Radiotherapy is the standard adjuvant treatment for glioma patients; however, the efficacy is limited by radioresistance. The function of Interleukin-1 receptor associated kinase 1 (IRAK1) in ...tumorigenesis and radioresistance remains to be elucidated. IRAK1 expression and its correlation with prognosis were analyzed in glioma tissues. We found that glioma patients with overexpressed IRAK1 show a poor prognosis. Notably, ionizing radiation (IR) remarkably induces IRAK1 expression, which was decreased by STING antagonist H-151 treatment. JASPAR prediction, ChIP assays, and dual luciferase reporter assays indicated that transcription factor FOXA2, suppressed by STING inhibition, directly binds to the IRAK1 promoter region and activates its transcription. IRAK1 knockdown inhibits malignancy and enhances the radiosensitivity of glioma in vitro and in vivo. To explore the potential IRAK1 interacting targets mediating the radioresistance of glioma cells, IP/Co-IP, LC-MS/MS, GST pull-down, and ubiquitination analyses were conducted. Mechanistically, IRAK1 bound to PRDX1, a major member of antioxidant enzymes, and further prevents ubiquitination and degradation of PRDX1 mediated by E3 ubiquitin ligase HECTD3; Both the DOC and HECT domains of HECTD3 directly interacted with PRDX1 protein. Overexpression of PRDX1 reverses the radiotherapy sensitization effect of IRAK1 depletion by diminishing autophagic cell death. These results suggest the IRAK1-PRDX1 axis provides a potential therapeutic target for glioma patients.
Replacing a carbon atom with silicon (see figure) on the main chain of a conjugated polythiophene gives a polysilole with higher crystallinity, improved charge transport, reduced bimolecular ...recombination, and reduced formation of charge transfer complexes when blended with a fullerene derivative. Optimized bulk heterojunction solar cells using this blend give certified efficiencies of 5.2% under AM1.5 illumination.
Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma (ESCC), but its efficacy is limited by radioresistance. MicroRNAs play a crucial role in posttranscriptional ...regulation, which is linked to the cancer response to radiation.
We successfully established a radioresistant cell line model by using fractionated irradiation. qRT-PCR was adopted to detect the expression of miR-4443 in human normal esophageal cell lines, tumor cells, and radioresistant cells. Next, CCK-8, colony formation, apoptosis, and cell cycle assays were used to assess the biological effect of miR-4443. Weighted gene coexpression network analysis (WGCNA) was performed to identify potential radiosensitivity-related genes. Additionally, we predicted the probable targets of the miRNA using bioinformatic methods and confirmed them using Western blot.
miR-4443 was significantly upregulated in radioresistant ESCC cells. Enhancement of miR-4443 further decreased the radiosensitivity of ESCC cells, while inhibition of miR-4443 increased the radiosensitivity of ESCC cells. Notably, miR-4443 modulated radiosensitivity by influencing DNA damage repair, apoptosis, and G2 cycle arrest. By using WGCNA and experimental validation, we identified PTPRJ as a key target for miRNA-4443 to regulate radiosensitivity. The effects of miR-4443 overexpression or inhibition could be reversed by increasing or decreasing PTPRJ expression.
In this study, miR-4443 is found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, which provides a new perspective and clue to alleviate radioresistance.
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Since autophagy-related genes (ARGs) play a key role in the pathogenesis of many tumors, including ESCC, the ...purpose of this study is to establish an autophagy-related prognostic risk signature based on ARGs expression profile, and to provide a new method for improving prediction of clinical outcomes. We obtained the expression profiles of ESCC from public data (GSE53625) and extracted the portion of ARGs. Differential expression analysis and enrichment analysis were performed to confirm abnormal autophagy-related biological functions. Univariate and multivariate Cox regression analyses were performed on RNA microarray data (GSE53625) to construct a prognostic risk signature associated with autophagy. The performance of the model was evaluated by receiver operating characteristic (ROC) analysis, survival analysis and Brier score. The model was subjected to bootstrap internal validation. The potential molecular mechanism of gene signature was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and immune status and ferroptosis. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in ESCC cell lines and ESCC tissues. We constructed and validated an autophagy-related prognostic risk signature in 179 patients with ESCC. The long-term survival of patients in high-risk group was lower than that in low-risk group (log-rank, P value < 0.001). ROC analysis and Brier score confirmed the reliability of the signature. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk ESCC patients and immunoregulatory signaling pathways in the low-risk ESCC patients. Correlation analysis showed that the risk signature can effectively predict the effect of immunotherapy. About 33.97% (71/209) ferroptosis-related genes were significantly correlated with risk scores. Finally, the results of qRT-PCR and immunohistochemistry experiments were consistent with bioinformatics analysis. In brief, we constructed a novel autophagy-related gene signature (VIM, UFM1, TSC2, SRC, MEFV, CTTN, CFTR and CDKN1A), which could improve the prediction of clinical outcomes in patients with ESCC.
•A novel 2D ultrawide-bandgap semiconductor BiO(IO3) is predicted.•2D BiO(IO3) systems display robust in-plane piezoelectricity without the odd–even effect.•Monolayer BiO(IO3) possesses the high ...carrier mobility.•2D BiO(IO3) materials have potential application in micro-electro-mechanical devices.
Ultrawide-bandgap (UWBG) semiconductors, surpassing GaN with a bandgap of 3.4 eV, offer distinct advantages in high-temperature, high-frequency, and radiation-resistant applications. Specifically, two-dimensional (2D) UWBG materials play a crucial role in the miniaturization of practical devices. Here, employing first-principles calculations, we explore the properties of the polar iodate BiO(IO3) in its 2D monolayer configuration, boasting a bandgap of 3.61 eV. Our calculations confirm the feasibility of deriving 2D BiO(IO3) monolayer from its bulk counterpart while retaining structural stability at room temperature. The UWBG BiO(IO3) monolayer exhibits remarkable ultraviolet absorption, mechanical flexibility, and favorable electronic transport behavior. Notably, the estimated electron mobility reaches an impressive 1353.13 cm2 V−1 s−1. Importantly, the 2D structure of BiO(IO3) displays robust in-plane piezoelectricity without the odd–even effect commonly observed in other 2D piezoelectric materials. The piezoelectric coefficients d21 and d22 of monolayer reach high values of 13.87 and 16.66 pm V−1, respectively, surpassing or closely approaching those of most well-studied 2D systems. The direct stacking configuration enables 2D BiO(IO3) materials to maintain robust piezoelectricity at different thicknesses. Charge injection simulations validate the electromechanical conversion process, aligning well with its piezoelectric properties. This suggests the promising application potential of 2D BiO(IO3) in devices such as micro-electro-mechanical systems.
Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC). However, HPV infection related radioresistance caused poor prognosis of ESCC. The function of SOCS6, which has been ...shown to be a tumor suppressor in several cancers, has not been fully investigated up till now. In this manuscript, we aim to further investigate the role of SOCS6 in regulating ESCC radioresistance.
Fifty-seven ESCC patients were enrolled for survival analysis. SOCS6 was stably overexpressed in HPV
ESCC and ESCC cells, and cells were treated with radiation and then subjected to colony formation assays. Expression of DNA damage repair regulating proteins were examined by Western blotting. Cell growth, cell migration and cisplatin sensitivity were then analyzed. Sphere formation assays and flow cytometry were used to investigate changes in cancer stem cell (CSC) properties. Immunofluorescent staining and confocal microscopy were used to locate SOCS6 and c-Kit. Ubiquitylation level of c-Kit were analyzed after immunoprecipitation. Then, coimmunoprecipitation (CoIP) of SOCS6 and c-Kit were performed. In vivo, xenograft animal models were treated with radiation to examine the radiosensitivity.
SOCS6 is correlated with better prognosis in ESCC patients. Radioresistance is impaired by SOCS6 upregulation, which inhibited cell growth, migration and increased sensitivity to cisplatin. SOCS6 significantly decreased the population of CSCs expressing the surface biomarker CD271 or CD24
/CD44
and their ability of sphere formation. SOCS6 and c-Kit were collocated in the cytoplasm. Blotting of ubiquitin and CoIP experiments indicated that the mechanism was related to ubiquitylation and degradation of the receptor c-Kit. Xenograft tumor mouse model showed that SOCS6 inhibited tumor growth and promoted radiosensitivity in vivo.
Our findings suggest that SOCS6 can promote the radiosensitivity of HPV
ESCC and ESCC cells and reduce their stemness via ubiquitylation and degradation of c-Kit. Thus, SOCS6 is a potential target for overcoming radioresistance of ESCC.
Ovarian cancer is prone to recurrence and chemotherapy resistance. Ovarian tumours of some patients have been positive for anaplastic lymphoma kinase fusion gene expression (ALK+). Preclinical ...studies indicate that anaplastic lymphoma kinase inhibitor can suppress the growth of ovarian cancer cells and transplantation tumours. Here, we present a patient with metastatic ALK+ high-grade serous ovarian cancer that testing positive for EML4-ALK (microtubule-associated protein-like 4 gene, fused to the anaplastic lymphoma kinase gene), experienced dramatic benefit after administration of the anaplastic lymphoma kinase inhibitor alectinib. This is the first clinical evidence that treatment with alectinib may provide a personalized maximum benefit for patients with high-grade serous ovarian cancer who are positive for EML4-ALK.
In the process of the continuous development of subway construction, the safe evacuation of subway passengers has been paid much attention to. As the subway itself has the characteristics of limited ...space and high passenger density, once a fire emergency occurs, it can cause huge losses only by passive rescue. Therefore, it is important to actively plan for evacuation to reduce life and property losses due to fires in subways. This study aims to develop a fault tree analysis method for identifying scenarios that lead to evacuation failure in subways due to impassability incurred by fires. First, a virtual evacuation model is established using an agent modeling technique, with collected passenger characteristics to calibrate local evacuation behaviors. Then, fire impassability scenarios (e.g. fire(s) in the escalator(s), in emergency stairs, or the combination) are evaluated using the established agent model. Eventually, a fault tree analysis is constructed to identify scenarios that lead to evacuation failures. The research results show that the passability of escalator(s) is critical for subway fire resilience. It is important to use stationary escalator(s) as evacuation pathways for more evacuation capacity. Fire risk management around escalator(s) should be stricter. Passengers and staff are advised to learn how to stop a running escalator to avoid evacuation failures.
To investigate the effects of repeated mifepristone and levonorgestrel use on estrous cycle and expression of ovarian follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor ...(LHR) in mice.
Ovarian FSHR and LHR mRNA expression was measured using real-time quantitative reverse transcription-polymerase chain reaction, while the protein levels were measured using immunohistochemistry.
Repeated use of mifepristone and levonorgestrel significantly lengthened the estrous cycle and decreased FSHR and LHR mRNA and protein expression in the ovaries of mice at 4, 24, and 48 days after discontinuing drug use. Repeated use of mifepristone and levonorgestrel had significant main effects on estrous cycle length and the mRNA expression and protein level of ovarian FSHR and LHR. Repeated mifepristone and levonorgestrel use and withdrawal time had a significant interaction with mouse estrous cycle (F = 16.65, P < 0.05), ovarian LHR and FSHR mRNA expression (F = 563.072, P < 0.05), and protein level (F = 6.536, P < 0.05).
Repeated use of mifepristone and levonorgestrel can lead to sustained damage to ovarian function through inhibition of ovarian FSHR and LHR expression in mice.
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal carcinoma. Protein coding genes and non-coding RNAs can be powerful prognostic factors in multiple cancers, including ESCC. ...However, there is currently no model that integrates multiple types of RNA expression signatures to predict clinical outcomes.
The sequencing data (RNA-sequencing and miRNA-sequencing) and clinical data of ESCC patients were obtained from The Cancer Genome Atlas (TCGA) database, and Differential gene expression analysis, Cox regression analysis and Spearman correlation analysis were used to construct prognosis-related lncRNA-mRNA co-expression network and scoring system with multiple types of RNA. The potential molecular mechanisms of prognostic mRNAs were explored by functional enrichment analysis.
A total of 62 prognostic lncRNAs, eight prognostic miRNAs and 66 prognostic mRNAs were identified in ESCC (
-value < 0.05) and a prognosis-related lncRNA-mRNA co-expression network was created. Five prognosis-related hub RNAs (CDCA2, MTBP, CENPE, PBK, AL033384.1) were identified. Biological process analysis revealed that mRNAs in prognosis-related co-expression RNA network were mainly enriched in cell cycle, mitotic cell cycle and nuclear division. Additionally, we constructed a prognostic scoring system for ESCC using ten signature RNAs (MLIP, TNFSF10, SIK2, LINC01068, LINC00601, TTTY14, AC084262.1, LINC01415, miR-5699-3p, miR-552-5p). Using this system, patients in the low-risk group had better long-term survival than those in the high-risk group (log-rank,
-value < 0.0001). The area under the ROC curve (AUCs) revealed that the accuracy of the prediction model was higher than the accuracy of single type of RNA prediction model.
In brief, we constructed a prognostic scoring system based on multiple types of RNA for ESCC that showed high predicting prognosis performance, and deeply understood the regulatory mechanism of prognosis-related lncRNA-mRNA co-expression network.
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