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ABSTRACTWe show here that silver nanoparticles (AgNP) were intrinsically antibacterial, whereas gold nanoparticles (AuNP) were antimicrobial only when ampicillin was bound to their surfaces. Both AuNP and AgNP functionalized with ampicillin were effective broad-spectrum bactericides against Gram-negative and Gram-positive bacteria. Most importantly, when AuNP and AgNP were functionalized with ampicillin they became potent bactericidal agents with unique properties that subverted antibiotic resistance mechanisms of multiple-drug-resistant bacteria.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and causing the global coronavirus pandemic. The viral dynamics of SARS-CoV-2 infection have not been quantitatively investigated. In this paper, we use mathematical models to study the pathogenic features of SARS-CoV-2 infection by examining the interaction between the virus, cells and immune responses. Models are fit to the data of SARS-CoV-2 infection in patients and non-human primates. Data fitting and numerical simulation show that viral dynamics of SARS-CoV-2 infection have a few distinct stages. In the initial stage, viral load increases rapidly and reaches the peak, followed by a plateau phase possibly generated by lymphocytes as a secondary target of infection. In the last stage, viral load declines due to the emergence of adaptive immune responses. When the initiation of seroconversion is late or slow, the model predicts viral rebound and prolonged viral persistence, consistent with the observation in non-human primates. Using the model we also evaluate the effect of several potential therapeutic interventions for SARS-CoV-2 infection. Model simulation shows that anti-inflammatory treatments or antiviral drugs combined with interferon are effective in reducing the duration of the viral plateau phase and diminishing the time to recovery. These results provide insights for understanding the infection dynamics and might help develop treatment strategies against COVID-19.

Abstract-Insulin resistance is associated with obesity and may be accompanied by left ventricular diastolic dysfunction and myocardial remodeling. Decreased insulin metabolic signaling and increased oxidative stress may promote these maladaptive changes. In this context, the ␤-blocker nebivolol has been reported to improve insulin sensitivity, increase endothelial NO synthase activity, and reduce NADPH oxidase-induced superoxide generation. We hypothesized that nebivolol would attenuate diastolic dysfunction and myocardial remodeling by blunting myocardial oxidant stress and promoting insulin metabolic signaling in a rodent model of obesity, insulin resistance, and hypertension. Six-week-old male Zucker obese and age-matched Zucker lean rats were treated with nebivolol (10 mg ⅐ kg Ϫ ⅐ day Ϫ1 ) for 21 days, and myocardial function was assessed by cine MRI. Compared with untreated Zucker lean rats, untreated Zucker obese rats exhibited prolonged diastolic relaxation time (27.7Ϯ2.5 versus 40.9Ϯ2.0 ms; PϽ0.05) and reduced initial diastolic filling rate (6.2Ϯ0.5 versus 2.8Ϯ0.6 L/ms; PϽ0.05) in conjunction with increased homeostatic model assessment of insulin resistance (7Ϯ2 versus 95Ϯ21; PϽ0.05), interstitial and pericapillary fibrosis, abnormal cardiomyocyte histoarchitecture, 3-nitrotyrosine, and NADPH oxidase-dependent superoxide. Nebivolol improved diastolic relaxation (32.8Ϯ0.7 ms; PϽ0.05 versus untreated Zucker obese), reduced fibrosis, and remodeling in Zucker obese rats, in concert with reductions in nitrotyrosine, NADPH oxidase-dependent superoxide, and improvements in the insulin metabolic signaling, endothelial NO synthase activation, and weight gain (381Ϯ7 versus 338Ϯ14 g; PϽ0.05). Results support the hypothesis that nebivolol reduces myocardial structural maladaptive changes and improves diastolic relaxation in concert with improvements in insulin sensitivity and endothelial NO synthase activation, concomitantly with reductions in oxidative stress. (Hypertension. 2010;55:880-888.) Key Words: nebivolol Ⅲ oxidative stress Ⅲ insulin resistance Ⅲ diastolic relaxation Ⅲ MRI O besity-induced cardiomyopathy is characterized by impaired left ventricular (LV) relaxation in association with insulin resistance (IR). 1,2 This cardiomyopathy develops independent of blood pressure, ischemia, impaired systolic function, and age. 1,2 Impaired insulin metabolic signaling and increased generation of reactive oxygen species (ROS) play important roles in maladaptive myocardial remodeling 3-5 and impaired diastolic relaxation. 6,7 Excessive ROS in the heart and vasculature, derived from several enzymatic sources, including NADPH oxidase, 8 can lead to decreased bioavailable NO and reduced delivery of glucose and insulin to myocardial tissue. 4,9 ␤-Adrenergic receptor blockers have clinical use in treating heart failure, but traditional ␤-blockers have been associated with weight gain and worsening of IR. Nebivolol, a third-generation ␤ 1 -receptor blocker improves diastolic dysfunction 10 and reduces mortality in elderly he...