Xiaohui Li

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: , MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.

Abstract Intergranular cracking of Ni‐rich layered LiNi 1‐x‐y Co x Mn y O 2 (1‐x‐y ≥ 0.8) cathode particles deteriorate the chemo–electro–mechanical stability of high‐energy lithium‐ion batteries (LIBs), thus presenting a challenge to typical modification methods to establish robust structures with highly efficient lithium‐ion storage. Herein, the ZrTiO 4 (ZTO) as an epitaxial layer to enhance mechanical stability of ultrahigh‐Ni LiNi 0.9 Co 0.05 Mn 0.05 O 2 (NCM90) is reported for the first time. Intensive exploration from structure characterizations (X‐ray absorption spectroscopy and in situ X‐ray diffraction techniques), multi‐physics field analysis, and first‐principles calculations disclose that the conformal ZTO layers and Zr doping effectively suppresses the internal strain and the release of lattice oxygen, which prodigiously restrains the local stress accumulation during whole (de)lithiation processes, thereby maintaining good mechanical stability of the materials. Meanwhile, the protective ZTO layer also prevents electrolyte erosion, thus keeping an intact surface structure of NCM90. Notably, ZTO‐modified NCM90 achieves significantly improved cyclability under high‐voltage (4.5 V) operation, expressing a 17% increase in capacity retention (71% vs 88%) after 100 cycles. Overall, this work reveals the role of internal strain in the original degradation behavior and effectiveness of surface engineering strategy to solve the challenge, emphasizing that the conformal surface protection mitigates the internal stress of Ni‐rich NCM by anchoring the lattice oxygen.