As more is learned about lactate, it acts as both a product and a substrate and functions as a shuttle system between different cell populations to provide the energy for sustaining tumor growth and proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural and osteogenic differentiation and maturation) and diseases (e.g., tumors, fibrosis and inflammation, etc.). These views are critically significant and first described in detail in this review. Hence, here, we focused on a new target, protein lactylation, which may be a “double-edged sword” of human health and diseases. The main purpose of this review was to describe how protein lactylation acts in multiple physiological and pathological processes and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for treating different diseases and accelerate translation from bench to bedside.

Introduction: Since the coronavirus disease 2019 (COVID-19) pandemic, the value of mRNA vaccine has been widely recognized worldwide. Messenger RNA (mRNA) therapy platform provides a promising alternative to DNA delivery in non-viral gene therapy. Lipid nanoparticles (LNPs), as effective mRNA delivery carriers, have been highly valued by the pharmaceutical industry, and many LNPs have entered clinical trials. Methods: We developed an ideal lipid nanoformulation, named LNP3, composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and cholesterol, and observed its release efficiency, sustained release, organ specific targeting and thermal stability. Results: In vitro studies showed that the transfection efficiency of LNP3 was higher than that of LNPs composed of DOTAP-DOPE and DOTAP-cholesterol. The positive to negative charge ratio of LNPs is a determinant of mRNA transfer efficiency in different cell lines. We noted that the buffer affected the packaging of mRNA LNPs and identified sodium potassium magnesium calcium and glucose solution (SPMCG) as a favorable buffer formulation. LNP3 suspension can be lyophilized into a thermally stable formulation to maintain activity after rehydration both in vitro and in vivo. Finally, LNP3 showed sustained release and organ specific targeting. Conclusion: We have developed an ideal lipid nanoformulation composed of DOTAP, DOPE and cholesterol for effective mRNA delivery.

Original Article The efficacy of vonoprazan combined with different dose amoxicillin on eradication of Helicobacter pylori: an open, multicenter, randomized clinical study Yimin Lin, Huimei Xu, Jianwei Yun, Xiaohui Yu, Yuping Shi, Dekui Zhang

Fibrosis is a common pathological feature of most types of chronic liver injuries. There is no specific treatment for liver fibrosis at present. The liver microenvironment, which fosters the surviv...