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The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5′-UTR and 3′-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies., RNA secondary structure is important for viral replication, transcription and translation. Here the authors employ SPLASH method and map in vivo RNA interactions and dynamics of SARS-CoV-2 RNA genome in different viral life cycles.

With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC.This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized.Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure.We summarized practical recommendations about standardized and improved PLA treatment for PTMC.

The M1 of influenza A virus (IAV) is important for the virus life cycle, especially for the assembly and budding of viruses, which is a multistep process that requires host factors. Identifying novel host proteins that interact with M1 and understanding their functions in IAV replication are of great interest in antiviral drug development. In this study, we identified 19 host proteins in DF1 cells suspected to interact with the M1 protein of an H5N6 virus through immunoprecipitation (IP)/mass spectrometry. Among them, PSMD12, a 26S proteasome regulatory subunit, was shown to interact with influenza M1, acting as a positive host factor in IAV replication in avian and human cells. The data showed that PSMD12 promoted K63-linked ubiquitination of M1 at the K102 site. H5N6 and PR8 with an M1-K102 site mutant displayed a significantly weaker replication ability than the wild-type viruses. Mechanistically, PSMD12 promoted M1-M2 virus-like particle (VLP) release, and an M1-K102 mutation disrupted the formation of supernatant M1-M2 VLPs. An H5N6 M1-K102 site mutation or knockdown PSMD12 disrupted the budding release of the virus in chicken embryo fibroblast (CEF) cells, which was confirmed by transmission electron microscopy. Further study confirmed that M1-K102 site mutation significantly affected the virulence of H5N6 and PR8 viruses in mice. In conclusion, we report the novel host factor PSMD12 which affects the replication of influenza virus by mediating K63-linked ubiquitination of M1 at K102. These findings provide novel insight into the interactions between IAV and host cells, while suggesting an important target for anti-influenza virus drug research.

With the rapid development of UAV-related directions, intelligent UAVs have been applied to various industries of modern production and life. One particularly popular application is “delivery UAV.” By giving commands to the UAV, It can accomplish complex tasks such as target point flight and cargo delivery autonomously. On the one hand, human resources can be liberated; on the other hand, fully automated operations can greatly improve production efficiency. Our team used STM32 produced by Stmicroelectronics as the main control of the UAV, OpenMV from SingTown Technology, and K210 from Canaan Technology as the vision processor to design and develop a delivery quadrotor. The UAV uses an optical flow module to achieve hover and cruise and is equipped with a laser ranging module to assist the UAV in obtaining height. K210 and OpenMV are used for target detection, and the Hanging basket can be raised and lowered to simulate “delivery.” The UAV can realize automatic cruise, target-point “delivery,” target detection, obstacle avoidance, and many other functions.

Background Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition responsible for rapidly progressive glomerulonephritis. This disease is usually mediated by IgG autoantibodies against the noncollagenous domain of the α3(IV) collagen chain. In rare cases, IgA or IgM anti-GBM antibodies are involved. This raises the question of whether there are different types of antibody-mediated anti-GBM disease at the same time. Case report A 37-year-old woman with anti-GBM disease mediated by IgG and IgA. The patient developed rapidly progressive glomerulonephritis with nephrotic syndrome. Indirect immunofluorescence analysis indicated the presence of IgG and IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoadsorbent assay and Western blotting as the α3(IV) collagen chain. After plasmapheresis and immunotherapy (steroids and cyclophosphamide), much improved the massive proteinuria and renal function. Follow up to date, she had normal renal function without proteinuria. Conclusions This is the first case report of anti-GBM disease mediated by IgG and IgA. If the clinical presentation and histopathological findings are suggestive of atypical anti-GBM disease, alternative laboratory tests such as Western blotting analysis can be used to confirm the diagnosis.

COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19., GRAPHICAL ABSTRACT

The influenza A virus (IAV) infection is usually restricted to the respiratory tract and only rarely enters the central nervous system (CNS) and causes neurological symptoms. However, the roles of host factors involved in IAV infection in the CNS remain largely undetermined. Therefore, we aimed to characterize the host responses to IAV infection in the brain. We isolated a strain of IAV H5N6, which is neurotoxic and highly pathogenic to mice. High-throughput RNA sequencing (RNA-seq) revealed 240 differentially expressed genes in IAV-infected brains. Among the significantly downregulated genes, we focused on the gene encoding progesterone receptor membrane component-1 (PGRMC1) and observed that IAV H5N6 infection clearly inhibited PGRMC1 in both neuroblastoma and glioma cells. Furthermore, treatment with AG205, a PGRMC1-specific inhibitor, or PGRMC1 knockout promoted H5N6 multiplication in vitro, while overexpression of PGRMC1 resulted in opposite effects. Furthermore, AG205 treatment or PGRMC1 knockout significantly inhibited the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and reduced the levels of several antiviral proteins (Mx1 and ISG15). In addition, PGRMC1-mediated regulation of IFN signaling relied on inhibition of the expression and ubiquitination of RIG-I. The loss of PGRMC1 leads to an increased susceptibility of mice (brain and lung) to influenza A virus infection. Conclusively, our results show for the first time that IAV H5N6 downregulates PGRMC1 expression to contribute to virus proliferation by inhibiting RIG-I-mediated IFN-β production in the brain. These findings may offer new insights regarding the interplay between IAV and host factors that may impact IAV pathogenicity in the brain. IMPORTANCE Central nervous system (CNS) disease is one of the most common extra-respiratory tract complications of influenza A virus (IAV) infections. However, there is still little knowledge about IAV regulating host responses in brain. In this study, we identified progesterone receptor membrane component-1 (PGRMC1) as a novel host factor involved in the replication and propagation of IAV H5N6 in the host brain. We also observed that PGRMC1 antagonism was required for viral evasion from the host immune response during IAV infection via inhibition of the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-β) signaling pathway and downstream antiviral gene expression. This study revealed a newly identified regulatory mechanism used by IAV H5N6 to ensure its life cycle in the CNS.

China's unprecedented lockdown to contain the spread of the novel coronavirus disease (COVID-19) in early 2020, provided a tragic natural experiment to investigate the responses of atmospheric pollution to emission reduction at regional scale. Primarily driven by primary emissions, particulate trace elements is vitally important due to their disproportionally adverse impacts on human health and ecosystem. Here 14 trace elements in PM2.5 were selected for continuous measurement hourly in urban representative site of Shanghai, for three different phases: pre-control period (1–23 January 2020), control period (24 January-10 February 2020; overlapped with Chinese Lunar New Year holiday) and post control period (11–26 February 2020) the city's lockdown measures. The results show that all meteorological parameters (including temperature, RH, mixing layer height et al.) were generally consistent among different periods. Throughout the study period, the concentrations of most species displayed a “V-shaped” trend, suggesting significant effects by the restriction measures imposed during the lockdown period. While this is not the case for species like K, Cu and Ba, indicating their unusual origins. As a case study, the geographical origins of Cu were explored. Seven major sources, i.e., Vehicle-related emission (including road dust; indicative of Ca, Fe, Ba, Mn, Zn, Cu; accounting for 30.1%), shipping (Ni; 5.0%), coal combustion (As, Pb; 4.2%), Se and Cr industry (24.9%), nonferrous metal smelting (Au, Hg; 7.5%) and fireworks burning (K, Cu, Ba; 28.3%) were successfully pinpointed based on positive matrix factorization (PMF) analysis. Our source apportionment results also highlight fireworks burning was one of the dominant source of trace elements during the Chinese Lunar New Year holiday. It is worth noting that 56% of the total mass vehicular emissions are affiliated with non-exhaust sources (tire wear, brake wear, and road surface abrasion)., Graphical abstract Image 1

Influenza is a highly known contagious viral infection that has been responsible for the death of many people in history with pandemics. These pandemics have been occurring every 10 to 30 years in the last century. The most recent global pandemic prior to COVID-19 was the 2009 influenza A (H1N1) pandemic. A decade ago, the H1N1 virus caused 12,500 deaths in just 19 months globally. Now, again, the world has been challenged with another pandemic. Since December 2019, the first case of a novel coronavirus (COVID-19) infection was detected in Wuhan. This infection has risen rapidly throughout the world; even the World Health Organization (WHO) announced COVID-19 as a worldwide emergency to ensure human health and public safety. This review article aims to discuss important issues relating to COVID-19, including clinical, epidemiological, and pathological features of COVID-19 and recent progress in diagnosis and treatment approaches for the COVID-19 infection. We also highlight key similarities and differences between COVID-19 and influenza A to ensure the theoretical and practical details of COVID-19.

Hepatitis-hydropericardium syndrome (HHS) is an infectious disease caused by fowl adenovirus serotype 4 (FAdV-4). Several structural and non-structural proteins of FAdV-4 have been expressed in Escherichia coli and baculovirus expression system to develop candidate subunit vaccines. However, the protective efficiency of baculovirus-expressed penton base protein has not been assessed. In this study, two recombinant capsid proteins, penton base and fiber-2, were constructed. And then, penton base and fiber-2 were administrated alone or together to specific pathogen-free (SPF) chickens at 14 days of life and boosted at 28 days of life. At 42 days of life, the immunized groups and the control group were challenged with FAdV-4 virulent strain. Results show that inoculating penton base or penton base+fiber-2 provided 100% protection to the chickens. All groups vaccinated with the recombinant protein produced detectable antibodies and showed no apparent lesions. Thus, baculovirus-expressed penton base protein is a promising candidate subunit vaccine.

Background IgG4-related disease (IgG4-RD) often affects multiple organs and tissues, especially the kidneys, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membranous nephropathy). Case presentation In this article, we report a patient with nephrotic syndrome as the only initial manifestation. Membranous nephropathy was confirmed by renal biopsy, but without any renal interstitial lesions. The nephrotic syndrome completely resolved after treatment with immunosuppressants but recurred after drug withdrawal, which was accompanied by acute kidney injury. Ultimately, IgG4-related interstitial nephritis with membranous nephropathy was confirmed by a second renal biopsy. After routine administration of steroids and cyclophosphamide, renal function returned to normal after 2 months, and nephrotic syndrome was ameliorated after 5 months. Conclusion Special attention should be paid to this rare condition in the clinical setting. In patients with membranous nephropathy (MN) that is accompanied by multi-system damage, impaired renal function, elevated IgG4 levels (absolute or relative value), negative PLA2R, and/or renal interstitial plasma cell infiltration, the possibility of IgG4-related kidney disease (IgG4-RKD) should be carefully assessed.

Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSCs) carrying microRNA-224-3p (miR-224-3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM-MSCs-derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR-224-3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR-224-3p was found to be down-regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up-regulated in ONFH. Traumatic ONFH exosomes resulted in the up-regulation of FIP200 and down-regulation of miR-224-3p. FIP200 was confirmed to be a target gene of miR-224-3p. Exosomes were internalized by vascular endothelial cells. The down-regulation of exosomal miR-224-3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR-224-3p levels in exosomes derived from BM-MSCs promote angiogenesis of traumatic ONFH by up-regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.-Xu, H.-J., Liao, W., Liu, X.-Z., Hu, J., Zou, W.-Z., Ning, Y., Yang, Y., Li, Z.-H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Summary The novel coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has resulted in an unprecedented public health crisis and economic losses. Although several cases of cats and dogs infected with SARS‐CoV‐2 have been reported during this outbreak, the prevalence of SARS‐CoV‐2 in dog and its transmission among other companion animals are still unknown. Here, we report an extensive serological study of SARS‐CoV‐2 infection in dogs in Wuhan and analyze the infection rates at different stages of the pandemic outbreak. A total of 946 dogs serum samples were collected from Wuhan, of which 36 samples were obtained prior to the pandemic outbreak. Indirect enzyme linked immunosorbent assay (ELISA) showed that 16 sera collected during the outbreak were detected as positive through the receptor binding domain (RBD) of SARS‐CoV‐2. Of these 16 sera, 10 exhibited measurable SARS‐CoV‐2 specific neutralizing antibodies whose titers ranged from 1/20 to 1/180. No serological cross‐reactivity was detected between SARS‐CoV‐2 and canine coronavirus (CCV). Furthermore, with the effective control of the outbreak, a decrease in the SARS‐CoV‐2 seropositive dog number was observed. Our results suggest that SARS‐CoV‐2 has infected companion dogs during the outbreak, and that COVID‐19 patient families have a higher risk of dog infection. Our findings deepen our understanding of the infection of SARS‐CoV‐2 in dogs and provide an important reference for prevention of COVID‐19.

Aged BALB/c mice are in use as a model of disease caused by SARS-CoV-2. Our research demonstrated SARS-CoV-2 can rapidly adapt in aged BALB/c mice through causing mutations at the RBD of the S protein., Age is a risk factor for coronavirus disease 2019 (COVID-19)-associated morbidity and mortality in humans; hence, in this study, we compared the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and aged BALB/c mice. We found that SARS-CoV-2 isolates replicated in the respiratory tracts of 12-month-old (aged) mice and caused pathological features of pneumonia upon intranasal infection. In contrast, rapid viral clearance was observed 5 days following infection in 2-month-old (young) mice with no evidence of pathological changes in the lungs. Infection with SARS-CoV-2 elicited significantly upregulated production of cytokines, especially interleukin 6 and interferon gamma, in aged mice, whereas this response was much weaker in young mice. Subsequent challenge of infected aged BALB/c mice with SARS-CoV-2 resulted in neutralized antibody responses, a significantly reduced viral burden in the lungs, and inflammation mitigation. Deep sequencing showed a panel of mutations potentially associated with the enhanced infection in aged BALB/c mice, such as the Q498H mutation, which is located at the receptor-binding domain (RBD) of the spike (S) protein. We further found that the isolates cannot only multiply in the respiratory tract of mice, but also cause disease in aged mice. Overall, viral replication and rapid adaption in aged BALB/c mice were associated with pneumonia, confirming that the age-related susceptibility to SARS-CoV-2 in mice resembled that in humans. IMPORTANCE Aged BALB/c mice are in use as a model of disease caused by SARS-CoV-2. Our research demonstrated SARS-CoV-2 can rapidly adapt in aged BALB/c mice through causing mutations at the RBD of the S protein. Moreover, SARS-CoV-2-infected aged BALB/c mice indicated that alveolar damage, interstitial pneumonia, and inflammatory immune responses were similar to the clinical manifestations of human infections. Therefore, our aged BALB/c challenge model will be useful for further understanding the pathogenesis of SARS-CoV-2 and for testing vaccines and antiviral agents.

The SARS-CoV-2 coronavirus, which causes the COVID-19 pandemic, is one of the largest positive strand RNA viruses. Here we developed a simplified SPLASH assay and comprehensively mapped the in vivo RNA-RNA interactome of SARS-CoV-2 RNA during the viral life cycle. We observed canonical and alternative structures including 3’-UTR and 5’-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in cells and in virions. We provide direct evidence of interactions between Transcription Regulating Sequences (TRS-L and TRS-Bs), which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE, forming a “high-order pseudoknot” embedding FSE, which might help ribosome stalling at frameshift sites. More importantly, we found that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome cyclization is weakened and genome domains remain stable. Our data provides a structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, describes dynamics of RNA structures during life cycle of SARS-CoV-2, and will help to develop antiviral strategies.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-γ)-secreting cells to total CD4+ and CD8+ cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFN-γ-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2, P = 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection. Electronic supplementary material The online version of this article (10.1007/s12250-020-00308-0) contains supplementary material, which is available to authorized users.

SummaryCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. Previous studies suggested cat could be a potential susceptible animal of SARS-CoV-2. Here, we investigated the infection of SARS-CoV-2 in cats by detecting specific serum antibodies. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among the positive samples, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between the SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). Our data demonstrates that SARS-CoV-2 has infected cat population in Wuhan during the outbreak.

Whether mudflats are an important source of atmospheric ammonia (NH3) remains an open question, despite the fact that over half of the world's population live within 3 km of surface water bodies. Here, we established three sites (lake, river, and sea) that are representative of tide-influenced mudflats across the Yangtze Delta in eastern China. Online field measurements of NH3 and auxiliary hydrometeorological parameters were simultaneously performed over a 9 month period. Surprisingly, the average NH3 concentrations measured at these locations are as low as regional background levels. No pulses of increased NH3 were found at these sites when mudflats were exposed due to receding water levels. High atmospheric NH3 concentrations are persistently associated with high temperatures, but their geographical origins have no overlap with the locations of water bodies. The potential mechanism is also discussed. Collectively, we provide the first direct observational evidence concerning mudflat as a source of NH3, SCOPUS: ar.j, info:eu-repo/semantics/published

It is a puzzle as to why more severe haze formed during the New Year Holiday in 2020 (NYH‐20), when China was in an unprecedented state of shutdown to contain the coronavirus (COVID‐19) outbreak, than in 2019 (NYH‐19). We performed a comprehensive measurement and modeling analysis of the aerosol chemistry and physics at multiple sites in China (mainly in Shanghai) before, during, and after NYH‐19 and NYH‐20. Much higher secondary aerosol fraction in PM2.5 were observed during NYH‐20 (73%) than during NYH‐19 (59%). During NYH‐20, PM2.5 levels correlated significantly with the oxidation ratio of nitrogen (r 2 = 0.77, p < 0.01), and aged particles from northern China were found to impede atmospheric new particle formation and growth in Shanghai. A markedly enhanced efficiency of nitrate aerosol formation was observed along the transport pathways during NYH‐20, despite the overall low atmospheric NO2 levels., Key Points Higher concentrations and distinct compositions of aerosol particles were observed during the COVID‐19 shutdownFast formation of secondary inorganic aerosol contributed to high aerosol mass loadingLonger‐range, regional transport facilitated and enhanced particulate nitrate formation

14 pags., 12 figs., 1 tab., High resolution satellite maps are useful for the identification of pollution hotspots. In this work, nitrogen dioxide (NO) and sulfur dioxide (SO) observations from the Ozone Monitoring Instrument (OMI) have been averaged and gridded for Shanghai and surrounding areas with a spatial resolution of 0.01° × 0.01°. The pollution maps have been used to investigate the spatio-temporal variations in NO and SO from 2008 to 2017. The averaged tropospheric NO and planetary boundary layer (PBL) SO columns in Shanghai are on average 1.40 × 10 molec·cm and 1.21 × 10 molec·cm, respectively. As the government has put a lot of effort to improve the air quality, both the NO and SO columns reveal a significant decline in Shanghai during the past decade, with a reduction of ∼24% and ∼56%, respectively, which is also confirmed by the good agreement between satellite observations and ground-based in-situ measurements. The NO and SO time series also show distinct seasonal characteristics with higher pollution level during winter and lower in the summer. Due to the impact of ship and industrial emissions, the hotspots of NO and SO are concentrated in the northern part of Shanghai, while the pollution level is lower in the southern and eastern regions. Decreasing trends in NO and SO are found for most areas of Shanghai during the past decade, though the strongest decrease in the northern part of the city (1.4 × 10 molec·cm·year for NO and 3.0 × 10 molec·cm·year for SO). Comparisons with the China Multi-Resolution Emissions Inventory (MEIC) indicate that the driving factors for the decline of NO and SO are mainly denitration and desulfurization in the power sector, and the reduction of emissions in the industry sector. We also use aerosol optical depth (AOD) measurements from MODerate-resolution Imaging Spectroradiometer (MODIS) to investigate the relationship between gas phase pollutants and formation of secondary aerosol. Compared to SO, the contribution of NO to secondary aerosol formation increased in the central part of Shanghai. Although Chongming Eco-Island has developed rapidly in recent years, both the SO and NO levels decreased significantly. This is mainly related to the strict emission control policy and improved urban planning, and indicates that ecological development is achievable under the guidance of policies., This research was supported by grants from National Key Research and Development Program of China (2016YFC0200401,2017YFC0210002), National Natural Science Foundation of China(41775113, 21777026), Shanghai Pujiang Talent Program(17PJC015). This work was also supported by The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning and Shanghai Thousand Talents Program.

In mammals, IFN regulatory factor (IRF) 1 can activates cellular genes and promotes viral resistance against some DNA and RNA viruses. Most IRFs have been identified as critical regulators in the IFN responses in both mammals and fish. In ducks, however, the functional role of IRF1 remains unknown. Here, we identified duck IRF1 (duIRF1) is essential to counteract viral invasion. duIRF1 is most abundant in duck spleen, and virus infection or poly(I:C) stimulation significantly induced duIRF1 expression in vivo and in vitro. Overexpression of duRF1 induces the expression of type I IFN-β, type III IFN-λ, and interferon stimulated genes (ISGs) in duck embryo fibroblasts (DEFs), initiating cells resistant to avian viruses infection. More importantly, we found duIRF1 interacts with duck myeloid differentiation factor 88 (duMyD88) to activate duck IFN-β, different from IRF3 and IRF7, which involve in IFN expression through the retinoic acid–inducible gene I (RIG-I)–like receptor pathway in mammals. Together, these results indicate that duIRF1 effectively inhibits viral replication through the induction of IFN and antiviral ISGs. This will help with understanding the role of duIRF1 mediated antiviral responses by innate immune mechanisms.

Non-structural 1 (NS1) protein is a key virulence factor that regulates replication of influenza virus. A recombinant H5N1 virus lacking the eIF4GI-binding domain of NS1 (rNS1-SD30) exhibits significantly lower pathogenicity than H5N1 virus with an intact eIF4GI-binding domain (rNS1-wt). To further investigate this phenomenon, we performed comparative proteomics analyses to profile host proteins in chicken embryo fibroblasts (CEFs) infected with rNS1-wt and rNS1-SD30 viruses. In total, 81 differentially expressed (DE) proteins were identified at 12, 24, and 36 h post-infection. These proteins are mainly involved in the cytoskeletal, apoptotic and stress responses, transcription regulation, transport and metabolic processes, mRNA processing and splicing, and cellular signal transduction. Overexpression of DE proteins revealed that ANXA7 suppresses propagation of rNS1-SD30, but not rNS1-wt viruses. Moreover, ALDH7A1, ANXA7, and DCTN2 strongly enhanced IFN-β promoter activity induced by chicken MDA5 (chMDA5), and in the case of ANXA7, also by the rNS1-SD30 viral strain. NS1-wt co-transfection suppressed the ANXA7-mediated increase in IFN-β promoter activity induced by chMDA5. These findings highlight the role of NS1 eIF4GI binding domain in H5N1 pathogenicity, and may contribute to the design of antiviral strategies to reduce the high morbidity and mortality associated with this pathogen.

In order to detect the sleep spindles simply and efficiently, a novel time-domain approach to detect sleep spindles based on the principles of visual organization is proposed. The code idea of the visual organization is to organize the primary visual elements according to some rules of organization, and to form a more meaningful object of visual processing, as the input of next process. After the collected EEG is processed with the merging algorithm based on the principle of visual organization, it can extract the time-domain feature frequency and duration time better. Use these features with a simple algorithm to detect spindles achieving sensitivity of 92.5% and specificity of 98.1%, which verifies the validity of this method to detect the sleep spindles.

Background Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. Results Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. Conclusions These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.

Ammonia (NH3) is the predominant alkaline gas in the atmosphere contributing to formation of fine particles—a leading environmental cause of increased morbidity and mortality worldwide. Prior findings suggest that NH3 in the urban atmosphere derives from a complex mixture of agricultural (mainly livestock production and fertilizer application) and nonagricultural (e.g., urban waste, fossil fuel-related emissions) sources; however, a citywide holistic assessment is hitherto lacking. Here we show that NH3 from nonagricultural sources rivals agricultural NH3 source contributions in the Shanghai urban atmosphere. We base our conclusion on four independent approaches: (i) a full-year operation of a passive NH3 monitoring network at 14 locations covering urban, suburban, and rural landscapes; (ii) model-measurement comparison of hourly NH3 concentrations at a pair of urban and rural supersites; (iii) source-specific NH3 measurements from emission sources; and (iv) localized isotopic signatures of NH3 sources integrated in a Bayesian isotope mixing model to make isotope-based source apportionment estimates of ambient NH3. Results indicate that nonagricultural sources and agricultural sources are both important contributors to NH3 in the urban atmosphere. These findings highlight opportunities to limit NH3 emissions from nonagricultural sources to help curb PM2.5 pollution in urban China.