A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

Objective: The aim of this study is to investigate the recurrence and progression of liver cancer by focusing on the energy metabolism of liver cancer stem cells. Methods: A comprehensive literature search was conducted using databases including CNKI, PubMed, Wanfang, and Citexs to analyze the etiology and treatment of hepatocellular carcinoma (HCC), the factors and mechanisms contributing to HCC recurrence, and the impact of energy metabolism in HCC stem cells on the development of HCC. Furthermore, the association between HCC recurrence and the energy metabolism of HCC stem cells was examined. Results: The primary targets associated with the glycolytic metabolism of HCC stem cells included HK2, PFK, PK, LDH, among others. Glutamine metabolism primarily involves the tricarboxylic acid (TCA) cycle, with main targets such as mTORC1 and reactive oxygen species (ROS). The principal pathway in lipid metabolism is fatty acid (FA) biosynthesis, with key targets being fatty acid synthase (FASN), acetyl-coenzyme A carboxylase (ACC), stearoyl-coenzyme A desaturase-1 (SCD1), and adenosine monophosphate-activated protein kinase (AMPK). Targets in the oxidative phosphorylation pathway include PGC1a. Finally, key targets in iron metabolism encompass System Xc, glutathione peroxidase 4 (GPX4), and DMT1. Conclusion: The glycolytic metabolism of HCC stem cells represents a primary metabolic pathway in HCC stem cells, with key targets including HK2, PFK, PK, and LDH warranting closer attention. Glutamine metabolism should focus on the TCA cycle and targets such as mTORC1 and ROS. Lipid metabolism pathway involves FA biosynthesis, with significant targets being FASN, ACC, SCD1, and AMPK. Iron metabolism, specifically System Xc, GPX4, and DMT1 targets, should be carefully considered. Therefore, interventions for the prevention and treatment of liver cancer recurrence should be directed towards these aspects of liver cancer stem cells.