Publications by authors named "Yipeng Sun"

81 Publications

IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.

Nat Microbiol 2021 May 13. Epub 2021 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during influenza virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the antiviral response.
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http://dx.doi.org/10.1038/s41564-021-00907-xDOI Listing
May 2021

Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.

J Virol 2021 Mar 17. Epub 2021 Mar 17.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.Avian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.
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http://dx.doi.org/10.1128/JVI.01578-20DOI Listing
March 2021

Investigation of the Active Ingredients and Mechanism of in Asthma Based on Network Pharmacology and Experimental Verification.

Drug Des Devel Ther 2021 9;15:1075-1089. Epub 2021 Mar 9.

Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, People's Republic of China.

Background: is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of and to further explore the potential molecular mechanism in asthma by using network pharmacology.

Methods: The active ingredients and their targets related to were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining.

Results: Twelve active ingredients in and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that and resveratrol (one active ingredient of ) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased HO induced MUC5AC overexpression in airway epithelial NCI-H292 cells.

Conclusion: Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of in the treatment of asthma.
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http://dx.doi.org/10.2147/DDDT.S275228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955765PMC
March 2021

Mink is a highly susceptible host species to circulating human and avian influenza viruses.

Emerg Microbes Infect 2021 Dec;10(1):472-480

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.

Pandemic influenza, typically caused by the reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remains unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive "mixing vessels" for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented.
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http://dx.doi.org/10.1080/22221751.2021.1899058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993395PMC
December 2021

Deep Learning Algorithm Trained with COVID-19 Pneumonia Also Identifies Immune Checkpoint Inhibitor Therapy-Related Pneumonitis.

Cancers (Basel) 2021 Feb 6;13(4). Epub 2021 Feb 6.

Departmental Faculty of Medicine and Surgery, Unit of Diagnostic Imaging and Interventional Radiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy.

Background: Coronavirus disease 2019 (COVID-19) pneumonia and immune checkpoint inhibitor (ICI) therapy-related pneumonitis share common features. The aim of this study was to determine on chest computed tomography (CT) images whether a deep convolutional neural network algorithm is able to solve the challenge of differential diagnosis between COVID-19 pneumonia and ICI therapy-related pneumonitis.

Methods: We enrolled three groups: a pneumonia-free group ( = 30), a COVID-19 group ( = 34), and a group of patients with ICI therapy-related pneumonitis ( = 21). Computed tomography images were analyzed with an artificial intelligence (AI) algorithm based on a deep convolutional neural network structure. Statistical analysis included the Mann-Whitney U test (significance threshold at < 0.05) and the receiver operating characteristic curve (ROC curve).

Results: The algorithm showed low specificity in distinguishing COVID-19 from ICI therapy-related pneumonitis (sensitivity 97.1%, specificity 14.3%, area under the curve (AUC) = 0.62). ICI therapy-related pneumonitis was identified by the AI when compared to pneumonia-free controls (sensitivity = 85.7%, specificity 100%, AUC = 0.97).

Conclusions: The deep learning algorithm is not able to distinguish between COVID-19 pneumonia and ICI therapy-related pneumonitis. Awareness must be increased among clinicians about imaging similarities between COVID-19 and ICI therapy-related pneumonitis. ICI therapy-related pneumonitis can be applied as a challenge population for cross-validation to test the robustness of AI models used to analyze interstitial pneumonias of variable etiology.
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http://dx.doi.org/10.3390/cancers13040652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914551PMC
February 2021

WeChat as a Platform for Baduanjin Intervention in Patients With Stable Chronic Obstructive Pulmonary Disease in China: Retrospective Randomized Controlled Trial.

JMIR Mhealth Uhealth 2021 02 2;9(2):e23548. Epub 2021 Feb 2.

Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Pulmonary rehabilitation is a crucial part of the nonpharmacological treatment of stable chronic obstructive pulmonary disease (COPD), but management remains problematic. WeChat could serve as a useful tool in patient management. Baduanjin is a popular exercise in China that is usually applied in pulmonary rehabilitation, which has been confirmed to be effective in improving lung function and life quality.

Objective: This study aimed to explore the efficiency of WeChat in the management of Baduanjin exercise in COPD patients.

Methods: A total of 200 patients from the respiratory department of Putuo Hospital participated in the Baduanjin rehabilitation project from September 2018 to October 2019, and were randomly assigned to the WeChat and control groups and followed up using the WeChat platform or telephone for 12 weeks. The frequency of Baduanjin exercise, lung function (percentage of forced expiratory volume in 1 second predicted, FEV1% predicted), and COPD assessment test (CAT) scores were collected and compared between the two groups. The number of message exchanges and a satisfaction survey on the WeChat platform were used to assess the feasibility of WeChat management outside the hospital.

Results: The Baduanjin exercise frequency significantly differed between the control group and WeChat group (F=33.82, P<.001) and across various time points (F=214.87, P<.001). After the follow-up on WeChat, there were fewer patients not performing Baduanjin exercise. The FEV1% predicted value significantly differed before and after Baduanjin exercise in the control group (Z=-3.686, P<.001) and the WeChat group (Z=-6.985, P<.001). A significant difference in the FEV1% predicted value was observed after Baduanjin exercise between the two groups (Z=-3.679, P<.001). The CAT score significantly differed before and after Baduanjin exercise in the control group (Z=-4.937, P<.001) and the WeChat group (Z=-5.246, P<.001). A significant difference in the CAT score was observed after Baduanjin exercise between the two groups (Z=-5.246, P<.001). The number of completed Baduanjin exercises, lung function, and CAT scores in active patients were higher than those in nonactive patients. All satisfaction survey items were scored with more than 4 points. Among the items, the highest score (mean 4.54, SD 0.77) was for continued WeChat management, followed by the effective management of Baduanjin exercise (mean 4.46, SD 0.87). The patients in the WeChat group showed much higher enthusiasm for and compliance with Baduanjin exercise, resulting in better life quality and lung function. The patients were very satisfied with the WeChat management because of the obvious curative effect and home feeling.

Conclusions: The WeChat platform provided a feasible, effective, and sustainable management plan for Baduanjin rehabilitation.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1900028248; http://www.chictr.org.cn/showprojen.aspx?proj=46995.
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http://dx.doi.org/10.2196/23548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886617PMC
February 2021

Atomic/molecular layer deposition for energy storage and conversion.

Chem Soc Rev 2021 Mar 1;50(6):3889-3956. Epub 2021 Feb 1.

Department of Mechanical & Materials Engineering, University of Western Ontario, London, ON N6A 5B9, Canada.

Energy storage and conversion systems, including batteries, supercapacitors, fuel cells, solar cells, and photoelectrochemical water splitting, have played vital roles in the reduction of fossil fuel usage, addressing environmental issues and the development of electric vehicles. The fabrication and surface/interface engineering of electrode materials with refined structures are indispensable for achieving optimal performances for the different energy-related devices. Atomic layer deposition (ALD) and molecular layer deposition (MLD) techniques, the gas-phase thin film deposition processes with self-limiting and saturated surface reactions, have emerged as powerful techniques for surface and interface engineering in energy-related devices due to their exceptional capability of precise thickness control, excellent uniformity and conformity, tunable composition and relatively low deposition temperature. In the past few decades, ALD and MLD have been intensively studied for energy storage and conversion applications with remarkable progress. In this review, we give a comprehensive summary of the development and achievements of ALD and MLD and their applications for energy storage and conversion, including batteries, supercapacitors, fuel cells, solar cells, and photoelectrochemical water splitting. Moreover, the fundamental understanding of the mechanisms involved in different devices will be deeply reviewed. Furthermore, the large-scale potential of ALD and MLD techniques is discussed and predicted. Finally, we will provide insightful perspectives on future directions for new material design by ALD and MLD and untapped opportunities in energy storage and conversion.
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http://dx.doi.org/10.1039/d0cs00156bDOI Listing
March 2021

Benzo(a)pyrene induces MUC5AC expression through the AhR/mitochondrial ROS/ERK pathway in airway epithelial cells.

Ecotoxicol Environ Saf 2021 Mar 8;210:111857. Epub 2021 Jan 8.

Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, PR China. Electronic address:

Objectives: Benzo(a)pyrene (BaP) is a ubiquitous air pollutants, and BaP exposure leads to a risk of respiratory diseases. The oversecretion of airway mucus and high expression of mucin 5AC (MUC5AC) are associated with common respiratory disorders caused by air pollution. We aimed to investigate the effect of BaP on MUC5AC expression, especially the mechanisms by which BaP induces MUC5AC gene expression.

Methods: The human airway epithelial cell NCI-H292 was used to test the effects of BaP on the expression of MUC5AC in vitro. MUC5AC mRNA and protein expression were assessed with real-time quantitative PCR, immunochemistry, and western blotting. A luciferase assay was conducted to detect the activity of the promoter. The total cellular ROS and mitochondrial ROS were measured by corresponding probes. Small-interfering RNAs were used for gene silencing. AhR-overexpressing cell lines were constructed by transfection with AhR overexpression lentivirus.

Results: We found that BaP stimulation upregulated the MUC5AC mRNA and protein levels and activated the ERK pathway. Suppressing ERK with U0126 (an ERK inhibitor) or knocking down ERK with siRNA decreased BaP-induced MUC5AC expression. The luciferase activity transfected with the MUC5AC promoter and cAMP-response element (CRE) was increased after BaP treatment, whereas CREB siRNA suppressed the BaP-induced overexpression of MUC5AC. In addition, BaP increased mitochondrial ROS production, and Mito-TEMP, a mitochondrial ROS inhibitor, inhibited BaP-induced MUC5AC expression and ERK activation. BaP increased the mRNA levels of CYP1A1 and CYP1B1, while Alizarin, a CYP1s inhibitor, suppressed the effects of BaP, including the MUC5AC overexpression, ERK activation and mitochondrial ROS generation. BaP induced the translocation of aryl hydrocarbon receptor (AhR) from the cytoplasm to the nucleus. SiRNA-mediated knockdown or chemical inhibition of AhR decreased the BaP-induced expression of MUC5AC, while the overexpression of AhR significantly enhanced the BaP-induced expression of MUC5AC. ITE, an endogenous AhR ligand, also upregulated the mRNA and protein expression of MUC5AC. Furthermore, resveratrol treatment inhibited the BaP-induced MUC5AC overexpression, AhR translocation, mitochondrial ROS production and ERK pathway activation.

Conclusion: Here, we highlighted the crucial role of AhR/mitochondrial ROS/ERK pathway activation in BaP-induced MUC5AC overexpression and identified resveratrol as a promising drug to reduce BaP-induced MUC5AC overexpression.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111857DOI Listing
March 2021

A flexible electron-blocking interfacial shield for dendrite-free solid lithium metal batteries.

Nat Commun 2021 Jan 8;12(1):176. Epub 2021 Jan 8.

Department of Mechanical and Materials Engineering, University of Western Ontario, London, ON, N6A 5B9, Canada.

Solid-state batteries (SSBs) are considered to be the next-generation lithium-ion battery technology due to their enhanced energy density and safety. However, the high electronic conductivity of solid-state electrolytes (SSEs) leads to Li dendrite nucleation and proliferation. Uneven electric-field distribution resulting from poor interfacial contact can further promote dendritic deposition and lead to rapid short circuiting of SSBs. Herein, we propose a flexible electron-blocking interfacial shield (EBS) to protect garnet electrolytes from the electronic degradation. The EBS formed by an in-situ substitution reaction can not only increase lithiophilicity but also stabilize the Li volume change, maintaining the integrity of the interface during repeated cycling. Density functional theory calculations show a high electron-tunneling energy barrier from Li metal to the EBS, indicating an excellent capacity for electron-blocking. EBS protected cells exhibit an improved critical current density of 1.2 mA cm and stable cycling for over 400 h at 1 mA cm (1 mAh cm) at room temperature. These results demonstrate an effective strategy for the suppression of Li dendrites and present fresh insight into the rational design of the SSE and Li metal interface.
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http://dx.doi.org/10.1038/s41467-020-20463-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794502PMC
January 2021

Neurovirulence of avian influenza virus is dependent on the interaction of viral NP protein with host factor FMRP in the murine brain.

J Virol 2021 Jan 6. Epub 2021 Jan 6.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China

Avian influenza viruses (AIVs) are zoonotic viruses that exhibit a range infectivity and severity in the human host. Severe human cases of AIVs infection are often accompanied by neurological symptoms, however, the factors involved in the infection of the central nervous system (CNS) are not well known. In this study, we discovered that avian-like sialic acid (SA)-α2, 3 Gal receptor is highly presented in mammalian (human and mouse) brains. In the generation of a mouse-adapted neurotropic H9N2 AIV (SD16-MA virus) in BALB/c mice, we identified key adaptive mutations in its hemagglutinin (HA) and polymerase basic protein 2 (PB2) genes that conferred viral replication ability in mice brain. The SD16-MA virus showed binding affinity for avian-like SA-α2, 3 Gal receptor, enhanced viral RNP polymerase activity, increased viral protein production and transport that culminated in elevated progeny virus production and severe pathogenicity. We further established that host Fragile X Mental Retardation Protein (FMRP), a highly expressed protein in the brain that physically associated with viral nucleocapsid protein (NP) to facilitate RNP assembly and export, was an essential host factor for the neuronal replication of neurotropic AIVs (H9N2, H5N1 and H10N7 viruses). Our study identified a mechanistic process for AIVs to acquire neurovirulence in mice. Infection of the CNS is a serious complication of human cases of AIVs infection. The viral and host factors associated with neurovirulence of AIVs infection are not well understood. We identified and functionally characterized specific changes in the viral HA and PB2 genes of a mouse-adapted neurotropic avian H9N2 virus responsible for enhanced virus replication in neuronal cells and pathogenicity in mice. Importantly, we showed that host FMRP was a crucial host factor that was necessary for neurotropic AIVs (H9N2, H5N1 and H10N7 viruses) to replicate in neuronal cells. Our findings have provided insights into the pathogenesis of neurovirulence of AIV infection.
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http://dx.doi.org/10.1128/JVI.01272-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092684PMC
January 2021

Swine MicroRNAs and Restrict the Cross-Species Infection of Avian Influenza Virus.

J Virol 2020 11 9;94(23). Epub 2020 Nov 9.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

Avian influenza virus (AIV) can cross species barriers to infect humans and other mammals. However, these species-cross transmissions are most often dead-end infections due to host restriction. Current research about host restriction focuses mainly on the barriers of cell membrane, nuclear envelope, and host proteins; whether microRNAs (miRNAs) play a role in host restriction is largely unknown. In this study, we used porcine alveolar macrophage (PAM) cells as a model to elucidate the role of miRNAs in host range restriction. During AIV infection, 40 dysregulation expressed miRNAs were selected in PAM cells. Among them, two (; swine) miRNAs, and , could inhibit the infection and replication of AIV in PAM cells by directly targeting viral genome and inducing cell apoptosis via inhibiting the expression of anti-apoptotic protein HMBOX1. Avian but not swine influenza virus caused upregulated expressions of and in PAM cells. We further found that NF-κB P65 was more effectively phosphorylated upon AIV infection and that P65 functioned as a transcription activator to regulate the AIV-induced expression of Importantly, we found that and could also be specifically upregulated upon AIV infection in newborn pig tracheal epithelial (NPTr) cells and also exerted anti-AIV function. In summary, our study indicated that miRNAs act as a host barrier during cross-species infection of influenza A virus. The host range of an influenza A virus is determined by species-specific interactions between virus and host cell factors. Host miRNAs can regulate influenza A virus replication; however, the role of miRNAs in host species specificity is unclear. Here, we show that the induced expression of and in swine cells is modulated by NF-κB P65 phosphorylation in response to AIV infection but not swine influenza virus infection. and exerted antiviral function via targeting viral RNAs and causing apoptosis by inhibiting the expression of HMBOX1 in host cells. These findings uncover miRNAs as a host range restriction factor that limits cross-species infection of influenza A virus.
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http://dx.doi.org/10.1128/JVI.01700-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654260PMC
November 2020

Qi-Xian Decoction Upregulated E-cadherin Expression in Human Lung Epithelial Cells and Ovalbumin-Challenged Mice by Inhibiting Reactive Oxygen Species-Mediated Extracellular-Signal-Regulated Kinase (ERK) Activation.

Med Sci Monit 2020 Aug 24;26:e922003. Epub 2020 Aug 24.

Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China (mainland).

BACKGROUND Loss of the epithelial barrier is characterized by a reduction in E-cadherin expression and is a hallmark of asthma. Qi-xian decoction (QXT) is a Chinese medicinal formula that has been used to effectively treat asthma. This study aimed to investigate the effect of QXT on E-cadherin expression in human lung epithelial 16HBE cells and ovalbumin-challenged mice and to explore the underlying molecular mechanism. MATERIAL AND METHODS Ovalbumin (OVA)-induced mice were used as a model of asthma. Real-time PCR and Western blotting were utilized to examine mRNA and protein levels. Lung tissue reactive oxygen species (ROS) levels were evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA). Serum superoxide dismutase (SOD) and the total antioxidant capacity (TAOC) were measured via enzyme-linked immunosorbent assay (ELISA)-based analyses. 16HBE cells were utilized to explore the effect of QXT or hydrogen peroxide (H₂O₂) on the expression of E-cadherin in vitro. RESULTS We found that QXT treatment increased E-cadherin expression and decreased extracellular-signal-regulated kinase (ERK) phosphorylation levels in the lung tissues of OVA-challenged mice. QXT also downregulated ROS levels and increased serum SOD and TAOC levels in OVA-challenged mice. In vitro studies demonstrated that increased ROS generation induced by H₂O₂ resulted in decreased E-cadherin expression levels in 16HBE cells, which was attenuated by inhibition of ERK signaling. Moreover, the H₂O₂-induced downregulation of E-cadherin expression, increased ROS generation, and ERK activation in 16HBE cells were restored by treatment with QXT water or ethanol extract. CONCLUSIONS These data demonstrate that one mechanism by which QXT protects against asthma is to restore E-cadherin expression in vivo and in vitro by inhibiting ROS-mediated ERK activation.
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http://dx.doi.org/10.12659/MSM.922003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461650PMC
August 2020

Dynamic CT assessment of disease change and prognosis of patients with moderate COVID-19 pneumonia.

J Xray Sci Technol 2020 ;28(5):851-861

Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi, China.

Objectives: To assess prognosis or dynamic change from initial diagnosis until recovery of the patients with moderate coronavirus disease (COVID-19) pneumonia using chest CT images.

Materials And Methods: In this retrospective study, 33 patients (18 men, 15 women; median age, 49.0 years) with confirmed with moderate COVID-19 pneumonia in a multicenter hospital were included. The patients underwent at least four chest non-contrast-enhanced computed tomography (CT) scans at approximately 5-day intervals. We analyzed the clinical and CT characteristics of the patients. Moreover, the total CT score and the sum of lung involvement were determined for every CT scan.

Results: The most widespread presenting symptoms were fever (32/33, 97.0%) and cough (17/33, 51.5%), which were often accompanied by decreased lymphocyte count (15/33, 45.5%) and increased C-reactive protein levels (18/33, 54.6%). Bilateral, multifocal ground glass opacities (32/33, 97.0%), consolidation (25/33, 75.8%), vascular thickening (23/33, 69.7%), and bronchial wall thickening (21/33, 63.6%) with peripheral distribution were the most frequent CT findings during moderate COVID-19 pneumonia. In patients recovering from moderate COVID-19 pneumonia, four stages (stages 1-4) of evolution were identified on chest CT with average CT scores of 3.4±2.3, 6.0±4.4, 5.6±3.8, and 4.9±3.2, respectively, from the onset of symptoms. For most patients, the peak of average total CT score increased for approximately 8 days after the onset of symptoms, after which it decreased gradually. The mean CT score of all patients was 4.7 at the time of discharge.

Conclusion: The moderate COVID-19 pneumonia CT score increased rapidly in a short period of time initially, followed by a slow decline over a relatively long time. The peak of the course occurred in stage 2. Complete recovery of patients with moderate COVID-19 pneumonia with high mean CT score at the time of discharge requires longer time.
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http://dx.doi.org/10.3233/XST-200711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592657PMC
October 2020

Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness and Decrease Pandemic Potential.

J Virol 2020 09 15;94(19). Epub 2020 Sep 15.

The Pirbright Institute, Pirbright, United Kingdom

H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T) and 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in field isolates in 2019. To investigate the potential threat of serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability, and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly and They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor-binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in the HA protein may pose a reduced pandemic risk but remain a heightened threat for poultry. Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in virus-specific antiserum gives rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunized or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chicken embryos as well as (ii) increased acid and thermal stability but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing the indicated mutations remain a significant risk to poultry due to antigenic drift and improved fitness for poultry.
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http://dx.doi.org/10.1128/JVI.00216-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495387PMC
September 2020

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection.

Proc Natl Acad Sci U S A 2020 07 29;117(29):17204-17210. Epub 2020 Jun 29.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 100193 Beijing, China;

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.
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http://dx.doi.org/10.1073/pnas.1921186117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382246PMC
July 2020

Truncation of PA-X Contributes to Virulence and Transmission of H3N8 and H3N2 Canine Influenza Viruses in Dogs.

J Virol 2020 07 16;94(15). Epub 2020 Jul 16.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

Equine-origin H3N8 and avian-origin H3N2 canine influenza viruses (CIVs) prevalent in dogs are thought to pose a public health threat arising from intimate contact between dogs and humans. However, our understanding of CIV virulence is still limited. Influenza A virus PA-X is a fusion protein encoded in part by a +1 frameshifted open reading frame (X-ORF) in segment 3. The X-ORF can be translated in full-length (61-amino-acid) or truncated (41-amino-acid) form. Genetic analysis indicated that the X-ORFs of equine H3N8 and avian H3N2 influenza viruses encoded 61 amino acids but were truncated after introduction into dogs. To determine the effect of PA-X truncation on the biological characteristics of CIVs, we constructed four recombinant viruses on H3N8 and H3N2 CIV backgrounds bearing truncated or full-length PA-Xs. We observed that truncation of PA-X increased growth of both H3N8 and H3N2 CIVs in MDCK cells and suppressed expression from cotransfected plasmids in MDCK cells. Furthermore, truncation of PA-X enhanced viral pathogenicity in dogs, as shown by aggravated clinical symptoms and histopathological changes, increased viral replication in the respiratory system, and prolonged virus shedding. Additionally, CIVs with truncated PA-Xs were transmitted more efficiently in dogs. Global gene expression profiling of the lungs of infected dogs revealed that differentially expressed genes were mainly associated with inflammatory responses, which might contribute to the pathogenicity of PA-X-truncated CIVs. Our findings revealed that truncation of PA-X might be important for the adaptation of influenza viruses to dogs. Epidemics of equine-origin H3N8 and avian-origin H3N2 influenza viruses in canine populations are examples of successful cross-species transmission of influenza A viruses. Genetic analysis showed that the PA-X genes of equine H3N8 or avian H3N2 influenza viruses were full-length, with X-ORFs encoding 61 amino acids; however, those of equine-origin H3N8 or avian-origin H3N2 CIVs were truncated, suggesting that PA-X truncation occurred after transmission to dogs. In this study, we extended the PA-X genes of H3N8 and H3N2 CIVs and compared the biological characteristics of CIVs bearing different lengths of PA-X. We demonstrated that for both H3N8 and H3N2 viruses, truncation of PA-X increased virus yields in MDCK cells and enhanced viral replication, pathogenicity, and transmission in dogs. These results might reflect enhanced suppression of host gene expression and upregulation of genes related to inflammatory responses. Collectively, our data partially explain the conservation of truncated PA-X in CIVs.
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http://dx.doi.org/10.1128/JVI.00949-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375373PMC
July 2020

A D200N hemagglutinin substitution contributes to antigenic changes and increased replication of avian H9N2 influenza virus.

Vet Microbiol 2020 Jun 30;245:108669. Epub 2020 Apr 30.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. Electronic address:

Influenza virus hemagglutinin (HA) plays an important role in viral antigenicity, replication and host range. However, few amino acid positions in HA were reported to play multiple functions in both viral antigenicity and replication. In the present study, through analyzing the amino acid sequences of H9N2 avian influenza viruses (AIVs) isolated from China, we identified a multi-functional substitution of D200N in HA1 protein. Firstly, the substitution of D200N changed the antigenicity of H9N2 AIVs. Secondly, the D200N increased the HA cleavage efficiency and reduced acid and thermal stability of HA protein, which triggered viral-endosomal membrane fusion whereby promoted the release of viral genome into the host cytoplasm. Finally, residue 200-N increased the replication of H9N2 viruses in both chicken embryo fibroblast (CEF) cells and chicken embryonated eggs. In summary, the D200N substitution is a newly identified antigenicity and replication determinant of H9N2 AIVs, which should be paid more attention during surveillance.
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http://dx.doi.org/10.1016/j.vetmic.2020.108669DOI Listing
June 2020

An R195K Mutation in the PA-X Protein Increases the Virulence and Transmission of Influenza A Virus in Mammalian Hosts.

J Virol 2020 05 18;94(11). Epub 2020 May 18.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

In the 21st century, the emergence of H7N9 and H1N1/2009 influenza viruses, originating from animals and causing severe human infections, has prompted investigations into the genetic alterations required for cross-species transmission. We previously found that replacement of the human-origin PA gene segment in avian influenza virus (AIV) could overcome barriers to cross-species transmission. Recently, it was reported that the PA gene segment encodes both the PA protein and a second protein, PA-X. Here, we investigated the role of PA-X. We found that an H9N2 avian influenza reassortant virus bearing a human-origin H1N1/2009 PA gene was attenuated in mice after the loss of PA-X. Reverse genetics analyses of PA-X substitutions conserved in human influenza viruses indicated that R195K, K206R, and P210L substitutions conferred significantly increased replication and pathogenicity on H9N2 virus in mice and ferrets. PA-X R195K was present in all human H7N9 and H1N1/2009 viruses and predominated in human H5N6 viruses. Compared with PA-X 195R, H7N9 influenza viruses bearing PA-X 195K showed increased replication and transmission in ferrets. We further showed that PA-X 195K enhanced lung inflammatory responses, potentially due to decreased host shutoff function. A competitive transmission study in ferrets indicated that 195K provides a replicative advantage over 195R in H1N1/2009 viruses. In contrast, PA-X 195K did not influence the virulence of H9N2 AIV in chickens, suggesting that the effects of the substitution were mammal specific. Therefore, future surveillance efforts should scrutinize this region of PA-X because of its potential impact on cross-species transmission of influenza viruses. Four influenza pandemics in humans (the Spanish flu of 1918 [H1N1], the Asian flu of 1957 [H2N2], the Hong Kong flu of 1968 [H3N2], and the swine origin flu of 2009 [H1N1]) are all proposed to have been caused by avian or swine influenza viruses that acquired virulence factors through adaptive mutation or reassortment with circulating human viruses. Currently, influenza viruses circulating in animals are repeatedly transmitted to humans, posing a significant threat to public health. However, the molecular properties accounting for interspecies transmission of influenza viruses remain unclear. In the present study, we demonstrated that PA-X plays an important role in cross-species transmission of influenza viruses. At least three human-specific amino acid substitutions in PA-X dramatically enhanced the adaptation of animal influenza viruses in mammals. In particular, PA-X 195K might have contributed to cross-species transmission of H7N9, H5N6, and H1N1/2009 viruses from animal reservoirs to humans.
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http://dx.doi.org/10.1128/JVI.01817-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269435PMC
May 2020

Decreasing Arl4c expression by inhibition of AKT signal in human lung adenocarcinoma cells.

Life Sci 2020 Apr 11;246:117428. Epub 2020 Feb 11.

Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. Electronic address:

Purpose: Arl4c is overexpressed in several cancer tissues and is involved in cancer development. Nevertheless, the exact mechanism that regulates Arl4c expression in lung cancer has not been fully elucidated. The aim of this study was to investigate the regulatory mechanism of Arl4c and to explore potential chemotherapeutic drugs targeting Arl4c.

Methods: Immunohistochemistry was used to examine Arl4c expression levels in human lung adenocarcinoma cancer specimens. Protein expression was detected by western blot. Overexpression of Arl4c-Flag protein was used to detect the ubiquitination of Arl4c. A short interfering RNA against Arl4c was used for gene silencing.

Results: Arl4c was overexpressed in lung cancer tissues, and knockdown of Arl4c expression by siRNA decreased lung cancer A549 and 95-D cell proliferation. In addition, Arl4c expression was downregulated via inhibition of the AKT pathway in A549 and 95-D cells, whereas exposure to benzo (a) pyrene (a carcinogen in smoke) increased Arl4c expression in 16HBE cells via AKT activation. Finally, we found that chemotherapy drug hydroxycamptothecin (HCPT) could decrease Arl4c expression levels by inhibiting the activation of the AKT pathway in A549 and 95-D cells. Moreover, accumulation of ubiquitinated Arl4c protein was increased by HCPT and LY294002 (an AKT inhibitor) treatment whereas the proteasome inhibitor MG-132 attenuated the inhibitory effect of HCPT and LY294002 on Arl4c expression.

Conclusion: Here, we highlighted the AKT pathway as an important regulatory pathway for Arl4c expression in lung cancer cells and identified HCPT as a promising drug for lung adenocarcinoma treatment that functioned by targeting Arl4c expression.
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http://dx.doi.org/10.1016/j.lfs.2020.117428DOI Listing
April 2020

Mouse-adapted H9N2 avian influenza virus causes systemic infection in mice.

Virol J 2019 11 12;16(1):135. Epub 2019 Nov 12.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.

Background: H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages - A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage -and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses.

Finding: ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses.

Conclusions: Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.
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http://dx.doi.org/10.1186/s12985-019-1227-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852949PMC
November 2019

Characterization of fowl adenovirus serotype 4 circulating in chickens in China.

Vet Microbiol 2019 Nov 23;238:108427. Epub 2019 Sep 23.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100094, China. Electronic address:

Outbreaks of fowl adenovirus (FAdV) has resulted in huge economic losses in poultry industry in China since 2015. This study detected the pathogens from diseased chickens and determined that fowl adenovirus serotype 4 (FAdV-4) and co-infection of immunosuppressive pathogens were the causes of the outbreaks. Phylogenetic analysis results indicated that these pandemic strains originated from previously FAdV-4 predecessor in China and had obtain gene mutations that might contribute to enhanced pathogenicity of these strains. Compared with early strains, the pathogenicity of novel FAdV-4 strains significantly increased, which led to systemic infections and injuries to multiple organs in the infected chickens. Our study could provide useful information for understanding of the FAdV-4 and favorable theory basis for clinical prevention and control of the disease.
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http://dx.doi.org/10.1016/j.vetmic.2019.108427DOI Listing
November 2019

Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling.

PLoS Pathog 2019 10 4;15(10):e1008062. Epub 2019 Oct 4.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infection. Using a PGRN knockdown assay and PGRN-deficient mice model, we demonstrated that influenza virus-inducing PGRN negatively regulated type I IFNs production by inhibiting the activation of NF-κB and IRF3 signaling. Furthermore, we showed that PGRN directly interacted with NF-κB essential modulator (NEMO) via its Grn CDE domains. We also verified that PGRN recruited A20 to deubiquitinate K63-linked polyubiquitin chains on NEMO at K264. In addition, we found that macrophage played a major source of PGRN during influenza virus infection, and PGRN neutralizing antibodies could protect against influenza virus-induced lethality in mice. Our data identify a PGRN-mediated IFN evasion pathway exploited by influenza virus with implication in antiviral applications. These findings also provide insights into the functions and crosstalk of PGRN in innate immunity.
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http://dx.doi.org/10.1371/journal.ppat.1008062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795447PMC
October 2019

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-β induction in human cells.

J Gen Virol 2019 09 15;100(9):1273-1281. Epub 2019 Jul 15.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-β induction than that of its predecessor PB2-292I. IFN-β attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-β. In the mouse model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.
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http://dx.doi.org/10.1099/jgv.0.001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414430PMC
September 2019

Infection of chicken H9N2 influenza viruses in different species of domestic ducks.

Vet Microbiol 2019 Jun 12;233:1-4. Epub 2019 Apr 12.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100193, China. Electronic address:

Domestic ducks are considered as the interface between wild aquatic birds and terrestrial poultry and play an important role in the transmission and evolution of avian influenza viruses (AIVs). However, the infectivity of H9N2 AIVs in different domestic duck species has not been systematically evaluated. Here we investigated the infectivity of various genotypes of chicken H9N2 AIVs in Pekin duck (Anas Platyrhynchos), Mallard duck (Anas Platyrhynchos) and Muscovy duck (Cairina Moschata) through intranasal inoculation. We found that Pekin ducks and Mallard ducks were generally resistant to chicken H9N2 virus infection, while Muscovy ducks were relatively susceptible to H9N2 AIVs. All the tested viruses were isolated from oropharynx, trachea and lung tissues of Muscovy ducks. Additionally, genotype 57 (G57) H9N2 AIVs, which was predominant in chickens since 2010, showed increased virus replication in this duck species, indicating an improved interspecies transmission ability of recent H9N2 viruses from chickens to ducks. Our results demonstrated the role of Muscovy ducks in the ecology of H9N2 AIVs. More attentions should be paid to this host during viral surveillances. Additionally, inactivated H9N2 vaccine may be unnecessarily used in Pekin and Mallard ducks.
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http://dx.doi.org/10.1016/j.vetmic.2019.04.018DOI Listing
June 2019

H3N2 canine influenza virus and Enterococcus faecalis coinfection in dogs in China.

BMC Vet Res 2019 Apr 11;15(1):113. Epub 2019 Apr 11.

College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing, 100193, China.

Background: In May 2017, 17 dogs in a German Shepherd breeding kennel in northern China developed respiratory clinical signs. The owner treated the dogs with an intravenous injection of Shuang-Huang-lian, a traditional Chinese medicine, and azithromycin. The respiratory signs improved 3 days post-treatment, however, cysts were observed in the necks of eight dogs, and three of them died in the following 2 days.

Case Presentation: Quantitative real-time PCR was used to detect canine influenza virus (CIV). All of the dogs in this kennel were positive and the remaining 14 dogs had seroconverted. Two of the dogs were taken to the China Agricultural University Veterinary Teaching Hospital for further examination. Two strains of influenza virus (A/canine/Beijing/0512-133/2017 and A/canine/Beijing/0512-137/2017) isolated from the nasal swabs of these dogs were sequenced and identified as avian-origin H3N2 CIV. For the two dogs admitted to the hospital, hematology showed mild inflammation and radiograph results indicated pneumonia. Cyst fluid was plated for bacterial culture and bacterial 16 s rRNA gene PCR was performed, followed by Sanger sequencing. The results indicated an Enterococcus faecalis infection. Antimicrobial susceptibility tests were performed and dogs were treated with enrofloxacin. All 14 remaining dogs recovered within 16 days.

Conclusions: Coinfection of H3N2 CIV and Enterococcus faecalis was detected in dogs, which has not been reported previously. Our results highlight that CIV infection might promote the secondary infection of opportunistic bacteria and cause more severe and complicated clinical outcomes.
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http://dx.doi.org/10.1186/s12917-019-1832-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460796PMC
April 2019

Mitigating the Interfacial Degradation in Cathodes for High-Performance Oxide-Based Solid-State Lithium Batteries.

ACS Appl Mater Interfaces 2019 Feb 29;11(5):4954-4961. Epub 2019 Jan 29.

Department of Mechanical and Materials Engineering , University of Western Ontario , London , Ontario N6A 5B9 , Canada.

Solid-state lithium batteries (SSLBs) are the promising next-generation energy storage systems because of their attractive advantages in terms of energy density and safety. However, the interfacial engineering and battery building are of huge challenges, especially for stiff oxide-based electrolytes. Herein, we construct SSLBs by a cosintering method using LiBO as a sintering agent to bind the cathode materials LiNiMnCoO (NMC) and solid-state electrolytes LiLaZrTaO. Small NMC primary particles are compared with large secondary particles to study the effects on interfacial adhesion, mechanical retention, internal resistance evolution, and electrochemical performance. Our results reveal that the interfacial resistance decreases during charging and increases during discharging, resulting in an overall increase in the interfacial resistance after one cycle. The main reason is attributed to the microcracks induced by the volumetric changes of NMC during the electrochemical process. The mechanical degradations at the interfaces accumulated upon cycling can cause capacity decay and low Coulombic efficiency. The SSLB constructed from small NMC primary particles shows regulation of particle distribution, mitigation in local volumetric change, and alleviation in mechanical degradation at the interfaces, leading to smaller resistance change and better electrochemical performance. The findings shed lights on designing SSLBs with good mechanical retention and electrochemical performance.
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http://dx.doi.org/10.1021/acsami.8b17881DOI Listing
February 2019

Recombinant turkey herpesvirus expressing H9 hemagglutinin providing protection against H9N2 avian influenza.

Virology 2019 03 4;529:7-15. Epub 2019 Jan 4.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

H9N2 avian influenza viruses (AIVs) were prevailing in chickens, causing great economic losses and public health threats. In this study, turkey herpesviruses (HVT) was cloned as an infectious bacterial artificial chromosomes (BAC). Recombinant HVT (rHVT-H9) containing hemagglutinin (HA) gene from H9N2 virus were constructed via galactokinase (galK) selection and clustered regularly interspaced short palindromic repeats/associated 9 (CRISPR/Cas9) gene editing system. The recombinant rHVT-H9 showed no difference with parent HVT in plague morphology and virus replication kinetics. H9 protein expression of rHVT-H9 could be detected by western blot and indirect immunofluorescence assay (IFA) in vitro and in vivo. Immunization with rHVT-H9 could induce robust humoral and cellular immunity in chickens. In the challenge study, no chicken shed H9N2 virus from oropharynx and cloaca, and no H9N2 virus was found in viscera in vaccination groups. The result suggests that rHVT-H9 provides effective protection against H9N2 AIV in chickens.
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http://dx.doi.org/10.1016/j.virol.2019.01.004DOI Listing
March 2019

A Novel Organic "Polyurea" Thin Film for Ultralong-Life Lithium-Metal Anodes via Molecular-Layer Deposition.

Adv Mater 2019 Jan 5;31(4):e1806541. Epub 2018 Dec 5.

Department of Mechanical and Materials Engineering, University of Western Ontario, London, Ontario, N6A 5B9, Canada.

Metallic Li is considered as one of the most promising anode materials for next-generation batteries due to its high theoretical capacity and low electrochemical potential. However, its commercialization has been impeded by the severe safety issues associated with Li-dendrite growth. Non-uniform Li-ion flux on the Li-metal surface and the formation of unstable solid electrolyte interphase (SEI) during the Li plating/stripping process lead to the growth of dendritic and mossy Li structures that deteriorate the cycling performance and can cause short-circuits. Herein, an ultrathin polymer film of "polyurea" as an artificial SEI layer for Li-metal anodes via molecular-layer deposition (MLD) is reported. Abundant polar groups in polyurea can redistribute the Li-ion flux and lead to a uniform plating/stripping process. As a result, the dendritic Li growth during cycling is efficiently suppressed and the life span is significantly prolonged (three times longer than bare Li at a current density of 3 mA cm ). Moreover, the detailed surface and interfacial chemistry of Li metal are studied comprehensively. This work provides deep insights into the design of artificial SEI coatings for Li metal and progress toward realizing next-generation Li-metal batteries.
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http://dx.doi.org/10.1002/adma.201806541DOI Listing
January 2019