Foxp3+ T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. ...Here we identified Foxp3+ T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT+ Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.
•TIGIT defines a distinct Foxp3+ Treg cell subset•TIGIT induces transcription and secretion of the effector molecule Fgl2 in Treg cells•TIGIT+ Treg cells suppress proinflammatory Th1 and Th17 not Th2 cell responses•Selective suppression by TIGIT+ Treg cells is Fgl2 dependent
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Correlations between water cloud effective radius (CER) and aerosol optical depth (AOD) from the Moderate Resolution Imaging Spectroradiometer (MODIS) are examined over seven sub-regions in Eastern ...China for 2003–2012. Water phase cloud is defined as having a cloud top pressure greater than 800 hPa. Significant negative correlation coefficients (r = −0.79 ∼ −0.94) between AOD and CER are derived over the East Sea and the South China Sea for grid cells with AOD < 0.3. However, positive correlations (r = 0.01–0.91) are calculated for cells with AOD > 0.3. In contrast, significant positive correlations (r = 0.67–0.95) are derived over the Eastern China mainland and Yellow Sea. Further analysis for North China Plain shows that variations in wind speed and relative humidity may account for such positive correlations. Southerly winds carry high levels of pollutants and abundant water vapor, resulting in coincident increases in both AOD and CER in North China Plain, while the northerly winds transport dry and clean air from high latitudes, leading to decreases in AOD and CER. Both processes contribute to the positive correlations between AOD and CER over Eastern China, suggesting that the influence of background weather conditions need to be considered when studying the interactions between aerosol and cloud.
•We studied the first aerosol indirect effect over Eastern China.•Twomey effect was observed over ocean.•Positive correlations between aerosol optical depth and cloud effective radius were found over land for most seasons.•We attributed the positive effect to the associated changes in relative humidity and wind fields.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This work reports the chemical and light extinction characteristics of the atmospheric particles collected from January to November 2014 in suburban Nanjing. Size-segregated measurement results ...showed that more than 80% of the major aerosol components were concentrated in PM2.5. The concentration of PM2.5 was highest in winter and lowest in autumn. Specifically, K+ concentration peaked in late spring indicating heavy influences from straw burning, while sulfate concentration was highest in summer and its daytime concentration was also higher than its nighttime concentration, both reflecting a significant role of photochemical production. Nevertheless, except for sulfate, all other components had higher concentrations during nighttime, signifying the role of unfavorable meteorological conditions in exacerbating the air pollution. The IMPROVE formula was employed, which can reconstruct the PM2.5 mass and light extinction well. The light extinction was mainly contributed by (NH4)2SO4 and NH4NO3 (together 58.3%). Mass concentrations of all PM2.5 components increased significantly with the increase of pollution levels, but nitrate increased most rapidly; correspondingly, the contribution of nitrate to light extinction also increased quickly when pollution became heavy. Such results were different from those observed in Beijing-Tianjin-Hebei where sulfate increased most quickly. Our results thus highlight that reduction of vehicular NO2 is likely a priority for air quality improvement in Nanjing. Back trajectory analysis showed the dominance of the local air mass and the one from Huanghai, yet the air mass originated from Bohai, and passed though Shandong and north of Jiangsu province could deliver highly-polluted air to Nanjing, as well.
Acid rain and dust events are both serious environmental problems striking China nowadays. This study investigates the distribution and change of precipitation pH and discusses the influence of dust ...events on precipitation acidity qualitatively and quantitatively in China. Acid rain exhibits remarkable regionality with strong acidic in South China and the acidity gradually decreases from the South to the North. This distribution is decided not only by the concentration of SO2 in atmosphere but also has relationship to the occurrence of dust events. Comparing the monthly changes of precipitation pH in the semiarid region (which is influenced by dust events) with those in the humid region (which is acid rain areas), it is found that the variation trends are just opposite in the two regions and there is an obvious peak value of pH in spring in semiarid region which coincides with the increase of dust event days. Chemical analysis results of precipitation in Lanzhou (a semiarid city intruded by dust events frequently, especially in spring) indicate that the ratio of Ca2+ plus Mg2+ concentrations (indicators of soil dust) to the total cation concentrations is the highest in spring, and the Ca2+ and Mg2+ concentrations are 1.8 and 1.9 times higher in spring than in summer respectively. The acidity of precipitation can be restrained by dust events qualitatively by increasing alkaline materials in the atmosphere and precipitation. The analysis of daily dust events and precipitation data at 6 stations in Northwest China indicates that the pH of precipitation influenced by dust events is greater than the precipitation not influenced by dust events. The increase degrees are different between different stations and have lagging effects. The direct increases are from 0.03 to 0.91 for the precipitation pH. Dust events can promote the precipitation pH to a certain extent quantitatively.
•We discuss the influence of dust events on precipitation acidity in China.•The spatial distribution of pH has relation with the distribution of dust event days.•In semiarid region, pH rises in spring which coincides with the rise of dust events.•Alkaline ions rise greatly in rainwater in spring as dust events happen frequently.•Dust events can increase precipitation pH from 0.03 to 0.91 in different stations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the ...effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1− TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8+ T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7/Tcf1 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8+ T cell responses upon immunotherapy.
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•Checkpoint blockade induces transcriptional changes in PD-1−CD8+ and PD-1+CD8+ TILs•PD-1−CD8+ TILs contain naive-, memory-precursor-, and effector-like subsets•Memory-precursor- and effector-like PD-1−CD8+ TILs expand upon checkpoint blockade•Tcf7 is required for memory-precursor-like cells and efficacy of immunotherapies
Kurtulus et al. examine the dynamics of the effector CD8+ T cell response in the tumor microenvironment in response to checkpoint blockade immunotherapy. Checkpoint blockade induced a shift from naive-like to memory-precursor- and effector-like subsets within PD-1−CD8+ T cells in tumors. The memory-precursor-like subset is maintained by the transcriptional regulator Tcf7/Tcf1, which is required for efficacy of checkpoint blockade and other immunotherapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Two years of mid-latitude cirrus cloud macrophysical and optical properties over North China are described from Earth-orbiting Cloud-Aerosol Lidar with Orthogonal Polarization（CALIOP） satellite ...measurements. Global cloud climatological studies based on active remote sensing data sets benefit from more accurate resolution of vertical structure and more reliable detection of optically thin layers.The mean values for cirrus cases over North China are 0.19±0.18 for infrared emittance,0.41±0.68 for visible optical depth, 0.26±0.12 for integrated depolarization ratio,and 0.72±0.22 for integrated color ratio.When studied using reasonable assumptions for the relationship between extinction and ice crystal backscatter coefficients,our results show that most of the cirrus clouds profiled using the 0.532μm channel data stream correspond with an optical depth of less than 1.0.The dependence of cirrus cloud properties on cirrus cloud mid-cloud temperature and geometry thickness are generally similar to the results derived from the ground-based lidar, which are mainly impacted by the adiabatic process on the ice cloud content.However,the differences in macrophysical parameter variability indicate the limits of spaceborne-lidar and dissimilarities in regional climate variability and the nature and source of cloud nuclei in different geographical regions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Identifying signals in the tumor microenvironment (TME) that shape CD8+ T cell phenotype can inform novel therapeutic approaches for cancer. Here, we identified a gradient of increasing ...glucocorticoid receptor (GR) expression and signaling from naïve to dysfunctional CD8+ tumor-infiltrating lymphocytes (TILs). Conditional deletion of the GR in CD8+ TILs improved effector differentiation, reduced expression of the transcription factor TCF-1, and inhibited the dysfunctional phenotype, culminating in tumor growth inhibition. GR signaling transactivated the expression of multiple checkpoint receptors and promoted the induction of dysfunction-associated genes upon T cell activation. In the TME, monocyte-macrophage lineage cells produced glucocorticoids and genetic ablation of steroidogenesis in these cells as well as localized pharmacologic inhibition of glucocorticoid biosynthesis improved tumor growth control. Active glucocorticoid signaling associated with failure to respond to checkpoint blockade in both preclinical models and melanoma patients. Thus, endogenous steroid hormone signaling in CD8+ TILs promotes dysfunction, with important implications for cancer immunotherapy.
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•Endogenous glucocorticoid signaling shapes CD8+ T cell differentiation in tumors•The glucocorticoid receptor transactivates IL-10 and checkpoint receptor expression•Tumor monocyte-macrophage lineage cells produce glucocorticoid•Glucocorticoid signaling in CD8+ T cells reduces immune checkpoint blockade efficacy
Acharya et al. uncover a gradient of increasing glucocorticoid signaling from naïve to dysfunctional CD8+ tumor-infiltrating lymphocytes. This gradient regulates effector transition and development of dysfunction. Glucocorticoid is produced locally by tumor-associated monocyte-macrophage lineage cells, and presence of active glucocorticoid signaling associates with poor response to immune checkpoint blockade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients ...and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+ tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+ TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact.
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•Distinct gene modules for T cell dysfunction and activation can be uncoupled•Single-cell profiling of CD8 TILs shows that these modules are exclusive•Metallothioneins, zinc regulators, promote T cell dysfunction•CRISPR-Cas9 targeting shows Gata-3, a zinc-finger TF, promotes dysfunction
Single-cell profiling of tumor-infiltrating lymphocytes identifies critical regulators of T cell dysfunction in cancer, opening new avenues for targeting dysfunctional T cell states while leaving activation programs intact.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surface radiation is crucial to atmospheric boundary layer development and air pollution formation. Several studies have revealed that surface radiation plays a vital role in developing the daytime ...convective boundary layer that controls the explosive growth of PM2.5 concentration; however, less attention has been paid to the effects of changing nighttime surface radiation on the near-surface temperature inversion layer and PM2.5 accumulation. In this study, we used long-term observations of meteorological and environmental data and atmospheric boundary layer measurements during a severe PM2.5 pollution event to investigate the effect of changes in nocturnal surface radiation on the increase in PM2.5 concentrations. The results showed that surface radiation cooling was enhanced (weakened) by decreased (increased) cloud cover fraction by changing longwave radiation at night; this strengthened (weakened) near-surface temperature inversion intensity and promoted (prevented) the accumulated increase in PM2.5. This observational study using 5-year data further confirmed the cloud radiative effect on the nighttime accumulation of PM2.5 with a significant negative correlation between nighttime averages of surface PM2.5 concentrations and cloud cover fractions. This reveals an important mechanism for the impact of surface radiation cooling modulated by cloud cover change on the nighttime accumulated increase in PM2.5. This finding extends our understanding of air pollutant accumulation at night with potential implications for atmospheric environment change.
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•Nighttime elevated PM2.5 levels occur primarily under the condition of strong surface radiation cooling.•Surface radiation cooling is enhanced by a decrease in cloud cover promoting an increase in PM2.5.•A mechanism for the cloud effect on PM2.5 pollution at night is revealed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Wind power forecasting system is useful to increase the wind energy penetration level. Latest statistics show that China has been the biggest wind energy market throughout the world. However, few ...studies have been published to introduce the wind energy forecasting technologies in China. This paper presents the performance evaluation and accuracy enhancement of a novel day-ahead wind power forecasting system in China. This system consists of a numerical weather prediction (NWP) model and artificial neural networks (ANNs). The NWP model is established by coupling the Global Forecasting system (GFS) with the Weather Research and Forecasting (WRF) system together to predict meteorological parameters. In addition, Kalman filter has been integrated in this system to reduce the systematic errors in wind speed from WRF and enhance the forecasting accuracy. The numerical results from a real world case are proven the effectiveness of this forecasting system in terms of the raw wind speed correction and wind power forecasting accuracy. The Normalized Root Mean Square Error (NRMSE) has a month average value of 16.47%, which is an acceptable error margin for allowing the use of the forecasted values in electric market operations. This forecasting system is profitable for increasing the wind energy penetration level in China.
► A novel day-ahead wind power forecasting system in China is proposed. ► The combination of WRF and neural network for wind power forecasting. ► Using Kalman filter to post-process the outputs of WRF model for enhancing accuracy. ► Numerical results for a single wind farm show a good performance of the system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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