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.

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.

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.

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.

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.

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.

Characterizing the Relationship Between Neutralization Sensitivity and env Gene Diversity During ART Suppression.

Although antiretroviral therapy (ART) successfully suppresses HIV-1 replication, ART-treated individuals must maintain therapy to avoid rebound from an integrated viral reservoir. Strategies to limit or clear this reservoir are urgently needed. Individuals infected for longer periods prior to ART appear to harbor more genetically diverse virus, but the roles of duration of infection and viral diversity in the humoral immune response remain to be studied. We aim to clarify a role, if any, for autologous and heterologous antibodies in multi-pronged approaches to clearing infection. To that end, we have characterized the breadths and potencies of antibody responses in individuals with varying durations of infection and HIV-1 envelope (env) gene diversity as well as the sensitivity of their inducible virus reservoir to broadly neutralizing antibodies (bNAbs). Plasma was collected from 8 well-characterized HIV-1+ males on ART with varied durations of active infection. HIV envs from reservoir-derived outgrowth viruses were amplified and single genome sequenced in order to measure genetic diversity in each participant. IgG from plasma was analyzed for binding titers against gp41 and gp120 proteins, and for neutralizing titers against a global HIV-1 reference panel as well as autologous outgrowth viruses. The sensitivity to bNAbs of these same autologous viruses was measured. Overall, we observed that greater env diversity was associated with higher neutralizing titers against the global panel and also increased resistance to certain bNAbs. Despite the presence of robust anti-HIV-1 antibody titers, we did not observe potent neutralization against autologous viruses. In fact, 3 of 8 participants harbored viruses that were completely resistant to the highest tested concentration of autologous IgG. That this lack of neutralization was observed regardless of ART duration or viral diversity suggests that the inducible reservoir harbors 'escaped' viruses (that co-evolved with autologous antibody responses), rather than proviruses archived from earlier in infection. Finally, we observed that viruses resistant to autologous neutralization remained sensitive to bNAbs, especially CD4bs and MPER bNAbs. Overall, our data suggest that the inducible reservoir is relatively resistant to autologous antibodies and that individuals with limited virus variation in the env gene, such as those who start ART early in infection, are more likely to be sensitive to bNAb treatment.

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.

Exploration of a Sequential Gp140-Gp145 Immunization Regimen with Heterologous Envs to Induce a Protective Cross-Reactive HIV Neutralizing Antibody Response In Non-human Primates.

Raising a heterologous tier 2 neutralizing antibody (nAb) response remains a daunting task for HIV vaccine development. In this study, we explored the utility of diverse HIV-1 envelope (Env) immunogens in a sequential immunization scheme as a solution to this task. This exploration stemmed from the rationale that gp145, a membrane-bound truncation form of HIV Env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode. We first showed that gp140 DNA prime-gp145 Tiantan vaccinia (TV) boost likely represents a general format for inducing potent nAb response in mice. However, when examined in rhesus macaque, this modality showed little effectiveness. To improve the efficacy, we extended the original modality by adding a strong protein boost, namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle (NP), which was generated by a newly developed click approach. The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule. Importantly, the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge. Collectively, our studies highlighted that diversification of Env immunogens, in both types and formulations, under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.

HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA).

The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.

Engineered Antigen-Specific T Cells Secreting Broadly Neutralizing Antibodies: Combining Innate and Adaptive Immune Response against HIV.

While antiretroviral therapy (ART) can completely suppress viremia, it is not a cure for HIV. HIV persists as a latent reservoir of infected cells, able to evade host immunity and re-seed infection following cessation of ART. Two promising immunotherapeutic strategies to eliminate both productively infected cells and reactivated cells of the reservoir are the adoptive transfer of potent HIV-specific T cells and the passive administration of HIV-specific broadly neutralizing antibodies also capable of mediating antibody-dependent cellular cytotoxicity (ADCC). The simultaneous use of both as the basis of a single therapeutic has never been explored. We therefore sought to modify HIV-specific T cells from HIV-naive donors (to allow their use in the context of allotransplant, a promising platform for sterilizing cures) so they are able to secrete a broadly neutralizing antibody (bNAb) directed against the HIV envelope to elicit ADCC. We designed an antibody construct comprising bNAb 10-1074 heavy and light chains, fused to IgG3 Fc to elicit ADCC, with truncated cluster of differentiation 19 (CD19) as a selectable marker. HIV-specific T cells were expanded from HIV-naive donors by priming with antigen-presenting cells expressing overlapping HIV antigens in the presence of cytokines. T cells retained specificity against Gag, Nef, and Pol peptides (218.55 ± 300.14 interferon γ [IFNγ] spot-forming cells [SFC]/1 × 105) following transduction (38.92 ± 25.30) with the 10-1074 antibody constructs. These cells secreted 10-1074 antibodies (139.04 ± 114.42 ng/mL). The HIV-specific T cells maintained T cell function following transduction, and the secreted 10-1074 antibody bound HIV envelope (28.13% ± 19.42%) and displayed ADCC activity (10.47% ± 4.11%). Most critically, the 10-1074 antibody-secreting HIV-specific T cells displayed superior in vitro suppression of HIV replication. In summary, HIV-specific T cells can be engineered to produce antibodies mediating ADCC against HIV envelope-expressing cells. This combined innate/adaptive approach allows for synergy between the two immune arms, broadens the target range of the immune therapy, and provides further insight into what defines an effective anti-HIV response.

Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV.

PURPOSE OF REVIEW: 'Broadly neutralizing antibodies' (bNAbs), are rare HIV-specific antibodies which exhibit the atypical ability to potently neutralize diverse viral isolates. While efforts to elicit bNAbs through vaccination have yet to succeed, recent years have seen remarkable preclinical and clinical advancements of passive immunization approaches targeting both HIV prevention and cure. We focus here on the potential to build upon this success by moving beyond neutralization to additionally harness the diverse effector functionalities available to antibodies via fragment crystallizable-effector (Fc) functions. RECENT FINDINGS: Recent studies have leveraged the ability to engineer bNAb Fc domains to either enhance or abrogate particular effector functions to demonstrate that activities such as antibody-dependent cell-mediated cytotoxicity contribute substantially to in-vivo antiviral activity. Intriguingly, recent studies in both nonhuman primates and in humans have suggested that passive bNAb infusion can lead to durable immunity by enhancing virus-specific T-cell responses through a 'vaccinal effect'. SUMMARY: The combination of antibody engineering strategies designed to enhance effector functions, with the broad and potent antigen recognition profile of bNAbs, has the potential to give rise to powerful new therapeutics for HIV. We aim to provide a timely review of recent advances to catalyze this development.

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.

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.

BCL-2 antagonism sensitizes cytotoxic T cell-resistant HIV reservoirs to elimination ex vivo.

Curing HIV infection will require the elimination of a reservoir of infected CD4+ T cells that persists despite HIV-specific cytotoxic T cell (CTL) responses. Although viral latency is a critical factor in this persistence, recent evidence also suggests a role for intrinsic resistance of reservoir-harboring cells to CTL killing. This resistance may have contributed to negative outcomes of clinical trials, where pharmacologic latency reversal has thus far failed to drive reductions in HIV reservoirs. Through transcriptional profiling, we herein identified overexpression of the prosurvival factor B cell lymphoma 2 (BCL-2) as a distinguishing feature of CD4+ T cells that survived CTL killing. We show that the inducible HIV reservoir was disproportionately present in BCL-2hi subsets in ex vivo CD4+ T cells. Treatment with the BCL-2 antagonist ABT-199 was not sufficient to drive reductions in ex vivo viral reservoirs when tested either alone or with a latency-reversing agent (LRA). However, the triple combination of strong LRAs, HIV-specific T cells, and a BCL-2 antagonist uniquely enabled the depletion of ex vivo viral reservoirs. Our results provide rationale for novel therapeutic approaches targeting HIV cure and, more generally, suggest consideration of BCL-2 antagonism as a means of enhancing CTL immunotherapy in other settings, such as cancer.

Seasonal characteristics of biogenic secondary organic aerosols at Mt. Wuyi in Southeastern China: Influence of anthropogenic pollutants.

Thirteen secondary organic aerosol (SOA) tracers of isoprene, monoterpenes and sesquiterpenes were measured for PM2.5 aerosols collected at the summit of Mt. Wuyi (1139 m, a.s.l.), to investigate their seasonality and formation mechanism. Concentrations of the isoprene and monoterpene SOA tracers were much higher in summer than those in other seasons. In contrast, ß-caryophyllinic acid was found to be the lowest in summer. Concentrations of those BSOA tracers showed a positive correlation with temperature (R2 = 0.52-0.70), and a negative correlation with relative humidity (R2 = 0.43-0.78). Moreover, thermodynamic model (i.e., ISORROPIA-II) calculation results showed that acidity conditions are favorable for BSOA formation. Robust linear correlations between the BSOA tracers and anthropogenic pollutants such as SO2 (R2 = 0.53-0.7) and NO2 (R2 = 0.37-0.54) were observed for all the samples, suggesting that SO2 and NOx can enhance BSOA production in the remote mountain area of southeast China, which is related to an acid-catalyzed heterogeneous chemistry. Moreover, we also found a significant correlation between the concentrations of the BSOA tracers and levoglucosan especially for ß-caryophyllinic acid, indicating that biomass burning plumes from the distant lowland regions could influence the production of BSOA in the mountain free troposphere. Our results clearly demonstrated that anthropogenic emissions in China could enhance BSOA formation in the distant mountain regions.

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.

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.