SQSTM1 downregulates avian metapneumovirus subgroup C replication via mediating selective autophagic degradation of viral M2-2 protein.

Avian metapneumovirus subgroup C (aMPV/C), an important pathogen causing acute respiratory infection in chickens and turkeys, contributes to substantial economic losses in the poultry industry worldwide. aMPV/C has been reported to induce autophagy, which is beneficial to virus replication. Sequestosome 1 (SQSTM1/P62), a selective autophagic receptor, plays a crucial role in viral replication by clearing ubiquitinated proteins. However, the relationship between SQSTM1-mediated selective autophagy and aMPV/C replication is unclear. In this study, we found that the expression of SQSTM1 negatively regulates aMPV/C replication by reducing viral protein expression and viral titers. Further studies revealed that the interaction between SQSTM1 and aMPV/C M2-2 protein is mediated via the Phox and Bem1 (PB1) domain of the former, which recognizes a ubiquitinated lysine at position 67 of the M2-2 protein, and finally degrades M2-2 via SQSTM1-mediated selective autophagy. Collectively, our results reveal that SQSTM1 degrades M2-2 via a process of selective autophagy to suppress aMPV/C replication, thereby providing novel insights for the prevention and control of aMPV/C infection.IMPORTANCEThe selective autophagy plays an important role in virus replication. As an emerging pathogen of avian respiratory virus, clarification of the effect of SQSTM1, a selective autophagic receptor, on aMPV/C replication in host cells enables us to better understand the viral pathogenesis. Previous study showed that aMPV/C infection reduced the SQSTM1 expression accompanied by virus proliferation, but the specific regulatory mechanism between them was still unclear. In this study, we demonstrated for the first time that SQSTM1 recognizes the 67th amino acid of M2-2 protein by the interaction between them, followed by M2-2 degradation via the SQSTM1-mediated selective autophagy, and finally inhibits aMPV/C replication. This information supplies the mechanism by which SQSTM1 negatively regulates viral replication, and provides new insights for preventing and controlling aMPV/C infection.

Ubiquitination-dependent degradation of nucleolin mediated by porcine circovirus type 3 capsid protein.

IMPORTANCE: Porcine circovirus type 3 (PCV3) is an emerging pathogen that causes multisystem disease in pigs and poses a severe threat to the swine industry. However, the mechanisms of how PCV3 uses host proteins to regulate its own life cycle are not well understood. In this study, we found that PCV3 capsid protein interacts with nucleolin and degrades it. Degradation of nucleolin by the PCV3 capsid protein requires recruitment of the enzyme RNF34, which is transported to the nucleolus from the cytoplasm in the presence of the PCV3 capsid protein. Nucleolin also decreases PCV3 replication by promoting the release of interferon ß. These findings clarify the mechanism by which nucleolin modulates PCV3 replication in cells, thereby facilitating to provide an important strategy for preventing and controlling PCV3 infection.

Circular RNA hsa_circ_0050386 suppresses non-small cell lung cancer progression via regulating the SRSF3/FN1 axis.

BACKGROUND: Lung cancer is the most prevalent cancer worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all cases. Circular RNAs(circRNA) play crucial roles in regulating the progression of lung cancer. Despite the identification of a large number of circRNAs, their expression patterns, functions, and mechanisms of action in NSCLC development remain unclear.This study aims to investigate the transcriptional expressions, functions, and potential mechanisms of circRNA hsa_circ_0050386 in NSCLC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for the analysis of hsa_circ_0050386 expression. Cell proliferation was detected using the IncuCyte Live Cell Analysis System and clone formation assays. Migration and invasion of NSCLC cells were evaluated through Transwell assays. Flow cytometry was performed to assay cell cycle and apoptosis. Western blot was used to investigate protein expression. Protein binding analysis was conducted by employing pull-down assays, RNA immunoprecipitation (RIP), and mass spectrometry. The role of hsa_circ_0050386 in vivo was evaluated through the use of a xenograft model. RESULTS: The study discovered that hsa_circ_0050386 displayed lower expression levels in NSCLC tissues when compared to adjacent normal tissues. Patients exhibiting lower levels of hsa_circ_0050386 expression exhibited an inverse correlation with the Clinical Stage, T-stage, and M-stage of NSCLC. Functionally, hsa_circ_0050386 suppressed the proliferation and invasion of NSCLC cells both in vitro and in vivo. A comprehensive examination exposed the interaction between hsa_circ_0050386 and RNA binding protein Serine and arginine-rich splicing factor 3 (SRSF3), resulting in the down-regulation of Fibronectin 1 (FN1) expression, which inhibits the progression of NSCLC. CONCLUSIONS: Our study shows that hsa_circ_0050386 suppresses the malignant biological behavior of NSCLC cells by down-regulating the expression of FN1, and may serve as a potential biomarker and therapeutic target for NSCLC treatment.

A Receptor Integrin ß1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif.

Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin ß1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host factor benefiting aMPV/C attachment or internalization. The transient expression of avian ITGB1-rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) is susceptible to aMPV/C infection. Kinetic replication of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to efficiently infect human non-small cell lung cancer (A549) cells. This may be a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells, facilitating aMPV/C infection.

Anionic Chemistry Modulation Enabled Environmental Self-Charging Aqueous Zinc Batteries: The Case of Carbonate Ions.

Anionic chemistry modulation represents a promising avenue to enhance the electrochemical performance and unlock versatile applications in cutting-edge energy storage devices. Herein, we propose a methodology that involves anionic chemistry of carbonate anions to tailor the electrochemical oxidation-reduction reactions of bismuth (Bi) electrodes, where the conversion energy barrier for Bi (0) to Bi (III) has been significantly reduced, endowing anionic full batteries with enhanced electrochemical kinetics and chemical self-charging property. The elaborately designed batteries with an air-switch demonstrate rapid self-recharging capabilities, recovering over 80% of the electrochemical full charging capacity within a remarkably short timeframe of 1 hour and achieving a cumulative self-charging capacity of 5 Ah g-1. The aqueous self-charging battery strategy induced by carbonate anion, as proposed in this study, holds the potential for extending to various anionic systems, including seawater-based Cl- ion batteries. This work offers a universal framework for advancing next-generation multi-functional power sources.

Transmission dynamics of SARS-CoV-2 in a mid-size city of China.

BACKGROUND: An outbreak of pneumonia, COVID-19 associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then rapidly spread to other cities. Wenzhou is located approximately 900 km from Wuhan, which was experiencing an outbreak that was severe at the time but is considered modest as the epidemic became a pandemic. We described the epidemiological characteristics of SARS-CoV-2 outside of the epicenter to help understand the transmission pattern in a mid-sized Chinese city. METHODS: To investigate the epidemiological and clinical characteristics of the COVID-19, we described case series of 473 patients with confirmed COVID-19 in Wenzhou, China from January 27 to March 16, 2020. We described the public health interventions of COVID-19 and evaluated the effect of interventions by the effective reproduction number (Rt). RESULTS: The median age of all patients was 47.6 years, 48.4% of whom were female. 33.8% of the patients had a history of residence in Wuhan. Fever (71.7%) and cough (43.1%) were the most common symptoms. In addition, three kinds of unconventional cases were observed, namely 4.9% asymptomatic patients, 7.6% confirmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 12.9% confirmed patients who had an unknown source of transmission. We estimated that the basic reproductive number (R0) was 2.75 (95% CI: 2.37-3.23). The Rt fluctuated within the range of 2.50 to 3.74 from January 11 to January 16 while gradually reached a peak of 3.74 on January 16. Rt gradually decreased after January 16 and decreased to 1.00 on January 30. Rt continually decreased and reached the lowest point (0.03) on February 21, 2020. CONCLUSION: Our study presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and transmission by these three kinds of unconventional patients in Wenzhou may be an important characteristic of SARS-CoV-2 transmission. The evaluation showed that a series of multifaceted interventions proved effective in controlling the epidemic of COVID-19. These findings might provide valuable examples of control policies for countries or areas in combatting the global pandemic of COVID-19.

DNA damage of human derived liver cell line HL-7702 induced by organic extracts from surface water in Pearl River Delta, China.

Many organic pollutants attract public health concern due to their genotoxicity. To investigate the genotoxicity of organic matter in surface water of the Pearl River Delta (PRD). Organic substances of 24 samples (dry and wet season) from North River, West River and East River were extracted from 60 L source water by XAD-2 macroporous resin. DNA damage effect of organic extracts was tested in human derived liver cells (HL-7702), using single cell gel electrophoresis (SCGE) assay. The results showed that 100% organic extracts (24/24) could induce DNA damage in HL-7702 cells when the concentration was above 1.0 L surface water/ml culture, no significant difference of DNA damage between dry and wet seasons was observed. The organic substance-induced DNA damage in HL-7702 cells was significantly (P < 0.05) correlated with the contents of Dissolved Organic Carbon in both seasons and Total Suspended Solids in dry season. In conclusion, organic extracts induced genetic damage in HL-7702 cells, indicating potential genotoxicity of organic pollutants of surface water from PRD, South China.

Bacillus aerolatus sp. nov., a novel member of the genus Bacillus, isolated from bioaerosols in a school playground.

A Gram-positive, endospore-forming, rod-shaped bacterium with a single flagellum, and a motile strain, designated CX253, was isolated from bioaerosols. The isolate is facultatively anaerobic, is able to grow at 25-45 â„ƒ (optimum 37 â„ƒ) and pH 6.5-10.0 (optimum 7.5), and can tolerate up to 5.0% NaCl (w/v) under aerobic conditions. The diagnostic diamino acid in the cell wall of strain CX253T is meso-diaminopimelic acid, while major isoprenoid quinone is menaquinone 6 (MK-6) along with a smaller amount of MK-7 (20%). The polar lipid profile is composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phospholipids and glycolipids. The major cellular fatty acid is iso-C15:0 and anteiso-C15:0. Phylogenetic analysis based on 16S rRNA gene and genome sequence grouped strain CX253T into the genus Bacillus. The strain was most closely related to Bacillus thermotolerans CCTCC AB 2012108 T by comparison of 16S rRNA gene sequence (97.2% similarity) and to Bacillus wudalianchiensis CCTCC AB 2015266 T by comparison of gyrB gene sequence (80.1% similarity). The draft genome of strain CX253T comprised 3,929,195 bp with a G + C content of 43.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain CX253T and phylogenetically related Bacillus species were lower than 95% and 70%, respectively. Thus, the polyphasic evidence generated through phenotypic, chemotaxonomic and genomic methods confirmed that strain CX253T (= GDMCC 1.1608 T = KACC 21318 T) was a novel species of the genus Bacillus, for which the name Bacillus aerolatus sp. nov. is proposed.

On How High-Latitude Chorus Waves Tip the Balance Between Acceleration and Loss of Relativistic Electrons.

Modeling and observations have shown that energy diffusion by chorus waves is an important source of acceleration of electrons to relativistic energies. By performing long-term simulations using the three-dimensional Versatile Electron Radiation Belt code, in this study, we test how the latitudinal dependence of chorus waves can affect the dynamics of the radiation belt electrons. Results show that the variability of chorus waves at high latitudes is critical for modeling of megaelectron volt (MeV) electrons. We show that, depending on the latitudinal distribution of chorus waves under different geomagnetic conditions, they cannot only produce a net acceleration but also a net loss of MeV electrons. Decrease in high-latitude chorus waves can tip the balance between acceleration and loss toward acceleration, or alternatively, the increase in high-latitude waves can result in a net loss of MeV electrons. Variations in high-latitude chorus may account for some of the variability of MeV electrons.

Co/Mon Invigorated Bilateral Kinetics Modulation for Advanced Lithium-Sulfur Batteries.

Sluggish sulfur redox kinetics and Li-dendrite growth are the main bottlenecks for lithium-sulfur (Li-S) batteries. Separator modification serves as a dual-purpose approach to address both of these challenges. In this study, the Co/MoN composite is rationally designed and applied as the modifier to modulate the electrochemical kinetics on both sides of the sulfur cathode and lithium anode. Benefiting from its adsorption-catalysis function, the decorated separators (Co/MoN@PP) not only effectively inhibit polysulfides (LiPSs) shuttle and accelerate their electrochemical conversion but also boost Li+ flux, realizing uniform Li plating/stripping. The accelerated LiPSs conversion kinetics and excellent sulfur redox reversibility triggered by Co/MoN modified separators are evidenced by performance, in-situ Raman detection and theoretical calculations. The batteries with Co/MoN@PP achieve a high initial discharge capacity of 1570 mAh g-1 at 0.2 C with a low decay rate of 0.39%, uniform Li+ transportation at 1 mA cm-2 over 800 h. Moreover, the areal capacity of 4.62 mAh cm-2 is achieved under high mass loadings of 4.92 mg cm-2. This study provides a feasible strategy for the rational utilization of the synergistic effect of composite with multifunctional microdomains to solve the problems of Li anode and S cathode toward long-cycling Li-S batteries.

Potential Role of MAP3K14 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis and Validation.

According to reports, MAP3K14 is considered an oncogene and is aberrantly expressed in various types of tumor cells. Its abnormal expression is closely associated with the occurrence and progression of various cancers. MAP3K14 also plays a significant role in the development of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma and its connection to tumor stem cells. The prognostic value of MAP3K14 in HCC, as well as its potential functions and roles, requires further elucidation. We evaluated the potential role of MAP3K14 in HCC based on data mining from a range of public databases. The bioinformatics analysis of TCGA, GEO, TIMER, cBioportal, Kaplan-Meier plotter, MethSurv, ENCORI and CellMiner databases was carried out. The expression of MAP3K14 protein in HCC was detected by immunohistochemical method. The mRNA and protein expression levels of MAP3K14 in tumor tissues were higher than those in normal tissues (p < 0.05). The expression of MAP3K14 was correlated with Pathologic T stage (p=0.026), Pathologic stage (p=0.032), Tumor status (p=0.024) and AFP (p=0.002). HCC patients with high expression of MAP3K14 had poor overall survival (OS), progression free survival (PFS) and recurrence free survival (RFS). Multivariate Cox regression analysis showed that the Pathologic stage (p < 0.001) and MAP3K14 expression levels (p < 0.05) is an independent prognostic factor affecting the survival of patients with liver cancer. GO/KEGG analysis suggested that key biological processes (PI3K-Akt signaling pathway) may be the mechanism promoting HCC development. In addition, MAP3K14 was significantly correlated with the infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05). MAP3K14 is up-regulated in HCC and is closely related to the prognosis of HCC patients. MAP3K14 may serve as a potential biomarker for poor prognosis of HCC.

Trend analysis and age-period-cohort effects on morbidity and mortality of liver cancer from 2010 to 2020 in Guangzhou, China.

Introduction: Liver cancer is one of the most common malignant gastrointestinal tumors worldwide. This study intends to provide insight into the epidemiological characteristics and development trends of liver cancer incidence and mortality from 2010 to 2020 in Guangzhou, China. Methods: Data were collected from the Cancer Registry and Reporting Office of Guangzhou Center for Disease Control and Prevention. Cross-sectional study, Joinpoint regression (JPR) model, and Age-Period-Cohort (APC) model were conducted to analyze the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) trend of liver cancer among the entire study period. Results: The age-standardized incidence and mortality of liver cancer in Guangzhou showed an overall decreasing trend. The disparity in risk of morbidity and mortality between the two sexes for liver cancer is increasing. The cohort effect was the most significant among those born in 1965~1969, and the risk of liver cancer incidence and mortality in the total population increased and then decreased with the birth cohort. Compared with the birth cohort born in 1950~1954 (the reference cohort), the risk of liver cancer incidence and mortality in the males born in 1995~1999 decreased by 32% and 41%, respectively, while the risk in the females decreased by 31% and 32%, respectively. Conclusions: The early detection, prevention, clinical diagnosis, and treatment of liver cancer in Guangzhou have made remarkable achievements in recent years. However, the risk of liver cancer in the elderly and the middle-aged males is still at a high level. Therefore, the publicity of knowledge related to the prevention and treatment of liver cancer among the relevant population groups should be actively carried out to enhance the rate of early diagnosis and treatment of liver cancer and to advocate a healthier lifestyle.

Global validation of data-assimilative electron ring current nowcast for space weather applications.

The hazardous plasma environment surrounding Earth poses risks to satellites due to internal charging and surface charging effects. Accurate predictions of these risks are crucial for minimizing damage and preparing for system failures of satellites. To forecast the plasma environment, it is essential to know the current state of the system, as the accuracy of the forecast depends on the accuracy of the initial condition of the forecast. In this study, we use data assimilation techniques to combine observational data and model predictions, and present the first global validation of a data-assimilative electron ring current nowcast during a geomagnetic storm. By assimilating measurements from one satellite and validating the results against another satellite in a different magnetic local time sector, we assess the global response and effectiveness of the data assimilation technique for space weather applications. Using this method, we found that the simulation accuracy can be drastically improved at times when observations are available while eliminating almost all of the bias previously present in the model. These findings contribute to the construction of improved operational models in estimating surface charging risks and providing realistic 'source' populations for radiation belt simulations.

DEAD-box RNA helicase 21 interacts with porcine circovirus type 2 Cap protein and facilitates viral replication.

Porcine circovirus type 2 (PCV2) is the etiological agent of PCV2-associated diseases that pose a serious threat to the swine industry. PCV2 capsid (Cap) protein has been shown to interact with DEAD-box RNA helicase 21 (DDX21), an important protein that regulates RNA virus replication. However, whether the interaction between DDX21 and the PCV2 Cap regulates PCV2 replication remains unclear. Herein, by using western blotting, interaction assays, and knockdown analysis, we found that PCV2 infection induced the cytoplasmic relocation of DDX21 from the nucleolus in cultured PK-15 cells. Moreover, the nuclear localization signal (NLS) of PCV2 Cap interacted directly with DDX21. The NLS of PCV2 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 were essential for the dual interaction. Upon shRNA-mediated DDX21 depletion in PK-15 cells, we observed impaired PCV2 replication via a lentivirus-delivered system, as evidenced by decreased levels of viral protein expression and virus production. In contrast, the replication of PCV2 increased in transiently DDX21-overexpressing cells. Our results indicate that DDX21 interacts with PCV2 Cap and plays a crucial role in virus replication. These results provide a reference for developing novel potential targets for prevention and control of PCV2 infection.

A large-scale nationwide study of urinary phenols in the Chinese population.

Bisphenol A (BPA), tetrabromobisphenol A (TBBPA), and their substitutes are commonly used in everyday products. However, large-scale internal exposure levels of them in China, the factors influencing on them, and the associated health risks were not systematically investigated still. In the present study, there were 1157 morning urine samples collected from residents of 26 provincial capitals in China for the measurement of BPA and seven bisphenol analogues, as well as TBBPA and its substitutes, i.e., tetrachlorobisphenol A and 4,4'-sulphonylbis(2,6-dibromophenol). The concentrations of Σ8bisphenols and Σ3TBBPAs ranged from

A missing dusk-side loss process in the terrestrial electron ring current.

The Earth's magnetic field traps charged particles which are transported longitudinally around Earth, generating a near-circular current, known as the ring current. While the ring current has been measured on the ground and space for many decades, the enhancement of the ring current during geomagnetic storms is still not well understood, due to many processes contributing to its dynamics on different time scales. Here, we show that existing ring current models systematically overestimate electron flux observations of 10-50 keV on the nightside during storm onset. By analyzing electron drift trajectories, we show that this systematic overestimation of flux can be explained through a missing loss process which operates in the pre-midnight sector. Quantifying this loss reveals that the theoretical upper limit of loss has to be reached over a broad region of space in order to reproduce the observations. This missing loss may be attributed to inaccuracies in the parameterization of the loss due to chorus wave interactions, combined with the scattering by electrostatic electron cyclotron harmonic waves which is currently not included in ring current models.

Diffuse auroral precipitation driven by lower-band chorus second harmonics.

Diffuse aurora at the Earth's high latitude regions is mainly caused by the low-energy (0.1-30 keV) electron precipitation which carries the major energy flux into the nightside upper atmosphere. Previous studies have demonstrated that combined scattering by the upper- and lower- band chorus waves acts as the dominant cause of diffuse auroral precipitation, but that is not necessarily the case as these two types of waves do not always occur simultaneously, with the lower-band more often. Here we report that the lower-band chorus satisfying the preferred condition can generate their second harmonics so as to trigger the diffuse auroral electron precipitation. We find that the lower-band chorus alone can only cause the precipitation of electrons greater than 4 keV, while the self-consistently generated second harmonic is weak but still able to result in the electron precipitation below 4 keV. The combined effect of those modes results in the observed pancake electron distributions and the diffuse aurora. Our results clearly demonstrate an alternative but universal mechanism of chorus-driven diffuse aurora in the Earth, which may also apply to the auroral formation in other planetary magnetospheres.

Knowledge, attitudes, and practices (KAP) toward seasonal influenza vaccine among college students under the COVID-19 pandemic in South China.

BACKGROUND: The control measures of the coronavirus disease 2019 (COVID-19) pandemic had influenced the activity of the influenza virus, and we were wondering the knowledge, attitudes, and practices (KAP) toward seasonal influenza vaccine among college students were having at the context of the COVID-19 pandemic. METHODS: Online questionnaire survey of the college students was conducted and the data was collected anonymously, cross-sectional study were used to describe the distribution of the KAP. RESULTS: There were 815 respondents in our study. Most participants have a high recognition of the effectiveness and safety of the influenza vaccine. However, a low awareness rate of influenza vaccine knowledge and vaccination rate (18%) against influenza was observed among college students. The education level and major would have a higher weight on the influence of KAP among the college students. Binary logistic regression analysis showed that the sex (OR = 2.163, p < .001), age (OR = 2.242, p < .001), heard of the influenza vaccine (OR = 2.655, p = .014), and "How necessary do you think vaccinating every year is?" (OR = 3.947, p < .001) of the college students were the main factors that affect the KAP on influenza vaccination. CONCLUSIONS: Our study provided an insight into the KAP of influenza vaccine among college students in South China. The vaccination rate and acceptability of influenza vaccine in college students are higher than that in the whole population.

The role of meteorological factors on influenza incidence among children in Guangzhou China, 2019-2022.

Objective: Analyzing the epidemiological characteristics of influenza cases among children aged 0-17 years in Guangzhou from 2019 to 2022. Assessing the relationships between multiple meteorological factors and influenza, improving the early warning systems for influenza, and providing a scientific basis for influenza prevention and control measures. Methods: The influenza data were obtained from the Chinese Center for Disease Control and Prevention. Meteorological data were provided by Guangdong Meteorological Service. Spearman correlation analysis was conducted to examine the relevance between meteorological factors and the number of influenza cases. Distributed lag non-linear models (DLNM) were used to explore the effects of meteorological factors on influenza incidence. Results: The relationship between mean temperature, rainfall, sunshine hours, and influenza cases presented a wavy pattern. The correlation between relative humidity and influenza cases was illustrated by a U-shaped curve. When the temperature dropped below 13°C, Relative risk (RR) increased sharply with decreasing temperature, peaking at 5.7°C with an RR of 83.78 (95% CI: 25.52, 275.09). The RR was increased when the relative humidity was below 66% or above 79%, and the highest RR was 7.50 (95% CI: 22.92, 19.25) at 99%. The RR was increased exponentially when the rainfall exceeded 1,625 mm, reaching a maximum value of 2566.29 (95% CI: 21.85, 3558574.07) at the highest rainfall levels. Both low and high sunshine hours were associated with reduced incidence of influenza, and the lowest RR was 0.20 (95% CI: 20.08, 0.49) at 9.4 h. No significant difference of the meteorological factors on influenza was observed between males and females. The impacts of cumulative extreme low temperature and low relative humidity on influenza among children aged 0-3 presented protective effects and the 0-3 years group had the lowest RRs of cumulative extreme high relative humidity and rainfall. The highest RRs of cumulative extreme effect of all meteorological factors (expect sunshine hours) were observed in the 7-12 years group. Conclusion: Temperature, relative humidity, rainfall, and sunshine hours can be used as important predictors of influenza in children to improve the early warning system of influenza. Extreme weather reduces the risk of influenza in the age group of 0-3 years, but significantly increases the risk for those aged 7-12 years.

Avian Metapneumovirus Subgroup C Phosphoprotein Suppresses Type I Interferon Production by Blocking Interferon Regulatory Factor 3 Nuclear Translocation.

Avian metapneumovirus subgroup C (aMPV/C) is an important pathogen that causes upper respiratory symptoms and egg production decline in turkeys and chickens. aMPV/C infection leads to inhibition of the host antiviral immune response. However, our understanding of the molecular mechanisms underlying host immune response antagonized by aMPV/C infection is limited. In this study, we demonstrated that the aMPV/C phosphoprotein (P) inhibits the IFN antiviral signaling pathway triggered by melanoma differentiation gene 5 (MDA5) and reduces interferon ß (IFN-ß) production and IFN-stimulated genes (ISGs) by targeting IFN regulatory factor 7 (IRF7) but not nuclear factor κB (NF-κB) in DF-1 cells. Moreover, we found that aMPV/C P protein only blocks the nuclear translocation of IRF3 by interacting with IRF3 in HEK-293T cells, instead of affecting IRF3 phosphorylation and inducing IRF3 degradation, which suppresses IRF3 signaling activation and results in a decrease in IFN-ß production. Collectively, these results reveal a novel mechanism by which aMPV/C infection disrupts IFN-ß production in the host. IMPORTANCE The innate immune response is the first defense line of host cells and organisms against viral infections. When RNA viruses infect cells, viral RNA induces activation of retinoic acid-induced gene I and melanoma differentiation gene 5, which initiates downstream molecules and finally produces type I interferon (IFN-I) to regulate antiviral immune responses. The mechanism for avian metapneumovirus (aMPV) modulating IFN-I production to benefit its replication remains unknown. Here, we demonstrate that phosphoprotein of aMPV subgroup C (aMPV/C) selectively inhibits the nuclear translocation of interferon regulatory 3 (IRF3), instead of affecting the expression and phosphorylation of IRF3, which finally downregulates IFN-I production. This study showed a novel mechanism for aMPV/C infection antagonizing the host IFN response.