As critical DNA structures capping the human chromosome ends, the stability and structural polymorphism of human telomeric G-quadruplex (G4) have drawn increasing attention in recent years. This work characterizes the equilibrium transitions of single-molecule telomeric G4 at physiological K+ concentration. We report three folded states of telomeric G4 with markedly different lifetime and mechanical stability. Our results show that the kinetically favored folding pathway is through a short-lived intermediate state to a longer-lived state. By examining the force dependence of transition rates, the force-dependent transition free energy landscape for this pathway is determined. In addition, an ultra-long-lived form of telomeric G4 structure with a much stronger mechanical stability is identified.

A DNA G-quadruplex (G4) formed at the oncogene c-MYC promoter region functions as a gene silencer. Due to its high stability at physiological K(+) concentrations, its thermodynamics and kinetic properties have not been characterized in physiological solution conditions. In this work, we investigated the unfolding and folding transitions of single c-MYC G4 and several of its truncated or point mutants at 100 mM KCl concentration under mechanical force. We found that the wild type could fold into multiple species, and the major specie has a slow unfolding rate of (1.4 ± 1.0) × 10(-6) s(-1). The force-dependent thermodynamics and kinetic properties of the major specie were obtained by studying a truncated mutant, Myc2345, that contains the G-tracts 2, 3, 4, and 5. As the c-MYC G4 is a prototype of many other intermolecular parallel-stranded G4's, our results provide important insights into the stability of a broad class of promoter G4's which also play a role in transcription regulation and are potential anticancer targets.

The differential structural–elastic properties of molecules between their transition and initial (native or denatured) states determine force-dependent transition rates.

To evaluate the performance of a multi-parametric MRI (mp-MRI)-based radiomics signature for discriminating between clinically significant prostate cancer (csPCa) and insignificant PCa (ciPCa). Materials and methods: Two hundred and eighty patients with pathology-proven PCa were enrolled and were randomly divided into training and test cohorts. Eight hundred and nineteen radiomics features were extracted from mp-MRI for each patient. The minority group in the training cohort was balanced via the synthetic minority over-sampling technique (SMOTE) method. We used minimum-redundancy maximum-relevance (mRMR) selection and the LASSO algorithm for feature selection and radiomics signature building. The classification performance of the radiomics signature for csPCa and ciPCa was evaluated by receiver operating characteristic curve analysis in the training and test cohorts. Results: Nine features were selected for the radiomics signature building. Significant differences in the radiomics signature existed between the csPCa and ciPCa groups in both the training and test cohorts (p < 0.01 for both). The AUC, sensitivity and specificity of the radiomics signature were 0.872 (95% CI: 0.823−0.921), 0.883, and 0.753, respectively, in the training cohort, and 0.823 (95% CI: 0.669−0.976), 0.841, and 0.727, respectively, in the test cohort. Conclusion: Mp-MRI-based radiomics signature have the potential to noninvasively discriminate between csPCa and ciPCa.