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The 2018 NASA Health and Air Quality Applied Science Team (HAQAST) Indicators Tiger Team collaboration between NASA-supported scientists and civil society stakeholders aimed to develop satellite-derived global air pollution and climate indicators. This Commentary shares our experience and lessons learned. Together, the team developed methods to track wildfires, dust storms, pollen counts, urban green space, nitrogen dioxide concentrations and asthma burdens, tropospheric ozone concentrations, and urban particulate matter mortality. Participatory knowledge production can lead to more actionable information but requires time, flexibility, and continuous engagement. Ground measurements are still needed for ground truthing, and sustained collaboration over time remains a challenge.

Natural killer (NK) cells not only are innate effector lymphocytes that directly participate in tumor surveillance but are also essential helpers in the antitumor CD8+ T‐cell response. However, the molecular mechanisms and potential checkpoints regulating NK cell helper functions remain elusive. Here, it is shown that the T‐bet/Eomes‐IFN‐γ axis in NK cells is essential for CD8+ T cell‐dependent tumor control, whereas T‐bet‐dependent NK cell effector functions are required for an optimal response to anti‐PD‐L1 immunotherapy. Importantly, NK cell‐expressed TIPE2 (tumor necrosis factor‐alpha‐induced protein‐8 like‐2) represents a checkpoint molecule for NK cell helper function, since Tipe2 deletion in NK cells not only enhances NK‐intrinsic antitumor activity but also indirectly improves the antitumor CD8+ T cell response by promoting T‐bet/Eomes‐dependent NK cell effector functions. These studies thus reveal TIPE2 as a checkpoint for NK cell helper function, whose targeting might boost the antitumor T cell response in addition to T cell‐based immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Air pollution health studies have been increasingly using prediction models for exposure assessment even in areas without monitoring stations. To date, most studies have assumed that a single exposure model is correct, but estimated effects may be sensitive to the choice of exposure model.Methods: We obtained county-level daily cardiovascular (CVD) admissions from the New York (NY) Statewide Planning and Resources Cooperative System (SPARCS) and four sets of fine particulate matter (PM2.5) spatio-temporal predictions (2002-2012). We employed overdispersed Poisson models to investigate the relationship between daily PM2.5 and CVD, adjusting for potential confounders, separately for each state-wide PM2.5 dataset.Results: For all PM2.5 datasets, we observed positive associations between PM2.5 and CVD. Across the modeled exposure estimates, effect estimates ranged from 0.23% (95%CI: -0.06, 0.53%) to 0.88% (95%CI: 0.68, 1.08%) per 10 µg/m3 increase in daily PM2.5. We observed the highest estimates using monitored concentrations 0.96% (95%CI: 0.62, 1.30%) for the subset of counties where these data were available.Conclusions: Effect estimates varied by a factor of almost four across methods to model exposures, likely due to varying degrees of exposure measurement error. Nonetheless, we observed a consistently harmful association between PM2.5 and CVD admissions, regardless of model choice. [ABSTRACT FROM AUTHOR]

Ambient exposure to ground-level ozone (O3) is estimated to cause more than 250,000 globalpremature deaths per year. O3is produced from photochemical reactions involving itsprecursors: nitrogen oxides (NOx) and volatile organic compounds (VOCs). A majorchallenge in lowering ground-level O3 in urban areas is to determine whether O3 productionis limited by NOx (NOx-limited) or VOCs (VOC-limited) or both (transitional). Whilesatellites cannot retrieve the abundance of ground-level O3, they have providedcontinuous global observations of O3precursors, namely tropospheric columns of NO2and formaldehyde (HCHO, a proxy for VOCs), for over two decades. To assessthe extent to which satellite retrievals of O3 precursors can capture the non-linearchemistry of ground-level O3, we pair daily satellite retrievals of NO2and HCHO fromOzone Monitoring Instrument (OMI) with ground-based observations of surfaceO3from the U.S. EPA Air Quality System (AQS) network. For urban areas, wefind O3 exceedances (> 70 ppbv) are more likely to occur with NOx reductions(NOx-saturated or VOC-limited) when OMI HCHO/NO2 is lower than 1.8, butless likely to occur with NOx reduction (NOx-limited) when OMI HCHO/NO2is higher than 2.8. We further contrast how the O3-NOx-VOC sensitivity differson high-ozone versus "average" ozone days. Next, we construct 20-year (1996to 2016) time series of the O3sensitivity indicator ratio (HCHO/NO2) using thestate-of-art, harmonized multi-satellite products of tropospheric NO2and HCHO verticalcolumns from the Quality Assurance for Essential Climate Variables (QA4ECV)project that retrieves products consistently from four satellites, including GOME,SCIAMACHY, GOME-2 and OMI. We analyze the long-term trend in the ratio of HCHOto NO2 over major cities across the world. Our study aims to demonstrate howsatellite HCHO/NO2 products can complement in-situ O3networks by providinginformation on the spatial heterogeneity and long-term evolution of O3chemical regimes. [ABSTRACT FROM AUTHOR]

Background: To enhance the efficacy of adoptive NK cell therapy against solid tumors, NK cells must be modified to resist exhaustion in the tumor microenvironment (TME). However, the molecular checkpoint underlying NK cell exhaustion in the TME remains elusive., Methods: We analyzed the correlation between TIPE2 expression and NK cell functional exhaustion in the TME both in humans and mice by single-cell transcriptomic analysis and by using gene reporter mice. We investigated the effects of TIPE2 deletion on adoptively transferred NK cell therapy against cancers by using NK cells from NK-specific Tipe2- deficient mice or peripheral blood-derived or induced pluripotent stem cell (iPSC)-derived human NK cells with TIPE2 deletion by CRISPR/Cas9. We also investigated the potential synergy of double deletion of TIPE2 and another checkpoint molecule, CISH ., Results: By single-cell transcriptomic analysis and by using gene reporter mice, we found that TIPE2 expression correlated with NK cell exhaustion in the TME both in humans and mice and that the TIPE2 high NK cell subset correlated with poorer survival of tumor patients. TIPE2 deletion promoted the antitumor activity of adoptively transferred mouse NK cells and adoptively transferred human NK cells, either derived from peripheral blood or differentiated from iPSCs. TIPE2 deletion rendered NK cells with elevated capacities for tumor infiltration and effector functions. TIPE2 deletion also synergized with CISH deletion to further improve antitumor activity in vivo., Conclusions: This study highlighted TIPE2 targeting as a promising approach for enhancing adoptive NK cell therapy against solid tumors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear. Methods: TGF-β1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-β1-induced NSCLC metastasis were studied by gain- and loss-of-function assays both in vitro and in vivo . The underlying mechanisms were studied using molecular biology assays. Results: We found that knockdown of NgBR inhibited TGF-β1-induced cell migration and invasion in NSCLC cells. In contrast, NgBR overexpression promoted TGF-β1-induced EMT of A549 cells. Mechanically, we found that knockdown of NgBR facilitated ubiquitination and degradation of TβRI, leading to downregulation of TβRI expression in NSCLC cells. Moreover, we confirmed a positive correlation between NgBR and TβRI in NSCLC tissues. Conclusions: Our findings provide a novel role of NgBR in modulating TGF-β1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)