Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective: To explore the biocompatibility of hydroxyapatite and dexamethasone composite coatings on the surface of TiO2 nanotubes . Methods: A composite coating was constructed by loading hydroxyapatite and dexamethasone on the surface of titanium nanotubes . Field emission scanning electron microscopy , atomic force microscopy , and contact angle measurement instrument was used to observe the characteristics of sample substrates , and in vitro biological evaluation was conducted to evaluate the effect of the coating on the adhesion and proliferation of human skull osteoblasts . Results : The microstructure , three_dimensional morphology and hydrophilic properties of the modified composite coating had changed . After cytological examination , it could significantly promote the adhesion and proliferation of osteoblasts . Conclusion By simulating the immersion of body fluids and the method of adding dropwise loads , the titanium nanotube_hydroxyapatite_dexamethasone composite coating is successfully constructed , which has good biocompatibility.

A 55-year-old male patient was admitted to the hospital due to "recurrent chest pain for 8 months, with worsening symptoms for 2 weeks". After admission, comprehensive relevant examinations led to the consideration of a giant chronic left ventricular pseudoaneurysm caused by myocardial infarction with non-obstructive coronary arteries. Surgical treatment was performed at our hospital. We discuss the diagnosis and treatment of this patient.