The study of liver disease models, drug screening, and toxicity assessment has been hindered by the lack of faithful representations of liver models. This work unveiled key signaling pathways in liver zonation and constructed genetically modified liver sinusoidal endothelial cells. It was found that SK-Hep1 cells overexpressing WNT2 and DLL4 promote zonated functional differentiation of primary hepatic organoids. Further investigation revealed that genetically modified SK-Hep1 cells regulate hepatocyte functional differentiation through ligand-receptor interactions. Moreover, this modification enhanced the sensitivity of hepatocytes to hepatotoxic drugs and simulated drug-induced injury repair and regeneration processes in hepatic organoids. A co-culture system of liver organoids and genetically modified SK-Hep1 cells was established for liver disease modeling and drug screening. Finally, we successfully employed 3D bioprinting technology to fabricate liver lobule models with specific morphological and functional architectures. These models effectively demonstrated region-specific hepatic injuries induced by pharmaceutical agents. These findings provide new insights into the understanding of liver functional differentiation and offer valuable references for liver disease treatment and drug screening research.

Wider voltage windows accelerate voltage decay at Mn³⁺/Mn²⁺ plateau in LMFP cathodes. Huazhong University researchers attribute this to irreversible lattice distortion and deteriorated lithium-ion diffusion, providing a roadmap for stable high-energy batteries.