Heartland virus (HRTV) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (SFTSV), another phlebovirus causing life-threatening disease in humans. Previous ...findings have suggested that SFTSV can antagonize the host interferon (IFN) system via viral nonstructural protein (NSs)-mediated sequestration of antiviral signaling proteins into NSs-induced inclusion bodies. However, whether and how HRTV counteracts the host innate immunity is unknown. Here, we report that HRTV NSs (HNSs) also antagonizes IFN and cytokine induction and bolsters viral replication, although no noticeable inclusion body formation was observed in HNSs-expressing cells. Furthermore, HNSs inhibited the virus-triggered activation of IFN-β promoter by specifically targeting the IFN-stimulated response element but not the NF-κB response element. Consistently, HNSs blocked the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3, an IFN-stimulated response element-activating transcription factor). Reporter gene assays next showed that HNSs blockades the antiviral signaling mediated by RIG-I-like receptors likely at the level of TANK-binding kinase 1 (TBK1). Indeed, HNSs strongly interacts with TBK1 as indicated by confocal microscopy and pulldown analyses, and we also noted that the scaffold dimerization domain of TBK1 is required for the TBK1-HNSs interaction. Finally, pulldown assays demonstrated that HNSs expression dose-dependently diminishes a TBK1-IRF3 interaction, further explaining the mechanism for HNSs function. Collectively, these data suggest that HNSs, an antagonist of host innate immunity, interacts with TBK1 and thereby hinders the association of TBK1 with its substrate IRF3, thus blocking IRF3 activation and transcriptional induction of the cellular antiviral responses.
Objectives
COVID-19 has a varied clinical presentation. Elderly patients with comorbidities are more vulnerable to severe disease. This study identifies specific symptoms and comorbidities predicting ...severe COVID-19 and intensive care unit (ICU) admission.
Methods
A literature search identified studies indexed in MEDLINE, EMBASE and Global Health before 5th March 2020. Two reviewers independently screened the literature and extracted data. Quality appraisal was performed using STROBE criteria. Random effects meta-analysis identified symptoms and comorbidities associated with severe COVID-19 or ICU admission.
Results
Seven studies (including 1813 COVID-19 patients) were included. ICU patients were older (62.4 years) than non-ICU (46 years), with a greater proportion of males. Dyspnoea was the only symptom predictive for severe disease (pOR 3.70, 95% CI 1.83–7.46) and ICU admission (pOR 6.55, 95% CI 4.28–10.0). COPD was the strongest predictive comorbidity for severe disease (pOR 6.42, 95% CI 2.44–16.9) and ICU admission (pOR 17.8, 95% CI 6.56–48.2), followed by cardiovascular disease and hypertension.
Conclusions
Dyspnoea was the only symptom predictive for severe COVID-19 and ICU admission. Patients with COPD, cardiovascular disease and hypertension were at higher risk of severe illness and ICU admission.
The objective of generalized sampling expansion (GSE) is the reconstruction of an unknown, continuously defined function f (t) from samples of the responses from M linear time-invariant (LTI) systems ...that are each sampled using the 1/Mth Nyquist rate. In this paper, we investigate the GSE for lowpass and bandpass signals with multiple sampling rates in the fractional Fourier transform (FRFT) domain. First, we propose an improvement of Papoulis' GSE, which has multiple sampling rates in the FRFT domain. Based on the proposed GSE, we derive the periodic nonuniform sampling scheme and the derivative interpolation method by designing different fractional filters and selecting specific sampling rates. In addition, the Papoulis GSE and the previous GSE associated with FRFT are shown to be special instances of our results. Second, we address the problem of the GSE of fractional bandpass signals. A new GSE for fractional bandpass signals with equal sampling rates is derived. We show that the restriction of an even number of channels in the GSE for fractional bandpass signals is unnecessary, and perfect signal reconstruction is possible for any arbitrary number of channels. Further, we develop the GSE for a fractional bandpass signal with multiple sampling rates. Lastly, we discuss the application of the proposed method in the context of single-image super-resolution reconstruction based on GSE. Illustrations and simulations are presented to verify the validity and effectiveness of the proposed results.
•A new SOS algorithm is introduced to solve engineering optimization.•Twenty-six mathematical problems and five engineering design problems are tested.•The results obtained by SOS are compared with ...other optimization methods.•Obtained results confirm the excellent performance of the SOS method.
This paper applies a new robust and powerful metaheuristic algorithm called Symbiotic Organisms Search (SOS) to numerical optimization and engineering design problems. SOS simulates the symbiotic interaction strategies adopted by organisms to survive and propagate in the ecosystem. Twenty-six unconstrained mathematical problems and four structural engineering design problems are tested and obtained results compared with other well-known optimization methods. Obtained results confirm the excellent performance of the SOS method in solving various complex numerical problems.
The offset linear canonical transform (OLCT) plays an important role in many fields of optics and signal processing. In this paper, we address the problem of signal filtering and reconstruction in ...the OLCT domain based on new convolution theorems. Firstly, we propose new convolution and product theorems for the OLCT, which state that a modified ordinary convolution in the time domain is equivalent to simple multiplication operations for the OLCT and the Fourier transform (FT). Moreover, it is expressible by a one dimensional integral and is easy to implement in designing filters. The classical convolution theorem in the FT domain is shown to be a special case of our derived results. Then, a practical multichannel sampling expansion for band-limited signal with the OLCT is introduced. This sampling expansion constructed by the new convolution structure can reduce the effect of spectral leakage and is easy to implement. By designing OLCT filters, we can obtain derivative sampling and second-order derivative interpolation. Furthermore, potential applications of the multichannel sampling are discussed. Last, based on the new convolution structure, we investigate and discuss several applications, including swept-frequency filter analysis, image denosing and image encryption. Some illustrations and simulations are presented to verify the validity and effectiveness of the proposed method.
In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial ...chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population.
In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m
, leucovorin 400 mg/m
, fluorouracil bolus 400 mg/m
on day 1, and fluorouracil infusion 2,400 mg/m
for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment.
Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75;
< .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 46%
28 18%;
< .001) and a longer median progression-free survival (9.6 95% CI, 7.4 to 11.9
5.4 months 95% CI, 3.8 to 7.0,
< .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30%
19%,
= .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related.
FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.
•Preprocess the host image and watermark image with image enlargement technology.•Use redistribution invariant wavelet and discrete cosine to get the mixed domain.•Double-encrypt pre-processed ...watermark image to improve security and reliability.•A dual embedding technique is proposed to embed watermark.•Use multi-parameter particle swarm algorithm to obtain embedding factor matrices.
The existing watermarking algorithms invariant wavelet domain are weak at resisting geometric attacks and have small embedding capacities. In this paper, a robust double-encrypted watermarking algorithm based on the fractional Fourier transform (FRFT) and discrete cosine transform (DCT) in invariant wavelet domain is proposed. A hybrid domain is obtained by applying the redistributed invariant wavelet transform (RIDWT) and cosine transform to the enlarged host image. The low-frequency and high-frequency regions of the domain have advantages against different attacks; thus, the two components are both selected for watermark embedding. To solve the false positive problem, the enlarged watermark is double-encrypted by the Arnold transform and the FRFT before a singular value decomposition is applied to it, which enhances the security of the algorithm due to the generation of more keys. Multiparameter particle swarm optimization (MP-PSO) is used to obtain the optimal embedding factors for achieving the balance between invisibility and robustness. The simulation results and comparative experiments show that the proposed algorithm exhibits high robustness under the premise of satisfying security, reliability and invisibility, especially for geometric attacks such as rotation, cropping and translation.
For stem cell differentiation, the microenvironment can play an important role, and hydrogels can provide a three‐dimensional microenvironment to allow native cell growth in vitro. A challenge is ...that the stem cell's differentiation can be influenced by the matrix stiffness. We demonstrate a low‐toxicity method to create different stiffness matrices, by using a photopolymerizable gelatin methacrylate (GelMA) hydrogel cross‐linked by blue light (440 nm). The stiffness and porosity of GelMA hydrogel is easily modified by altering its concentration. We used human bone marrow mesenchymal stem cells (MSCs) as a cell source and cultured the GelMA‐encapsulated cells with EGM‐2 medium to induce endothelial differentiation. In our GelMA blue light hydrogel system, we found that MSCs can be differentiated into both endothelial‐like and osteogenic‐like cells. The mRNA expressions of endothelial cell markers CD31, von Willebrand factor, vascular endothelial growth factor receptor‐2, and CD34 were significantly increased in softer GelMA hydrogels (7.5% and 10%) compared with stiffer matrices (15% GelMA). On the other hand, the enhancements of osteogenic markers mRNA expressions (Alkaline phosphatase (ALP), Runx2, osteocalcin, and osteopontin) were highest in 10% GelMA. We also found that 10% GelMA hydrogel offered optimal conditions for MSCs to form capillary‐like structures. These results suggest that the mechanical properties of the GelMA hydrogel can influence both endothelial and osteogenic differentiation of MSCs and sequent capillary‐like formation.
Three-dimensional printing has the potential for clinical applications, and additive manufacturing materials for dental use merit further investigation.
The purpose of this in vitro study was to ...evaluate the properties of materials formulated with ethoxylated bisphenol A-dimethacrylate (Bis-EMA), urethane dimethacrylate (UDMA), and triethylene glycol dimethacrylate (TEGDMA) as 3D printing resins for ultraviolet digital light processing (UV-DLP) 3D printers and to characterize the mechanical and biological properties and accuracy of the printed objects.
Ten different light-polymerized resins were formulated using Bis-EMA, UDMA, and TEGDMA. Their viscosities were measured, and only 7 resins with viscosities lower than 1500 centipoise (cP) were selected for 3D printing and further material characterization. The light-polymerized resins were printed into representative shapes using a custom-made 3D printer equipped with a 405-nm UV-DLP projector as the light source. The printed specimens were subjected to biologic, mechanical, and accuracy tests, and the data were submitted to 1-way ANOVA and Tukey post hoc comparisons (α=.05).
Photopolymerizable resins made of Bis-EMA, UDMA, and TEGDMA were successfully formulated for 3D printing to fabricate objects of various shapes and sizes. TEGDMA served as the diluent to reduce the viscosity and increase the degree of conversion, while UDMA and Bis-EMA provided strength as demonstrated by the mechanical testing. All the printed objects passed cytotoxicity testing. The flexural strengths of the printed specimens ranged between 60 MPa and 90 MPa; flexural modulus ranged between 1.7 GPa and 2.1 GPa; and surface hardness ranged between 14.5 HV and 24.6 HV. These represent similar mechanical properties to those of currently used clinical resin materials. In the accuracy test, the resin mixture composed of 80% Bis-EMA, 10% UDMA, and 10% TEGDMA had the highest accuracy, with a 0.051-mm deviation from the original design.
Bis-EMA, UDMA, and TEGDMA are good candidates for the formulation of 3D printing resins for dental use. The printed objects demonstrated favorable biological and mechanical properties. Further, the accuracy of the printed specimens showed potential for clinical application.