, and downregulation of NOG and NELL2, indicating barrier loosening, chronic inflammation, and reduced regenerative potential. These findings suggest that aging of the vermiform appendix recapitulates key processes of intestinal aging, including oxidative stress, inflammaging, and neuronal loss, supporting its potential use as a model tissue for studying gut aging mechanisms. Full article

The tropical gar (Atractosteus tropicus) has significant ecological, economic, and cultural importance in southeast Mexico, where aquaculture is increasing and fish are frequently exposed to stress. In this sense, feed additives such as sage (Salvia officinalis) strengthen organisms’ growth, immune systems, antioxidant capacities, and digestive capabilities. A 30-day experiment was conducted on larvae to determine the effect of different concentrations of sage essential oil (0%, 0.5%, 1%, 1.5%, and 2% treatments) supplemented in balanced diets. Significant differences (p < 0.05) between 0.5% and 2% sage oil supplement treatments for average weight were found. The highest acid and alkaline proteases, chymotrypsin, leucine aminopeptidase, amylase, and lipase activities were obtained for the sage oil-supplemented treatments. In contrast, trypsin showed the highest activity for treatment 0%, followed by diets with 0.5% and 2% sage oil. Regarding the antioxidant enzymatic activity for GPx, CAT and SOD, the highest activity was obtained in the diet with 1% sage oil, while in PEROx, the highest activity was recorded in the treatment with 0%, 1.5% and 2% S. officinalis supplementation. On the other hand, for relative gene expression, the highest expression was observed in sage-supplemented treatments for the nod, zo-1, zo-2, and occ genes. In contrast, the lowest expression was found in supplemented treatments for the il-10 and muc2 genes. These findings suggest that incorporating sage essential oil into the diets of tropical gar larvae, particularly at concentrations of 1.66% and 1.77%, holds potential for enhancing aquaculture practices for this important species. Full article