Purpose: This study aims to reveal the mechanism underlying baicalin-suppressing ovarian cancer stemness. Methods: OVCAR-3 and the primary ovarian cancer cells were used for cell model. The ovarian cancer stem cells were isolated by suspension culture. Cell viability and clonogenicity were examined by CCK-8 assay and colony formation assay. The self-renewal of the cells was evaluated by the determination of sphere-forming capacity and the frequency of in vitro sphere-forming and in vivo tumor-initiating cells. The mRNA and protein levels were relatively quantified by qRT-PCR and Western blot. The transcription regulation of target genes was tested by luciferase reporter assay and a modified nuclear rn-on qRT-PCR assay. Results: Treatment with a non-toxic dose of baicalin significantly inhibited the spherogenicity of ovarian cancer cells. Moreover, a non-toxic dose of baicalin treatment suppressed the frequency of sphere-forming and tumor-initiating ovarian cancer cells. Furthermore, the expression of ovarian cancer stem cell markers (CD133 and ALDH1A1) was inhibited by a non-toxic dose of baicalin treatment. Baicalin inhibits YAP activity and suppresses RASSF6, a positive regulator of YAP, at the transcriptional level. Overexpression of both YAP and RASSF6 abolished the inhibitory effect of baicalin on the proliferation and stemness of ovarian cancer cells. Conclusion: The results in this study demonstrated that baicalin suppresses the stemness of ovarian cancer cells by attenuating YAP activity via inhibiting RASSF6 at the transcriptional level. This finding revealed baicalin as a novel YAP inhibitor that could serve as an anti-cancer drug for eradicating ovarian cancer stem cells.

Objective. We aimed to evaluate the performance of artificial intelligence (AI) system in detecting high-grade precancerous lesions. Methods. A retrospective and diagnostic study was conducted in Chongqing Cancer Hospital. Anonymized medical records with cytology, HPV testing, colposcopy findings with images, and the histopathological results were selected. The sensitivity, specificity, and areas under the curve (AUC) in detecting CIN2+ and CIN3+ were evaluated for the AI system, the AI-assisted colposcopy, and the human colposcopists, respectively. Results. Anonymized medical records from 346 women were obtained. The images captured under colposcopy of 194 women were found positive by the AI system; 245 women were found positive either by human colposcopists or the AI system. In detecting CIN2+, the AI-assisted colposcopy significantly increased the sensitivity (96.6% vs. 88.8%, ). The specificity was significantly lower for AI-assisted colposcopy (38.1%), compared with human colposcopists (59.5%, ) or the AI system (57.6%, ). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.741, 0.765, and 0.674, respectively. In detecting CIN3+, the sensitivities of the AI system and AI-assisted colposcopy were not significantly higher than human colposcopists (97.5% vs. 92.6%, ). The specificity was significantly lower for AI-assisted colposcopy (37.4%) compared with human colposcopists (59.2%, ) or compared with the AI system (56.6%, ). The AUCs for the human colposcopists, AI system, and AI-assisted colposcopy were 0.759, 0.674, and 0.771, respectively. Conclusions. The AI system provided equally matched sensitivity to human colposcopists in detecting CIN2+ and CIN3+. The AI-assisted colposcopy significantly improved the sensitivity in detecting CIN2+.

English pronunciation self-concept is formed in the process of pronunciation learning, which refers to the learners’ self-conception and assessment of one’s English pronunciation proficiency and pronunciation (Gimson, A. C. 1980). This paper reports an investigation on 237 non-English major college students into the relationship between English pronunciation self-concept and English performance, global English self-concept, English classroom anxieties; the relationship between global English self-concept and the sub-dimension of it. It was found that a moderate but statistically significant correlation obtained. Furthermore, English pronunciation self-concept correlated significantly to the global English self-concept and the latter exhibited a relatively high correlation to the English performance which is presented by test scores. These results suggest that language learners’ pronunciation self-concept is one of the most important factors which facilitate or hinder foreign language learning. Meanwhile, it has a negative correlation to English class anxiety (Arnold, J., 1999). Therefore, conclusion can be drawn that constructive suggestions are supposed to be put forward and endeavor should be made to improve one’s English pronunciation self-concept to facilitate the English acquisition.

Although surgical resection is an effective intervention for early-stage hepatocellular carcinoma (HCC), postoperative recurrence remains a major clinical hurdle. Delving into the mechanisms underlying relapse and pinpointing potential therapeutic targets are imperative for improving outcomes for patients with HCC. By comparing the microbiota composition in patients with early- and non-relapsing HCC, we identified that Lactobacillus was enriched in patients with relapse-free HCC, serving as an independent prognostic predictor of disease-free survival. Higher levels of intratumoral Lactobacillus johnsonii correlated with an increased abundance of IFNγ+PD-1+CD8+ T cells. Single-cell RNA sequencing, transcriptomic profiling of intratumoral CD45+ immune cells, and in vitro functional assays demonstrated that L. johnsonii preferentially enhanced this cytotoxic-exhausted T-cell population. Nicotinic acid (NA) served as a key metabolite derived from L. johnsonii that expanded IFNγ+PD-1+CD8+ T cells and upregulated effector (granzyme B) and exhaustion (CTLA4) markers. Mechanistically, both L. johnsonii and NA activated the NF-κB pathway, leading to increased IFNγ production and upregulation of the transcription factor NR4A2, which in turn sustained PD-1 expression on CD8+ T cells. Combining L. johnsonii or NA with anti–PD-1 therapy synergistically inhibited tumor relapse and tumor growth in immunocompetent or humanized mice. Crucially, the antitumor efficacy of L. johnsonii was CD8+ T cell–dependent, as depletion abolished its activity. This work unveils a mechanism by which L. johnsonii and its metabolite NA enrich intratumoral IFNγ+PD-1+CD8+ T cells, thereby reshaping the immune microenvironment to potentiate immunotherapy efficacy and suppress HCC recurrence. Significance: Lactobacillus johnsonii produces nicotinic acid that expands intratumoral IFNγ+PD-1+CD8+ T cells, which prevents hepatocellular carcinoma relapse and enhances the efficacy of anti-PD-1 therapy.