Publisher Correction: Evidence that CD32a does not mark the HIV-1 latent reservoir.

In this Brief Communications Arising Comment, the first three authors (Osuna, Lim and Kublin) should have been listed as equally contributing authors; this has been corrected online.

Pollution characteristics and health risk assessment of polycyclic aromatic hydrocarbons and nitrated polycyclic aromatic hydrocarbons during heating season in Beijing.

Polycyclic aromatic hydrocarbons (PAHs) and their nitrated derivatives (NPAHs) attract continuous attention due to their outstanding carcinogenicity and mutagenicity. In order to investigate the diurnal variations, sources, formation mechanism, and health risk assessment of them in heating season, particulate matter (PM) were collected in Beijing urban area from December 26, 2017 to January 17, 2018. PAHs and NPAHs in PM were quantitatively analyzed via gas chromatography-mass spectrometry (GC-MS) . Average daily concentrations of PAHs and NPAHs were (78 ± 54) ng/m3 and (783 ± 684) pg/m3, respectively. The concentrations of them were significantly higher at nighttime than at daytime, and NPAHs concentrations were 1-2 orders of magnitude lower than PAHs concentrations. In the heating season, the dominant species of PAHs include benzo[b]fluoranthene, fluoranthene, pyrene, and chrysene, while 9-nitroanthracene, 2+3-nitrofluoranthene, and 2-nitropyrene were dominant species for NPAHs. NPAHs were found to have a single peak during heating and to be primarily distributed in the 0.4-0.7 µm particle size. Primary emissions such as biomass burning, coal combustion, and traffic emissions were the major sources of PAHs. NPAHs were produced by the primary source of vehicle emissions and the secondary reaction triggered by OH radicals, as well as biomass burning during daytime. According to the health risk assessment, the total carcinogenic risk was higher in adults than in children. While upon oral ingestion, the carcinogenic risk in children was higher than that of adults, but the risk of adults was higher than children through skin contact and respiratory inhalation.

Selective BCL-XL Antagonists Eliminate Infected Cells from a Primary-Cell Model of HIV Latency but Not from Ex Vivo Reservoirs.

HIV persists, despite immune responses and antiretroviral therapy, in viral reservoirs that seed rebound viremia if therapy is interrupted. Previously, we showed that the BCL-2 protein contributes to HIV persistence by conferring a survival advantage to reservoir-harboring cells. Here, we demonstrate that many of the BCL-2 family members are overexpressed in HIV-infected CD4+ T cells, indicating increased tension between proapoptotic and prosurvival family members-and suggesting that inhibition of prosurvival members may disproportionately affect the survival of HIV-infected cells. Based on these results, we chose to study BCL-XL due to its consistent overexpression and the availability of selective antagonists. Infection of primary CD4+ T cells with HIV resulted in increased BCL-XL protein expression, and treatment with two selective BCL-XL antagonists, A-1155463 and A-1551852, led to selective death of productively infected CD4+ T cells. In a primary cell model of latency, both BCL-XL antagonists drove reductions in HIV DNA and in infectious cell frequencies both alone and in combination with the latency reversing agent bryostatin-1, with little off-target cytotoxicity. However, these antagonists, with or without bryostatin-1 or in combination with the highly potent latency reversing agent combination phorbol myristate acetate (PMA) + ionomycin, failed to reduce total HIV DNA and infectious reservoirs in ex vivo CD4+ T cells from antiretroviral therapy (ART)-suppressed donors. Our results add to growing evidence that bona fide reservoir-harboring cells are resistant to multiple "kick and kill" modalities-relative to latency models. We also interpret our results as encouraging further exploration of BCL-XL antagonists for cure, where combination approaches, including with immune effectors, may unlock the ability to eliminate ex vivo reservoirs. IMPORTANCE Although antiretroviral therapy (ART) has transformed HIV infection into a manageable chronic condition, there is no safe or scalable cure. HIV persists in "reservoirs" of infected cells that reinitiate disease progression if ART is interrupted. Whereas most efforts to eliminate this reservoir have focused on exposing these cells to immune-mediated clearance by reversing viral latency, recent work shows that these cells also resist being killed. Here, we identify a "prosurvival" factor, BCL-XL, that is overexpressed in HIV-infected cells, and demonstrate selective toxicity to these cells by BCL-XL antagonists. These antagonists also reduced reservoirs in a primary-cell latency model but were insufficient to reduce "natural" reservoirs in ex vivo CD4+ T cells-adding to growing evidence that the latter are resilient in a way that is not reflected in models. We nonetheless suggest that the selective toxicity of BCL-XL antagonists to HIV-infected cells supports their prioritization for testing in combinations aimed at reducing ex vivo reservoirs.

Evolution of aerosol chemistry in Beijing under strong influence of anthropogenic pollutants: Composition, sources, and secondary formation of fine particulate nitrated aromatic compounds.

Nitrated aromatic compounds (NACs) constitute a key segment of brown carbon (BrC), thereby contributing to the light-absorbing characteristics of aerosols in the atmosphere. However, until recently, there is a scarcity of research on their generation in the urban environment. The current study is based upon an extensive field study of NACs from fine particle samples obtained at an urban location in Beijing in the spring and summer of 2017, which was characterized by both high anthropogenic volatile organic compounds (VOCs) and high-NOx dominated conditions. The mean total concentration of the nine NACs was 8.58 ng m-3 in spring and 8.54 ng m-3 in summer. In the spring, the most abundant NACs were 4-nitrophenol (33.7%) and 4-nitrocatechol (19.3%), while in the summer, the most abundant NACs were 4-nitroguaiacol (34.9%) and 2, 4-dinitrophenol (23%). Atmospheric NACs were primarily produced from coal combustion (52%) and biomass burning (32%) in spring, and originated from the secondary formation (37%) and traffic (35%) in summer. NO2 could promote the formation of NACs with a significant effect on their compositions, especially for nitrophenols and nitrocatechols. It can also affect the formation of nitrated aerosols and their existing form. Inorganic nitrates were increased to conversion in the daytime when NO2 concentrations were higher than 30 ppb, but the corresponding oxidation products shifted to primarily organic ones at night. The transition was VOC-sensitive regimes for NAC formation, and nitration of toluene was a more important pathway during the campaign in Beijing.

Integrated Assessment of Viral Transcription, Antigen Presentation, and CD8+ T Cell Function Reveals Multiple Limitations of Class I-Selective Histone Deacetylase Inhibitors during HIV-1 Latency Reversal.

Clinical trials investigating histone deacetylase inhibitors (HDACi) to reverse HIV-1 latency aim to expose reservoirs in antiretroviral (ARV)-treated individuals to clearance by immune effectors, yet have not driven measurable reductions in the frequencies of infected cells. We therefore investigated the effects of the class I-selective HDACi nanatinostat and romidepsin on various blocks to latency reversal and elimination, including viral splicing, antigen presentation, and CD8+ T cell function. In ex vivo CD4+ T cells from ARV-suppressed individuals, both HDACi significantly induced viral transcription, but not splicing nor supernatant HIV-1 RNA. In an HIV-1 latency model using autologous CD8+ T cell clones as biosensors of antigen presentation, neither HDACi-treated CD4+ T cell condition induced clone degranulation. Both HDACi also impaired the function of primary CD8+ T cells in viral inhibition assays, with nanatinostat causing less impairment. These findings suggest that spliced or cell-free HIV-1 RNAs are more indicative of antigen expression than unspliced HIV-RNAs and may help to explain the limited abilities of HDACi to generate CD8+ T cell targets in vivoIMPORTANCE Antiretroviral (ARV) drug regimens suppress HIV-1 replication but are unable to cure infection. This leaves people living with HIV-1 burdened by a lifelong commitment to expensive daily medication. Furthermore, it has become clear that ARV therapy does not fully restore health, leaving individuals at elevated risk for cardiovascular disease, certain types of cancers, and neurocognitive disorders, as well as leaving them exposed to stigma. Efforts are therefore under way to develop therapies capable of curing infection. A key focus of these efforts has been on a class of drugs called histone deacetylase inhibitors (HDACi), which have the potential of exposing hidden reservoirs of HIV-1 to elimination by the immune system. Unfortunately, clinical trial results with HDACi have thus far been disappointing. In the current study, we integrate a number of experimental approaches to build a model that provides insights into the limited activity of HDACi in clinical trials and offers direction for future approaches.

Structure-Activity Relationship Analysis of Benzotriazine Analogues as HIV-1 Latency-Reversing Agents.

"Shock and kill" therapeutic strategies toward HIV eradication are based on the transcriptional activation of latent HIV with a latency-reversing agent (LRA) and the consequent killing of the reactivated cell by either the cytopathic effect of HIV or an arm of the immune system. We have recently found several benzotriazole and benzotriazine analogues that have the ability to reactivate latent HIV by inhibiting signal transducer and activator of transcription 5 (STAT5) SUMOylation and promoting STAT5 binding to the HIV long terminal repeat and increasing its transcriptional activity. To understand the essential structural groups required for biological activity of these molecules, we performed a systematic analysis of >40 analogues. First, we characterized the essential motifs within these molecules that are required for their biological activity. Second, we identified three benzotriazine analogues with similar activity. We demonstrated that these three compounds are able to increase STAT5 phosphorylation and transcriptional activity. All active analogues reactivate latent HIV in a primary cell model of latency and enhance the ability of interleukin-15 to reactivate latent HIV in cells isolated from aviremic participants. Third, this family of compounds also promote immune effector functions in vitro in the absence of toxicity or global immune activation. Finally, initial studies in mice suggest lack of acute toxicity in vivo A better understanding of the biological activity of these compounds will help in the design of improved LRAs that work via inhibition of STAT5 SUMOylation.

Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs.

Efforts to cure human immunodeficiency virus (HIV) infection are obstructed by reservoirs of latently infected CD4+ T cells that can reestablish viremia. HIV-specific broadly neutralizing antibodies (bNAbs), defined by unusually wide neutralization breadths against globally diverse viruses, may contribute to the elimination of these reservoirs by binding to reactivated cells, thus targeting them for immune clearance. However, the relationship between neutralization of reservoir isolates and binding to corresponding infected primary CD4+ T cells has not been determined. Thus, the extent to which neutralization breadths and potencies can be used to infer the corresponding parameters of infected cell binding is currently unknown. We assessed the breadths and potencies of bNAbs against 36 viruses reactivated from peripheral blood CD4+ T cells from antiretroviral (ARV)-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Single-antibody breadths ranged from 0 to 64% for neutralization (80% inhibitory concentration [IC80] of ≤10 µg/ml) and from 0 to 89% for binding, with two-antibody combinations (results for antibody combinations are theoretical/predicted) reaching levels of 0 to 83% and 50 to 100%, respectively. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (e.g., for 3BNC117, r = 0.82 and P < 0.0001). Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. Our results provide guidance on the selection of bNAbs for interventional cure studies, both by providing a direct assessment of intra- and interindividual variabilities in neutralization and infected cell binding in a novel cohort and by defining the relationships between these parameters for a panel of bNAbs.IMPORTANCE Although antiretroviral therapies have improved the lives of people who are living with HIV, they do not cure infection. Efforts are being directed towards harnessing the immune system to eliminate the virus that persists, potentially resulting in virus-free remission without medication. HIV-specific antibodies hold promise for such therapies owing to their ability to both prevent the infection of new cells (neutralization) and direct the killing of infected cells. We isolated 36 HIV strains from individuals whose virus was suppressed by medication and tested 14 different antibodies for neutralization of these viruses and for binding to cells infected with the same viruses (critical for engaging natural killer cells). For both neutralization and infected cell binding, we observed variation both between individuals and amongst different viruses within an individual. For most antibodies, neutralization activity correlated with infected cell binding. These data provide guidance on the selection of antibodies for clinical trials.

Persistent sulfate formation from London Fog to Chinese haze.

Sulfate aerosols exert profound impacts on human and ecosystem health, weather, and climate, but their formation mechanism remains uncertain. Atmospheric models consistently underpredict sulfate levels under diverse environmental conditions. From atmospheric measurements in two Chinese megacities and complementary laboratory experiments, we show that the aqueous oxidation of SO2 by NO2 is key to efficient sulfate formation but is only feasible under two atmospheric conditions: on fine aerosols with high relative humidity and NH3 neutralization or under cloud conditions. Under polluted environments, this SO2 oxidation process leads to large sulfate production rates and promotes formation of nitrate and organic matter on aqueous particles, exacerbating severe haze development. Effective haze mitigation is achievable by intervening in the sulfate formation process with enforced NH3 and NO2 control measures. In addition to explaining the polluted episodes currently occurring in China and during the 1952 London Fog, this sulfate production mechanism is widespread, and our results suggest a way to tackle this growing problem in China and much of the developing world.

Combination of thermal pretreatment and alcohol-assisted aqueous processing for rapeseed oil extraction.

BACKGROUND: The alcohol-assisted aqueous extraction processing (AAEP) of oil has many advantages such as no need for demulsification and relative low cost compared with enzymatic aqueous extraction processing (EAEP). Three kinds of thermal pretreatments including dry-heating, wet-heating and soak-heating followed by the AAEP of rapeseed oil were investigated. RESULTS: Both soak-heating and wet-heating had a higher contribution rate to oil yield than dry-heating due to the enhancement of heat transfer rate owing to the high moisture content in the rapeseed cells. However, oil from soak-heated rapeseeds showed a much lower level on peroxide value (0.41 mmol kg-1 ) than that of wet-heated rapeseeds (5.23 mmol kg-1 ). In addition, transmission electron microscopy images illustrated that promoting effects of soak-heating and wet-heating on oil release were attributed to the coalescence of oil bodies. A relative low concentration of alcohol solution as an extraction medium, the highest oil recovery of 92.77% was achieved when ground rapeseeds (mean particle size: 21.23 µm) were treated with 45% (v/v) alcohol for 2 h at 70 °C and pH 9.0. Both the acid value and the peroxide value are lower than the commercial oil produced by extrusion and hexane extraction. Furthermore, the oil produced from AAEP also had higher content of tocopherols and lower content of trans-fatty acids than the commercial oil. CONCLUSION: AAEP of oil from soak-heated rapeseeds is a promising alternative to conventional oil extraction methods. © 2019 Society of Chemical Industry.

Seasonal variation and size distribution of biogenic secondary organic aerosols at urban and continental background sites of China.

Size-resolved biogenic secondary organic aerosols (BSOA) derived from isoprene and monoterpene photooxidation in Qinghai Lake, Tibetan Plateau (a continental background site) and five cities of China were measured using gas chromatography/mass spectrometry (GC/MS). Concentrations of the determined BSOA are higher in the cities than in the background and are also higher in summer than in winter. Moreover, strong positive correlations (R2=0.44-0.90) between BSOA and sulfate were found at the six sites, suggesting that anthropogenic pollution (i.e., sulfate) could enhance SOA formation, because sulfate provides a surface favorable for acid-catalyzed formation of BSOA. Size distribution measurements showed that most of the determined SOA tracers are enriched in the fine mode (<3.3µm) except for cis-pinic and cis-pinonic acids, both presented a comparable mass in the fine and coarse (>3.3µm) modes, respectively. Mass ratio of oxidation products derived from isoprene to those from monoterpene in the five urban regions during summer are much less than those in Qinghai Lake region. In addition, in the five urban regions relative abundances of monoterpene oxidation products to SOA are much higher than those of isoprene. Such phenomena suggest that BSOA derived from monoterpenes are more abundant than those from isoprene in Chinese urban areas.

Chemical characteristics of haze particles in Xi'an during Chinese Spring Festival: Impact of fireworks burning.

Fireworks burning releases massive fine particles and gaseous pollutants, significantly deteriorating air quality during Chinese Lunar New Year (LNY) period. To investigate the impact of the fireworks burning on the atmospheric aerosol chemistry, 1-hr time resolution of PM2.5 samples in Xi'an during the winter of 2016 including the LNY were collected and detected for inorganic ions, acidity and liquid water content (LWC) of the fine aerosols. PM2.5 during the LNY was 167±87µg/m3, two times higher than the China National Ambient Air Quality Standard (75µg/m3). K+ (28wt.% of the total ion mass) was the most abundant ion in the LNY period, followed by SO42- (25wt.%) and Cl- (18wt.%). In contrast, NO3- (34wt.%) was the most abundant species in the haze periods (hourly PM2.5>75µg/m3), followed by SO42- (29.2wt.%) and NH4+ (16.3wt.%), while SO42 - (35wt.%) was the most abundant species in the clean periods (hourly PM2.5<75µg/m3), followed by NO3- (23.1wt.%) and NH4+ (11wt.%). Being different from the acidic nature in the non-LNY periods, aerosol in the LNY period presented an alkaline nature with a pH value of 7.8±1.3. LWC during the LNY period showed a robust linear correlation with K2SO4 and KCl, suggesting that aerosol hygroscopicity was dominated by inorganic salts derived from fireworks burning. Analysis of correlations between the ratios of NO3-/SO42- and NH4+/SO42- indicated that heterogeneous reaction of HNO3 with NH3 was an important formation pathway of particulate nitrate and ammonium during the LNY period.

Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection.

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1ß were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.

Boosting functional avidity of CD8+ T cells by vaccinia virus vaccination depends on intrinsic T-cell MyD88 expression but not the inflammatory milieu.

UNLABELLED: T-cell functional avidity is a crucial determinant for efficient pathogen clearance. Although recombinant DNA priming coupled with a vaccinia-vectored vaccine (VACV) boost has been widely used to mount robust CD8+ T-cell responses, how VACV boost shapes the properties of memory CD8+ T cells remains poorly defined. Here, we characterize the memory CD8+ T cells boosted by VACV and demonstrate that the intrinsic expression of MyD88 is critical for their high functional avidity. Independent of selection of clones with high-affinity T-cell receptor (TCR) or of enhanced proximal TCR signaling, the VACV boost significantly increased T-cell functional avidity through a decrease in the activation threshold. VACV-induced inflammatory milieu is not sufficient for this improvement, as simultaneous administration of the DNA vaccine and mock VACV had no effects on the functional avidity of memory CD8+ T cells. Furthermore, reciprocal adoptive transfer models revealed that the intrinsic MyD88 pathway is required for instructing the functional avidity of CD8+ T cells boosted by VACV. Taking these results together, the intrinsic MyD88 pathway is required for the high functional avidity of VACV-boosted CD8+ T cells independent of TCR selection or the VACV infection-induced MyD88-mediated inflammatory milieu. IMPORTANCE: Functional avidity is one of the crucial determinants of T-cell functionality. Interestingly, although it has been demonstrated that a DNA prime-VACV boost regimen elicits high levels of T-cell functional avidity, how VACV changes the low avidity of CD8+ T cells primed by DNA into higher ones in vivo is less defined. Here, we proved that the enhancement of CD8+ T cell avidity induced by VACV boost is mediated by the intrinsic MyD88 pathway but not the MyD88-mediated inflammatory milieu, which might provide prompts in vaccine design.

Nonlinear effect of NOx concentration decrease on secondary aerosol formation in the Beijing-Tianjin-Hebei region: Evidence from smog chamber experiments and field observations.

During the COVID-19 lockdown in the Beijing-Tianjin-Hebei (BTH) region in China, large decrease in nitrogen oxides (NOx) emissions, especially in the transportation sector, could not avoid the occurrence of heavy PM2.5 pollution where nitrate dominated the PM2.5 mass increase. To experimentally reveal the effect of NOx control on the formation of PM2.5 secondary components (nitrate in particular), photochemical simulation experiments of mixed volatile organic compounds (VOCs) under various NOx concentrations with smog chamber were performed. The proportions of gaseous precursors in the control experiment were comparable to ambient conditions typically observed in the BTH region. Under relatively constant VOCs concentrations, when the initial NOx concentration was reduced to 40% of that in the control experiment (labelled as NOx,0), the particle mass concentration was not significantly reduced, but when the initial NOx concentration decreased to 20 % of NOx,0, the mass concentration of particles as well as nitrate and organics showed a sudden decrease. A "critical point" where the mass concentration of secondary aerosol started to decline as the initial NOx concentration decreased, located at 0.2-0.4 NOx,0 (or 0.18-0.44 NO2,0) in smog chamber experiments. The oxidation capacity and solar radiation intensity played key roles in the mass concentration and compositions of the formed particles. In field observations in the BTH region in the autumn and winter seasons, the "critical point" exist at 0.15-0.34 NO2,0, which coincided mostly with the laboratory simulation results. Our results suggest that a reduction of NOx emission by >60% could lead to significant reductions of secondary aerosol formation, which can be an effective way to further alleviate PM2.5 pollution in the BTH region.

[Immunogenicities and comparison of DNA vaccines encoding pol genes derived from B`/C and A/E recombinant HIV-1 strains].

OBJECTIVE: To construct and compare the immunogenicities of DNA vaccines expressing pol genes derived from B`/C and A/E recombinant subtypes of HIV-1 in China. METHODS: Two DNA vaccines were constructed by inserting the codon optimized pol genes derived from B'/C and A/E subtypes of HIV-1 into mammalian expression vector pSV1.0. In vitro expression efficiencies of the two DNA vaccines were determined by Western blotting and their immunogenicities were compared by i.m. immunizing female BALB/c mice. After immunization, mice splenocytes were isolated sterilely and IFN-γ based enzyme linked immunospot assay (ELISPOT) was employed to read out the specific T cell immunity. RESULTS: The constructed DNA vaccines were validated by restriction enzyme digestion and DNA sequencing. Western blotting result showed both of the two DNA vaccines could be expressed at appreciable levels in vitro. Under the stimulation of Consensus B Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (636±178) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (468±265)SFCs/10(6) splenocytes (P=0.412). Under the stimulation of HIV-1 AE2f Pol peptide pools, specific T cell frequency elicited by pSVAE-Pol was (1378±611) SFCs/10(6) splenocytes; specific T cell frequency elicited by pSVCN-Pol was (713±61) SFCs/10(6) splenocytes (P=0.134). Further analysis suggested pSVAE-Pol induced specific T cell responses mainly focused on Pol 1 peptide pool, while, in addition to induce Pol 1 specific T cell responses, pSVCN-Pol could also elicit T cell responses against consensus B Pol 2 peptide pool. CONCLUSION: Although pSVAE-Pol was more immunogenic, pSVCN-Pol could induce T cell responses against broader epitope spectrum. Rational vaccine design may need combine them together.

PAHs and nitro-PAHs in urban Beijing from 2017 to 2018: Characteristics, sources, transformation mechanism and risk assessment.

Polycyclic aromatic hydrocarbons (PAHs) and their nitrated derivatives (NPAHs) attract continuous attention due to their distinct carcinogenicity and mutagenicity. To investigate the characteristics, sources, formation mechanism and health risk assessment of PAHs and NPAHs, PM2.5 were collected at an urban site in Beijing from 2017 to 2018. The highest PAHs and NPAHs concentrations were 77.92 ± 54.62 ng/m3 and 963.71 ± 695.06 pg/m3 in the winter campaign, which were several times larger than those in other seasonal campaigns. Distinct diurnal variations of nocturnal levels higher than daytime levels were shown for PAHs and NPAHs. Source analysis indicated that besides vehicle exhaust, biomass burning and coal combustion were important sources of PAHs and NPAHs in the fall and winter campaigns. Secondary formation in atmosphere was another source of NPAHs especially in the spring and summer campaigns. NO2 and RH could positively influence the heterogeneous formation of NPAHs when RH was less than 60%. Quantum calculation results confirmed the formation pathway of 2N-FLA from the OH/NO3-initiated oxidation of FLA. The results of health risk assessment showed the potential health risks for the residents, especially in the winter campaign. These results indicated that PAHs and NPAHs still deserve attention following with the decrease concentrations of particulate matter.

A sensitive simultaneous detection approach for the determination of 30 atmospheric carbonyls by 2,4-dinitrophenylhydrazine derivatization with HPLC-MS technique and its preliminary application.

Atmospheric carbonyls are important precursors of PM2.5 and ground-level ozone, and some carbonyls are toxic and harmful; thus, it is crucial to obtain accurate information on the ambient levels of carbonyls. However, the detection of carbonyls is difficult due to their relatively higher reactivities and chemical instabilities; therefore, accurate determination of atmospheric carbonyls is important. In this study, an analytical method for atmospheric carbonyls with high concentration or reactivity was developed, the precursor ion of each carbonyl compound was selected, and the declustering potential (DP) and entrance potential (EP) for each precursor ion were optimized. A 2,4-dinitrophenylhydrazine cartridge derivatization-high performance liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (DNPH-HPLC/APCI-MS) method for the determination of 30 carbonyls was established. The results showed that the linear range of 24 carbonyls was 1.2-600 ng/mL, while other 6 carbonyls was 1.2-300 ng/mL, and the detection limits of 30 carbonyls ranged from 0.092 to 0.947 ng/mL (0.005-0.049 µg/m3 with an ambient air sampling volume of 96 L). The intra-day and inter-day repeatability ranges were 0.55-4.20% and 1.40-12.48%, respectively. A preliminary application of the method was carried out in the urban area of Beijing in spring and summer of 2021, and it was found that the mean total mass concentration of 30 carbonyls was 35.894 µg/m3. This study provided additional concentration information for 14 atmospheric carbonyls, including mono-, di-, oxygen-containing and heterocyclic carbonyls, which accounted for 38% and 35% of the total mass concentration and OH radical reactivities of 30 carbonyls, respectively. This is the first investigation of simultaneous quantitative analysis of multiple atmospheric carbonyls based on commercial standard derivatives. The optimized method could provide more comprehensive information for atmospheric carbonyls and further support research concerning the role of chemical reaction processes and health effects than traditional measuring techniques.

Immunogenicity of an inactivated SARS-CoV-2 vaccine in people living with HIV-1: a non-randomized cohort study.

BACKGROUND: Inactivated COVID-19 vaccines are safe and effective in the general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). METHODS: 42 HIV-1 infected individuals who were stable on combination antiretroviral therapy (cART) and 28 healthy individuals were enrolled in this open-label two-arm non-randomized study at Hubei Provincial Center for Disease Control and Prevention, China. Two doses of an inactivated COVID-19 vaccine (BBIBP-CorV) were given on April 22, 2021 and May 25, 2021, respectively. The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. FINDINGS: All the HIV-1 infected participants had a CD4+ T cell count >200 cells/µL both at baseline (659·0 ± 221·9 cells/µL) and 4 weeks after vaccination (476·9 ± 150·8 cells/µL). No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. PLWH with low baseline CD4+/CD8+ T cell ratios (<0·6) generated lower antibody responses after vaccination than PLWH with medium (0·6∼1·0) or high (≥1·0) baseline CD4+/CD8+ T cell ratios (P<0·01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination (P<0·0001), but it did not lead to any adverse clinical manifestation. Moreover, we found that the general HIV-1 viral load among the PLWH cohort decreased significantly after vaccination (P=0·0192). The alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation (P>0·2). INTERPRETATION: Our data demonstrated that the inactivated SARS-CoV-2 vaccine was safe, immunogenic in PLWH who are stable on cART with suppressed viral load and CD4+ T cell count > 200 cells/µL. However, the persistence of the vaccine-induced immunities in PLWH need to be further investigated.