Targeting DNA junction sites by bis-intercalators induces topological changes with potent antitumor effects.

Targeting inter-duplex junctions in catenated DNA with bidirectional bis-intercalators is a potential strategy for enhancing anticancer effects. In this study, we used d(CGTATACG)2, which forms a tetraplex base-pair junction that resembles the DNA-DNA contact structure, as a model target for two alkyl-linked diaminoacridine bis-intercalators, DA4 and DA5. Cross-linking of the junction site by the bis-intercalators induced substantial structural changes in the DNA, transforming it from a B-form helical end-to-end junction to an over-wounded side-by-side inter-duplex conformation with A-DNA characteristics and curvature. These structural perturbations facilitated the angled intercalation of DA4 and DA5 with propeller geometry into two adjacent duplexes. The addition of a single carbon to the DA5 linker caused a bend that aligned its chromophores with CpG sites, enabling continuous stacking and specific water-mediated interactions at the inter-duplex contacts. Furthermore, we have shown that the different topological changes induced by DA4 and DA5 lead to the inhibition of topoisomerase 2 activities, which may account for their antitumor effects. Thus, this study lays the foundations for bis-intercalators targeting biologically relevant DNA-DNA contact structures for anticancer drug development.

Electromagnetically induced transparency and quantum enhancement of transmission via dressed bloch photons in an array of three-level Λ-type atoms.

We investigate the interactions between an array of three-level atoms and two photon fields with distinct frequencies employing quantum electrodynamics (QED). The control beam, as expected, has a considerably higher intensity than the probe beam, and the probe photon's eigenstate notably then appears as a distinctive dressed Bloch wave. We calculate the dispersion relation and quantum amplitude of the probe photons for their transmission. At positions predicting electromagnetically induced transparency (EIT) phenomena, we unveil remarkable enhancements in the transmission of the probe beam. Crucially, these enhancements are intricately linked to the unique characteristics of the dressed Bloch wave eigenstate. Moreover, we demonstrate that modulating frequency and intensity of the control beam and the lattice constant would further tune these enhancements. Our study highlights the crucial role of the dressed Bloch wave eigenstate in substantially amplifying targeted light beams, thereby significantly enhancing the detection sensitivity for minute electromagnetic signals and emphasizing its pivotal role in unveiling intriguing phenomena.

Proactive consultation of laboratory medicine increased diagnostic rate of multiple myeloma: One single center's 12-year experience.

Multiple myeloma (MM) was one of the hardest cancers to diagnose because of numerous nonspecific symptoms, leading to diagnostic delay. Proactive consultation of laboratory medicine (PCLM) could help timely diagnosis of blood cancers, avoiding diagnostic delay. This study aimed to evaluate the effect of PCLM on diagnosis and outcomes in MM. This retrospective study was conducted in newly diagnosed MM patients from 2011 to 2022. Implementation of PCLM initiated in 2015 with a laboratory-oriented algorithm. The annual diagnostic rate, patient demographics, the time intervals from symptom onset to diagnosis and to treatment, and clinical outcomes were analyzed. A total of 134 patients were newly diagnosed during the study interval. The diagnostic rate increased from 4.65 ±â€…1.59 to 7.43 ±â€…1.52 per million patient-visits after implementation of PCLM. The median time interval from symptom onset to diagnosis was significantly shortened after implementation of PCLM (50 days with interquartile range [IQR]: 24-136 days vs 150 days with IQR: 41-385 days, P = .003). Besides, the 1-year survival was significantly higher in patients diagnosed as MM after implementation of PCLM (72.4% vs 51.7%, P = .035). Implementation of PCLM not only increased diagnostic rate of MM and improved outcomes, but also raise awareness for MM and promote multidisciplinary collaboration in healthcare.