Jiangxi Science & Technology Normal University

Golgi protein 73 (GP73) has emerged as a critical biomarker for the diagnosis of hepatocellular carcinoma (HCC), and its detection is essential for the effective treatment of this disease. In this study, we developed a colorimetric/electrochemical dual-mode aptasensor for GP73 detection using a hemin-reduced graphene oxide‑manganese oxide (H-rGO-Mn₃O₄) nanozyme and the bifunctional probe, 3,3',5,5'-tetramethylbenzidine (TMB). The GP73-specific aptamer (Apt) was conjugated to the H-rGO-Mn₃O₄ nanozyme, which was then immobilized on the surface of a gold nanoparticle-modified screen-printed electrode (Au NPs/SPE) through hybridization with a complementary DNA strand (cDNA) attached to the electrode. TMB served as a dual-signal probe for both colorimetric and electrochemical detection. In the presence of GP73, Apt binds specifically to the target, forming a H-rGO-Mn₃O₄-Apt/GP73 complex structure. This binding event causes the nanozymes to detach from the electrode surface, reducing its peroxidase activity while simultaneously restoring the electrochemical signal. Under optimized conditions, the dual-mode aptasensor exhibited excellent linear responses for GP73 concentrations ranging from 0.0001 to 100 ng/mL, with limits of detection (LOD) of 0.1 pg/mL for both the colorimetric and electrochemical modes. The aptasensor was successfully applied to measure GP73 levels in serum samples, yielding highly consistent results. Its performance was further validated by comparison with the standard ELISA method. Compared to single-signal aptasensors, this dual-mode approach not only improves detection sensitivity but also minimizes the risk of false positives or false negatives, making it a more reliable tool for accurate GP73 detection in clinical diagnostics.

In China, vocational high school students frequently encounter mental health challenges; however, they often exhibit largely unfavourable attitudes towards seeking psychological help, a situation demanding urgent attention. Our study aimed to comprehensively investigate the key factors influencing these students' psychological help-seeking attitudes and their complex interrelationships. We adopted a mixed-methods approach, commencing with in-depth interviews involving 28 vocational high school students. Drawing on grounded theory principles informed by the interview data and relevant literature, we identified crucial factors and constructed a hypothetical model. Subsequently, questionnaires were administered to 465 vocational high school students across six schools, yielding 417 valid responses. Thematic analysis using grounded theory indicated that self-stigma, public stigma, mental health literacy, and perceived social support emerged as significant variables predicting psychological help-seeking attitudes. Questionnaire results further confirmed that vocational high school students generally hold reserved attitudes towards seeking psychological health support. Structural equation modelling revealed that self-stigma and public stigma had a significant negative impact on help-seeking attitudes, whilst mental health literacy and perceived social support exerted a positive influence. Notably, perceived social support demonstrated the strongest positive effect, and public stigma the most negative. Furthermore, self-stigma was found to play a mediating role between mental health literacy and attitudes towards seeking psychological help. Both self-stigma and public stigma also mediated the relationship between perceived social support and attitudes towards seeking psychological help. To foster more positive psychological help-seeking attitudes among students, it is crucial to enhance the quality of mental health education in vocational high schools and strengthen emotional support from significant others.

Cereblon (CRBN), a core component of the CRL4 ubiquitin ligase complex, regulates substrate ubiquitination and degradation, thereby exerting broad control over essential cellular processes. Its pivotal role has been exploited in the development of therapeutic modalities such as proteolysis-targeting chimeras and molecular glues. However, most existing ligands are derived from immunomodulatory drug scaffolds, which present limitations including suboptimal selectivity and intellectual property restrictions. This underscores the need for novel chemotypes capable of engaging CRBN. To address this challenge, we performed extensive molecular dynamics (MD) simulations to explore the conformational dynamics of the CRBN ligand-binding pocket. Based on the MD trajectories, we constructed free energy landscapes and Markov state models to characterize the dynamics of key binding site residues. Our analysis identified multiple (meta)stable states defined primarily by the conformational and tautomeric variability of His378. Importantly, the dominant C1 conformation of His378 is associated with a previously unrecognized cavity adjacent to the canonical ligand-binding site, presenting new opportunities for the design of novel CRBN ligands. These insights provide a structural and dynamic framework for the discovery of next-generation CRBN binders with improved selectivity and therapeutic potential.