Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

By analyzing medical painting artworks from ancient and modern times， both in China and abroad， this paper explored the visual narrative functions and their historical evolution. The study revealed that in ancient times， medical painting art was mostly set against religious and mythological backgrounds， portraying the mysterious and supernatural aspects of disease. With the advent of the Renaissance， painting art gradually broke free from religious constraints and began to depict disease more realistically. In modern times， painting art has further embodied humanistic care and ethical spirit， and has gradually integrated narrative therapy and health communication， reflecting the integration of medical science and humanistic spirit. This evolutionary process not only witnessed the development of medical science and the transformation of human health concepts but also revealed the changes in the narrative characteristics of medical painting art from obscurity to clarity， from metaphor to concreteness， and from a one-sided focus on biological aspects to an emphasis on medical， social， and humanistic aspects.