Berberine (BBR), as a new medicine for hyperlipidemia, can reduce the blood lipids in patients. Mechanistic studies have shown that BBR activates the extracellular-signal regulated kinase pathway by stabilizing low-density-lipoprotein receptor mRNA. However, aside from inhibiting the intestinal absorption of cholesterol, the effects of BBR on other metabolic pathways of cholesterol have not been reported. This study aimed to investigate the action of BBR on the excretion of cholesterol in high-fat diet-induced hyperlipidemic hamsters. Golden hamsters were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia, followed by oral treatment with 50 and 100 mg/kg/day of BBR or 10 and 30 mg/kg/day of lovastatin for 10 days, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), transaminases, and total bile acid in the serum, liver, bile and feces were measured using an enzyme-linked immunosorbent assay. The cholesterol (as well as coprostanol) levels in the liver, bile and feces were determined by gas chromatography–mass spectrometry. The HFD hamsters showed significantly hyperlipidemic characteristics compared with the normal hamsters. Treatment with BBR for 10 days reduced the serum TC, TG and LDL-C levels in HFD hamsters by 44–70, 34–51 and 47–71 %, respectively, and this effect was both dose- and time-dependent. Initially, a large amount of cholesterol accumulated in the hyperlipidemic hamster livers. After BBR treatment, reductions in the liver cholesterol were observed by day 3 and became significant by day 7 at both doses (P < 0.001). Meanwhile, bile cholesterol was elevated by day 3 and significantly increased at day 10 (P < 0.001). BBR promoted cholesterol excretion from the liver into the bile in hyperlipidemic hamsters but not in normal hamsters, and these results provide a link between the cholesterol-lowering effect of BBR with cholesterol excretion into the bile. We conclude that BBR significantly promoted the excretion of cholesterol from the liver to the bile in hyperlipidemic hamsters, which led to large decreases in the serum TC, TG and LDL-C levels. Additionally, compared with lovastatin, the BBR treatment produced no obvious side effects on the liver function.

Polygonum capitatum Buch.-Ham.ex D. Don, a traditional Miao-nationality herbal medicine, has been widely used in the treatment of various urologic disorders. Recent pharmacological studies demonstrated that a pure compound, FR429, isolated from the ethanol extracts of P. capitatum could selectively inhibit the growth of four hepatocellular carcinoma (HCC) cell lines in a dose-dependent manner. Thus, P. capitatum probably exhibits potential antitumor activity. However, there is very little information on the metabolism of substances present in P. capitatum extracts. In this study, gallic acid, quercetrin, ethanol extracts and ethyl acetate fraction of ethnolic extract (EtOAc fraction) of P. capitatum were cultured anaerobically with rat intestinal bacteria. A highly sensitive and selective liquid chromatography electrospray ionization-ion trap-time of fight mass spectrometry (LC/MSⁿ-IT-TOF) technique was employed to identify and characterize the resulting metabolites. A total of 22 metabolites (M1–M22), including tannins, phenolic acids and flavonoids, were detected and characterized. The overall results demonstrated that the intestinal bacteria played an important role in the metabolism of P. capitatum, and the main metabolic pathways were hydrolysis, reduction and oxidation reactions. Our results provided a basis for the estimation of the metabolic transformation of P. capitatum in vivo.

Psoriasis is a chronic inflammatory skin disease characterized by a high relapse rate, primarily driven by tissue-resident memory T cells (TRM). This study aims to elucidate that the CXCR6/CXCL16 axis is a key regulator of TRM persistence and psoriasis relapse, and demonstrates that curcumol can mitigate psoriasis relapse via this axis and TRM modulation. By integrating single-cell RNA sequencing, spatial transcriptomics, and a CXCR6-knockout mouse model, we analyzed the characteristics of TRM cell subsets and the functional role of CXCR6 in psoriatic lesions. Using imiquimod-induced mouse models of psoriasis onset and relapse, we evaluated the impact of CXCR6 knockdown on TRM cell retention and inflammatory responses. Through in vitro cell experiments, immunofluorescence, and flow cytometry, we validated the inhibitory effect of curcumol on the CXCL16-CXCR6 axis and its role in suppressing TRM cell differentiation. Clinical sample analysis further confirmed the expression pattern of CXCR6 in recurrent psoriatic lesions. TRM cells, particularly the Tc17 subset, exhibit elevated CXCR6 expression in recurrent psoriatic lesions and drive inflammation via the TNF/CCL signaling network. CXCR6 knockout significantly ameliorates the psoriatic immune microenvironment by reducing TRM retention and disease relapse. Experimental studies on curcumol demonstrate that it inhibits CXCL16-CXCR6 interaction, downregulates pro-inflammatory cytokines, and diminishes TRM persistence, while maintaining anti-relapse efficacy even after treatment cessation. These research findings further validate the critical role of TRM cells in the relapse of psoriasis and suggest the potential value of curcumol as a CXCR6-targeted therapeutic agent in preventing the relapse of psoriasis.. This study integrates mechanistic exploration with translational innovation, providing a new therapeutic strategy to address the clinical challenge of psoriasis relapse.

Accurate and generalizable cancer diagnosis from whole slide images (WSIs) remains challenging due to limited fine-grained annotations, complex tumor architectures, and domain shifts across scanners and institutions¹. We introduce StructMIL, a structure-aware and prototype-driven multiple instance learning framework designed for robust and interpretable cancer detection and grading². StructMIL integrates graph-based topological priors with histological context, employs prototype-enhanced pooling for stable and transparent predictions, and incorporates a unified domain-generalization strategy that combines contrastive alignment, adversarial confusion, and consistency regularization. Evaluated on Camelyon16 for breast cancer metastasis detection and PANDA for prostate cancer Gleason grading, StructMIL achieves state-of-the-art performance. On Camelyon16, StructMIL improves cross-center AUC by +3.2% over standard MIL baselines, reaching an AUC of 0.967. On PANDA, it improves cross-scanner Gleason grading robustness with a +7.4% Cohen's Kappa gain compared with prior MIL models, demonstrating substantially reduced performance degradation under domain shift. StructMIL further provides interpretable prototype-based attribution maps that highlight biologically meaningful structures more reliably than conventional MIL and graph-free approaches³. By jointly improving accuracy, interpretability, and generalization across scanners and medical centers, StructMIL offers a practical and clinically aligned solution for large-scale deployment in multi-center computational pathology workflows⁴.

Introduction: In recent years, an increasing body of research has illustrated a strong correlation between gut microbiota and depression. However, there has yet to be a comprehensive discussion or summary of the latest advancements and trends in this field.Methods: We retrieved research articles focused on gut microbiota and depression through the WOS database from 2020 to 2024, using visual text analysis tools such as CiteSpace and VOSviewer.Results: The literature on the relationship between gut microbiota and depression surged from 396 papers in 2020 to 711 by 2024. During this period, the journal with the highest publication rate was Nutrients. China led the countries in contributions, while University College Cork topped the institutions. Kenji Hashimoto emerged as the most prolific author. The most cited paper was authored by Cryan JF et al., published in 2019 in Physiol Rev. The keywords “gut microbiota,” “depression,” and “anxiety” appeared most frequently, while recent years saw explosive increases in terms such as “growth performance,” “receptors,” “depression-like phenotypes,” “stress response,” “gastrointestinal symptoms,” “reliability,” and “neurogenesis.”Discussion: Our article displayed the overview of the relationship between the gut microbiome and depression from 2020 to 2024 using bibliometric methods, providing perspectives and research hotspots for studies exploring the correlation between the gut microbiome and depression.

Background: The mental health of university students, particularly depression, has become a significant public health concern in China. While previous studies have highlighted the link between self-efficacy and mental health, especially concerning depressive symptoms, the potential mediating role of the big five personality traits in this relationship remains underexplored. This study aims to examine the relationships among self-efficacy, the big five personality traits, and depressive symptoms through a mediation model.Methods: This cross-sectional study utilized a multi-stage stratified random sampling method to survey residents across 23 provinces in China, ultimately enrolling 1,193 university students aged 19-25. Measures included the PHQ-9 to assess depressive symptoms, the BFI-10 to evaluate personality traits, and the NGSES for self-efficacy. Hierarchical regression, random forest regression, mediation analyses, and restricted cubic spline (RCS) models were conducted using R software.Results: The prevalence of depressive symptoms among university students was 21.8%. Neuroticism (p<0.001) was a positive predictor of depressive symptoms, while agreeableness (P<0.001) and conscientiousness (P<0.001) were negative predictors. And agreeableness [Effect = -0.028, 95% CI (-0.045, -0.014)], conscientiousness [Effect = -0.043, 95% CI (-0.067, -0.023)], and neuroticism [Effect = -0.048, 95% CI (-0.070, -0.029)] significantly mediated the relationship between self-efficacy and depressive symptoms. Additionally, a potential nonlinear relationship (p for nonlinearity < 0.001) was identified between self-efficacy and depressive symptoms.Conclusions: Self-efficacy shows a direct positive association with depressive symptoms when controlling for personality traits, with neuroticism, agreeableness, and conscientiousness serving as key mediators. This highlights that the effect of self-efficacy on depression depends critically on personality, emphasizing the need to consider these traits in interventions for university students’ mental health.