TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is prevalent worldwide and is often challenged by treatment failure and recurrence due to resistance to radiotherapy. Here, we aimed to identify the elusive underlying molecular mechanisms of radioresistance in CRC. METHODS: Weighted gene co-expression network analysis was used to identify potential radiation-related genes. Colony formation and comet assays and multi-target single-hit survival and xenograft animal models were used to validate the results obtained from the bioinformatic analysis. Immunohistochemistry was performed to examine the clinical characteristics of ALDH1L2. Co-immunoprecipitation, immunofluorescence and flow cytometry were used to understand the molecular mechanisms underlying radioresistance. RESULTS: Bioinformatic analysis, in vitro, and in vivo experiments revealed that ALDH1L2 is a radiation-related gene, and a decrease in its expression induces radioresistance in CRC cells by inhibiting ROS-mediated apoptosis. Patients with low ALDH1L2 expression exhibit resistance to radiotherapy. Mechanistically, ALDH1L2 interacts with thioredoxin (TXN) and regulates the downstream NF-κB signaling pathway. PX-12, the TXN inhibitor, overcomes radioresistance due to decreased ALDH1L2. CONCLUSIONS: Our results provide valuable insights into the potential role of ALDH1L2 in CRC radiotherapy. We propose that the simultaneous application of TXN inhibitors and radiotherapy would significantly ameliorate the clinical outcomes of patients with CRC having low ALDH1L2.

Investigating the Driving Factors of Public Participation in Public-Private Partnership (PPP) Projects-A Case Study of China.

Public participation is an important procedure of the environmental impact assessment. Effective public participation is essential to the Public-Private Partnership (PPP) projects as such projects usually exert tremendous impacts on the environment and society. However, in literature, there are few studies investigating the driving factors of public participation in PPP projects, especially in the context of China. To bridge this research gap, this study proposed a theoretical model, which incorporates contextual factors (i.e., perceived benefit and perceived risk) into the classical Theory of Planned Behavior model, to explore the determinants. The initial proposed model was tested using structural equation modeling. Analysis results indicated that attitude towards behavior, subjective norm, perceived risk and perceived behavioral control were the four significant driving factors of public participation in PPP projects, whereas perceived benefit had limited impact. Furthermore, this study evaluated eight public participation approaches in PPP projects. Results revealed that the public were more willing to participate in public decisions through the internet platform, followed by the information disclosure or consultation provided by the government. The research findings derived in this study can provide valuable reference for the government to promulgate proper policies to attract more public participation in PPP projects. Moreover, the research idea and methods used in this study can be popularized in other countries to enhance the public participation in PPP projects.