Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.

Liposomal spherical nucleic acids possess a high density of nucleic acids, e.g., DNA, on a liposomal core. There are two approaches to conjugate DNA onto the zwitterionic liposomes, i.e., covalent and noncovalent conjugation, otherwise using cationic liposomes. However, complex and expensive DNA chemical modification methods need to seek a novel and easy-operating approach to decorating DNA onto liposomes. Inspired by the nanoparticle solution as nanoglues for gels and biological tissues, we use MnO 2 nanosheets to "glue" DNA onto liposomes without DNA modification. In tumor cells with a high glutathione concentration, MnO 2 -based nanoglues are degraded, generating water-soluble Mn 2+ ions, further "unglue" DNA (i.e., DNAzyme), and liposomes. Using the intelligent liposomal nanoglue (DNAzyme/MnO 2 /Lip) combining glutathione-sensitive MnO 2 nanosheets, gene silencing agent DNAzyme, and photosensitizer Chlorin e6 (Ce6) in liposomes, effective photo-gene therapy was demonstrated.

Daidzein improves doxorubicin-induced heart failure in mice by activating AMPKα and SIRT3/FOXO3a pathway-mediated energy balance and improving mitochondrial function, thereby inhibiting inflammation, fibrosis, apoptosis, oxidative stress in heart.

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