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Since the first human infection reported in 2013, H7N9 avian influenza virus (AIV) has been regarded as a serious threat to human health. In this study, we sought to identify the virulence determinant of the H7N9 virus in mammalian hosts. By comparing the virulence of the SH/4664 H7N9 virus, a non-virulent H9N2 virus, and various H7N9-H9N2 hybrid viruses in infected mice, we first pinpointed PB2 as the primary viral factor accounting for the difference between H7N9 and H9N2 in mammalian virulence. We further analyzed the in vivo effects of individually mutating H7N9 PB2 residues different from the closely related H9N2 virus and consequently found residue 473, alongside the well-known residue 627, to be critical for the virulence of the H7N9 virus in mice and the activity of its reconstituted viral polymerase in mammalian cells. The importance of PB2-473 was further strengthened by studying reverse H7N9 substitutions in the H9N2 background. Finally, we surprisingly found that species-specific usage of ANP32A, a family member of host factors connecting with the PB2-627 polymorphism, mediates the contribution of PB2 473 residue to the mammalian adaption of AIV polymerase, as the attenuating effect of PB2 M473T on the viral polymerase activity and viral growth of the H7N9 virus could be efficiently complemented by co-expression of chicken ANP32A but not mouse ANP32A and ANP32B. Together, our studies uncovered the PB2 473 residue as a novel viral host range determinant of AIVs via species-specific co-opting of the ANP32 host factor to support viral polymerase activity.IMPORTANCEThe H7N9 avian influenza virus has been considered to have the potential to cause the next pandemic since the first case of human infection reported in 2013. In this study, we identified PB2 residue 473 as a new determinant of mouse virulence and mammalian adaptation of the viral polymerase of the H7N9 virus and its non-pathogenic H9N2 counterparts. We further demonstrated that the variation in PB2-473 is functionally linked to differential co-opting of the host ANP32A protein in supporting viral polymerase activity, which is analogous to the well-known PB2-627 polymorphism, albeit the two PB2 positions are spatially distant. By providing new mechanistic insight into the PB2-mediated host range determination of influenza A viruses, our study implicated the potential existence of multiple PB2-ANP32 interfaces that could be targets for developing new antivirals against the H7N9 virus as well as other mammalian-adapted influenza viruses.

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Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.

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INTRODUCTION: The principal voltage-gated Na+ channel, NaV1.5 governs heart excitability and conduction. NaV1.5 dysregulation is responsible for ventricular arrhythmias and subsequent sudden cardiac death (SCD) in post-infarct hearts. The transcription factor Meis1 performs a significant role in determining differentiation fate and regenerative capability of cardiomyocytes. However, the functions of Meis1 in ischemic arrhythmias following myocardial infarction (MI) are still largely undefined. OBJECTIVES: Here we aimed to study whether Meis1 could act as a key regulator to mediate cardiac Na+ channel and its underlying mechanisms. METHODS: Heart-specific Meis1 overexpression was established by AAV9 virus injection in C57BL/6 mice. The QRS duration, the incidence of ventricular arrhythmias and cardiac conduction velocity were evaluated by ECG, programmed electrical stimulation and optical mapping techniques respectively. The conventional patch clamp technique was performed to explore the INa characteristics of isolated mouse ventricular myocytes. In vitro, Meis1 was also overexpressed in hypoxic-treated neonatal cardiomyocytes. The analysis of immunoblotting and immunofluorescence were used to detect the changes in the expression of NaV1.5 in each group. RESULTS: We found that forced expression of Meis1 rescued the prolongation of QRS complex, produced anti-arrhythmic activity and improved epicardial conduction velocity in infarcted mouse hearts. In terms of mechanisms, cardiac electrophysiological changes of MI mice can be ameliorated by the recovery of Meis1, which is characterized by the restoration of INa current density and NaV1.5 expression level of cardiomyocytes in the marginal zone of MI mouse hearts. Furthermore, in vitro studies showed that Meis1 was also able to rescue hypoxia-induced decreased expression and dysfunction of NaV1.5 in ventricular myocytes. We further revealed that E3 ubiquitin ligase CDC20 led to the ubiquitination and degradation of Meis1, which blocked the transcriptional regulation of SCN5A by Meis1 and ultimately led to the electrophysiological remodeling in ischemic-hypoxic cardiomyocytes. CONCLUSION: CDC20 mediates ubiquitination of Meis1 to govern the transcription of SCN5A and cardiac electrical conduction in mouse cardiomyocytes. This finding uncovers a new mechanism of NaV1.5 dysregulation in infarcted heart, and provides new therapeutic strategies for malignant arrhythmias and sudden cardiac death following MI.

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Lead ions are one of many common environmental pollutants, that can cause posing a serious threat to people's health, thus, their efficient and sensitive detection is important. We propose a cascade signal amplification sensor using a DNAzyme-based strand displacement amplification (SDA) and hybridization chain reaction (HCR) for the high-sensitivity detection of Pb2+. In the demonstrated sensor system, the target metal ion can activate DNAzyme to cause a strand displacement reaction. Under the synergistic action of polymerase and nickase, large numbers of DNA strands are generated that can initiate HCR. The subsequent HCR can restore the fluorescence intensity of the FAM quenched for the fluorescence resonance energy transfer effect, which exhibits a strong fluorescence signal. The DNAzyme-based sensor allowed the detection of Pb2+ down to 16.8 pM and resulted in a good dynamic line relationship ranging from 50 pM to 500 nM, and the biosensor also showed good selectivity. Furthermore, we confirmed that the proposed sensor can still detect lead ions in complex environments such as lake water, milk, and serum. We believe these findings will provide new ideas for the detection of toxic elements ions in the environment and food.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), binds to host receptor angiotensin-converting enzyme 2 (ACE2) through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. However, the expression of ACE2 is extremely low in a variety of human tissues, especially in the airways. Thus, other coreceptors and/or cofactors on the surface of host cells may contribute to SARS-CoV-2 infection. Here, we identified nonmuscle myosin heavy chain IIA (MYH9) as an important host factor for SARS-CoV-2 infection of human pulmonary cells by using APEX2 proximity-labeling techniques. Genetic ablation of MYH9 significantly reduced SARS-CoV-2 pseudovirus infection in wild type (WT) A549 and Calu-3 cells, and overexpression of MYH9 enhanced the pseudovirus infection in WT A549 and H1299 cells. MYH9 was colocalized with the SARS-CoV-2 S and directly interacted with SARS-CoV-2 S through the S2 subunit and S1-NTD (N-terminal domain) by its C-terminal domain (designated as PRA). Further experiments suggested that endosomal or myosin inhibitors effectively block the viral entry of SARS-CoV-2 into PRA-A549 cells, while transmembrane protease serine 2 (TMPRSS2) and cathepsin B and L (CatB/L) inhibitors do not, indicating that MYH9 promotes SARS-CoV-2 endocytosis and bypasses TMPRSS2 and CatB/L pathway. Finally, we demonstrated that loss of MYH9 reduces authentic SARS-CoV-2 infection in Calu-3, ACE2-A549, and ACE2-H1299 cells. Together, our results suggest that MYH9 is a candidate host factor for SARS-CoV-2, which mediates the virus entering host cells by endocytosis in an ACE2-dependent manner, and may serve as a potential target for future clinical intervention strategies.

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One big threat from influenza A viruses (IAVs) is that novel viruses emerge from mutation alongside reassortment. Some of them have gained the capability to transmit into human from the avian reservoir. Understanding the molecular events and the involved factors in breaking the cross-species barrier holds important implication for the surveillance and prevention of potential influenza outbreaks. In this review, we summarize recent progresses, including several ground-breaking findings, in how the interaction between host and viral factors, exemplified by the PB2 subunit of the influenza virus RNA polymerase co-opting host ANP32 protein to facilitate transcription and replication of the viral genome, shapes the evolution of IAVs from host specificity to cross-species infection.

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Infarcted myocardium is predisposed to cause lethal ventricular arrhythmias that remain the main cause of death in patients suffering myocardial ischemia. Liver-derived fibroblast growth factor 21 (FGF21) is an endocrine regulator, which exerts metabolic actions by favoring glucose and lipids metabolism. Emerging evidence has shown a beneficial effect of FGF21 on cardiovascular diseases, but the role of FGF21 on ventricular arrhythmias following myocardial infarction (MI) in humans has never been addressed. This study was conducted to investigate the pharmacological effects of FGF21 on cardiomyocytes after MI in humans. Patients with arrhythmia in acute MI and healthy volunteers were enrolled in this study. Serum samples were collected from these subjects on day 1 and days 7-10 after the onset of MI for measuring FGF21 levels using ELISA. Here, we found that the serum level of FGF21 was significantly increased on day 1 after the onset of MI and it returned to normal on days 7-10, relative to the Control samples. In order to clarify the regulation of FGF21 on arrhythmia, two kinds of arrhythmia animal models were established in this study, including ischemic arrhythmia model (MI rat model) and nonischemic arrhythmia model (ouabain-induced guinea pig arrhythmia model). The results showed that the incidence and duration time of ischemic arrhythmias in rhbFGF21-treated MI rats were significantly reduced at different time point after MI compared with normal saline-treated MI rats. Moreover, the onset of the first ventricular arrhythmias was delayed and the numbers of VF and maintenance were attenuated by FGF21 compared to the rhbFGF21-untreated group in the ouabain model. Consistently, in vitro study also demonstrated that FGF21 administration was able to shorten action potential duration (APD) in hydrogen peroxide-treated AC16 cells. Mechanically, FGF21 can ameliorate the electrophysiological function of AC16 cells, which is characterized by rescuing the expression and dysfunction of cardiac sodium current (I Na) and inward rectifier potassium (I k1) in AC16 cells induced by hydrogen peroxide. Moreover, the restorative effect of FGF21 on NaV1.5 and Kir2.1 was eliminated when FGF receptors were inhibited. Collectively, FGF21 has the potential role of ameliorating transmembrane ion channels remodeling through the NaV1.5/Kir2.1 pathway by FGF receptors and thus reducing life-threatening postinfarcted arrhythmias, which provides new strategies for antiarrhythmic therapy in clinics.

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Myocardial fibrosis in post-myocardial infarction is a self-healing process of the myocardium, making ventricular remodelling difficult to reverse and develop continuously. Fibroblast growth factor 21 (FGF21) plays an essential role in cardiovascular and metabolic diseases. However, the effect and mechanism of FGF21 action on cardiac inflammation and fibrosis caused by myocardial injury have rarely been reported. Adult male Sprague-Dawley rats administered with or without recombinant human basic FGF21 (rhbFGF21) were assessed using echocardiography and haematoxylin-eosin and Masson's trichrome staining to determine the cardiac function and cardiac inflammation and fibrosis levels. FGF21 might improve cardiac remodelling, as characterised by a decrease in the expression of a series of inflammatory and fibrosis-related factors. Moreover, when FGF receptors (FGFRs) were blocked, the effects of FGF21 disappeared. Mechanistically, we found that oxidative stress induced the downregulation of early growth response protein 1 (EGR1), which contributed to inflammatory factors and fibrosis reduction in cardiomyocytes treated with H2O2. Collectively, FGF21 effectively suppressed the inflammation and fibrosis in post-infarcted hearts by regulating FGFR-EGR1.

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Coronavirus disease 2019 (COVID-19) pneumonia is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly become a global public health concern. As the new type of betacoronavirus, SARS-CoV-2 can spread across species and between populations and has a greater risk of transmission than other coronaviruses. To control the spread of SARS-CoV-2, it is vital to have a rapid and effective means of diagnosing asymptomatic SARS-CoV-2-positive individuals and patients with COVID-19, an early isolation protocol for infected individuals, and effective treatments for patients with COVID-19 pneumonia. In this review, we will summarize the novel diagnostic tools that are currently available for coronavirus, including imaging examinations and laboratory medicine by next-generation sequencing (NGS), real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) analysis, immunoassay for COVID-19, cytokine and T cell immunoassays, biochemistry and microbiology laboratory parameters in the blood of the patients with COVID-19, and a field-effect transistor-based biosensor of COVID-19. Specifically, we will discuss the effective detection rate and assay time for the rRT-PCR analysis of SARS-CoV-2 and the sensitivity and specificity of different antibody detection methods, such as colloidal gold and ELISA using specimen sources obtained from the respiratory tract, peripheral serum or plasma, and other bodily fluids. Such diagnostics will help scientists and clinicians develop appropriate strategies to combat COVID-19.

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MicroRNAs (miRNAs) play a significant role in diverse biological processes. The abnormal expression of miRNAs is related to the development of cancers and various diseases. It is of great importance to sensitively and accurately detect miRNAs for early disease diagnosis and treatment. Here, a new fluorescence strategy was initially proposed for the enzyme-free sensing of let-7a by combining the strand displacement reaction (SDR) with the hybridization chain reaction (HCR). The sensor was successfully applied to the detection of the let-7a gene with a wide linear range from 25 pM to 250 nM and a limit of detection (LOD) of 9.01 pM. The fluorescence intensity has a good linear relationship with the logarithm of the target concentration. In addition, the biosensor allowed for the highly sensitive detection of the target genes even in complex human serum samples. With simple operation yet improved detection capability for let-7a, the developed fluorescent biosensor thus shows great potential for early clinical diagnosis as well as biological research.

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Zika virus (ZIKV) infection during pregnancy causes intrauterine growth defects and microcephaly, but knowledge of the mechanism through which ZIKV infects and replicates in the placenta remains elusive. Here, we found that ALPP, an alkaline phosphatase expressed primarily in placental tissue, promoted ZIKV infection in both human placental trophoblasts and astrocytoma cells. ALPP bound to ZIKV structural and nonstructural proteins and thereby prevented their proteasome-mediated degradation and enhanced viral RNA replication and virion biogenesis. In addition, the function of ALPP in ZIKV infection depends on its phosphatase activity. Furthermore, we demonstrated that ALPP was stabilized through interactions with BIP, which is the endoplasmic reticulum (ER)-resident heat shock protein 70 chaperone. The chaperone activity of BIP promoted ZIKV infection and mediated the interaction between ALPP and ZIKV proteins. Collectively, our findings reveal a previously unrecognized mechanism through which ALPP facilitates ZIKV replication by coordinating with the BIP protein.IMPORTANCE ZIKV is a recently emerged mosquito-borne flavivirus that can cause devastating congenital Zika syndrome in pregnant women and Guillain-Barré syndrome in adults, but how ZIKV specifically targets the placenta is not well understood. Here, we identified an alkaline phosphatase (ALPP) that is expressed primarily in placental tissue and promotes ZIKV infection by colocalizing with ZIKV proteins and preventing their proteasome-mediated degradation. The phosphatase activity of ALPP could be required for optimal ZIKV infection, and ALPP is stabilized by BIP via its chaperone activity. This report provides novel insights into host factors required for ZIKV infection, which potentially has implications for ZIKV infection of the placenta.

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The interaction between Tb(IV)-NR complex and herring sperm DNA in buffer solution of Tris-HCl was investigated with the use of acridine orange(AO) as a spectral probe. The binding modes and other information were provided by the UV-spectrophotometry and fluorescence spectroscopy. The thermodynamic functions expressed that the binding constants of Tb(IV)-NR complex with DNA was Kθ298.15K = 4.03 × 105 L·mol-1, Kθ310.15K =1.30 × 107 L·mol-1, and the ΔrGθ m 298.15 K＝-3.20 × 104 J·mol-1. The scatchard equation suggested that the interaction mode between Tb(IV)-NR complex and herring sperm DNA is electrostatic and weak intercalation bindings. FTIR spectroscopy results also indicate that there is a specific interaction between the Tb(IV)-NR complex and the A and G bases of DNA.

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Accurate and sensitive detection of the Pax-5a gene is of great importance in the early diagnosis and prognosis of acute leukaemia. Herein, a label-free electrochemical sensing system was proposed for the detection of the acute leukaemia Pax-5a gene based on enzyme-assisted signal amplification to generate abundant G-quadruplex/hemin DNAzyme. The presence of Pax-5a can open the hairpin probe (HP), which acts as a template. Under the action of the restriction enzymes Nt.BbvCI and Klenow fragment polymerase, the target gene Pax-5a is cycled to open the HP; On the other hand, a large number of G-quadruplex sequences are produced. The resulting G-quadruplex sequence is capable of forming the G-quadruplex/hemin complex on the surface of the electrode in the presence of hemin. The ultrasensitive label-free electrochemical detection of Pax-5a can be realized via the G-quadruplex/hemin complex-catalysed reduction of H2O2, and the detection limit was estimated to be as low as 4.6 fM. In addition, the biosensor has good specificity and stability, and also has excellent detection capabilities in a complex substrate environment. Therefore, the sensor shows great potential in bioanalysis and clinical diagnosis.

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A fluorometric assay is described for the tumor suppressor gene p53. The method is based on strand displacement amplification on gold nanoparticles (GNPs). A FAM-labeled hairpin probe (HPP) is used that can hybridize to the GNP-confined linker strand, and the green fluorescence of the FAM label is quenched by the GNPs. In the presence of the p53 gene, it will hybridize with the HPP. This leads to fluorescence recovery. The primer then hybridizes with the opened HPP and induces the polymerization/displacement reactions. As a result, the hybridized p53 gene is released and, in turn, hybridizes with another HPP on the surface of the GNPs. This triggers the next round of hybridization/enzymatic polymerization/displacement reactions. This results in efficient strand displacement amplification and generates a substantially amplified signal. The method is referred to as GNP-HPP because it involves the use of GNPs and a HPP. The method allows the target DNA (p53) to be quantified down to 1.6 pM concentrations with a linear response in the 5 pM to 1 nM concentration range. In addition, mutant p53 genes can be easily distinguished from the wild-type gene. The method is highly sensitive, selective, and has a low background signal. Graphical abstract Schematic presentation of a chain hybridization signal amplification system (GNP-HPP) based on the use of gold nanoparticles (GNP) as a quenching source for the tumor suppressor gene p53 detection. The hairpin probe (HPP) having a 5'-end modified fluorophore was used as a signalling probe.

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Avian H7N9 subtype influenza virus infects human with high case-fatality rate since it emerged in 2013. Although the vaccination has been rapidly used in poultry due to the emergence of highly pathogenic strain, this virus remains prevalent in this region. Thus, rapid diagnosis both in poultry and human clinic is critically important for the control and prevention of H7N9 infection. In this study, a batch of H7 subtype-specific monoclonal antibodies (mAbs) were developed and a pair of mAb, 2B6, and 5E9 were used to establish a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to quantify H7 protein and detect influenza A virus baring H7 subtype HA. The lowest detection limit for the recombinant H7 protein was 10 ng/mL and 0.5 HAU/50 µL of A/Guangdong/17SF003/2016(H7N9), 2 HAU/50 µL of A/Netherlands/219/2003(H7N7) and A/Anhui/1/2013(H7N9) for live virus, respectively. The ELISA could not only detect the prevailing H7N9 virus, but also antigenic drift H7 subtype viruses, showing excellent sensitivity and high specificity. Hence, it could serve as a valuable approach to diagnose H7 subtype virus which showed great potential to cause pandemic, as well as antigen quantification.

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Novel influenza A virus (H10N8) infected human with fatality in China during 2013-2014. It is important to detect such nonprevalent subtype influenza A virus in clinic and regular surveillance in the early stage for effective control and prevention from the potential pandemic. Unavailability of convenient rapid diagnosis for this subtype virus in resources-limited setting is an obstacle for timely recognizing human case. In the present study, a panel of mouse H10 specific monoclonal antibodies (mAbs) was generated, two of which were used to develop a sandwich enzyme-linked immunosorbent assay (ELISA) for detecting the hemagglutinin of avian influenza A (H10N8) virus. ELISA results showed high sensitivity with the lowest detection limit of 0.5HAU/50 µL for live virus, which laid a foundation for clinic use as a promising diagnostic methodology.

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Live poultry markets (LPM) are one of the most important sources of human infection with avian influenza virus (AIV). During our routine surveillance of AIV, we identified an H9N6 virus (JX-H9N6) in a LPM in Nanchang city, Jiangxi Province, China. Using Bayesian coalescent analysis, it was predicted that JX-H9N6 had originated from a reassortment event between H9N2 and H6N6 AIVs in early 2014, instead of being derived from an H9N6 virus reported previously. Mutations in HA, PB1, PA, M, and NS protein, which could increase mammalian transmission and virulence, were also detected. Currently, both H9N2 and H6N6 AIVs are widely distributed in poultry and contribute to the generation of novel reassortant viruses causing human infection. Our findings highlight the importance of enhanced surveillance in birds for early prediction of human infections.

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BACKGROUND: Recently, avian influenza virus has caused repeated worldwide outbreaks in humans. Live Poultry Markets (LPMs) play an important role in the circulation and reassortment of novel Avian Influenza Virus (AIVs). Aerosol transmission is one of the most important pathways for influenza virus to spread among poultry, from poultry to mammals, and among mammals. METHODS: In this study, air samples were collected from LPMs in Nanchang city between April 2014 and March 2015 to investigate possible aerosol transmission of AIVs. Air samples were detected for Flu A by Real-Time Reverse Transcription-Polymerase Chain Reaction (RRT-PCR). If samples were positive for Flu A, they were inoculated into 9- to 10-day-old specific-pathogen-free embryonated eggs. If the result was positive, the whole genome of the virus was sequenced by MiSeq. Phylogenetic trees of all 8 segments were constructed using MEGA 6.05 software. RESULTS: To investigate the possible aerosol transmission of AIVs, 807 air samples were collected from LPMs in Nanchang city between April 2014 and March 2015. Based on RRT-PCR results, 275 samples (34.1%) were Flu A positive, and one virus was successfully isolated with embryonated eggs. The virus shared high nucleotide homology with H9N2 AIVs from South China. CONCLUSIONS: Our study provides further evidence that the air in LPMs can be contaminated by influenza viruses and their nucleic acids, and this should be considered when choosing and evaluating disinfection strategies in LPMs, such as regular air disinfection. Aerosolized viruses such as the H9N2 virus detected in this study can increase the risk of human infection when people are exposed in LPMs.

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Previous observational studies have reported protective effects of hand-washing in reducing upper respiratory infections, little is known about the associations between hand-washing and good hygienic habits and seasonal influenza infection. We conducted a case-control study to test whether the risk of influenza transmission associated with self-reported hand-washing and unhealthy hygienic habits among residents in Fujian Province, southeastern China.Laboratory confirmed seasonal influenza cases were consecutively included in the study as case-patients (n = 100). For each case, we selected 1 control person matched for age and city of residence. Telephone interview was used to collect information on hand-washing and hygienic habits. The associations were analyzed using conditional logistic regression. Compared with the poorest hand-washing score of 0 to 3, odds ratios of influenza infection decreased progressively from 0.26 to 0.029 as hand-washing score increased from 4 to the maximum of 9 (P < 0.001). Compared with the poorest hygienic habit score of 0 to 2, odds ratios of influenza infection decreased from 0.10 to 0.015 with improving score of hygienic habits (P < 0.001). Independent protective factors against influenza infection included good hygienic habits, higher hand-washing score, providing soap or hand cleaner beside the hand-washing basin, and receiving influenza vaccine. Regular hand-washing and good hygienic habits were associated with a reduced risk of influenza infection. These findings support the general recommendation for nonpharmaceutical interventions against influenza.

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Three human cases of H10N8 virus infections were initially reported in China in late 2013 and early 2014, two of which were fatal. This was the first time the H10N8 subtype has been detected in humans, and the pathogenicity of this virus remains under characterized. We first assessed its pathogenicity by infecting BALB/c mice with two H10N8 isolates, A/Jiangxi-Donghu/346-1/2013 and A/Chicken/Jiangxi/102/2013. The human isolate (H346-1) demonstrated stronger capability of replication and induced higher cytokine response in vivo than the chicken isolate (C102). In addition, H346-1 was fatal to mice, while all mice (N = 14) in C102-infected group survived during the infection course without weight loss. We hypothesized that the 627K mutation in the PB2 gene (PB2-K627) in H346-1 was associated with high pathogenicity in mice. Taken together, this study based on mouse model provides some insight into understanding the pathogenicity of the emerging viruses in mammals.

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