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Background There is a need for vaccines that can induce effective systemic, respiratory mucosal and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA and cellular immunity. Methods The aim of the present study was to determine the effectiveness of a new administration method of intratracheal (IT) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AS03 (S1-AS03 vaccine). Results S1-SF-10-IT vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-IT showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AS03-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AS03-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF10-IT, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusion Based on the need for effective systemic, respiratory and cellular immunity, the S1-SF-10-IT vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.

Food allergy is one of the major existing health problems, but no effective treatment is available. In the current work, a murine model that closely mimics pathogenesis of human food allergy and its quantifiable diagnostic parameter design, even for mild hypersensitivity reactions, were established. BALB/c mice were epicutaneously sensitized with 1 mg chicken egg ovomucoid (OVM) or cow’s milk casein, free of adjuvants, five times a week for two consecutive weeks. Eleven days later, allergen-specific IgG1 and IgE in serum were measured by ELISA. On day 25, 20 mg OVM or 12 mg α-casein was administered orally, and allergic reactions such as the fall in rectal temperature, symptom scores during 90–120 min, serum mast cell protease-1 and cytokine levels were monitored. The detection of mild allergic reactions due to adjuvant-free allergen sensitization and oral allergen challenge routes was amplified by the combination of oral allergen and aspirin administration simultaneously or aspirin administration within 15–30 min before an allergen challenge. Quantification of the maximum symptom score and the frequency of symptoms during the monitoring period improved evaluation accuracy of food allergy signals. Based on these results, efficacy of casein oral immunotherapy for cow’s milk allergies, which are generally difficult to detect, was monitored adequately.

Organic aerosols (OA) are major components of fine particulate matter, yet their formation mechanism remains unclear, especially in polluted environments. In this study, we investigated the diurnal chemical compositions and formation processes of OA in carbonaceous particles during winter in Beijing using aerosol time-of-flight mass spectrometry. We found that 84.5% of the measured carbonaceous particles underwent aging processes, characterized by larger diameter and more secondary species compared to fresh carbonaceous particles, and presented different chemical compositions of OA in the daytime and nighttime. During the day, under high O

Microplastic (MP) pollution in the aquatic environment is a cause for increasing concern. However, analyzing MPs ingested by small organisms, such as zooplankton, is difficult because of the low content and small size of the ingested MPs. We attempted to determine the content of ingested MPs in individual zooplankton using pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). To establish zooplankton model of MP ingestion, individual Daphnia magna were cultivated separately in microplate cells with polystyrene (PS) microspheres (10 μm in diameter, 245,000 particles, 135 μg) under different conditions. To prepare calibration curves for determining ingested PS content, approximately 100-150 μg of commercially available Daphnia-based powdered fish food, roughly corresponding to the weight of a single D. magna organism, was mixed with PS microspheres (0.005-26 μg) and analyzed using Py-GC-MS at 600 °C. In the resulting pyrograms, peaks of the styrene monomer and trimer from PS were detected, and linear relationships were obtained between the relative peak area and the amount of added PS. Finally, the cultivated zooplankton were individually subjected to Py-GC-MS analysis, and the ingested PS content in each zooplankton was successfully determined. Individual zooplankton cultured with PS in the absence of food ingested 2.3-7.9 μg of PS particles, whereas that in the presence of food (Chlorella vulgaris) ingested only 0.1-0.2 μg of PS particles. This result suggests that zooplankton might preferentially ingest ordinary food when both food and MPs are present, although further systematic studies are necessary to validate this observation.

Antiviral neuraminidase inhibitors, such as oseltamivir, zanamivir, and peramivir, are widely used for treatment of influenza virus infection. We reported previously that oseltamivir inhibits the viral growth cycle, ameliorates symptoms, and reduces viral antigen quantities. Suppressed viral antigen production, however, induces a reduction of acquired antiviral humoral immunity, and increases the incidence of re-infection rate in the following year. To achieve effective treatment of influenza virus infection, it is necessary to overcome these adverse effects of antiviral neuraminidase inhibitors. Feeding of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 is reported to have immune-stimulatory effects on influenza virus infection in mice and humans. In the present study, we assessed the effect of feeding L. bulgaricus OLL1073R-1 yogurt cultures (YC) on local and systemic humoral immune responses, which were suppressed by oseltamivir treatment, in mice infected with influenza A virus. Yogurt culture (1.14 × 108 cfu/0.4 mL per mouse per day) or sterile water (vehicle) was administered by intragastric gavage for 35 d. At d 22, influenza A virus/Puerto Rico/8/34 (H1N1) (PR8; 0.5 pfu/15 μL per mouse) was instilled intranasally, followed immediately by oral administration of oseltamivir (50 μg/100 μL per mouse, twice daily) or 5% methylcellulose (100 μL/mouse) as a vehicle for 13 d. Titers of anti-PR8-specific IgG and IgA in serum and mucosal secretory IgA (S-IgA) and IgG in bronchoalveolar lavage fluid (BALF) were analyzed by ELISA at 14 d after infection. Oseltamivir significantly suppressed the induction of anti-PR8-specific IgG and IgA in serum and S-IgA and IgG in BALF after infection. Feeding YC mildly but significantly stimulated production of PR8-specific IgA in serum, S-IgA in BALF, and IgG in serum without changing the IgG2a:IgG1 ratio. We analyzed the neutralizing activities against PR8 in serum and BALF and found that oseltamivir also reduced protective immunity, and YC feeding abrogated this effect. The immune-stimulatory tendency of YC on anti-PR8-specific IgA and IgG titers in serum and BALF was also detected in mice re-infected with PR8, but the effect was insignificant, unlike the effect of YC in the initial infection.

Organic aerosols (OA) are major components of fine particulate matter, yet their formation mechanism remains unclear, especially in polluted environments. Laboratory studies have shown that the OA formation processes may be different under irradiated and dark conditions, but few studies have explored this aspect in ambient air. Here we investigate the diurnal chemical composition and formation processes of OA in carbonaceous particles during winter in Beijing using aerosol time-of-flight mass spectrometry. Our results show that 84.5% of carbonaceous particles undergo aging processes, characterized with larger size and more secondary species compared to fresh carbonaceous particles, and present different chemical compositions of OA in the daytime and nighttime. During the day, organosulfates and oligomers exist in the aged carbonaceous particles, which are mixed with a higher abundance of nitrate compared with sulfate. At night, distinct spectral signatures of hydroxymethanesulfonate and organic nitrogen compounds, and a minor abundance of other hydroxyalkylsulfonates and high molecular weight organic compounds are present in the aged carbonaceous particles, which are mixed with a higher abundance of sulfate compared with nitrate. Our results indicate that photochemistry dominates the formation of OA under high oxidant concentrations in the daytime, while aqueous chemistry plays an important role in the formation of OA under high relative humidity in the nighttime. The findings can help improve the performance of air quality and climate models on OA simulation.

An online field observation was conducted in Zibo, China from September 1, 2018 to February 28, 2019, covering autumn and winter. Within the investigation period, the mean mass concentrations of PM

To control the spread of COVID-19, China implemented a series of lockdowns, limiting various offline interactions. This provided an opportunity to study the response of air quality to emissions control. By comparing the characteristics of pollution in the summers of 2019 and 2020, we found a significant decrease in gaseous pollutants in 2020. However, particle pollution in the summer of 2020 was more severe; PM2.5 levels increased from 35.8 to 44.7 μg m−3, and PM10 increased from 51.4 to 69.0 μg m−3 from 2019 to 2020. The higher PM10 was caused by two sandstorm events on May 11 and June 3, 2020, while the higher PM2.5 was the result of enhanced secondary formation processes indicated by the higher sulfate oxidation rate (SOR) and nitrate oxidation rate (NOR) in 2020. Higher SOR and NOR were attributed mainly to higher relative humidity and stronger oxidizing capacity. Analysis of PMx distribution showed that severe haze occurred when particles within Bin2 (size ranging 1–2.5 μm) dominated. SO42−(1/2.5) and SO42−(2.5/10) remained stable under different periods at 0.5 and 0.8, respectively, indicating that SO42− existed mainly in smaller particles. Decreases in NO3−(1/2.5) and increases in NO3−(2.5/10) from clean to polluted conditions, similar to the variations in PMx distribution, suggest that NO3− played a role in the worsening of pollution. O3 concentrations were higher in 2020 (108.6 μg m−3) than in 2019 (96.8 μg m−3). Marked decreases in fresh NO alleviated the titration of O3. Furthermore, the oxidation reaction of NO2 that produces NO3− was dominant over the photochemical reaction of NO2 that produces O3, making NO2 less important for O3 pollution. In comparison, a lower VOC/NOx ratio (less than 10) meant that Beijing is a VOC-limited area; this indicates that in order to alleviate O3 pollution in Beijing, emissions of VOCs should be controlled.

Influenza A virus is one of the most common infectious pathogen and associated with significant morbidity and mortality. Infected patients with underlying diseases show rapid progression in disease severity. The initial pathogenic process of influenza virus infection is characterized by the induction of various proinflammatory cytokines as well as host cellular trypsin-type viral envelope-processing proteases in the airway, which enhance viral multiplication. This process has been termed the “influenza virus−cytokine−trypsin” cycle. In the advanced stage of infection, the cytokine storm induces disorders of glucose and lipid metabolism in the mitochondria, resulting in ATP crisis and various functional disorders particularly in organs and cells with high ATP consumption, such as vascular endothelial cells and cardiomyocytes. This process has been termed interconnection of the “metabolic disorders−cytokine” cycle with the “influenza virus−cytokine−trypsin” cycle. The interconnection exacerbates mitochondrial ATP crisis and could lead to multiple organ failure with severe edema. Breaking these cycles and interconnection is a promising therapeutic approach against severe influenza. In this review, we discuss the pathogenesis of severe influenza viral infection based on animal experiments and the potential therapeutic options.

Organic aerosols (OA) undergo sophisticated physiochemical processes in the atmosphere, playing a crucial role in extreme haze formations over the Northern China Plain. However, current understandings of the detailed composition and formation pathways are limited. In this study, high-molecular weight (HMW) species were observed in samples collected year-round in urban Beijing, especially in autumn and winter, during 2016–2017. The positive-ion-mode mass spectra of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) showed that higher signal intensities were obtained in the mass-to-charge (m/z) ranges of 200–500 and 800–900, with repetitive mass difference patterns of m/z 12, 14, 16, and 18. This provided sound evidence that high-molecular-weight oligomers were generated as haze episodes became exacerbated. These oligomer signal intensities were enhanced in the presence of high relative humidity, aerosol water content, and PM2.5 (particles with an aerodynamic diameter ≤ 2.5 μm) mass, proving that the multiphase reaction processes play a fundamental role in haze formation in Beijing. Our study can form a basis for improved air pollution mitigation measures aimed at OA to improve health outcomes.

Continuous haze monitoring was conducted from 12:00 3 April to 12:00 8 April 2016 in Beijing, China to develop a more detailed understanding of spring haze characteristics. The PM2.5 concentration ranged from 6.30 to 165 μg m−3 with an average of 63.8 μg m−3. Nitrate was the most abundant species, accounting for 36.4% of PM2.5, followed by organic carbon (21.5%), NH4+ (19.3%), SO42− (18.8%), and elemental carbon (4.10%), indicating the key role of nitrate in this haze event. Species contribution varied based on the phase of the haze event. For example, sulfate concentration was high during the haze formation phase, nitrate was high during the haze, and secondary organic carbon (SOC) had the highest contribution during the scavenging phase. The secondary transition of sulfate was influenced by SO2, followed by relative humidity (RH) and Ox (O3+NO2). Nitrate formation occurred in two stages: through NO2 oxidation, which was vulnerable to Ox; and by the partitioning of N (+5) which was susceptible to RH and temperature. SOC tended to form when Ox and RH were balanced. According to hourly species behavior, sulfate and nitrate were enriched during haze formation when the mixed layer height decreased. However, SOC accumulated prior to the haze event and during formation, which demonstrated the strong contribution of secondary inorganic aerosols, and the limiting contribution of SOC to this haze case. Investigating backward trajectories showed that high speed northwestern air masses following a straight path corresponded to the clear periods, while southwesterly air masses which traversed heavily polluted regions brought abundant pollutants to Beijing and stimulated the occurrence of haze pollution. Results indicate that the control of NO2 needs to be addressed to reduce spring haze. Finally, the correlation between air mass trajectories and pollution conditions in Beijing reinforce the necessity of inter-regional cooperation and control.

An online field observation was conducted in Zibo, China from September 1, 2018 to February 28, 2019, covering autumn and winter. Within the investigation period, the mean mass concentrations of PM1, PM2.5, and PM10 were 49.3, 86.1, and 136.5 μg m−3, respectively. OA (organic aerosol) was the most dominant species in PM2.5 (39.7 %), followed by NO3− (26.3 %) and SO42− (17.0 %), indicating the importance of secondary species on PM2.5. Increase of particles were always accompanied increasing relative humidity (RH), slow wind, and increasing precursors, contributing the secondary transition. SO42− was more susceptible to RH, indicating the dominant role of heterogeneous processes in its secondary formation. As RH increased, its strengthening effect on SO42− increased as well. Photochemistry was the main contributor to the secondary formation of NO3−. The morning and evening rush hours determined the peak of absolute NO3− throughout the day. By classifying particles into three bins, we found that smaller particles were the biggest contributors (larger PM1/PM2.5) of slight pollution (35

The influenza A virus (IAV)-cytokine-trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein-1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9.

Heavy haze pollution occurs frequently in northern China, most critically in the Beijing-Tianjin-Hebei area (BTH). Zibo, an industrial city located in Shandong province, is often listed as one of the top ten most polluted cities in China, particularly in winter. However, no studies of haze in Zibo have been conducted, which limits the understanding of the source and formation of haze pollution in this area, as well as mutual effects with the BTH area. We carried out online and continuous integrated field observation of particulate matter in winter, from 11 to 25 January 2015. SO42−, NO3−, and NH4+ (SIA) and organics were the main constituents of PM2.5, contributing 59.4% and 33.6%, respectively. With the increasing severity of pollution, the contribution of SIA increased while that of organics decreased. Meteorological conditions play an important role in haze formation; high relative humidity (RH) and low wind speed increased both the accumulation of pollutants and the secondary transition from gas precursors (gas-particle phase partitioning). Since RH and the presence of O3 can indicate heterogeneous and photochemistry processes, respectively, we carried out correlation analysis and linear regression to identify their relative importance to the three main secondary species (sulfate, nitrate, and secondary organic carbon (SOC)). We found that the impact of RH is in the order of SO42− > NO3− > SOC, while the impact of O3 is reversed, in the order of SOC > NO3− > SO42−, indicating different effect of these factors on the secondary formation of main species in winter. Cluster analysis of backward trajectories showed that, during the observation period, six directional sources of air masses were identified, and more than 90% came from highly industrialized areas, indicating that regional transport from industrialized areas aggravates the haze pollution in Zibo. Inter-regional joint prevention and control is necessary to prevent further deterioration of the air quality.

Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.

Haze episodes occurred in Beijing repeatedly in 2013, resulting in 189 polluted days. These episodes differed in terms of sources, formation processes, and chemical composition and thus required different control policies. Therefore, an overview of the similarities and differences among these episodes is needed. For this purpose, we conducted one-year online observations and developed a program that can simultaneously divide haze episodes and identify their shapes. A total of 73 episodes were identified, and their shapes were linked with synoptic conditions. Pure-haze events dominated in wintertime, whereas mixed haze-dust (PM2.5/PM10 < 60%) and mixed haze-fog (Aerosol Water/PM2.5 ∼ 0.3) events dominated in spring and summer-autumn, respectively. For all types, increase of ratio of PM2.5 in PM10 was typically achieved before PM2.5 reached ∼150 μg/m(3). In all PM2.5 species observed, organic matter (OM) was always the most abundant component (18-60%), but it was rarely the driving factor: its relative contribution usually decreased as the pollution level increased. The only OM-driven episode observed was associated with intensive biomass-burning activities. In comparison, haze evolution generally coincided with increasing sulfur and nitrogen oxidation ratios (SOR and NOR), indicating the enhanced production of secondary inorganic species. Applicability of these conclusions required further tests with simultaneously multisite observations.

Infrared waveguide spectroscopy using a sapphire rod coated with an amorphous fluoropolymer (Cytop, Asahi Glass Co., ltd, Japan) has been developed in order to directly observe CO2 in aqueous solutions. Since the amorphous fluoropolymer has a relatively high gas-permeability and hydrophobic feature, the aqueous CO2 transmits into the amorphous fluoropolymer coating film, but water cannot penetrate into the film. Good linearity of calibration curves for CO2 in the gas and the aqueous solution were obtained.

Changzhou, an industrial city in the Yangtze River Delta, has been experiencing serious haze pollution, particularly in winter. However, studies pertaining to the haze in Changzhou are very limited, which makes it difficult to understand the characteristics and formation of winter haze in this area, and develop effective control measures. In this study, we carried out continuous online observation of particulate matter, chemical components, and meteorology in Changzhou in February 2017. Our results showed that haze pollution occurred frequently in Changzhou winter and exhibited two patterns: dry haze with low relative humidity (RH) and wet haze with high RH. Water-soluble inorganic ions (SO42−, NO3−, and NH4+) accounted for ∼52.2% of the PM2.5 mass, of which sulfate was dominant in wet haze periods while nitrate was dominant in other periods. With the deterioration of haze pollution, the proportion of nitrate in PM2.5 increased, while sulfate proportion increased under wet haze and decreased under dry haze. Dry haze and wet haze appeared under slow north wind and south wind, respectively, and strong north wind or sea breeze scavenged pollution. We found that formation of nitrate occurred rapidly in daytime with high concentrations of odd oxygen (Ox = O3 + NO2), whereas formation of sulfate occurred rapidly during nighttime with high RH, indicating that photochemistry and heterogeneous reaction were the major formation mechanisms for nitrate and sulfate, respectively. Through the cluster analysis of 36-h backward trajectories, five sources of air masses from three directions were identified. High PM2.5 concentrations (84.1 μg m−3 on average) usually occurred under the influence of two clusters (46%) from the northwest, indicating that regional transport from northern China aggravated the winter haze pollution in Changzhou. Emission reduction, particularly the mobile sources, and regional joint prevention and control can help to mitigate the winter haze in Changzhou.

In the Northern China Plain (NCP), extreme haze events with high concentrations of fine particles occur frequently during the winter but rarely occur in autumn. In this study, we present a synthetic analysis of particulate constituents during the historically polluted transition period of autumn–winter in 2018, revealing that mixed-type haze episodes are the result of regional transport, homogeneous/heterogeneous conversion, and sandstorm influences. The hydrolysis process of N2O5 at higher relative humidity levels (>70%), which feature an enhanced nitrate oxidation ratio (0.30–0.70) and NO3− concentration (>60 μg m−3), was the driving factor for high PM2.5 mass concentrations during the observation periods. The long-distance transport of sandstorms, characterized by decreasing PM2.5/PM10 ratios (

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.

Organic aerosol (OA) are always the most abundant species in terms of relative proportion to PM2.5 concentration in Beijing, while in previous studies, poor link between carbonaceous particles and their gaseous precursors were established based on field observation results. Through this study, we provided a comprehensive analysis of critical carbonaceous species in the atmosphere. The concentrations, diurnal variations, conversions, and gas-particle partitioning (F-factor) of 8 carbonaceous species, carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), volatile organic compounds (VOCs), non-methane hydrocarbon (NMHC), organic carbon (OC), elemental carbon (EC), and water soluble organic compounds (WSOCs), in Beijing were analyzed synthetically. Carbonaceous gases (CO, CO2, VOCs, and CH4) and OC/EC ratios exhibited double-peak diurnal patterns with a pronounced midnight peak, especially in winter. High correlation between VOCs and OC during winter nighttime indicated that OC was formed from VOCs precursors via an unknown mechanism at relative humidity greater than 50% and 80%, thereby promoting WSOC formation in PM1 and PM2.5 respectively. The established F-factor method was effective to describe gas-to-particle transformation of carbonaceous species and was a good indicator for haze events since high F-factors corresponded with enhanced PM2.5 level. Moreover, higher F-factors in winter indicated carbonaceous species were more likely to exist as particles in Beijing. These results can help gain a comprehensive understanding of carbon cycle and formation of secondary organic aerosols from gaseous precursors in the atmosphere.

Nitrogenous species, as important chemical components in PM2.5, include organic nitrogen (ON) and inorganic nitrogen (IN), both of which have potential effects on human health, climate change and visibility degradation. In this study, we analyzed total nitrogen (TN) by CHN Elemental analyzer and inorganic nitrogen by ion chromatography (IC) respectively to obtain ON by calculating the difference between TN and IN. The results show that the mean ON concentrations in winter and summer are both 2.86 μg·m−3, ten times higher than other places reported on average. ON contributes about 20%–30% to TN on average in both seasons, presenting higher contribution in summer. N:C ratios are much higher in summer than winter. ON sources or formation were strengthened by heavy PM2.5 pollution loads, especially sensitive to sulfate. ON concentrations are higher at night in the both seasons, however with distinguished day and night difference patterns influenced by relative humidity (RH) conditions. In winter, ON concentrations increase with RH on average through low RH values to high RH values. The variations are far larger than the ones caused by day and night difference. However in summer, day and night difference dominates the variations of ON concentrations at low RH values, and RH conditions promote ON concentrations increase significantly only at high RH values. Dust related source and anthropogenic emission related secondary source are identified as important sources for ON. At heavy pollution loads, ON sources are more of secondary formation, possibly strengthened by combination influence of RH and acidity increase.

Extreme haze episodes repeatedly shrouded Beijing during the winter of 2012–2013, causing major environmental and health problems. To better understand these extreme events, we performed a model-assisted analysis of the hourly observation data of PM2.5 and its major chemical compositions. The synthetic analysis shows that (1) the severe winter haze was driven by stable synoptic meteorological conditions over northeastern China, and not by an abrupt increase in anthropogenic emissions. (2) Secondary species, including organics, sulfate, nitrate, and ammonium, were the major constituents of PM2.5 during this period. (3) Due to the dimming effect of high loading of aerosol particles, gaseous oxidant concentrations decreased significantly, suggesting a reduced production of secondary aerosols through gas-phase reactions. Surprisingly, the observational data reveals an enhanced production rate of secondary aerosols, suggesting an important contribution from other formation pathways, most likely heterogeneous reactions. These reactions appeared to be more efficient in producing secondary inorganics aerosols than organic aerosols resulting in a strongly elevated fraction of inorganics during heavily polluted periods. (4) Moreover, we found that high aerosol concentration was a regional phenomenon. The accumulation process of aerosol particles occurred successively from cities southeast of Beijing. The apparent sharp increase in PM2.5 concentration of up to several hundred μg m−3 per hour recorded in Beijing represented rapid recovery from an interruption to the continuous pollution accumulation over the region, rather than purely local chemical production. This suggests that regional transport of pollutants played an important role during these severe pollution events.

Continuous field observations of haze pollution were conducted in winter and summer during 2015 in Zibo, a highly industrialized city in the North China Plain that is adjacent to the Jing-Jin-Ji area. PM2.5 concentration averaged 146.7 ± 85.8 and 82.2 ± 44.3 μg m−3 in winter and summer, respectively. The chemical component contributions to PM2.5 showed obvious seasonal variation. Organics were high in winter, but secondary inorganic aerosols (SIA) were high in summer. From non-haze to haze days, the concentration of SIA increased, implying an important role of secondary processes in the evolution process of the pollution. The diurnal behavior of several pollutants during haze days appeared to fluctuate more, but during non-haze days, it was much more stable, suggesting that complex mechanisms are involved. Specifically, gaseous precursors, mixed layer height (MLH), photochemical activity, and relative humidity (RH) also played important roles in the diurnal variation of the pollutants. Normally, larger gaseous precursor concentrations, photochemical activity, and RH, and lower MLH favored high concentrations. In winter, the formation of sulfate was mainly influenced by RH, indicating the importance of heterogeneous reactions in its formation. In contrast, in summer, photochemistry and SO2 concentration had the largest impact on the sulfate level. We found that Zibo was an ammonia-rich city, especially in winter, meaning that the formation of nitrate was through homogeneous reactions between HNO3 and NH3 in the gas phase, followed by partitioning into the particle phase. The RH, NO2, and Excess NH4+ were the main influencing factors for nitrate in winter, whereas Excess NH4+, RH, and temperature were the key factors in summer. The secondary organic carbon (SOC) level depended on the MLH and photochemistry. In winter, the effect of the MLH was stronger than that of photochemistry, but a reversed situation occurred in summer because of the intensive photochemistry. Our work suggested that the inter-transport between Zibo, one of the most polluted cities in north China, and its adjacent areas should be taken into account when formulating air pollution control policy.

Severe regional haze pollution events occurred in eastern and central China in January 2013, which had adverse effects on the environment and public health. Extremely high levels of particulate matter with aerodynamic diameter of 2.5 μm or less (PM2.5) with dominant components of sulfate and nitrate are responsible for the haze pollution. Although heterogeneous chemistry is thought to play an important role in the production of sulfate and nitrate during haze episodes, few studies have comprehensively evaluated the effect of heterogeneous chemistry on haze formation in China by using the 3-D models due to of a lack of treatments for heterogeneous reactions in most climate and chemical transport models. In this work, the WRF-CMAQ model with newly added heterogeneous reactions is applied to East Asia to evaluate the impacts of heterogeneous chemistry and the meteorological anomaly during January 2013 on regional haze formation. As the parameterization of heterogeneous reactions on different types of particles is not well established yet, we arbitrarily selected the uptake coefficients from reactions on dust particles and then conducted several sensitivity runs to find the value that can best match observations. The revised CMAQ with heterogeneous chemistry not only captures the magnitude and temporal variation of sulfate and nitrate, but also reproduces the enhancement of relative contribution of sulfate and nitrate to PM2.5 mass from clean days to polluted haze days. These results indicate the significant role of heterogeneous chemistry in regional haze formation and improve the understanding of the haze formation mechanisms during the January 2013 episode.

Infrared waveguide spectroscopy using a sapphire rod coated with an amorphous fluoropolymer (Cytop, Asahi Glass Co., ltd, Japan) has been developed in order to directly observe CO

Extreme haze episodes repeatedly shrouded Beijing during the winter of 2012–2013, causing major environmental and health problems. To better understand these extreme events, we analyzed the hourly observation data of PM2.5 and its major chemical composition, with support of model simulations. Severe winter haze was shown to result from stable synoptic meteorological conditions over a large part of northeastern China, rather than from an abrupt increase in emissions. Build-up of secondary species, including organics, sulfate, nitrate, and ammonium, was the major driving force behind these polluted periods. The contribution of organic matter decreased with increasing pollution level while sulfate and nitrate contributions increased. Correspondingly, the ratio of secondary organic carbon to elemental carbon decreased and had a stable diurnal pattern during heavily polluted periods, indicating weakened photochemical activity due to the dimming effect of high loading of aerosol particles. Under such conditions, the strong increase in sulfate and nitrate contributions to PM2.5 was attributed to an elevated conversion ratio, reflecting more active heterogeneous reactions with gradually increasing relative humidity. Moreover, we found that high aerosol concentration was a regional phenomenon. The accumulation process of aerosol particles occurred successively from southeast cities to Beijing. The "apparent" sharp increase in PM2.5 concentration of up to several hundred μg m−3 per hour recorded in Beijing represented rapid "recovery" from an "interruption" to the continuous pollution accumulation over the region, rather than purely local chemical production. This suggests that regional transport of pollutants played an important role during these severe pollution events.

It was shown that acyclic intermediates play a role in the chemiexcitation of the chemiluminescence (CL) of lophine peroxides in addition to the dioxetane intermediates. Because the CL efficiencies of position-isomers (R)-9 and (R)-10, which theoretically give the common dioxetane intermediate, were different, the different CL efficiencies are attributable to the CL mechanism involving a partially cyclic transition structure at the chemiexcitation step.

Background We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. Objectives The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy. Methods We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed. Results and Conclusions Intranasal immunization with HA–SF–10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA–SF–10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA–SF–10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA–SF–10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially.

Four haze episodes (EPs) were observed in October 2014 in Beijing, China. For better understanding of the characteristics and the formation mechanisms of PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm), especially secondary water-soluble inorganic species in these haze events, hourly concentrations of PM2.5, sulfate, nitrate, and ammonium (SNA) were measured in this study. Concentrations of gaseous pollutants and meteorological parameters were also measured. The average concentration of PM2.5 was 106.6 ± 83.5 μg m−3, which accounted for around 53% of PM10 (particulate matter with an aerodynamic diameter ≤ 10 μm) mass. Nitrogen dioxide (NO2) concentration was much higher than that of sulfur dioxide (SO2) since October is a non-heating month. SNA is the most abundant secondary water-soluble inorganic species and contributed to 33% of PM2.5 mass concentration. Sulfur oxidation ratio (SOR) was much higher than nitrogen oxidation ratio (NOR). NOR and SOR increased with elevated PM2.5 levels and heterogeneous processes seemed to be the most plausible explanation of this increase. Relative humidity (RH), which is of great influence on aerosol liquid water content (ALWC), played a considerable role in the formation of secondary inorganic aerosols, accelerated the secondary transformation of gaseous precursors, and further aggravated haze pollution. The positive feedback loop associated with high aerosol levels and low planetary boundary layer (PBL) height led to the evolution and exacerbation of heavy haze pollution. Fire maps and 48-h air mass backward trajectories supported the significant impact of biomass burning activities and regional transport on haze formation over Beijing in October 2014.

Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD.The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA).Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD.Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

High molecular weight organic compounds (HMW-OCs), formed as secondary organic aerosols (SOA), have been reported in many laboratory studies. However, little evidence of HMW-OCs formation, in particular during winter season in the real atmosphere, has been reported. In January 2013, Beijing faced historically severe haze pollution, in which the hourly PM2.5 concentration reached as high as 974 μg m-3. Four typical haze events (HE1 to HE4) were identified, and HE2 (Jan. 9-16) was the most serious of these. Based on the hourly observed chemical composition of PM2.5 and the daily organic composition analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), we found that abundant ion peaks in m/z 200-850 appeared on heavy haze days, whereas these were negligible on a clear day, indicating the existence of HMW-OCs in the wintertime haze. A negative nonlinear correlation between HMW-OCs and O3 suggested that gas oxidation was not likely to be the dominant mechanism for HMW-OCs formation. During the heavy haze events, the relative humidity and mass ratio of H2O/PM2.5 reached as high as 80% and 0.2, respectively. The high water content and its good positive correlation with HMW-OCs indicated that an aqueous-phase process may be a significant pathway in wintertime. The evidence that acidity was much higher during HE2 (0.37 μg m-3) than on other days, as well as its strong correlation with HMW-OCs, indicated that acid-catalyzed reactions likely resulted in HMW-OCs formation during the heavy winter haze in Beijing.