To complement traditional antivirals, natural compounds that act via host targets and present high barriers to resistance are of increasing interest. In the work reported here, we detected that homoharringtonine (HHT) presents effective antiviral activity. HHT completely inhibited infections of vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), and porcine epidemic diarrhea virus (PEDV) at concentrations of 50, 100, and 500 nM in cell cultures, respectively. Treatment with HHT at doses of 0.05 or 0.2 mg/kg significantly reduced viral load and relieved severe symptoms in PEDV- or NDV-infected animals. HHT treatment, however, moderately inhibited avian influenza virus (AIV) infection, suggesting its potent antiviral action is restricted to a number of classes of RNA viruses. In this study, we also observed that HHT actively inhibited herpes simplex virus type 1 (HSV-1) replication with a 50% inhibitory concentration (IC50) of 139 nM; the treatment with HHT at 1000 nM led to reductions of three orders of magnitude. Moreover, HHT antagonized the phosphorylation level of endogenous and exogenous eukaryotic initiation factor 4E (p-eIF4E), which might regulate the selective translation of specific messenger RNA (mRNA). HHT provides a starting point for further progress toward the clinical development of broad-spectrum antivirals.
Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry.
The sudden outbreak of COVID-19 has exerted a tremendous impact on the psyche of people around the world, especially adolescents. In order to provide a valuable theoretical basis for effective measures to prevent psychological problems in adolescents during public health emergencies in the future, this study examined the mediating effect of coping style (CS, including positive coping style (PCS) and negative coping style (NCS)) and the moderating effect of emotional management ability (EMA) on the relationship between the psychological stress response (PSR) and aggression (AGG) in adolescents during the COVID-19 epidemic in China. The Buss–Warren Aggression Questionnaire, Simplified Coping Style Questionnaire, and Emotion Management Questionnaire were employed to investigate the mental health of Chinese adolescents from April 10–20 (Time point 1, T1) and May 20–30 (Time point 2, T2), 2020. A total of 1,931 adolescents (aged 10–25 years, M = 19.18 years, 51.4% male) were examined at T1 and 334 adolescents (aged 11–25 years, M = 19.97 years, 48.7% male) were reinvestigated at T2. Overall, 17.6% of the participants at T1 and 16.8% at T2 reported obvious PSR activation. NCS partly mediated the relationship between the PSR and AGG, and the indirect effect was moderated by EMA reported at T2. There were regional differences in the moderated mediation model in low-risk areas at T1. The moderated effects of EMA at T1 and T2 were opposite. Specifically, high EMA resulted in a stronger relationship between NCS and AGG at T1, whereas high EMA resulted in a weaker relationship between NCS and AGG at T2. Psychological reactions resulting from sudden public health events may trigger AGG in younger individuals. However, EMA may have a buffering effect on the onset of AGG. This research expands our understanding of the development of AGG in adolescents during the pandemic.
Objective To build a combined model that integrates clinical data, contrast-enhanced ultrasound, and magnetic resonance perfusion-weighted imaging-based radiomics for predicting the possibility of biochemical recurrence of prostate carcinoma and develop a nomogram tool. Method We retrospectively analyzed the clinical, ultrasound, and magnetic resonance imaging data of 206 patients pathologically confirmed with prostate carcinoma and receiving radical prostatectomy at Xiangyang No. 1 People’s Hospital from February 2015 to August 2021. Based on one to 7 years of follow-up (prostate specific antigen [PSA] level≥0.2 ng/mL, indicative of prostate carcinoma–biochemical recurrence), the patients were divided into biochemical recurrence group (n = 77) and normal group (n = 129). The training and testing sets were formed by dividing the patients at a 7:3 ratio. In training set, The magnetic resonance perfusion-weighted imaging–based radiomics radscore was generated using lasso regression. Several predictive models were built based on the patients’ clinical imaging data. The predictive efficacy (area under the curve) of these models was compared using the MedCalc software. The decision curve analysis was conducted using the R to compare the net benefit. Finally, an external validation was carried out on the testing set, and the nomogram tool was developed for predicting prostate carcinoma–biochemical recurrence. Result The univariate analysis confirmed that Tumor diameter, tumor node metastasis classification stage of tumor, lymph node metastasis or distance metastasis, Gleason grade, preoperative PSA, ultrasound (peak intensity, arrival time, and elastography grade), and magnetic resonance imaging-radscore1/2 were predictors of prostate carcinoma–biochemical recurrence. On the training set, the combined model based on the above factors had the highest predictive efficacy for prostate carcinoma–biochemical recurrence (area under the curve: 0.91; odds ratio 0.02, 95% confidence interval: 0.85-0.95). The predictive performance of the combined model was significantly higher than that of the model based on general clinical data (area under the curve: 0.74; odds ratio 0.04, 95% confidence interval: 0.67-0.81, P < .05), contrast-enhanced ultrasound (area under the curve: 0.61; odds ratio 0.05 95% confidence interval: 0.53-0.69, P < .05), and the magnetic resonance imaging–based radiomics model (area under the curve: 0.85; odds ratio 0.03, 95% confidence interval: 0.78-0.91, P = .01). The decision curve analysis also indicated the maximum net benefit derived from the combined model, which agreed with the validation results on the testing set. The nomogram tool developed based on the combined model achieved a good performance in clinical applications. Conclusion The magnetic resonance imaging texture parameters extracted by magnetic resonance perfusion-weighted imaging Lasso regression could help increase the accuracy of the predictive model. The combined model and the nomogram tool provide support for the clinical screening of the populations at a risk for biochemical recurrence.
Mesoporous Hydroxyapatite (MHAP), featuring high porosity, high surface area, and three-dimensional ordered passageways, has diverse applications in several fields. Thus, an in-depth understanding of the synthesis strategies and practical applications...
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