Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC WP0 potently degraded PD-L1 and induced T-cell-mediated tumor killing against HepG2 cells, highlighting the potential therapeutic applications. The development of GLTAC technology expands the scope of TPD strategies and opens new avenues for discovering novel therapeutic modalities against challenging protein targets.

Purpose/Significance To understand the behavioral characteristics of patients with eye diseases,and to optimize the smart medical service strategies for eye diseases.Method/Process Guided by Anderson's medical service utilization model,the elec-tronic medical records(EMR)data of 17 602 patients in a hospital are collected,and chi-square test and pedigree clustering method are used to explore the behavioral characteristics of patients with eye diseases from four dimensions.The satisfaction of 702 patients with eye diseases on smart medical services is investigated,and the main influencing factors are analyzed by ordinal logistic regression.Re-sult/Conclusion According to the demographic characteristics of patients with eye diseases,registration methods,common ophthalmic diseases and incidence data,settlement methods,etc.,suggestions and strategies for smart medical services for eye diseases are put for-ward from four aspects:resource layout,technical compatibility,service mode and optimized settlement.