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Regulation of T cell immunity by C5a has been suggested from recent studies. However, the underlying mechanisms, particularly the involved cells and biochemical basis, are not well defined. In this study, the direct modulation of dendritic cell (DC) activation and its function in T cell stimulation by C5a-C5aR interaction and the involved signaling pathways were investigated. We show that DCs from C5aR−/− mice and normal DCs treated with C5aR antagonist have less-activated phenotype characterized with increased IL-10 and decreased IL-12p70 production in response to LPS stimulation, lowered surface expression of MHC class II, B7.2, and consequently have reduced capacity to stimulate allospecific T cells. Conversely, C5a stimulation up-regulates DC activation and its function in allostimulation. Furthermore, stimulation of C5aR mediates the inhibition of cAMP production and protein kinase A activity and is involved in activation of PI3K/AKT and NF-κB signaling in DCs. These results demonstrate that C5a acts directly on C5aR expressed on DCs resulting in the cell activation and subsequently enhances its capacity for allospecific T cell stimulation. It also suggests that NF-κB signaling induced by down-regulation of cAMP/ protein kinase A pathway and up-regulation of PI3K/AKT pathway following C5a stimulation may contribute to up-regulation of DC function.

Satellite observations of tropospheric NO 2 columns are extensively used to infer trends in anthropogenic emissions of nitrogen oxides (NO x ≡ NO + NO 2 ), but this may be complicated by trends in NO x lifetime. Here we use 2004-2018 observations from the Ozone Monitoring Instrument (OMI) satellite-based instrument (QA4ECV and POMINO v2 retrievals) to examine the seasonality and trends of tropospheric NO 2 columns over central-eastern China, and we interpret the results with the GEOS-Chem chemical transport model. The observations show a factor of 3 increase in NO 2 columns from summer to winter, which we explain in GEOS-Chem as reflecting a longer NO x lifetime in winter than in summer (21 h versus 5.9 h in 2017). The 2005-2018 summer trends of OMI NO 2 closely follow the trends in the Multi-resolution Emission Inventory for China (MEIC), with a rise over the 2005-2011 period and a 25 % decrease since. We find in GEOS-Chem no significant trend of the NO x lifetime in summer, supporting the emission trend reported by the MEIC. The winter trend of OMI NO 2 is steeper than in summer over the entire period, which we attribute to a decrease in NO x lifetime at lower NO x emissions. Half of the NO x sink in winter is from N 2 O 5 hydrolysis, which counterintuitively becomes more efficient as NO x emissions decrease due to less titration of ozone at night. The formation of organic nitrates also becomes an increasing sink of NO x as NO x emissions decrease but emissions of volatile organic compounds (VOCs) do not.Published by Copernicus Publications on behalf of the European Geosciences Union.

BackgroundThe clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions.MethodsFor our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD.ResultsCompared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area.ConclusionsThese findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.

Learning science in the context of socio-scientific issues (SSI) can promote scientific literacy that links science to everyday life and society. In this position paper, we argue that developing and using multiple models equip students with the appropriate knowledge and skills needed to deal with complex issues. We draw upon literature from science education and philosophy of science and advance our theoretical argument about why it is critical for students to develop and use multiple models as part of their science learning experiences in general, and how the practice benefits students in the context of SSI in particular. We posit that students should engage in both scientific and socio-scientific models as they explore a complex societal issue because (1) engagement in multiple scientific models promotes students’ understanding about the phenomena relevant to the focal issue, and (2) engagement in socio-scientific models helps students to use that scientific knowledge in the larger social contexts and reason about how interacting science and social factors may impact students’ positions on the complex issue. We take COVID-19 as the learning context and present exemplar models students can develop and use as they learn about the pandemic. We conclude the paper by discussing the teaching aspects of the proposed modeling approach for SSI-based instruction as well as identifying possible areas for future research.

Severe PM2.5 air pollution in China and the First Grand National Standard (FGNS), implemented in 2016 (annual PM2.5 concentration target of less than 35 µg m−3), necessitate urgent reduction strategies. This study applied the nested‐grid version of the Goddard Earth Observing System (GEOS) chemical transport model (GEOS‐Chem) to quantify 2000–2050 changes in PM2.5 air quality and related direct radiative forcing (DRF) in China, based on future emission changes under the representative concentration pathway (RCP) scenarios of RCP2.6, RCP4.5, RCP6.0, and RCP8.5. In the near term (2000–2030), a projected maximum increase in PM2.5 concentrations of 10–15 µg m−3 is found over east China under RCP6.0 and RCP8.5 and less than 5 µg m−3 under RCP2.6 and RCP4.5. In the long term (2000–2050), PM2.5 pollution clearly improves, and the largest decrease in PM2.5 concentrations of 15–30 µg m−3 is over east China under all RCPs except RCP6.0. Focusing particularly on highly polluted regions, we find that Beijing‐Tianjin‐Hebei (BTH) wintertime PM2.5 concentrations meeting the FGNS occur after 2040 under RCP2.6, RCP4.5, and RCP8.5, and summertime PM2.5 concentrations reach this goal by 2030 under RCP2.6 and RCP4.5. In Sichuan Basin (SCB), wintertime PM2.5 concentrations below the FGNS occur only in 2050 under RCP2.6 and RCP4.5, although future summertime PM2.5 will be well controlled. The difficulty in controlling future PM2.5 concentrations relates to unmitigated high levels of nitrate, although NOx and SO2 emissions show substantial reductions during 2020–2040. The changes in aerosol concentrations lead to positive aerosol DRF over east China (20°–45°N, 100°–125°E) by 1.22, 1.88, and 0.66 W m−2 in 2050 relative to 2000 under RCP2.6, RCP4.5, and RCP8.5, respectively. When considering both health and climate effects of PM2.5 over China, for example, PM2.5 concentrations averaged over east China under RCP4.5 (RCP2.6) decrease by 54% (43%) in 2050 relative to 2000, but at the cost of warming with DRF of 1.88 (1.22) W m−2. Our results indicate that it will be possible to mitigate future PM2.5 pollution in China, but it will likely take two decades for polluted regions such as BTH and SCB to meet the FGNS, based on all RCP scenarios. At the same time, the consequent warming effects from reduced aerosols are also significant and inevitable.

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