Enhanced reactive oxygen species through direct copper sulfide nanoparticle-doxorubicin complexation.

CuS-based nanostructures loading the chemotherapeutic agent doxorubicin (DOX) exerted excellent cancer photothermal chemotherapy under multi-external stimuli. The DOX loading was generally designed through electrostatic interaction or chemical linkers. However, the interaction between DOX molecules and CuS nanoparticles has not been investigated. In this work, we use PEGylated hollow copper sulfide nanoparticles (HCuSNPs) to directly load DOX through the DOX/Cu2+ chelation process. Distinctively, the synthesized PEG-HCuSNPs-DOX release the DOX/Cu2+ complexes into surrounding environment, which generate significant reactive oxygen species (ROS) in a controlled manner by near-infrared laser. The CuS nanoparticle-mediated photothermal ablation facilitates the ROS-induced cancer cell killing effect. Our current work reveals a DOX/Cu2+-mediated ROS-enhanced cell-killing effect in addition to conventional photothermal chemotherapy through the direct CuS nanoparticle-DOX complexation.

Clinical Effectiveness of Genetic Testing Guidelines in Patients with Thoracic Aortic Aneurysms.

OBJECTIVE: To analyze the effectiveness of the current genetic testing guidelines for patients with thoracic aortic aneurysms (TAA). METHODS: We evaluated thoracic aortic disease (TAD) genetic tests from 2012 to 2023 in patients aged 18 and older with a thoracic aorta diameter greater than 4 cm. Mutation rates were compared by ACC/AHA testing criteria met by patients: age under 60, syndromic features of connective tissue diseases (CTD), family history, or none. Results were classified as pathogenic, variants of uncertain significance (VUS) or negative. Genes tested were analyzed in two categories: primary (strongly associated with heritable diseases) or secondary (less strongly associated). RESULTS: 1034 patients were included: 42.4% aged under 60, 19.1% with syndromic features of CTD, 41.8% with family history, and 30.7% meeting no criteria. Overall, 3.97% had pathogenic mutations and 27.27% had VUS. Mutation rates were highest in patients with syndromic features of CTD (13.2%), followed by patients aged under 60 (5.48%), family history (4.63%), and no criteria met (2.21%). Primary genes had pathogenic mutation rates of 3.29% and VUS rates of 12.19%. Secondary genes had lower pathogenic rates (0.68%) but higher VUS (17.5%). Mutation rates in primary genes peaked at 22% in patients meeting all criteria, whereas those under 60 years without family history or syndromic features of CTD had the lowest rate (0.54%). CONCLUSIONS: Refining genetic testing guidelines to incorporate multiple patient criteria could enhance risk stratification and support informed decision-making in TAD genetic testing. Limiting testing to genes strongly associated with TAD could lower VUS rates.