Pharmacological inhibition of β-catenin/BCL9 interaction modulates T _reg cells and improves immunotherapy.

Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC.

To date, the overall response rate of PD-1 blockade remains unsatisfactory, partially due to limited understanding of tumor immune microenvironment (TIME). B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, is highly expressed in cancers. By genetic depletion and pharmacological inhibition of BCL9 in tumors, we found that BCL9 suppression reduced tumor growth, promoted CD8⁺ T cell tumor infiltration, and enhanced response to anti-PD-1 treatment in mouse colon cancer models. To determine the underlying mechanism of BCL9’s role in TIME regulation, single-cell RNA-seq was applied to reveal cellular landscape and transcription differences in the tumor immune microenvironment upon BCL9 inhibition. CD155-CD226 and CD155-CD96 checkpoints play key roles in cancer cell/CD8⁺ T cell interaction. BCL9 suppression induces phosphorylation of VAV1 in CD8⁺ T cells and increases GLI1 and PATCH expression to promote CD155 expression in cancer cells. In The Cancer Genome Atlas database analysis, we found that BCL9 expression is positively associated with CD155 and negatively associated with CD226 expression. BCL9 is also linked to adenomatous polyposis coli (APC) mutation involved in patient survival following anti-PD-1 treatment. This study points to cellular diversity within the tumor immune microenvironment affected by BCL9 inhibition and provides new insights into the role of BCL9 in regulating CD226 and CD96 checkpoints

Prior studies have found associations between atopic dermatitis (AD) and comorbidities, including depression, obesity, asthma, and allergic rhinitis. Although observational studies often cannot establish robust causality between potential risk factors and AD, Mendelian randomization minimizes confounding when exploring causality by relying on random allelic assortment at birth. In this study, we systematically reviewed 30 Mendelian randomization studies in AD. Body mass index, gut microbial flora, the IL-18 signaling pathway, and gastroesophageal reflux disease were among the causal factors for AD, whereas AD was causal for several medical conditions, including heart failure, rheumatoid arthritis, and conjunctivitis. These insights may improve preventive counseling in AD.

Background: To validate the accuracy of ultra-wideband (UWB) wireless radar for the screening diagnosis of sleep apnea. Methods: One hundred and seventy-six qualified participants were successfully recruited. Apnea-hypopnea index (AHI) results from polysomnography (PSG) were reviewed by physicians, while the radar device automatically calculated AHI values with an embedded chip. All results were statistically analyzed. Results: A UWB radar-based AHI algorithm was successfully developed according to respiratory movement and body motion signals. Of all 176 participants, 63 exhibited normal results (AHI <5/hr) and the remaining 113 were diagnosed with obstructive sleep apnea. Significant correlation was detected between radar AHI and PSG AHI (Intraclass correlation coefficient 0.98, P<0.001). Receiver operating characteristic curve (ROC) analysis revealed high sensitivity and specificity. High concordance in participants with varying gender, age, BMI, and PSG AHI was reached. Conclusions: The UWB radar may be a portable, convenient, and reliable device for obstructive sleep apnea screening.