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Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 and World Health Organization-recognized priority pathogen requiring urgent Research & Development attention. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins by affinity purification-quantitative mass spectrometry and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in transmembrane transport, metabolism, oxidative stress, protein folding and glycosylation, etc., in line with the potential physiological actions of the viral glycoproteins. As a proof of principle, we detailedly elucidated the role of an identified cellular protein, HAX1, and therefore uncovered an interesting host antiviral strategy. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is indispensable for functional glycoprotein-mediated progeny virion packaging. Consistently, the notable inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections by series of loss/gain-of-function assays in cellular and animal infection models. Together, the findings not only provide a systematic CCHFV Gn/Gc-host protein-protein interaction map, but also unravel a novel cellular antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.

To produce high strength and ductility Mg alloys with high productivity and low energy consumption, the residual heat rolling (RHR) process was initially proposed. The microstucture and mechanical properties of AZ31 processed by RHR were investigated by optical micrscopy (OM), electron backscatter diffraction (EBSD), and electron universal testing machine. The yield strength (YS), ultimate tensile strength (UTS), and elongation to failure of RHRed AZ31 sheet were 194 MPa 311 MPa, and 22%, respectively. The RHRed AZ31 alloys after annealing have very fine and homogeneous grains. The symmetrical rolled (SR) and RHRed AZ31 exhibit typical {0002} basal textures. The RHRed AZ31 has double-peak basal texture distribution. The basal poles of RHRed AZ31 split from normal direction (ND) to rolling direction (RD). There are few hard orientation distributions on the basal slip and more soft orientation distributions on the prismatic slip in the RHRed AZ31 sheets than those in the SRed AZ31sheets.

Purpose Coronary sinus-related arrhythmias are common; however, it is difficult to perform radiofrequency (RF) ablation at these sites efficiently and safely. High-power, short-duration ablation (HPSD) is a proven alternative strategy for pulmonary vein isolation (PVI); whether it can be applied to ablation of the coronary sinus is unknown. The purpose of this preliminary study was to evaluate the feasibility and safety of HPSD ablation in the coronary sinus. Methods Firstly, we demonstrated 4 clinical cases of 3 types of arrhythmias who had unsuccessful ablation with standard power initially, but received successful ablations with HPSD. Secondly, RF ablation was performed in the coronary sinus ostium (CSO) and middle cardiac vein (MCV) of 4 in vitro swine hearts. Two protocols were compared: HPSD (45 W/5 S×5 rounds) and a conventional strategy that used low-power, long-duration ablation (LPLD: 25 W/10 S ×5 rounds). The total duration of HPSD protocol was 25 s, and which of LPLD was 50 s. Results A total of 28 lesions were created. HPSD can produce longer, wider, deeper, and larger lesions than LPLD. This difference was more pronounced when the ablation was in the MCV. One instance of steam pop occurred during LPLD in the MCV. Conclusions HPSD is an effective alternative strategy for ablation in coronary sinus according to clinical applications and preliminary animal study. However, the safety needs to be further evaluated based on more animal and clinical studies.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 (BSL-4) pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) characterized by hemorrhagic manifestation, multiple organ failure and high mortality rate, posing great threat to public health. Despite the recently increasing research efforts on CCHFV, host cell responses associated with CCHFV infection remain to be further characterized. Here, to better understand the cellular response to CCHFV infection, we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing (RNA-seq) technology. In total, 496 differentially expressed genes (DEGs), including 361 up-regulated and 135 down-regulated genes, were identified in CCHFV-infected cells. These regulated genes were mainly involved in host processes including defense response to virus, response to stress, regulation of viral process, immune response, metabolism, stimulus, apoptosis and protein catabolic process. Therein, a significant up-regulation of type III IFN signaling pathway as well as endoplasmic reticulum (ER) stress response was especially remarkable. Subsequently, representative DEGs from these processes were well validated by RT-qPCR, confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV. Furthermore, we demonstrate that not only type I but also type III IFNs (even at low dosages) have substantial anti-CCHFV activities. Collectively, the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV, which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV.

We reported a case with cardiomyopathy induced by frequent premature ventricular contractions (PVCs) and followed ventricular escape beats (VEBs). PVCs with VEBs in the compensatory pause which induced cardiomyopathy is rarely reported. Also, the case exhibited many characteristics of PVCs which were more likely to induce cardiomyopathy, like the location of origin, the longer coupling interval, and the QRS wave companied with the P wave.A 53-year-old man with left ventricular (LV) dysfunction presented with palpation, chest distress, and dyspnea for 3 years. Holter revealed a high burden of ventricular rhythm of PVCs and another wide QRS patterns (96,562 total beats with 87,330 wide QRS beats in 24 hours). The LV ejection fraction decreased to 34% and the left ventricle, right and left atria all dilated.He was diagnosed with PVC-induced cardiomyopathy.The patient experienced intracardiac electrophysiological examination which revealed frequent PVCs followed by VEBs in the compensatory pause. Activation mapping of the PVCS and ablation were performed.PVCs and VEBs disappeared after ablation. The LV ejection fraction increased to 46% at 2 days after the procedure. The diameters of the right and left atria were also significantly reduced.VEBs may occur during the compensatory pause of PVCs. PVCs with VEBs can lead to a high burden of ventricular rhythm and LV dysfunction. Ablation of the PVCs can also eliminate VEBs and improve the LV function.

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease of global concerns due to the increasing incidence and lack of effective treatments. The causative agent, CCHF virus (CCHFV), has been characterized for years; however, its tropism in cell lines of different host and tissue origins remains unclear. This study characterized the susceptibility of 16 human and 6 animal cell lines to CCHFV. Increased viral load and viral nucleoprotein expression, and productive CCHFV replication were detected in human vascular (HUVEC), renal (SW-13 and HEK-293), hepatic (Huh7), and cerebral (U-87 MG) cell lines, which were considered CCHFV-highly permissive cell lines. Renal cell lines derived from monkey and dog could also support CCHFV replication. This study evaluated the susceptibility of different cell lines to CCHFV and identified CCHFV-permissive cell lines. Our findings raise concerns regarding the use of cell lines in ex vivo studies of CCHFV and may have important implications for further fundamental research, which would promote understanding of CCHFV pathogenesis and transmission, as well as benefit designing strategies for disease prevention and control.

Rationale: Dual atrioventricular node non-reentrant tachycardia (DAVNNRT) is a rare arrhythmia. We present a case of inappropriate implantable cardioverter defibrillator (ICD) therapy caused by DAVNNRT. DAVNNRT is easily misdiagnosed as atrial fibrillation and is often identified as ventricular tachycardia (VT) by the supraventricular tachycardia-ventricular tachycardia (SVT-VT) discriminator of the ICD. Patient concerns: A 73-year-old man with ischemic heart disease (IHD) presented with palpitations accompanied by dyspnea and syncope. Frequent multifocal premature ventricular beats and non-sustained ventricular tachycardia were observed on ambulatory electrocardiography. The left ventricular ejection fraction decreased to 32%. Diagnosis: He was diagnosed with IHD, heart failure with reduced ejection fraction (HFrEF), and VT. Interventions : Initially, the patient received a single-chamber ICD implantation for secondary prevention of sudden death. He then suffered from inappropriate anti-tachycardia pacing (ATP)/shock therapy many times after the procedure. DAVNNRT was confirmed in an electrophysiology study (EPS), and radiofrequency ablation of the slow pathway successfully terminated this tachycardia. Outcomes: No episode of inappropriate ICD therapy or tachycardia occurred during the follow-up. Lessons: In conclusion, it is essential to have a full understanding of DAVNNRT and eliminate slow pathways for patients with DAVNNRT and be prepared to implant an ICD.

Background Atrioventricular node (AVN) ablation combined with His bundle pacing is an effective strategy for permanent atrial fibrillation (AF) with rapid ventricular rate refractory to pharmacological therapy. We aimed to access the feasibility and efficiency of His bundle pacing and AVN ablation guided by three-dimensional (3-D) mapping system throughout the procedure. Methods Eighteen patients with permanent AF with refractory rate and symptoms were referred for His bundle pacing and AVN ablation guided by 3-D mapping (CARTO3). Electroanatomic 3-D mapping of the right atrium and right ventricle was performed by the ablation catheter with CARTO 3 system, followed by the visualization of the leads for implantation and AVN ablation. Results Implantation of His bundle and ventricular leads and AVN ablation were achieved successfully with the help of 3-D mapping in 17 patients. Selective His bundle pacing was achieved in five patients (29.4%), and the other (70.6%) were nonselective His bundle pacing. The mean procedure duration was 99.4 ± 16.4 minutes. The mean fluoroscopy time was 7.0 ± 2.6 minutes. The time spent on His lead implantation was 6.1 ± 3.2 minutes. One patient experienced AVN ablation from left side under aortic valves due to no effect of ablation in right atrium. Conclusion His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.

Both phosphate and organic carbon can serve as nutrients for microorganism growth. Simultaneous removal of both nutrients would realize the antibacterial strategy of nutrient starvation better to ensure water quality safety. In addition, a short treatment time is the premise for the application of a material in water treatment. Herein, carbon-coated lanthanum nanorods with a uniform distribution of La and C (C-La-MOF) were rationally prepared through glucose and La-MOF hydrothermal treatment and further carbonization to synchronously and rapidly remove phosphate and organic matter. The carbon layer thickness was tuned by varying the hydrothermal time to find the optimal balance between excellent phosphate intake and low lanthanum leakage. C-La-MOF had a strong anti-interference ability and high phosphate capture capacity over a wide pH range of 2-12. Impressively, when phosphate and organic carbon coexisted in solution, their removal performances remained relatively unchanged compared with that when the two nutrients existed independently, and their adsorption equilibriums could be easily reached within 10 min. All of the above results prove that C-La-MOF is a promising material for practical drinking water treatment.

Pooling is an important operation in deep convolutional neural networks (CNNs). In the learning process of CNNs, the pooling layer needs to preserve feature information while significantly reduce computation amount. The conventional pooling methods, such as average pooling and max pooling cannot preserve feature information effectively in pooling layers. Therefore, a more effective and adaptive pooling mechanism is needed for pooling layers. In this paper, we propose a novel pooling mechanism to preserve feature information effectively. The novel pooling method considers the value distribution of the activations within pooling regions and operates on salient activations accordingly. This pooling method can be realized by clustering the activations in pooling regions into salient and trivial activations, and use salient activations only to compute pooling output. Compared with traditional average and max pooling methods, our pooling method is more adaptive and more likely to preserve feature information in pooling layers. Experimental results on several benchmark image datasets show that our adaptive salience preserving (ASP) pooling method outperforms existing pooling methods. Furthermore, our proposed ASP pooling can provide a "middle zone" between average pooling and max pooling. By using ASP pooling in the right stages of CNNs, we could significantly improve the network performance. For example, the performance of VGG network can be improved by changing the last two pooling layers to be ASP pooling.

Recently, Zika virus (ZIKV) has generated extraordinary concern because of its severe neurotoxicity. Disturbingly, there is no vaccine or specific drug to prevent or treat the diseases caused by ZIKV infection. Thus, it is extremely urgent to characterize the pathogenesis of ZIKV. It has been documented that ZIKV can evade antiviral responses of host cells. Here, we demonstrate that ZIKV strain SZ-WIV01 down-regulates the production of type I IFN and IFN-stimulated genes along with the expression of mitochondrial antiviral signaling protein (MAVS) and mediator of IFN regulatory factor 3 activation (MITA). In the mechanism, ZIKV nonstructural (NS) 3 and NS2B3 negatively regulate IFN-related retinoic acid-inducible gene I-like receptor signaling pathway by targeting MAVS and MITA, respectively. Overexpression of ZIKV NS3 and NS2B3 dramatically inhibits expression of IFN-β. ZIKV NS3 interacts with MAVS, and NS2B3 interacts with MITA, which catalyzes K48-linked polyubiquitination of MAVS and MITA for degradation. Further investigations suggest that ZIKV NS2B3 impairs polyinosinic:polycytidylic acid-triggered K63-linked polyubiquitination of MITA, thereby subverting the activation of downstream sensors. Our study reveals an undiscovered mechanism for ZIKV to escape the innate immune response, providing new insights into clinical study of vaccines or effective drugs.-Li, W., Li, N., Dai, S., Hou, G., Guo, K., Chen, X., Yi, C., Liu, W., Deng, F., Wu, Y., Cao, X. Zika virus circumvents host innate immunity by targeting the adaptor proteins MAVS and MITA.

To explore the correlation between dietary protein intake and metabolic syndrome( MS) among the men and women of Hubei Province.Data were obtained from the 2010-2012 Chinese National Nutrition and Health Survey in Hubei Province. Cross-sectional data on 1827 men and women aged l8 years and above was gathered from 6 monitoring sites by multi-stage stratified and Probability Proportionate to Size( PPS) cluster random sampling method. All subjects took the dietary survey with the 24-hour recall method for 3 consecutive days, medical examination and blood assay. Prevalence of MS was defined under the diagnostic criteria of Joint Interim Statement( JIS2009), and the logistic regression was used to explore the possible relationships between dietary protein intake and MS among 18 years old and above adults, when calculating the OR and its 95% CI of MS.After adjusting for covariates, increased risks of MS were related with percentage of energy from protein( OR = 1. 44, 95% CI 1. 19-2. 03) and percentage of protein from animal foods( OR = 1. 16, 95% CI2. 02-2. 08) among men. Meanwhile, no significant correlations were shown betweendietary protein intake and MS among women.There are gender differences at the correlation between dietary protein intake and MS. Percentage of energy from protein and percentage of protein from animal foods could possibly be the risk factors of MS among men.

Gadolinium aluminate (GdAlO3, GAP) is a rare earth compound with perovskite structure. Its optical isotropic structure prevents the defects of refractive index difference in any direction. GAP has unique and excellent properties in electricity, magnetism, luminescence and catalysis, especially as a high-quality luminescent matrix material. Sol-gel method has the advantages of accurate control of chemical composition, particle size and purity of products. The main preparation parameters include chelating agent concentration, alcohol water ratio, calcination temperature and so on. In this paper, the citric acid chelating agent was used to prepare gadolinium aluminate nanoparticles by sol-gel method, thermogravimetry-differential thermal analysis (TG-DTA), x-ray diffraction (XRD) and scanning electron microscope (SEM) were employed to analyze the effects of chelating agent, dispersant, solvent and calcination temperature on the phase and morphology changing in precursor and final product. The results show that GAP nanoparticles with high degree of crystallinity, nearly spherical morphology and 60–100 nm particle size can be obtained at the molar ratio of citric acid to cationic of 1:1, the ammonium citrate to citric acid of 1.5:1 and the calcination temperature of 900 °C for 4 h. When the calcination temperature is higher than 1100 °C, a new phase of Gd3Al5O12 (GdAG) will be formed with calcination neck shape.

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Microcrystalline Ni-W alloy layers with different thickness were electroplated on the surface of Cu substrate. The mechanical properties of coating samples with different thickness were analyzed. The microstructure and fracture morphology between the substrate and the coating were observed by SEM (scanning electron microscopy) and EDS (energy dispersion spectrum). The results show that the coating thickness increases linearly from 0.031 μm to 7.77 μm with the increase of electroplating time. With the Ni-W coating thickness increasing, the microstructure of fracture changes from cross cracks to straight cracks, the number of cracks per unit area decreases, and the crack spacing increases from 0.79 ± 0.35 μm to 153.56 ± 35.16 μm. The strength and plasticity of samples with Ni-W coating are higher than those of Cu substrate film because of the restriction in dislocation movement and surface work hardening. At the same time, the coating cracks hinder the dislocation movement, absorb energy and restrain the crack growth. When the coating breaks, the dislocation slip behavior will change into plastic deformation, and there is a synergistic mechanism of interface strengthening between the substrate and the coating.

Gadolinium aluminate (GdAlO3, GAP) nano whiskers were synthesized by the hydrothermal-solid state method, Fourier-transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and thermogravimetry-differential thermal analysis (TG-DTA) were employed to analyze the phase change and the nucleation mechanism of GAP during calcing process. The results show that the precursor of GAP prepared by hydrothermal is (NH4)xGdAl(OH)y(NO3)z·nH2O. When the calcination temperature is higher than 900 °C, the precursor recrystallizes, forming the needle shape GAP under the synergistic effect factors. The best preparation conditions are as follows: ammonia water as mineralizer, pH = 9, calcination temperature 1100 °C and holding time 3 h.

Based on the strong adsorption, bacteriostatic and bactericidal effects of fulvic acid and silver ions, the preparation of silver alginate deodorizing gel with fulvic acid and its adsorption properties for formaldehyde toxic and harmful gas were studied. In the experiment, silver fulvate was used as the main ingredient, then sodium alginate was used as stabilizer. Under the heating condition, the mixture of fulvic acid silver and sodium alginate was mixed by mass ratio of 0, 0.3:1, 0.5:1, 0.7:1 and 0.9:1, and then immersed in calcium chloride solution to form gel. The new type of silver alginate deodorant gel was prepared and the deodorization of silver fulvate and sodium fulvate silver alginate was prepared. The colloid was characterized. IR analysis showed that fulvic acid was complexed with Ag+. Thermogravimetric analysis showed that the stability of the deodorant gel was greatly improved when the mass ratio of fulvic acid to Ag+ was 1:10.

The baculovirus-insect cell expression system has been widely used for heterologous protein expression and virus-like particles (VLPs) expression. In this study, we established a new method for antiviral screening targeting to glycoprotein E of flaviviruses based on the baculovirus expression system. ZIKV is a mosquito-borne flavivirus and has posed great threat to the public health. It has been reported that ZIKV infection was associated with microcephaly and serious neurological complications. Our study showed that either ZIKV E or prME protein expressed in insect cells can form VLPs and induce membrane fusion between insect cells. Therefore, the E protein, which is responsible for receptor binding, attachment, and virus fusion during viral entry, achieved proper folding and retained its fusogenic ability in VLPs when expressed in this system. The syncytia in insect cells were significantly reduced by the anti-ZIKV-E specific polyclonal antibody in a dose-dependent manner. AMS, a thiol-conjugating reagent, was also shown to have an inhibitory effect on the E protein induced syncytia and inhibited ZIKV infection by blocking viral entry. Indeed the phenomenon of syncytial formation induced by E protein expressed VLPs in insect cells is common among flaviviruses, including Japanese encephalitis virus (JEV), Dengue virus type 2 (DENV-2), and tick-borne encephalitis virus (TBEV). This inhibition effect on syncytial formation can be developed as a novel, safe, and simple antiviral screening approach for inhibitory antibodies, peptides, or small molecules targeting to E protein of ZIKV and other flaviviruses.

Human detection is a key problem in computer vision, with several applications that have the potential to positively impact quality of life. In recent years, the number of approaches to detect human in video sequences has grown steadily. This paper proposed a novel approach to improve the capability of human detection. After investigating the image texture analysis methods, we adopt the new good texture descriptor, Local Binary Pattern histogram Fourier (LBPHF). Then we combine the LBPHF with the Histograms of Oriented Gradients (HOG) as feature sets, and use linear SVM to train our classifier. In the experiment on the INRIA personal dataset which is well known relatively good human detection's dataset, it is shown that our detector combining with the LBPHF significantly outperforms the other methods. Moreover, the time cost is much less and the dimension is reduced.

Monolayers of third-generation amphiphilic poly(amido amine) (PAMAM) dendrimer were prepared at the air/water interface and then were successfully transferred onto silicon wafers by a horizontal li...