Unraveling immunotherapeutic targets for endometriosis: a transcriptomic and single-cell analysis.

Background: Endometriosis (EMs), a common gynecological disorder, adversely affects the quality of life of females. The pathogenesis of EMs has not been elucidated and the diagnostic methods for EMs have limitations. This study aimed to identify potential molecular biomarkers for the diagnosis and treatment of EMs. Methods: Differential gene expression (DEG) and functional enrichment analyses were performed using the R language. WGCNA, Random Forest, SVM-REF and LASSO methods were used to identify core immune genes. The CIBERSORT algorithm was then used to analyse the differences in immune cell infiltration and to explore the correlation between immune cells and core genes. In addition, the extent of immune cell infiltration and the expression of immune core genes were investigated using single-cell RNA (scRNA) sequencing data. Finally, we performed molecular docking of three core genes with dienogest and goserelin to screen for potential drug targets. Results: DEGs enriched in immune response, angiogenesis and estrogen processes. CXCL12, ROBO3 and SCG2 were identified as core immune genes. RT-PCR confirmed that the expression of CXCL12 and SCG2 was significantly upregulated in 12Z cells compared to hESCs cells. ROC curves showed high diagnostic value for these genes. Abnormal immune cell distribution, particularly increased macrophages, was observed in endometriosis. CXCL12, ROBO3 and SCG2 correlated with immune cell levels. Molecular docking suggested their potential as drug targets. Conclusion: This study investigated the correlation between EMs and the immune system and identified potential immune-related biomarkers. These findings provided valuable insights for developing clinically relevant diagnostic and therapeutic strategies for EMs.

Silencing of NLRP3 Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin.

Background: Ovarian cancer is a fatal gynecological malignancy. The resistance to chemotherapy in ovarian cancer treatment has been a thorny issue. This study is aimed at probing the molecular mechanism of cisplatin (DDP) resistance in ovarian cancer. Methods: Bioinformatics analysis was conducted to examine the role of Nod-like receptor protein 3 (NLRP3) in ovarian cancer. The NLRP3 level in DDP-resistant ovarian cancer tumors and cell lines (SKOV3/DDP and A2780/DDP) was evaluated by applying immunohistochemical staining, western blot, and qRT-PCR. Cell transfection was conducted to regulate the NLRP3 level. Cell abilities to proliferate, migrate, invade, and apoptosis were measured employing colony formation, CCK-8, wound healing, transwell, and TUNEL assays, respectively. Cell cycle analysis was completed via flow cytometry. Corresponding protein expression was measured by western blot. Results: NLRP3 was overexpressed in ovarian cancer, correlated with poor survival, and upregulated in DDP-resistant ovarian cancer tumors and cells. NLRP3 silencing exerted antiproliferative, antimigrative, anti-invasive, and proapoptotic effects in A2780/DDP and SKOV3/DDP cells. Additionally, NLRP3 silencing inactivated NLRPL3 inflammasome and blocked epithelial-mesenchymal transition via enhancing E-cadherin and lowering vimentin, N-cadherin, and fibronectin. Conclusion: NLRP3 was overexpressed in DDP-resistant ovarian cancer. NLRP3 knockdown hindered the malignant process of DDP-resistant ovarian cancer cells, providing a potential target for DPP-based ovarian cancer chemotherapy.

Efficient and stretchable organic light-emitting devices based on spontaneously formed disordered wrinkles.

We propose a facile, scalable strategy to introduce spontaneously formed disordered wrinkles into organic light-emitting devices (OLEDs) to enhance light extraction and realize stretchability of the devices. The luminance and current efficiency of the wrinkled OLEDs are improved by 37% and 18%, respectively, compared to the planar device. Meanwhile, broadband light scattering induced by the disordered wrinkles results in angle-stable electroluminescent spectra at wide viewing angles for the wrinkled OLEDs. The disordered wrinkles enable the OLEDs to be stretchable and withstand hundreds of stretching-releasing cycles at strain between 0% and 5%. This study provides a simple method to realize stretchable OLEDs with high efficiency.

RNF183 Is a Prognostic Biomarker and Correlates With Tumor Purity, Immune Infiltrates in Uterine Corpus Endometrial Carcinoma.

RNF183, a member of the E3 ubiquitin ligase, has been shown to involve in carcinogenesis and proposed as one of the biomarkers in Uterine Corpus Endometrial Carcinoma (UCEC). However, no research focused on the role of RNF183 in UCEC. We analyzed the expression and immune infiltration of RNF183 in UCEC. TIMER, UALCAN, and GEPIA were used to analyze the gene expression of RNF183. We emplored Kaplan-Meier Plotter to examine the overall survival and progression-free survival of RNF183, and applied GeneMANIA to identify RNF183-related functional networks. LinkedOmics was helpful to identify the differential gene expression of RNF183, and to further analyze gene ontology and the genome pathways in the Kyoto Protocol. Finally, we used TIMER to investigate the immune infiltration of RNF183 in UCEC. Otherwise, we partly verified the results of bioinformatics analysis that RNF183 controlled ERα expression in ERα-positive Ishikawa cells dependent on its RING finger domain. We also found that ERα increased the stability of RNF183 through the post-translational mechanism. Together, patients with a high level of RNF183 harbor favorable overall and progression-free survival. High expression of RNF183 was associated with a low stage, endometrioid, and TP53 Non-Mutant status in endometrial cancer. The RNF183 expression was greater at higher expression and the tumor stage was greater at the lower level. On the side of immunization, high level of RNF183 in UCEC is negatively related to tumor purity, infiltrating levels of CD4 + T cells, neutrophils, and dendritic cells. Besides, the expression of RNF183 in UCEC is significantly correlated with the expression of several immune cell markers, including B cell, M1 macrophage marker, M2 Macrophage, Dendritic cell, Th1 markers, Th2 markers, Treg markers, and T cell exhaustion markers, indicating its role in regulating tumor immunity. These results suggested that RNF183 may be considered as a novel prognostic factor in endometrial cancer and an early diagnostic indicator for patients with UCEC.