ABSTRACT
Objective@#The study aims to determine the latent class of roles in bullying victimization and perpetration among primary and secondary school students and to explore its relationship with academic achievement and screen use, to provide a reference for developing preventive measures and intervention plans.@*Methods@#A total of 29 099 students at grade 5,6,7,8,10, and 11 from Shenzhen were surveyed through convenient cluster sampling method by Olweus Bully/Victim Questionnaire. The latent class analysis was used for classifying bully/victim category.@*Results@#The latent class analysis revealed three classes, the noninvolvement group (low response rate at all items, 80.9%), the bullying victimization group (low response rate at bullying and high response rate at victimization items, 15.9%), and the bullying victimization and perpetration group (high response rate at all items,3.3%). Boys were more likely than girls to belong to the bullying victimization and perpetration at all study sections ( OR =0.83,0.74, 0.47 , P <0.05). Transfer students were at higher risk to be in the bullying victimization group in elementary and middle school ( OR = 1.21 ,1.21), while they were more likely to fall into the bullying victimization and perpetration group in high school ( OR =2.65)( P < 0.05). Students with poor academic performance were more likely to be in the bullying victimization group at all sections ( OR = 0.98 ,0.98,0.98) and in the bullying victimization and perpetration group at elementary and middle school ( OR =0.97, 0.98)( P < 0.05 ). Students spending longer time on screen had elevated risk in the bullying victimization group ( OR =1.06,1.04,1.08, P < 0.05 ).@*Conclusion@#Students with poor academic achievement and prolonged screen time are at higher risks to be involved in bullying victimization and perpetration. Collaboration between home and school are needed to preventing bullying victimization perpetration.
ABSTRACT
Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.
ABSTRACT
To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrapTM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L-1 FITC-TCF4 and 100 nmol·L-1 β-catenin. Under these optimized conditions, a high Z´factor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.