Intestinal Behçet’s disease is a rare, refractory subtype of systemic vasculitis, characterized by deep ileocecal ulcers and extensive clinical overlap with Crohn’s disease, while the cellular and molecular mechanisms underlying its pathogenesis remain poorly characterized. This study aimed to delineate the single-cell transcriptomic landscape of intestinal Behçet’s disease, characterize its putative disease-associated transcriptomic signatures, and identify potential candidates for differential diagnosis and targeted treatment. We performed single-cell RNA sequencing on paired inflamed and histologically normal terminal ileum biopsy specimens from 4 patients with active intestinal Behçet’s disease, and integrated our dataset with a public single-cell dataset from 12 Crohn’s disease patients and 6 healthy controls for systematic bioinformatic analysis. We thereby constructed the first single-cell transcriptomic atlas of human intestinal Behçet’s disease, profiling 98,119 high-quality cells to identify 3 major cell lineages, 20 distinct cell populations, and 41 functionally defined cell subtypes. Our analysis indicated that intestinal Behçet’s disease may be characterized by robust stromal compartment activation, extracellular matrix remodeling, and potentially distinct epithelial antimicrobial signatures, which showed notable differences from the prominent epithelial barrier dysfunction and interferon-driven immune activation observed in Crohn’s disease in this parallel intra-disease comparison framework. We further identified predicted pathogenic crosstalk between endothelial cells and neutrophils, which may be mediated by collagen/laminin-CD44 axes. Our findings thereby characterize the potential pathogenic features of intestinal Behçet’s disease, and provide hypothesis-generating clues for the clinical management of this rare disorder.

Chiral pesticide residues in food can pose enantioselective health risks. Nevertheless, the high-throughput separation and quantification of chiral pesticides remain challenging. We developed a novel, cost-effective analytical strategy that combines liquid chromatography-tandem mass spectrometry (LC-MS/MS) with liquid chromatography-diode array detection (LC-DAD) for the absolute quantification of 62 enantiomers originating from 30 chiral pesticides in vegetable samples. By determining the enantiomeric fraction (EF) of commercial standards via LC-DAD, individual calibration curves for each enantiomer were established and validated, thereby enabling their absolute quantification via LC-MS/MS in the absence of enantiopure standards. This method achieved rapid analysis of all 62 enantiomers within 10 min. 55 vegetable samples were analyzed, and six chiral pesticides were detected in 19 different samples. Among them, the selective enrichment of 1S,3S-bifenthrin was observed in cucumbers. This study provides an accurate quantitative method for the determination of chiral pesticides in food safety risk assessment.

Hepatocellular carcinoma (HCC) is a major health issue, but treatment options are limited. This study investigated the role of CCR4-NOT transcription complex subunit 9 (CNOT9) in the pathogenesis of HCC and its potential as a therapeutic target. Bioinformatics analysis was performed on RNA-seq data from the TCGA and GTEx databases to assess CNOT9 expression and prognostic significance. CNOT9 expression was validated in clinical samples and cell lines using qRT-PCR and Western blot. CNOT9 was knocked down in HCC cell lines, and its effects on proliferation, apoptosis, and cell cycle were investigated using functional assays (CCK-8, EdU, colony formation, and flow cytometry). The underlying molecular mechanisms were explored via RNA-seq and Western blot analysis of the AKT pathway and cell cycle regulators. Xenograft mouse models were used to confirm the oncogenic role of CNOT9 in vivo. CNOT9 mRNA and protein expression were upregulated in HCC patients and associated with poor prognosis. CNOT9 induces abnormal proliferation of HCC cells and G2/M phase cell cycle progression. Knocking down CNOT9 reduces cell proliferation, increases apoptosis, and causes cell arrest at the G2 phase. CNOT9 knockdown activates PTEN to inhibit the AKT pathway and suppresses the expression of cell cycle-related proteins p53, p21, CCNE1 and CDK2. CNOT9-deficient tumors exhibited reduced growth in mice, supporting its pro-oncogenic role. This study first elucidates the molecular mechanism by which CNOT9 drives HCC progression through post-transcriptional regulation of the PTEN/AKT/p53 axis, providing a theoretical basis for precision treatment strategies targeting CNOT9 or the PTEN/AKT/p53 pathway.

Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems.

BackgroundEndoscopic ultrasound-guided biliary drainage (EUS-BD) has become an established alternative for managing malignant biliary obstruction. While recurrent biliary obstruction—commonly due to tumor ingrowth or stent migration following EUS-BD—remains a major clinical challenge, food impaction within lumen-apposing metal stents (LAMSs) has been rarely reported.Case presentationA 75-year-old man with unresectable pancreatic carcinoma and duodenal invasion, who had undergone successful EUS-BD with LAMS placement 8 months previously, presented with recurrent obstructive jaundice. Initial imaging indicated no significant tumor progression compared with a follow-up CT performed three months earlier. No tumor ingrowth, overgrowth, or sludge accumulation was observed. Subsequent endoscopy revealed that the LAMS was occluded by food debris. Following endoscopic removal of the impacted food, purulent bile overflowed and a coaxial double-pigtail plastic stent was placed through the LAMS to maintain luminal patency. The patient recovered promptly. In retrospect, the patient reported no dietary restrictions since the previous EUS-BD. At 1-month follow-up, the patient remained asymptomatic, without recurrent jaundice or need for reintervention.ConclusionThis case highlights food impaction as an unusual but clinically significant cause of recurrent obstructive jaundice following EUS-BD with LAMS. Successful management with endoscopic debridement and coaxial plastic stent placement offers a potential endoscopic strategy for this subgroup of patients. Moreover, this case emphasizes the importance of long-term dietary counseling in patients with indwelling LAMS to prevent this rare but potentially severe complication.

Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy of the liver characterized by high mortality rates. While peptidylprolyl isomerase-like two (PPIL2) has been implicated in various malignancies, its functional contribution to HCC progression and the underlying molecular mechanisms remain poorly defined. In this study, we observed significant upregulation of PPIL2 in HCC tissues, which correlated with unfavorable patient prognosis. Functional assays showed that PPIL2 knockdown markedly inhibited HCC cell proliferation by inducing cell cycle arrest and cellular senescence. Mechanistically, PPIL2 depletion led to reduced c-Myc protein levels and a concomitant induction of p21. Critically, the tumor-suppressive effects induced by PPIL2 silencing were partially rescued upon c-Myc overexpression, confirming that PPIL2 exerts its oncogenic function predominantly through a c-Myc-dependent pathway. Furthermore, PPIL2 deficiency effectively hindered tumor growth in a xenograft mouse model. Collectively, these findings identify the PPIL2/c-Myc/p21 axis as a critical regulator of HCC proliferation and senescence, positioning PPIL2 as a promising therapeutic target.

Abstract Borderline resectable pancreatic cancer (BRPC) represents a complex clinical entity characterized by anatomical, biological, and conditional heterogeneity. Accurate assessments of resectability and the response to neoadjuvant chemotherapy (NAC) are crucial for determining surgical eligibility and improving overall survival. This review comprehensively summarizes current methods for predicting and evaluating the NAC response in patients with BRPC. A structured literature search was conducted in the PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov, focusing on imaging-based evaluations, serum and molecular biomarkers, and emerging radiomic and radiogenomic techniques. This review is a narrative synthesis of the current evidence. Imaging modalities such as contrast-enhanced computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography remain fundamental for assessing vascular involvement and the therapeutic response, whereas dynamic biomarkers, including carbohydrate antigen 19-9, circulating tumor DNA, and exosomal markers, provide complementary insights into biological activity. Radiomics-based models further increase the precision of the predictions by integrating quantitative imaging features with molecular signatures. However, despite promising advances, the current evidence is limited by heterogeneity in patient selection, small sample sizes, lack of standardized thresholds, and insufficient validation in prospective studies. A multidisciplinary strategy integrating imaging, biomarker, and clinical parameters within standardized assessment frameworks is essential for refining the resectability evaluation and guiding the personalized management of patients with BRPC.

High-altitude hypobaric hypoxia poses a significant threat to brain function, yet effective neuroprotective strategies remain limited. Emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a key mediator in high-altitude-induced cognitive impairment, positioning it as a potential therapeutic target. This review synthesizes current knowledge on how high-altitude exposure dynamically reshapes gut microbial ecology, characterized by reduced diversity, phylum-level instability, and functional metabolic shifts. Furthermore, we delineate how such altitude-induced dysbiosis has been associated with neural dysfunction through interconnected pathogenic mechanisms that are proposed to link gut ecology to brain outcomes: intestinal barrier disruption with metabolic dysregulation, LPS/TLR4-mediated neuroinflammation, vagal and enteric nervous system alterations, oxidative stress imbalance, and neuroendocrine dysregulation. Most current evidence is correlational, and further research is needed to establish causality. A critical unresolved question is whether short-term, transient gut dysbiosis at high altitude can instigate long-lasting neurological deficits independent of ongoing microbial perturbation. We further evaluate microbiota-targeted neuroprotective strategies, including probiotics, prebiotics, and fecal microbiota transplantation, highlighting their distinct mechanisms and summarizing the current evidence supporting MGBA-targeted interventions for high-altitude brain health. Preclinical studies suggest these approaches hold promise by restoring barrier integrity, attenuating inflammatory signaling, and rebalancing microbial metabolite profiles, while human intervention evidence remains scarce. Finally, we discuss critical challenges and future directions for translating these mechanistic insights into personalized interventions, emphasizing deeper mechanistic exploration and the synergistic interactions among microbial taxa. These insights may inform more effective therapeutic strategies for the growing populations residing in or traveling to high-altitude regions.

BACKGROUND:Endoscopic resection is the standard treatment for rectal neuroendocrine tumors (r-NETs) ≤10 mm, yet the optimal technique remains debated. Modified endoscopic mucosal resection (m-EMR) has been proposed as an alternative to endoscopic submucosal dissection (ESD), but prior evidence is mainly retrospective and recent randomized controlled trials (RCTs) are inconclusive. METHODS:We systematically searched CENTRAL, PubMed, Embase, and WanFang from January 1, 1970 to December 23, 2025, for RCTs comparing m-EMR and ESD in r-NETs ≤10 mm. Evidence certainty was evaluated using GRADE, and trial sequential analysis (TSA) was conducted to support the statistical stability of the pooled estimate. RESULTS:Six RCTs involving 440 patients were included. No significant differences were found between m-EMR and ESD in histologic complete resection (RR = 1.00, 95% CI 0.97-1.03; I² = 0%), en bloc resection (P = 0.75), or procedure-related adverse events (P = 0.94). m-EMR was associated with significantly shorter procedure time and lower hospitalization cost. Evidence certainty was moderate; TSA confirmed the reliability of the findings, and both cumulative and sensitivity analyses supported the robustness. CONCLUSION:m-EMR provides comparable short-term histologic efficacy to ESD, while being associated with shorter procedure time and lower hospitalization costs, supporting its consideration as a reasonable first-line option for r-NETs ≤10 mm.

In order to provide an additional tool for clinical prognosis evaluation, this research attempts to build a nomogram for predicting the survival of patients with advanced (stage Ⅲ/Ⅳ) pancreatic cancer and to preliminary evaluate its predictive impact. Data from 336 patients diagnosed with stage III/IV pancreatic cancer (2018-2025) across two Chinese hospitals were analyzed. Multivariate Cox regression identified independent predictors in the training set, which were used to construct a nomogram estimating 6-, 12-, and 24-month overall survival. The model underwent internal and external validation via ROC curves, calibration plots, and decision curve analysis. Multivariate Cox regression analysis of the training set revealed that serum albumin (P = 0.001), liver metastasis (P = 0.023), ALT≥40U/L (P = 0.010), and CA199 level (P = 0.037) were independent predictors of overall survival. Based on this, a nomogram model was constructed in the training cohort, with a C-index of 0.741. In the internal validation, the AUC values for predicting 6, 12, and 24-month survival rates were 0.806, 0.753, and 0.628, respectively, and in the external validation, they were 0.922, 0.662, and 0.650, respectively. The calibration curve showed that the predicted probabilities were in good agreement with the actual observed results. The discrimination and calibration of this model in internal verification are acceptable, but its incremental value for clinical decision-making is limited, and large-scale multi-center studies are required to further verify its generalizability.

Yogurt, a fermented dairy food, has been increasingly recognized for its potential to modulate gut microbiota and promote host health. Accumulating evidence suggests that yogurt consumption influences gut microbial composition, diversity, and functional activity. In this narrative review, we synthesized the findings on yogurt-related effects on the gut microbiota, intestinal barrier, microbial metabolites, immune responses, and selected extra-intestinal outcomes. We distinguished traditional yogurt, probiotic yogurt, synbiotic yogurt, fortified yogurt, and non-dairy or regional yogurt-like fermented products, and then organized proposed mechanisms into a hierarchical framework that separated direct yogurt-derived inputs, including starter cultures, added probiotic strains, fermentation-derived compounds, and dairy matrix components, from resident microbiota-mediated secondary metabolites and host downstream responses. Importantly, limitations and controversies, such as variability in yogurt formulations, strain-specific effects, and inter-individual responses, were critically evaluated. Finally, we highlighted future research directions that emphasize standardized study designs, defined endpoints, long-term randomized controlled trials, and integrative multi-omics approaches to support the development of personalized dietary strategies. Together, this review provides a structured framework for understanding the complex interactions between yogurt, gut microbiota, and host physiology, while outlining key steps needed to translate evidence into actionable nutritional recommendations.

Salmonella is a major foodborne pathogen worldwide, and its prevention and control are increasingly challenged by antibiotic resistance and drug residue concerns. In this study, a mouse model of colitis induced by Salmonella Typhimurium was established to evaluate the potential of the natural polyphenol resveratrol as an alternative to antibiotics. The results demonstrated that resveratrol significantly alleviated colonic histopathological damage and systemic inflammatory responses. Mechanistically, resveratrol modulated the gut microbiota composition by enriching beneficial bacteria and promoting the production of short-chain fatty acids. These changes subsequently inhibited the NF-κB signaling pathway and activated the Nrf2/HO-1 pathway, leading to reduced levels of pro-inflammatory cytokines, enhanced antioxidant enzyme activities, and restoration of intestinal barrier integrity. Notably, unlike ciprofloxacin, resveratrol exerted protective effects without inducing hepatorenal toxicity. Overall, this study highlights that resveratrol effectively mitigates bacterial colitis through multi-target regulation of the gut microbiota, providing a scientific basis for the development of safe, residue-free functional foods or feed additives.

The simultaneous quantification of key metabolites in the central carbon metabolism of biological samples remains challenging. Their high polarity results in low chromatographic retention, and their isomeric forms necessitate high-resolution separation. Moreover, efficient extraction from complex matrices, such as serum, remains a major analytical challenge. We address these challenges via an integrated HILIC-MS/MS strategy for the simultaneous quantification of 35 structurally diverse central carbon metabolites in serum, encompassing a wider range than that previously reported. By employing a systematically optimized chromatographic method with a Z-HILIC column under low-salt conditions, and using methylenediphosphonic acid as an additive in the mobile phase to improve peak shapes and compound responses, this method achieved effective separation of all analytes, including the baseline resolution of 11 critical isomers. To overcome extraction limitations, an EDTA-assisted strategy was implemented to dissociate metabolite-metal ion chelates, ensuring efficient recovery across all metabolite classes. This was coupled with a solid-phase extraction workflow using Oasis PRiME HLB cartridges that enhanced the sample purification efficiency while maintaining satisfactory recovery. The method was rigorously validated, and all analytes demonstrated excellent linearity, accuracy, and precision. To demonstrate its applicability, this method was employed to profile rat serum, successfully quantifying metabolites across a wide concentration range.

Elucidating the molecular mechanisms underlying hepatocellular carcinoma (HCC) pathogenesis is crucial for the development of targeted therapies. Makorin-2 (MKRN2), a member of the makorin RING zinc finger protein family, acts as an E3 ubiquitin ligase that regulates post-translational modifications. Although emerging evidence implicates MKRN2 in the oncogenesis of various malignancies, its biological role in HCC remains poorly characterized. In this study, we found that MKRN2 expression was significantly upregulated in HCC and correlated with poor patient prognosis. To functionally validate the role of MKRN2, we performed CCK-8, colony formation, and EdU assays. Consistently, the results showed that MKRN2 depletion markedly attenuated the proliferative capacity of HCC cells. Subsequently, RNA-seq analysis in Huh-7 cells indicated that MKRN2 was involved in cell cycle regulation and the p38 MAPK signaling pathway. Furthermore, flow cytometry assays demonstrated that MKRN2 depletion arrested the cell cycle at the G1/S transition. Mechanistically, MKRN2 was shown to regulate c-Myc activation via the p38 MAPK pathway, thereby promoting cell cycle progression and enhancing proliferation. In addition, in vivo experiments confirmed that MKRN2 knockdown suppressed tumor growth in xenograft mouse models. In conclusion, our results demonstrate that MKRN2 promotes cell cycle progression and drives proliferation through activation of the p38 MAPK signaling pathway in HCC cells, highlighting its potential as a therapeutic target for HCC.

Background: Primary biliary cholangitis (PBC) is a chronic immune-mediated disease that may partially exhibit a poor response to the first-line treatments, such as monotherapy (MU) with ursodeoxycholic acid (UDCA). Budesonide, a widely used and readily available medication, has shown promise in previous studies as an alternative to conventional drugs when combined with UDCA (CBU) for non-cirrhotic PBC. Therefore, this study aimed to confirm the role of CBU in patients with non-cirrhotic PBC. Methods: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases for randomized controlled trials (RCTs) comparing CBU and MU for non-cirrhotic PBC. The certainty of evidence was assessed using the grading of the recommendation assessment, development, and evaluation (GRADE) framework. Trial sequential analysis (TSA) was applied to control for the risk of random errors and to evaluate the conclusion validity. Results: Three high-quality RCTs comprising 170 patients were included. Moderate certainty of evidence revealed that CBU showed a significantly higher percentage improvement over MU in alkaline phosphatase (ALP) [mean difference (MD) =19.97, 95% confidence interval (CI): 6.59 to 33.35, P=0.003, I2=0%], liver histology (MD =27.04, 95% CI: 1.62 to 52.46, P=0.04, I2=46%), total bilirubin (P=0.01) and immunoglobulin G (IgG, P=0.002), with no significant difference in serious adverse drug reactions (ADRs) (P=0.06). There were no significant differences for other biochemical variable outcomes; however, positive trends were observed. TSA confirmed the reliability of the ALP and IgG percentage improvements. Conclusions: CBU might be superior to MU for non-cirrhotic PBC, possibly showing a better biochemical response and liver histology improvement with similar safety. Further large-sample studies are required in this subpopulation.

AimThis study aims to develo\p a population-adapted machine learning-based prediction model for hepatocellular carcinoma (HCC) lymph node metastasis (LNM) to identify high-risk patients requiring intensive surveillance.MethodsData from 23511 HCC patients in the SEER database and 57 patients from our hospital were analyzed. Seven LNM risk indicators were selected. Four machine learning algorithms—decision tree (DT), logistic Regression (LR), multilayer perceptron (MLP), and extreme gradient boosting (XGBoost)—were employed to construct prediction models. Model performance was evaluated using area under the curve, accuracy, sensitivity, and specificity.ResultsAmong 23511 SEER patients, 1679 (7.14%) exhibited LNM. Race, Sequence number, Tumor size, T stage and AFP were identified as independent predictors of LNM. The LR model achieved optimal performance (area under the curve: 0.751; accuracy: 0.707; sensitivity: 0.711; specificity: 0.661). External validation with 57 patients from our hospital confirmed robust generalizability (area under the curve: 0.73; accuracy: 0.737; sensitivity: 0.829; specificity: 0.5), outperforming other models.ConclusionsThe LR-based model demonstrates superior predictive capability for LNM in HCC, offering clinicians a valuable tool to guide personalized therapeutic strategies.