Ozone and SOA formation potential based on photochemical loss of VOCs during the Beijing summer.

Volatile organic compounds (VOCs) are easily degraded by oxidants during atmospheric transport. Therefore, the contribution of VOCs to ozone (O3) and secondary organic aerosol (SOA) formation at a receptor site is different from that in a source area. In this study, hourly concentrations of VOCs and other pollutants, such as O3, NOx, HONO, CO, and PM2.5, were measured in the suburbs (Daxing district) of Beijing in August 2019. The photochemical initial concentrations (PICs), in which the photochemical losses of VOCs were accounted for, were calculated to evaluate the contribution of the VOCs to O3 and SOA formation. The mean (±standard deviation) measured VOC concentrations and the PICs were 11.2 ± 5.7 and 14.6 ± 8.4 ppbv, respectively, which correspond to O3 formation potentials (OFP) of 57.8 ± 26.3 and 103.9 ± 109.4 ppbv and SOA formation potentials (SOAP) of 8.4 ± 4.1 and 10.3 ± 7.4 µg m-3, respectively. Alkenes contributed 80.5% of the consumed VOCs, followed by aromatics (13.3%) and alkanes (6.2%). The contributions of the alkenes and aromatics to the OFPPICs were 56.8% and 30.3%, respectively; while their corresponding contributions to the SOAPPICs were 1.9% and 97.3%, respectively. The OFPPICs was linearly correlated with the observed O3 concentrations (OFPPICs = 41.5 + 1.40 × cO3, R2 = 0.87). The O3 formation was associated with a VOC-limited regime at the receptor site based on the measured VOCs and changed to a transition regime and a NOx sensitive regime based on the PIC. Our results suggest that more attention should be paid to biogenic VOCs when studying O3 formation in summer in Beijing, while the control of anthropogenic aromatic compounds should be given priority in terms of SOA formation.

Identification, Quantification, and Imaging of the Biodistribution of Soot Particles by Mass Spectral Fingerprinting.

Soot is ubiquitous and has large detrimental effects on climate, air quality, and human health. However, identification of soot in carbonaceous media is very challenging due to its nanoscale carbon nature and complex sources. Due to the shortage in the methodology, until now, the fate and health effect of soot particles after inhalation are still poorly understood. Here, we report a new method for label-free identification, quantification, and imaging of soot particles in complex media based on laser desorption/ionization mass spectrometry fingerprinting. We found that soot particles from different origins and with different morphologies showed highly consistent mass spectral fingerprints deriving from peak ratios of small carbon cluster anions (C2--C10-), which enabled both accurate quantification of soot in fine particulate matter (PM2.5) samples and label-free imaging of soot particles in biological media. By using this technique, we tracked and imaged the suborgan distribution of soot particles in mice after exposure to PM2.5. The results showed that the lung is the main target organ for short-term inhalation exposure to soot particles. This study helps to better understand the inhalation toxicology of soot and also provides a practical novel methodological platform for identification, tracing, and toxicological studies of elemental carbon-based nanomaterials.

Resveratrol Promotes HIV-1 Tat Accumulation via AKT/FOXO1 Signaling Axis and Potentiates Vorinostat to Antagonize HIV-1 Latency.

BACKGROUND: The latent reservoir of HIV-1 is a major barrier to achieving the eradication of HIV-1/AIDS. One strategy is termed "shock and kill", which aims to awaken the latent HIV-1 using latency reversing agents (LRAs) to replicate and produce HIV-1 particles. Subsequently, the host cells containing HIV-1 can be recognized and eliminated by the immune response and anti-retroviral therapy. Although many LRAs have been found and tested, their clinical trials were dissatisfactory. OBJECTIVE: To aim of the study was to investigate how resveratrol reactivates silent HIV-1 transcription and assess if resveratrol could be a candidate drug for the "shock" phase in "shock and kill" strategy. METHODS: We used established HIV-1 transcription cell models (HeLa-based NH1 and NH2 cells) and HIV-1 latent cell models (J-Lat A72 and Jurkat 2D10 cells). We performed resveratrol treatment on these cell lines and studied the mechanism of how resveratrol stimulates HIV-1 gene transcription. We also tested resveratrol's bioactivity on primary cells isolated from HIV-1 latent infected patients. RESULTS: Resveratrol promoted HIV-1 Tat protein levels, and resveratrol-induced Tat promotion was found to be dependent on the AKT/FOXO1 signaling axis. Resveratrol could partially dissociate P-TEFb (Positive Transcription Elongation Factor b) from 7SK snRNP (7SK small nuclear Ribonucleoprotein) and promote Tat-SEC (Super Elongation Complex) interaction. Preclinical studies showed that resveratrol potentiated Vorinostat to awaken HIV-1 latency in HIV-1 latent infected cells isolated from patients. CONCLUSION: We found a new mechanism of resveratrol stimulating the production of HIV-1. Resveratrol could be a promising candidate drug to eradicate HIV-1 reservoirs.

Particle growth with photochemical age from new particle formation to haze in the winter of Beijing, China.

Secondary aerosol formation in the aging process of primary emission is the main reason for haze pollution in eastern China. Pollution evolution with photochemical age was studied for the first time at a comprehensive field observation station during winter in Beijing. The photochemical age was used as an estimate of the timescale attributed to the aging process and was estimated from the ratio of toluene to benzene in this study. A low photochemical age indicates a fresh emission. The photochemical age of air masses during new particle formation (NPF) days was lower than that on haze days. In general, the strongest NPF events, along with a peak of the formation rate of 1.5 nm (J1.5) and 3 nm particles (J3), were observed when the photochemical age was between 12 and 24 h while rarely took place with photochemical ages less than 12 h. When photochemical age was larger than 48 h, haze occurred and NPF was suppressed. The sources and sinks of nanoparticles had distinct relation with the photochemical age. Our results show that the condensation sink (CS) showed a valley with photochemical ages ranging from 12 to 24 h, while H2SO4 concentration showed no obvious trend with the photochemical age. The high concentrations of precursor vapours within an air mass lead to persistent nucleation with photochemical age ranging from 12 to 48 h in winter. Coincidently, the fast increase of PM2.5 mass was also observed during this range of photochemical age. Noteworthy, CS increased with the photochemical age on NPF days only, which is the likely reason for the observation that the PM2.5 mass increased faster with photochemical age on NPF days compared with other days. The evolution of particles with the photochemical age provides new insights into understanding how particles originating from NPF transform to haze pollution.

Influence of Chinese New Year overlapping COVID-19 lockdown on HONO sources in Shijiazhuang.

Nitrous acid (HONO) is an important precursor of hydroxyl radical (OH) in the atmosphere. It is also toxic to human health. In this work, HONO concentrations were measured in Shijiazhuang using a Monitor for AeRosols and Gases in ambient Air (MARGA) from December 15, 2019 to March 15, 2020, which covered the heavy air pollution season, the Chinese New Year (CNY) vocation and the Corona Virus Disease-19 (COVID-19) lockdown period. During & after CNY overlapping COVID-19 lockdown, the air quality was significantly improved because of both the emission reduction and the increase in diffusion ability of air masses. The mean HONO concentration was 2.43 ± 1.08 ppbv before CNY, while it decreased to 1.53 ± 1.16 ppbv during CNY and 0.97 ± 0.76 ppbv after CNY. The lockdown during & after CNY reduced ~31% of ambient HONO along with ~62% of NO and ~36% of NO2 compared with those before CNY after the improvement of diffusion ability had been taken into consideration. Heterogeneous reaction of NO2 on ground surface dominated the nocturnal HONO sources, followed by heterogeneous reaction on aerosol surface, vehicle emission, reaction between NO and OH and emission from soil on pollution days throughout the observation. Except for elevated soil emission, other nighttime HONO sources and sinks decreased significantly during & after CNY. The relative importance of heterogeneous reaction of NO2 on surfaces further increased because of both the decrease in vehicle emission and the increase in the heterogeneous conversion kinetics from NO2 to HONO during & after CNY.

The KAT5-Acetyl-Histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency.

The bromodomain protein Brd4 promotes HIV-1 latency by competitively inhibiting P-TEFb-mediated transcription induced by the virus-encoded Tat protein. Brd4 is recruited to the HIV LTR by interactions with acetyl-histones3 (AcH3) and AcH4. However, the precise modification pattern that it reads and the writer for generating this pattern are unknown. By examining a pool of latently infected proviruses with diverse integration sites, we found that the LTR characteristically has low AcH3 but high AcH4 content. This unusual acetylation profile attracts Brd4 to suppress the interaction of Tat with the host super elongation complex (SEC) that is essential for productive HIV transcription and latency reversal. KAT5 (lysine acetyltransferase 5), but not its paralogs KAT7 and KAT8, is found to promote HIV latency through acetylating H4 on the provirus. Antagonizing KAT5 removes AcH4 and Brd4 from the LTR, enhances the SEC loading, and reverses as well as delays, the establishment of latency. The pro-latency effect of KAT5 is confirmed in a primary CD4+ T cell latency model as well as cells from ART-treated patients. Our data thus indicate the KAT5-AcH4-Brd4 axis as a key regulator of latency and a potential therapeutic target to reactivate latent HIV reservoirs for eradication.

Design, synthesis, and biological evaluation of AV6 derivatives as novel dual reactivators of latent HIV-1.

The "shock and kill" strategy might be a promising therapeutic approach for HIV/AIDS due to the existence of latent viral reservoirs. A major challenge of the "shock and kill" strategy arises from the general lack of clinically effective latency-reversing agents (LRAs). The 2-methylquinoline derivative, antiviral 6 (AV6) has been reported to induce latent HIV-1 expression and act synergistically with a HDAC inhibitor VA to reverse HIV latency. We report herein the design and identification of AV6 analogues which possess the zinc-binding group of HDAC inhibitors and have dual acting mechanism for the reactivation of HIV-1 from latency. Evaluation of compounds for the reactivation of HIV-1 latency identified two excellent active compounds 12c and 12d. Further bioassays revealed that these two compounds reactivated latent HIV-1 through dual mechanism, the inhibition of HDACs and NFAT-required for early HIV-1 gene expression. Additionally, it was found that 12c and 12d could reactivate HIV-1 transcription by releasing P-TEFb from the inactive complex 7SK snRNP. At last, molecular docking identified their orientation and binding interactions at the active site of HDAC2. This experimental data suggests that 12c and 12d can be served as effective HIV-1 LRAs which can be taken up for further studies.