Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the major nosocomial pathogens to cause frequent and serious infections that are associated with various biomedical surfaces. This study demonstrated that surface modified with host defense peptide-mimicking β-peptide polymer, has surprisingly high bactericidal activities against Escherichia coli ( E. coli) and MRSA. As surface-tethered β-peptide polymers cannot move freely to adopt the collaborative interactions with bacterial membrane and are too short to penetrate the cell envelop, we proposed a mode of action by diffusing away the cell membrane-stabilizing divalent ions, Ca and Mg. This hypothesis was supported by our study that Ca and Mg supplementation in the assay medium causes up to 80% loss of bacterial killing efficacy and that the addition of divalent ion chelating ethylenediaminetetraacetic acid into the above assay medium leads to significant recovery of the bacterial killing efficacy. In addition to its potent bacterial killing efficacy, the surface-tethered β-peptide polymer also demonstrated excellent biocompatibility by displaying no hemolysis and supporting mammalian cell adhesion and growth. In conclusion, this study demonstrated the potential of β-peptide polymer-modified surface in addressing nosocomial infections that are associated with various surfaces in biomedical applications.

Background/Aims: Nuclear erythroid 2-related factor-2 (Nrf2) is a major stress-response transcription factor that has been implicated in regulating ischemic angiogenesis. We investigated the effects of Nrf2 in regulating revascularization and modulating acute lung injury. Methods: The expression of Nrf2 and sirtuin1 (Sirt1) was assessed in lung tissue by western blotting and immunofluorescence staining after intestinal ischemia/reperfusion (IIR) in Nrf2–/– and wild-type (WT) mice. The involvement of Nrf2 in angiogenesis, cell viability, and migration was investigated in human pulmonary microvascular endothelial cells (PMVECs). Additionally, the influence of Nrf2 expression on NOX pathway activation was measured in PMVECs after oxygen–glucose deprivation/reoxygenation. Results: We found activation and nuclear accumulation of Nrf2 in lung tissue after IIR. Compared to IIR in WT mice, IIR in Nrf2–/– mice significantly enhanced leukocyte infiltration and collagen deposit, and inhibited endothelial cell marker CD31 expression. Nrf2 upregulation and translocation into the nucleus stimulated by Sirt1 overexpression exhibited remission of histopathologic changes and enhanced CD31 expression. Nrf2 knockdown repressed non-phagocytic cell oxidase 4 (NOX4), hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) expression after IIR. Nrf2 upregulation by Sirt1 enhances NOX4, HIF-1α and VEGF expression after IIR in WT mice. Furthermore, Nrf2 knockdown suppressed cell viability, capillary tube formation and cell migration in PMVECs after oxygen–glucose deprivation/reoxygenation and also inhibited NOX4, HIF-1 and VEGF expression. Moreover, NOX4 knockdown in PMVECs decreased the levels of VEGF, HIF-1α and angiogenesis. Conclusion: Nrf2 stimulation by Sirt1 plays an important role in sustaining angiogenic potential through NOX4-mediated gene regulation.

Our findings suggest that lidocaine downregulates the GOLT1A expression to repress the proliferation of lung cancer cells.

Background Exposure to anesthetics during early life may impair cognitive functions. However, the underlying mechanisms remain largely unknown. We set out to determine effects of sevoflurane anesthesia on folate metabolism and myelination in young non-human primates, mice and children. Methods Young rhesus macaque and mice received 2.5 to 3% sevoflurane daily for three days. DNA and RNA sequencing and immunohistochemistry among others were used in the studies. We performed unbiased transcriptome profiling in prefrontal cortex of rhesus macaques and mice after the sevoflurane anesthesia. We constructed a brain blood barrier-crossing AAV-PHP.EB vector to harbor ERMN expression in rescue studies. We measured blood folate levels in children after anesthesia and surgery. Findings We found that thymidylate synthase ( TYMS ) gene was downregulated after the sevoflurane anesthesia in both rhesus macaque and mice. There was a reduction in blood folate levels in children after the anesthesia and surgery. Combined with transcriptome and genome-wide DNA methylation analysis, we identified that ERMN was the primary target of the disrupted folate metabolism. Myelination was compromised by the anesthesia in the young mice, which was rescued by systematic administration of folic acid or expression of ERMN in the brain through brain-specific delivery of the adeno-associated virus. Moreover, folic acid and expression of ERMN alleviated the cognitive impairment caused by the sevoflurane anesthesia in the mice. Interpretation General anesthesia leads to disrupted folate metabolism and subsequently defects in myelination in the developmental brain, and ERMN is the important target affected by the anesthesia via epigenetic mechanisms.

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At present, little is known about brain functional connectivity and its small-world topologic properties in first-episode schizophrenia (SZ) patients during cool executive function task. In this paper, the Trail Making Test-B (TMT-B) task was used to evaluate the cool executive function of first-episode SZ patients and electroencephalography (EEG) data were recorded from 14 first-episode SZ patients and 14 healthy controls during this cool executive function task. Brain functional connectivity between all pairs of EEG channels was constructed based on mutual information (MI) analysis. The constructed brain functional networks were filtered by three thresholding schemes: absolute threshold, mean degree, and a novel data-driven scheme based on orthogonal minimal spanning trees (OMST), and graph theory was then used to study the topographical characteristics of the filtered brain graphs. Results indicated that the graph theoretical measures of the theta band showed obvious difference between SZ patients and healthy controls. In the theta band, the characteristic path length was significantly longer and the cluster coefficient was significantly smaller in the SZ patients for a wide range of absolute threshold T. However, the cluster coefficient showed no significant changes, and the characteristic path length was still significantly longer in SZ patients when calculated as a function of mean degree K. Interestingly, we also found that only the characteristic path length was significantly longer in SZ patients compared with healthy controls after using the OMST scheme. Pearson correlation analysis showed that the characteristic path length was positively correlated with executive time of TMT-B for the combined SZ patients and healthy controls (r = 0.507, P = 0.006), but not for SZ patients alone (r = 0.072, P = 0.612). The above results suggested a less optimal organization of the brain network and could be useful for understanding the pathophysiologic mechanisms underlying cool executive dysfunction in first-episode SZ patients.