Air quality was a vital concern for the Beijing Olympic Games in 2008. To strictly control air pollutant emissions and ensure good air quality for the Games, Beijing municipal government announced an "Air Quality Guarantee Plan for the 29th Olympics in Beijing". In order to evaluate the effectiveness of the guarantee plan, this study analyzed the air pollutant emission reductions during the 29th Olympiad in Beijing. In June 2008, daily emissions of SO(2), NO(X), PM(10), and NMVOC in Beijing were 103.9 t, 428.5 t, 362.7 t, and 890.0 t, respectively. During the Olympic Games, the daily emissions of SO(2), NO(X), PM(10), and NMVOC in Beijing were reduced to 61.6 t, 229.1 t, 164.3 t, and 381.8 t -41%, 47%, 55%, and 57% lower than June 2008 emission levels. Closing facilities producing construction materials reduced the sector's SO(2) emissions by 85%. Emission control measures for mobile sources, including high-emitting vehicle restrictions, government vehicle use controls, and alternate day driving rules for Beijing's 3.3 million private cars, reduced mobile source NO(X) and NMVOC by 46% and 57%, respectively. Prohibitions on building construction reduced the sector's PM(10) emissions by approximately 90% or total PM(10) by 35%. NMVOC reductions came mainly from mobile source and fugitive emission reductions. Based on the emission inventories developed in this study, the CMAQ model was used to simulate Beijing's ambient air quality during the Olympic Games. The model results accurately reflect the environmental monitoring data providing evidence that the emission inventories in this study are reasonably accurate and quantitatively reflect the emission changes attributable to air pollution control measures taken during the 29th Olympic Games in 2008.

Smart magnetic resonance (MR) contrast agents, by which MR contrast can be selectively enhanced under acidic tumor microenvironment, are anticipated to significantly improve the diagnostic accuracy. Here, we report pH-sensitive iron oxide nanoparticle assemblies (IONAs) that are cross-linked by small-molecular aldehyde derivative ligands. The dynamic formation and cleavage of hydrazone linkages in neutral and acidic environments, respectively, allow the reversible response of the nanoassemblies to pH variations. At neutral pH, IONAs are structurally robust due to the cross-linking by the strong hydrazone bonds. In acidic tumor microenvironment, the hydrazone bonds are cleaved so that the IONAs are quickly disassembled into a large number of hydrophilic extremely small-sized iron oxide nanoparticles (ESIONs). As a result, significantly enhanced T1MR contrast is achieved, as confirmed by the measurement of r1 values at different pH conditions. Such acidity-targeting MR signal amplification by the pH-sensitive IONAs was further validated in vivo, demonstrating a novel T1 magnetic resonance imaging (MRI) strategy for highly sensitive imaging of acidic tumors.

The coronavirus causing the COVID-19 pandemic, SARS-CoV-2, uses −1 programmed ribosomal frameshifting (−1 PRF) to control the relative expression of viral proteins. As modulating −1 PRF can inhibit viral replication, the RNA pseudoknot stimulating −1 PRF may be a fruitful target for therapeutics treating COVID-19. We modeled the unusual 3-stem structure of the stimulatory pseudoknot of SARS-CoV-2 computationally, using multiple blind structural prediction tools followed by μs-long molecular dynamics simulations. The results were compared for consistency with nuclease-protection assays and single-molecule force spectroscopy measurements of the SARS-CoV-1 pseudoknot, to determine the most likely conformations. We found several possible conformations for the SARS-CoV-2 pseudoknot, all having an extended stem 3 but with different packing of stems 1 and 2. Several conformations featured rarely-seen threading of a single strand through junctions formed between two helices. These structural models may help interpret future experiments and support efforts to discover ligands inhibiting −1 PRF in SARS-CoV-2.

SARS-CoV-2 uses −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins. Because modulating −1 PRF can attenuate the virus, ligands binding to the RNA pseudoknot that stimulates −1 PRF may have therapeutic potential. Mutations in the pseudoknot have occurred during the pandemic, but how they affect −1 PRF efficiency and ligand activity is unknown. Studying a panel of six mutations in key regions of the pseudoknot, we found that most did not change −1 PRF levels, even when base-pairing was disrupted, but one led to a striking 3-fold decrease, suggesting SARS-CoV-2 may be less sensitive to −1 PRF modulation than expected. Examining the effects of a small-molecule −1 PRF inhibitor active against SARS-CoV-2, it had a similar effect on all mutants tested, regardless of basal −1 PRF efficiency, indicating that anti-frameshifting activity can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of −1 PRF.