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Short designed peptide amphiphiles are attractive at killing bacteria and inhibiting cancer cell growth, and the flexibility in their structural design offers a great potential for improving their potency and biocompatibility to mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n≥3) have been shown to be membrane lytic, but terminal amino acid modifications could impose a huge influence on their performance. We report in this work how terminal amino acid modifications to G(IIKK)3I-NH2 influence its α-helical structure, membrane penetrating ability, and selective actions against different cell types. Deletion of an N-terminal Gly or a C-terminal Ile did not affect their antibacterial activity much, an observation consistent with their binding behavior to negatively charged membrane lipid monolayers. However, the cytotoxicity against mammalian cells was much worsened by the N-terminal Gly deletion, consistent with an increase in its helical content. Despite little impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal amino acids greatly reduced its antitumor activity. Cholesterol present in tumor cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into the cancerous membranes, evident from its lowest surface physical activity at penetrating model lipid membranes. On the other hand, its low toxicity to normal mammalian cells and high antibacterial activity in vitro and in vivo made it an attractive antibacterial agent. Thus, terminal modifications can help rebalance the different interactions involved and are highly effective at manipulating their selective membrane responses.

On the basis of cell cultures involving bacterial strains (Escherichia coli 5α and Bacillus subtilis 168) and a mammalian cell line (NIH 3T3), the potent antibacterial activity and distinct selectivity from designed amphiphilic peptides G(IIKK)nI-NH2 (n = 2-4) have been demonstrated. This work extends these studies to multidrug resistant pathogens (ESBL-producing E. coli) and primary human cells (HDFa), followed by the in vivo mouse model investigation of ESBL-producing bacterial infection. G(IIKK)3I-NH2 exhibits high antibacterial activity against the pathogenic strain both in vitro and in vivo while displaying low toxicity toward the primary cells and the mice. Peptide molecules can kill bacteria by selectively interacting with bacterial membranes, causing structural disruptions. Furthermore, multidrug resistant ESBL-producing bacteria do not develop resistance after multiple treatments with G(IIKK)3I-NH2. The high cellular selectivity, low toxicity toward mammalian hosts and noninducing bacterial resistance indicate great potential for developing the peptides as anti-infection agents.

Background: Medical students are affected by high levels of general anxiety disorder. However, few studies have specifically focused on the applicability of universal anxiety screening tools in this sample. This study was aimed to evaluate the psychometric property of the 7-item Generalized Anxiety Disorder Scale (GAD-7) among Chinese medical university students.Methods: A questionnaire survey was conducted among 1,021 medical postgraduates from six polyclinic hospitals. Internal consistency and convergent validity of the GAD-7 were evaluated. Factor analyses were used to test the construct validity of the scale. An item response theory (IRT) framework was used to estimate the parameters of each item. Multi-group confirmatory analyses and differential item function analyses were used to evaluate the measurement equivalence of the GAD-7 across age, gender, educational status, and residence.Results: Cronbach's α coefficient was 0.93 and the intraclass correlation coefficients ranged from 0.71 to 0.87. The GAD-7 summed score was significantly correlated with measures of depression symptoms, perceived stress, sleep disorders, and life satisfaction. Parallel analysis and confirmatory factor analysis supported the one-factor structure of the GAD-7. Seven items showed appropriate discrimination and difficulty parameters. The GAD-7 showed good measurement equivalence across demographic characteristics. The total test information of the scale was 22.85, but the test information within the range of mild symptoms was relatively low.Conclusions: The GAD-7 has good reliability, validity, and measurement invariance among Chinese medical postgraduate students, but its measurement precision for mild anxiety symptoms is insufficient.