Peptide-based antimicrobial materials are recognized as promising alternatives to antibiotics to circumvent the emergence of antibiotic-resistant bacteria or to combat multiple resistant bacteria by targeting the bacterial cell membrane. The components and conformations of antimicrobial peptides are extensively explored to achieve broad-spectrum and effective antimicrobial activity. Here, star-shaped antimicrobial polypeptides are fabricated by employing homologs of poly(l-lysine)s (i.e., poly(l-ornithine)s, poly(l-lysine)s, and poly(l- ,-diaminoheptylic acid)s) with the aim of modulating their charge/hydrophobicity balance and rationalizing their structure-antimicrobial property relationships. The in vitro antibacterial investigation reveals that unnatural amino-acid-based star-shaped poly(l-ornithine)s have remarkable proteolytic stability, excellent biofilm-disrupting capacity, and broad-spectrum antimicrobial activity, even against difficult-to-kill Gram-negative Pseudomonas aeruginosa. Furthermore, star-shaped poly(l-ornithine)s significantly reduce the microbial burden and improve the burn wound healing of mouse skin infected with P. aeruginosa. These results demonstrate that unnatural amino-acid-based star-shaped poly(l-ornithine)s can serve as emerging long-term and biofilm-disrupting antimicrobial agents to treat biofilm-related infections in burn, especially caused by notorious P. aeruginosa.

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BackgroundPapillary thyroid carcinoma (PTC) is one of the most common malignant carcinomas in the endocrine system, and it has a growing incidence worldwide. Despite the development of diagnosis and treatment modalities for thyroid carcinoma, the outcome remains uncertain. Autophagy participates in the process of cancer invasion, malignancy, metastasis, and drug resistance. Emerging research has shown that long noncoding RNAs (lncRNAs) play an important role in the process of different types of cancers. However, the interaction between the process of autophagy and lncRNA and the value of autophagy-related lncRNA for risk assessment, prediction of drug sensitivity, and prognosis prediction in PTC patients remains unknown.Materials and MethodsWe screened 1,283 autophagy-related lncRNAs and identified 144 lncRNAs with prognostic value in The Cancer Genome Atlas (TCGA) cohorts. Univariate and multivariate Cox regression analyses were used to establish the prognosis-related autophagy-related lncRNA risk classification consisting of 10 lncRNAs to indicate the level of risk, according to which the patients were grouped into high-risk group and low risk-group.ResultsThe high-risk group had dramatically worse overall survival compared with the low-risk group. Cox regression analysis was performed to confirm the independent prognostic value of the autophagy-related lncRNA risk stratification, and the time-dependent receiver operating characteristic curves of the risk stratification were 0.981 (1 year), 0.906 (3 years), and 0.963 (5 years). LncRNA CRNDE (LINC00180) is overexpressed in the tumor, and its high expression matched with poorer survival state. So, we chose it for further experiment. Finally, knockdown of the CRNDE in PTC increased the sensitivity to sorafenib.ConclusionCollectively, we successfully established a novel risk stratification for PTC based on the expression profiles of autophagy-related lncRNAs.

Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex Na[OsVI(N)(tpm)2] (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that Na[OsVI(N)(tpm)2] modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.