The emergence of multidrug-resistant bacteria has dramatically increased the lethality, level of resistance, and difficulty of treatment. In this study, a series of new antimicrobial peptides (AMPs) based on the β-hairpin structure with the template (XY) 2 RRRF(YX) 2 -NH 2 (X: hydrophobic amino acids; Y: cationic amino acids) were synthesized; surprisingly, almost all of the new peptides have strong antibacterial activity and negligible hemolytic toxicity. Particularly, the therapeutic index (TI) values of F(RI)2R and F(KW)2K reached up to 115.9 and 70.7, respectively. In addition, they did not show induced drug resistance and inhibited the development of antibiotic resistance when combined and used with traditional antibiotics. In addition, their antibacterial mechanism was preliminarily studied. Moreover, the new peptides F(RI)2R and F(KW)2K showed excellent performance in the pulmonary bacterial infection model and low toxicity in mice. In conclusion, F(RI)2R and F(KW)2K are considered new antimicrobial alternatives to address the antimicrobial-resistance crisis.

Nonselective toxicity of antimicrobial peptides (AMPs) needs to be solved urgently for their application. Temporin-PE (T-PE, FLPIVAKLLSGLL-NH 2 ), an AMP extracted from skin secretions of frogs, has high toxicity and specific antimicrobial activity against Gram-positive bacteria. To improve the antimicrobial performance of T-PE, a series of T-PE analogues were designed and synthesized by glutamic acid full-scan, and then their key positions were replaced with lysine. Finally, E 11 K 4 K 10 , the highest therapeutic indicial AMP, was screened out. E 11 K 4 K 10 was not easy to induce and produce drug-resistant bacteria when used alone, as well as it could also inhibit the development of the drug resistance of traditional antibiotics when it was used in combination with the traditional antibiotics. In addition, E 11 K 4 K 10 had an excellent therapeutic effect on a mouse model of pulmonary bacterial infection. Taken together, this study provides a new approach for the further improvement of new antimicrobial peptides against the antimicrobial-resistance crisis.

Background:Hepatocellular carcinoma (HCC) is the most common form of liver cancer, which is known to be characterized by poor therapeutic effects and prognosis. The etiology of HCC is regionally variable, with hepatitis B virus (HBV) being the leading cause in most of Asia. Immunogenic cell death (ICD) is a form of cell death. Many studies have shown that ICD-related processes are closely associated with the treatment of HCC. Through this study, we tried to investigate the significance of ICD-related genes in the Asian HCC population and expected to provide new ideas for the treatment of HCC. Methods: We first downloaded transcriptomic data and clinical data related to HCC in Asian population from TCGA database. Then, we divided the samples into different subgroups based on the expression of ICD-related genes and performed tumor microenvironment differential analysis and enrichment analysis. In addition, we randomly divided the samples into train as well as test groups, and then constructed and validated an ICD gene-based risk-prognosis model for the Asian HCC population. Results: We divided the Asian HCC samples into two subgroups, including the ICD high expression and ICD low expression groups. We found that in the ICD low expression group, there was less immune cell and stromal cell infiltration, higher tumor purity, and better prognosis. We then also constructed a 5-gene risk-score prognostic model, including BAX, CASP8, HMGB1, HSP90AA1 and IL6, which was effective in predicting the prognosis of the Asian HCC population. Conclusion: Our study provides new insights into the role of ICDs in Asian HCC populations. The risk-score prognostic model based on five ICDs can assess the prognosis of Asian HCC populations, which also has the potential to be new targets for HCC treatment.