Search Results (265)

Background/Objectives: Doxorubicin is an anthracycline chemotherapeutic agent widely used in the treatment of breast cancer. However, its clinical utility is limited by the drug’s resistance development, low oral bioavailability, and dose-dependent side effects. The semi-essential amino acid, L-arginine, has gained attention as a potential adjuvant that could improve the drug distribution and cytotoxic effectiveness of chemotherapeutics. This study aimed to explore the multifunctional effect of L-arginine on the intestinal absorption and anti-breast cancer activity of doxorubicin. Methods: The rabbit in situ intestinal perfusion technique was employed to investigate the membrane transport parameters of doxorubicin both in the absence and presence of L-arginine. Furthermore, the effect of L-arginine on the cytotoxic activity of doxorubicin against breast cancer cells (MCF-7) was assessed using the MTT assay. Results: Co-perfusion of L-arginine with doxorubicin enhanced the fraction of doxorubicin absorbed, with a recorded 4.3-fold enhancement in the jejuno-ileum and a 1.5-fold enhancement in the colon segment. In MCF-7 cells, co-treatment with L-arginine resulted in a significant potentiation of doxorubicin cytotoxicity. At L-arginine concentrations of 10 μM and 50 μM, the recorded IC₅₀ decreased from 41.3 μM to 8.2 μM and to 22.1 μM, respectively. The superior efficacy of 10 μM L-arginine compared to 50 μM reflected a biphasic concentration-dependent response. Conclusions: L-arginine modulated two critical aspects of doxorubicin efficacy, intestinal absorption and cytotoxic activity. The biphasic response emphasizes the importance of L-arginine dose optimization. These findings support the potential of L-arginine as a safe adjuvant for developing oral doxorubicin formulations. This approach can reduce the dose-related toxicity of doxorubicin and improve therapeutic outcomes. Full article

Low-accessible Cultural Heritage, including hypogeal sites, rupestrian architectures, and fragile structures, represents a major challenge for conservation, documentation, and continuous monitoring. These limitations stem from multiple inaccessibility factors, classified as physical (morphological complexity), asset risk (microclimatic instability), health and safety (structural vulnerability), managerial (lack of public access), and cognitive (lack of documentation). This research aims to transform digital models from mere representational tools into integrated cognitive and operational systems supporting decision-making and preventive conservation. The proposed methodological workflow is structured into five main phases: Preliminary Knowledge and Multidisciplinary Data Structuring (Ph1. PK–MDS), Comprehensive Digital Survey (Ph2. CDS), Development of Integrated Digital Models (Ph3. IDMs), Advanced Diagnosis and Monitoring (Ph4. ADM) and the implementation of an Integrated Digital Environment for Hypogeal Heritage Management (Ph5. IDE). Ph4 operates on two complementary scales: at the site scale, range-based point clouds enable the semi-automatic identification of extensive decay patterns, such as biological colonization. At the detail scale, the Random Forest algorithm enables the segmentation and quantification of material loss on frescoed surfaces through a diachronic comparison of historical and current data. Validated on the San Pellegrino complex in Matera, selected as a paradigmatic case study of low-accessibility hypogeal sites, representative of a broader system comprising approximately 150 rupestrian cult architectures, the methodology demonstrates how immersive digital environments function as shared knowledge spaces, supporting more informed, inclusive, and resilient heritage conservative management. Full article

Zearalenone (ZEN) is a widely distributed estrogenic mycotoxin that compromises intestinal health in pigs, but its spatial difference ZEN and niche-specific regulatory effects on the intestinal microbiota remain largely unelucidated. In this study, 12 healthy three-way crossbred weaned piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments. The control group (CON) was fed with the basal diet, and the treatment group (ZEN) was supplemented with 1.5 mg ZEA/kg of the basal diet for 28 days. Chyme and mucosal microorganisms in the duodenum, jejunum, ileum, colon and cecum were profiled by using 16S rDNA sequencing. The results indicated that ZEN significantly reduced the α-diversity of ileal chyme, while the abnormal increase in α-diversity of ileal and cecal mucosa represented a pathological signature of intestinal mucosal barrier damage induced by ZEN, which was detrimental to intestinal health. β-Diversity analysis revealed ZEN altered the microbial community composition of the cecal chyme. LEfSe analysis revealed gut segment-specific and niche-specific biomarker taxa among the groups, and functional prediction further indicated that ZEN exposure significantly perturbed key metabolic pathways: it downregulated nicotinate and nicotinamide metabolism as well as the citrate cycle in ileal chyme and upregulated the pentose and glucuronate interconversions pathway in cecal chyme. Collectively, this study demonstrated the effects of ZEN on the intestinal microbiota across spatial difference and ecological niches in weaned piglets, providing a basis for elucidating the microecological mechanisms underlying ZEN-induced intestinal injury in pigs. Full article

Staphylococcus epidermidis is a leading opportunistic pathogen in medical device-associated infections due to its ability to adhere to abiotic materials and develop biofilms that are difficult to eradicate. This study investigated the antibiofilm potential of an ethanolic extract of the red seaweed Gracilaria fisheri and its purified constituent, N-benzylcinnamamide, against S. epidermidis. Antibacterial activity was determined, and antibiofilm effects were assessed using the crystal violet assay and confocal laser scanning microscopy (CLSM). Early bacterial adhesion on glass and polyurethane (PU) surfaces was measured. The effect on catheter-associated biofilms was evaluated by scanning electron microscopy (SEM). Transcripts of biofilm- and quorum-sensing-associated genes (icaA and luxS) were assessed by semi-quantitative RT-PCR. Cytotoxicity was evaluated by MTT assay. At 200 µg/mL, biofilm biomass decreased to 48.21 ± 5.52% with the extract and to 36.65 ± 6.82% with N-benzylcinnamamide. CLSM time-course imaging showed delayed biofilm maturation and less consolidated, discontinuous structures. Surface exposure to the extract markedly reduced early attachment on both materials. On PU catheter segments, SEM demonstrated that N-benzylcinnamamide markedly reduced surface coverage and disrupted three-dimensional biofilm architecture. At the molecular level, transcription of icaA and luxS was reduced. Both the extract and N-benzylcinnamamide showed minimal cytotoxicity in HeLa cells. These findings support further evaluation of these marine-derived agents as candidates for antibiofilm surface treatments to reduce early medical device colonization. Full article

Colorectal cancer, as a malignant tumor with a high incidence rate worldwide, relies on the precise segmentation of polyps during colonoscopy for its early diagnosis. However, clinical colonoscopy images often face challenges such as low contrast, blurred boundaries, large differences in morphological scale, and interference from intestinal wall folds, resulting in insufficient accuracy of traditional segmentation methods. To address the above problems, this paper proposes a PCA-TransUNet model based on the parallel cross-attention mechanism, taking TransUNet as the baseline framework and introducing the parallel cross-attention module in its skip connections. This module consists of two branches: channel cross-attention and spatial cross-attention. The channel branch enhances the semantic feature discrimination through cross-scale channel interaction, while the spatial branch optimizes the boundary positioning accuracy by using long-range dependency relationships. The outputs of the two are adaptively integrated through a dynamic weighted fusion mechanism to form multi-scale enhanced features, significantly improving the segmentation robustness in complex scenarios. Experiments on the CVC-ClinicDB and Kvasir-SEG datasets show that the model proposed in this paper outperforms the comparison models in multiple indicators. PCA-TransUNet achieved mIoU of 92.89% and Dice of 95.79% on CVC-ClinicDB, and 90.81% and 95.25%, respectively, on Kvasir-SEG, providing reliable technical support for clinical auxiliary diagnosis. Full article

Background and Aims: Adequate bowel preparation is the cornerstone of high-quality colonoscopy. The Boston Bowel Preparation Scale (BBPS) is the gold standard for assessment, yet its application suffers from inter-observer variability and lacks a fully automated solution for entire video analysis. This study proposes EndoClean, a novel, fully automated deep learning framework designed to compute the full-segment BBPS score from colonoscopy videos, aiming to provide a standardized, objective, and near expert-level assessment. Methods: EndoClean integrates three distinct models: frame selection, anatomical segmentation, and BBPS scoring. Its performance was rigorously evaluated against a reference standard established by senior experts and compared with junior endoscopists. We assessed assessment precision, inter-rater agreement (quadratic weighted Kappa), and consistency across all colonic segments. Results: The EndoClean system demonstrated superior reliability, achieving a global accuracy of 97.8% for the total BBPS score, with satisfying agreement with senior experts (κ = 0.984; 95% CI: 0.976–0.989). Notably, EndoClean performed significantly better than junior endoscopists in overall BBPS agreements (κ: 0.984 vs. 0.949, p < 0.001) and overall accuracy (97.8% vs. 94.6%, p = 0.037). In segment-specific analysis, the EndoClean surpassed junior doctors particularly in the transverse colon (Accuracy: 97.5% vs. 90.4%, p < 0.001) and effectively reduced misclassifications in clinically ambiguous intermediate scores. For binary adequacy classification, the system achieved a sensitivity of 98.2% and a specificity of 97.3%. Conclusions: EndoClean represents a robust solution in automated quality control, demonstrating performance comparable to senior experts in bowel preparation assessment. By significantly reducing the variability seen in junior endoscopists and providing objective, full-video BBPS scoring, this framework offers a viable, standardized, and efficient solution for clinical practice and large-scale quality monitoring. Full article

Objective: This study assessed the ability of capsule formulations to improve the oral delivery and retain activity of an acid-sensitive enzyme during gastrointestinal transit. Methods: The dissolution characteristics of five capsule formulations—single DRcaps^® [DR], single Vcaps^® Plus [VCP], and three DUOCAP^® capsule-in-capsule combinations, DRcaps^® inside DRcaps^® (DR-in-DR), DRcaps^® inside Vcaps^® Plus (DR-in-VCP), and Vcaps^® Plus inside DRcaps^® (VCP-in-DR)—were evaluated in an in vitro simulation of a healthy human upper gastrointestinal tract under fasting and fed conditions using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)^® platform. Capsules contained caffeine as a marker of capsule dissolution, and pancreatin as an active ingredient for which activity was determined by the conversion of tributyrin. Readouts included visual capsule scoring, the analysis of caffeine release, and the quantification of tributyrin-to-butyrate conversion at the end of each gastrointestinal tract segment. Results: The single VCP capsules had a high level of caffeine release at the end of the stomach incubation with low butyrate recovery (16–21%), suggesting the rapid release and gastric degradation of the unprotected enzyme. The single DR, DR-in-VCP, and VCP-in-DR formulations showed caffeine release at the end of the duodenum and/or jejunum and had high butyrate recovery, ranging from 53% to 87%. The DR-in-DR formulation had the most delayed release, with incomplete caffeine release and low-to-moderate butyrate recovery (10–36%). Conclusions: Fast capsule dissolution led to the reduced enzymatic activity of the active ingredient, while delayed dissolution resulted in inadequate time for the enzymatic conversion of tributyrin to butyrate. These results highlight that capsule selection should align with the intended use and targeted nutrient delivery, with DUOCAP^® formulations being best suited for small intestinal (VCP-in-DR and DR-in-VCP) and colonic (DR-in-DR) delivery. Full article

Chlamydia suis, a close relative of the human pathogen C. trachomatis, can be detected in the porcine gut, yet its prevalence and viability across intestinal segments remain poorly defined. This study aimed to assess the segment-specific prevalence, isolation success, and tetracycline susceptibility of C. suis in grower-finisher pigs. Jejunal, ileal, and colonic samples (n = 200 per intestinal segment) were collected from 600 pigs at slaughter and analyzed using C. suis-specific real-time PCR and culture. PCR revealed significantly higher detection rates in the colon (40%) than in the jejunum or ileum (both 4.5%), accompanied by significantly higher calculated bacterial loads in colonic samples. In contrast, viable C. suis was most frequently isolated from ileal material, indicating that the ileum may provide a more favorable condition for active bacterial replication. Among 24 culture-confirmed isolates, 75% were susceptible to tetracycline (MIC/MBC < 2 µg/mL), 12.5% exhibited an intermediate phenotype (2 µg/mL < MIC/MBC < 4 µg/mL) and another 12.5% were resistant (MIC/MBC > 4 µg/mL). Intermediate phenotypes were recovered from the jejunum and ileum, whereas resistant isolates were found in the ileum and colon. These findings suggest that the porcine colon may serve as an intestinal reservoir for C. suis, while the ileum supports more robust bacterial replication. Overall, these data contribute to our understanding of the intestinal ecology of C. suis under field conditions and its tetracycline susceptible patterns. Full article

Segmented filamentous bacteria (SFB) are host-specific, immune-modulating microorganisms that colonize the small intestine of various vertebrate species, playing a crucial role in stimulating immune maturation during early life. Previous research on the genomes of SFB from humans, rats, and mice has revealed significant differences among SFB strains associated with various hosts, suggesting that their evolution is closely linked to their relationships with specific hosts. However, the genome of SFB from chickens has not been extensively investigated. In this study, we present the metagenomic reconstruction of an SFB genome derived from the ileum of layer Lohmann Select Leghorn (LSL) chickens. We utilized Hi-C sequencing techniques to assemble the LSL-SFB and annotate the avian SFB from both turkeys and chickens. Our reference-guided consensus assembly, followed by Hi-C scaffolding, produced a high-quality genome for LSL-SFB. Our pangenomic analysis revealed substantial conservation of core gene clusters among mammalian SFB strains, but we also identified a distinct repertoire of genes in chicken and turkey SFB. Furthermore, metabolic network analysis indicated a reduced capacity for biosynthesis, signifying an increased reliance on the host, as shown by the absence of key biosynthetic and utilization pathways. We also discovered a unique flagellin subunit (fliC-2) in chicken SFB from different genetic lines and confirmed its interaction with the chicken flagellin receptor, Toll-like receptor five. This study provides the first high-quality genome and annotation of LSL-SFB, alongside that of turkeys, offering valuable insights into the mechanisms of host specificity and adaptation. Understanding the interactions between host-specific SFB and their hosts, as well as their role in promoting immune maturation, is essential for improving intestinal health. Full article

The aquaporin 0 (AQP0)/major intrinsic protein of eye lens (MIP) cDNA was cloned and sequenced. Initial studies of the tissue distribution of mRNA expression proved to be incorrect. Subsequent experiments showed that AQP0 mRNA is expressed strongly in the eye with moderately strong expression in the kidneys and some expression was seen in the brain and muscle tissue, and very low expression in the esophagus/fundic stomach. Another set of PCR reactions with five times the amount of cDNA additionally showed mRNA/cDNA expression in the liver, rectal gland, and a very low level in the intestine. Sporadic expression of different pieces of AQP0 cDNA was seen in various experiments in gill and pyloric stomach. A custom polyclonal antibody was produced against a region near the C-terminal end of the AQP0 protein sequence. The antibody gave a band of around the correct size (for the AQP0 protein) on the Western blot, which also showed a few other higher-molecular-weight bands. The antibody was also used in immunohistochemistry, and in the kidney, it showed staining in the proximal II (PII), intermediate segment I (IS I), and late distal tubule (LDT) parts of the sinus zone region of nephrons as well as some staining in the bundle zone tubule segments, suggesting a role for AQP0 as a water channel. In the rectal gland, the antibody showed weak apical membrane staining in a few secretory tubules near the duct, but also somewhat stronger staining in cells appearing to connect various secretory tubules, suggesting a role in cell–cell adhesion. In the spiral valve intestine side wall and valve flap, after signal amplification, weak antibody staining was seen in the apical and lateral membranes of epithelial cells adjacent to the luminal surface. There was also some staining in the intestinal muscle. In the rectum/colon, staining was seen in a layer of cells underlying the epithelium and in some muscle layers. In the gill, there was very weak staining in secondary lamellae epithelial cells and in connective tissue surrounding blood vessels and blood sinuses. The low level of transcript expression in the rectal gland, gill, and intestinal tissues suggests caution in the interpretation of the immunohistochemical staining in these tissues. Full article

This study systematically characterized functional compartmentalization along the intestinal tract of New Zealand rabbits by analyzing mucosal tissue and luminal contents from distinct segments, including the duodenum, jejunum, ileum, cecum, and colon, using RNA-seq and 16S rRNA sequencing. Transcriptomic analysis revealed that differentially expressed genes identified between the small and large intestines were mainly enriched in digestion, absorption, and immune functions. Genes associated with the transport of amino acids, sugars, vitamins, and bile salts showed significantly higher expression in the small intestine, whereas genes related to water absorption, short-chain fatty acids (SCFAs), nucleotides, and metal ion transport were preferentially expressed in the large intestine. From an immunological perspective, genes involved in fungal responses were enriched in the small intestine, while bacterial response pathways and pattern recognition receptor (PRR) signaling genes were upregulated in the large intestine. Microbiota analysis demonstrated significantly greater diversity and abundance in the large intestine compared with the small intestine. Specifically, Proteobacteria and Actinobacteria were enriched in the small intestine, whereas Firmicutes, Verrucomicrobia, and Bacteroidetes dominated the large intestine. Correlation analysis further identified significant associations between gut microbiota composition and host genes involved in nutrient digestion and absorption. Together, these findings provide transcriptome-based evidence for regional specialization of nutrient transport, immune responses, and microbial ecology along the rabbit intestine. Full article

Background/Objectives: Growing concerns about antibiotic-associated adverse events, including Clostridioides difficile infection, prompted implementation of an antibiotic stewardship program (ASP) in South Korea in November 2024. One year post-implementation, we evaluated changes in antibiotic consumption and C. difficile infection incidence. Methods: This study was conducted at Chung-Ang University Gwangmyeong Hospital, South Korea. Segmented regression and interrupted time series analyses were performed using weekly data on antibiotic use (days of therapy [DOT] per 1000 patient-days) and C. difficile infection or colonization (cases per 1000 patient-days) over 157 weeks (November 2022–October 2025). Weeks 1–105 defined the pre-ASP period, and weeks 106–157 the post-ASP period. A 4-week lag between antibiotic use and subsequent C. difficile infection was hypothesized. Results: Before ASP, weekly total antibiotic use increased (β₁ = 1.14, 95% CI, 0.76 to 1.51, p < 0.001). After ASP, the slope decreased significantly (β₃ = −1.50, 95% CI −2.62 to −0.39, p = 0.009), consistent across anti-pseudomonal penicillins and cephalosporins and fluoroquinolones. Pre-ASP C. difficile incidence increased (α₁ = 0.01, 95% CI, 0.01 to 0.02, p < 0.001); the upward trend attenuated post-ASP, though slope change was not significant (α₃ = −0.01, 95% CI, −0.03 to 0.004, p = 0.13). An increase of 1 DOT per 1000 patient-days was associated with a 0.005-case increase in C. difficile infection incidence after 4 weeks. Conclusions: The observed effects of proactive ASP strategies underscore the importance of maintaining stewardship in clinical practice. Further studies are warranted to assess the sustainability of these findings and evaluate additional factors influencing C. difficile infection incidence. Full article

The increasing environmental impact of synthetic antifouling paints has stimulated the search for natural, eco-friendly alternatives. In this study, alcoholic and aqueous extracts of the macroalgae Ulva ohnoi and Asparagopsis taxiformis were evaluated for their antifouling potential on aluminum substrates representative of boat hulls. Extracts were applied to aluminum plates coated with gelcoat under three different surface conditions (non-worn, worn, highly worn). The treated panels were submerged at 5 m and biofilm and fouling development was monitored every 96 h using digital imaging and quantitative segmentation. All treated surfaces exhibited significantly lower fouling colonization than the untreated control (p < 0.001). Among treatments, the aqueous extract of A. taxiformis produced the lowest degree of colonization across all surface conditions, while U. ohnoi extracts showed moderate antifouling activity. Increased surface wear enhanced overall colonization but did not suppress extract efficacy. These results demonstrate that both algal species possess active compounds capable of inhibiting early biofilm formation on marine substrates. Although less potent than conventional biocidal coatings, their biodegradability and absence of ecotoxicity represent a substantial environmental advantage. Future studies should focus on the chemical characterization of active metabolites, the formulation of hybrid bio-based coatings, and long-term field testing under dynamic marine conditions. Full article

This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × Large, body weight = 2.58 ± 0.05 kg) were divided into three treatment groups based on similar body weights and equal numbers of males and females: the blank control group (CON group), the PEDV infection group (PEDV group), and the NG intervention + PEDV infection group (NG + PEDV group) (n = 6 per group). The experiment lasted for 11 days, comprising a pre-feeding period from days 0 to 3 and a formal experimental period from days 4 to 10. On days 4–10 of the experiment, piglets in the NG + PEDV group were orally administered NG (10 mg/kg). On Day 8 of the experiment, piglets in the PEDV and NG + PEDV groups were inoculated with PEDV (3 mL, 10⁶ 50% tissue culture infective dose (TCID₅₀) per milliliter). On day 11 of the experiment, piglets were euthanized for sample collection. PEDV infection caused significant intestinal damage, including a decreased (p < 0.05) villus height in the duodenum and ileum and an increased (p < 0.05) crypt depth in all intestinal segments. This intestinal damage was accompanied by an impaired absorptive function, as indicated by reduced (p < 0.05) serum D-xylose. Further results showed that PEDV compromised the intestinal antioxidant capacity by decreasing (p < 0.05) glutathione peroxidase and catalase activities, and it stimulated the intestinal inflammatory response by upregulating (p < 0.05) the expression of key inflammatory genes, including regenerating family member 3 gamma (REG3G; duodenum, jejunum, colon), S100 calcium binding protein A9 (S100A9; ileum, colon), interleukin 1 beta (IL-1β; ileum, colon), and S100 calcium binding protein A8 (S100A8; colon). PEDV also suppressed the intestinal lipid metabolism pathway by downregulating (p < 0.05) the ileal expression of Solute Carrier Family 27 Member 4 (SLC27A4), Microsomal Triglyceride Transfer Protein (MTTP), Apolipoprotein A4 (APOA4), Apolipoprotein C3 (APOC3), Diacylglycerol O-Acyltransferase 1 (DGAT1), and Cytochrome P450 Family 2 Subfamily J Member 34 (CYP2J34). Moreover, PEDV suppressed the intestinal antiviral ability by downregulating (p < 0.05) interferon (IFN) signaling pathway genes, including MX dynamin like GTPase 1 (MX1) and ISG15 ubiquitin like modifier (ISG15) in the duodenum; weakened intestinal water and ion transport by downregulating (p < 0.05) aquaporin 10 (AQP10) and potassium inwardly rectifying channel subfamily J member 13 (KCNJ13) in the duodenum, aquaporin 7 (AQP7) and transient receptor potential cation channel subfamily V member 6 (TRPV6) in the ileum, and TRPV6 and transient receptor potential cation channel subfamily M member 6 (TRPM6) in the colon; and inhibited intestinal digestive and absorptive function by downregulating (p < 0.05) phosphoenolpyruvate carboxykinase 1 (PCK1) in the duodenum and sucrase-isomaltase (SI) in the ileum. Notably, NG effectively counteracted these detrimental effects. Moreover, NG activated the IFN signaling pathway in the jejunum and suppressed PEDV replication in the colon. In conclusion, NG alleviates PEDV-induced intestinal injury by enhancing the antioxidant capacity, suppressing inflammation, normalizing the expression of metabolic and transport genes, and improving the antiviral ability. Full article

Research indicates that TRF improves mammalian metabolism and health via the microbiota–gut–brain axis. Previous studies showed that TRF promotes pig growth, but the intestinal mechanisms remain unclear. This study explored the impact of TRF on pig intestinal functions. Twelve male pigs were split into ad libitum feeding (FA) and TRF groups. FA pigs had free access to feed, whereas TRF pigs were fed during 07:00–08:00, 12:00–13:00, and 17:00–18:00. TRF enhanced crude protein digestibility by 18.9% (p = 0.045) and increased pancreatic chymotrypsin and lipase activities, while reducing ileal amylase, sucrase, and lipase activities. Transcriptomic analysis identified 1339 differentially expressed genes (DEGs) in the jejunum and 268 in the colon, indicating segment-specific responses. Jejunal DEGs were associated with protein digestion and absorption (e.g., SLC1A1, SLC38A2, XPNPEP2), extracellular matrix–receptor interaction, and PI3K-Akt signaling, while colonic DEGs were linked to starch and sucrose metabolism and circadian entrainment. Importantly, TRF decreased colonic starch by 24% (p = 0.02) and cellulose by 18% (p = 0.04), with low impact on nitrogenous substrates. These results suggest that TRF improves protein absorption in the upper intestine and carbohydrate metabolism in the lower intestine, providing insights for refining TRF strategies in precision nutrition. Full article