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Cancer is one of the deadliest human diseases, causing high rates of illness and death. Lung cancer has the highest mortality rate among all malignancies worldwide. Effusanin B, a diterpenoid derived from Isodon serra, showed therapeutic potential in treating non-small-cell lung cancer (NSCLC). Further research on the mechanism indicated that effusanin B inhibited the proliferation and migration of A549 cells both in vivo and in vitro. The in vitro activity assay demonstrated that effusanin B exhibited significant anticancer activity. Effusanin B induced apoptosis, promoted cell cycle arrest, increased the production of reactive oxygen species (ROS), and altered the mitochondrial membrane potential (MMP). Based on mechanistic studies, effusanin B was found to inhibit the proliferation and migration of A549 cells by affecting the signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) pathways. Moreover, effusanin B inhibited tumor growth and spread in a zebrafish xenograft model and demonstrated anti-angiogenic effects in a transgenic zebrafish model. [ABSTRACT FROM AUTHOR]

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]

The marine environment is the material basis for the survival and development of fishery resources, and changes in the marine environment affect the fishery economy. Therefore, against the background of sustainability and environmental uncertainty, it is important to investigate the development of the marine environment and the marine fishery economy to improve the quality of both. Taking the panel data for 11 coastal cities in China from 2011 to 2020, we use several methods, including the entropy method, a coupling harmonious degree model, and a Tobit model, to measure the marine-environment quality and marine-fishery-economy quality, their coordination, and the factors affecting that coordination. We find that (1) the marine-environment quality and marine-fishery economy quality show a significant upward trend over time, but they are spatially unbalanced, with obvious interprovincial differences. (2) Coordination between the marine-environment quality and marine-fishery-economy quality has risen steadily, but the level of coordination is still low, remaining at the primary level in most areas. (3) The important factors affecting coordination between the marine-environment quality and marine-fishery-economy quality include the strength of the marine fishery industry, scale of the marine fishery economy, production capacity of marine fisheries, marine-environment quality, and quality of the marine environment and its resources. In light of these findings, we should increase the coordination between the marine-environment quality and marine-fishery-economy quality by upgrading the marine fishery industry, modernizing marine fisheries, linking the environmental governance of marine and land areas, and strengthening the ecological construction of the marine environment. [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]

Prior work suggests drought exacerbates US air quality by increasing surface ozone concentrations. We analyze 2005–2015 tropospheric column concentrations of two trace gases that serve as proxies for surface ozone precursors retrieved from the OMI/Aura satellite: Nitrogen dioxide (ΩNO2; NOx proxy) and formaldehyde (ΩHCHO; VOC proxy). We find 3.5% and 7.7% summer drought enhancements (classified by SPEI) for ΩNO2 and ΩHCHO, respectively, corroborating signals previously extracted from ground‐level observations. When we subset by land cover type, the strongest ΩHCHO drought enhancement (10%) occurs in the woody savannas of the Southeast US. By isolating the influences of precipitation and temperature, we infer that enhanced biogenic VOC emissions in this region increase ΩHCHO independently with both high temperature and low precipitation during drought. The strongest ΩNO2 drought enhancement (6.0%) occurs over Midwest US croplands and grasslands, which we infer to reflect the sensitivity of soil NOx emissions to temperature. Plain Language Summary: Projected increases in drought severity and frequency for this century raise questions regarding possible impacts on air quality. Surface ozone, an air pollutant estimated to cause over 1 million annual premature deaths globally, forms when its precursor gases react in the sunlit atmosphere. These precursor gases depend on temperature and precipitation and thus can respond to drought. We analyze over a decade of satellite observations of two trace gases relevant to ozone formation and find that, on average, their concentrations increase during summer droughts in the Eastern US. While higher temperatures during droughts are usually associated with observed increases in trace gas concentrations, in the Southeast US we find increases associated with low precipitation independent of temperature. Satellite detection of these changes implies promise for application to other regions and more generally for improving mechanistic understanding of air quality responses to drought and other climate extremes. Key Points: Satellite retrievals of tropospheric NO2 and HCHO show drought enhancements of 3.5% and 7.7%, respectively, during Eastern US summersLow precipitation and high temperatures both independently drive HCHO drought enhancement (10%) in Southeast US woody savannasHigh temperatures drive NO2 drought enhancement (6.0%) in Midwest US croplands and grasslands [ABSTRACT FROM AUTHOR]

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. Plain Language Summary: Recent advances in satellite remote sensing enable observation‐based tracking of climate change and air pollution with relatively high spatial resolution globally. The 2018 NASA Health and Air Quality Applied Science Team (HAQAST) "Indicators" Tiger Team launched a collaboration between ~20 NASA‐supported scientists and civil society stakeholders to develop satellite‐derived global air pollution and climate indicators. This Commentary demonstrates the range of air quality and climate change tracking uses for satellite data and shares our experience and lessons learned, which can inform future problem‐driven science‐stakeholder collaborative efforts. Together, the team developed methods to track wildfires, dust storms, pollen, urban green space, nitrogen dioxide concentrations and asthma burdens, tropospheric ozone concentrations, and urban fine particulate matter mortality. Lessons learned include that participatory knowledge production can lead to more actionable information for stakeholders but requires time and dedicated attention. Stakeholder engagement is valuable at each stage, from developing more nascent data sets to operationalizing mature data sets. Flexibility is critical, since stakeholder needs evolve and new synergies emerge when there are engagements across a wide range of stakeholders and teams. However, additional ground measurements are needed to ground truth satellite observations, and sustained collaboration between the researchers and stakeholders after extramural support ends remains a challenge. Key Points: The NASA Health and Air Quality Applied Science Team "Indicators" Tiger Team developed satellite‐based air quality and climate indicatorsParticipatory knowledge production can lead to more useful information for stakeholders but requires continuous engagement and flexibilityGround measurements are still needed, and sustained collaboration between the researchers and stakeholders over time remains a challenge [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is a well-established risk factor for public health. To support both health risk assessment and epidemiological studies, data are needed on spatial and temporal patterns of PM2.5 exposures. This review article surveys publicly available exposure datasets for surface PM2.5 mass concentrations over the contiguous U.S., summarizes their applications and limitations, and provides suggestions on future research needs. The complex landscape of satellite instruments, model capabilities, monitor networks, and data synthesis methods offers opportunities for research development, but would benefit from guidance for new users. Guidance is provided to access publicly available PM2.5 datasets, to explain and compare different approaches for dataset generation, and to identify sources of uncertainties associated with various types of datasets. Three main sources used to create PM2.5 exposure data are ground-based measurements (especially regulatory monitoring), satellite retrievals (especially aerosol optical depth, AOD), and atmospheric chemistry models. We find inconsistencies among several publicly available PM2.5 estimates, highlighting uncertainties in the exposure datasets that are often overlooked in health effects analyses. Major differences among PM2.5 estimates emerge from the choice of data (ground-based, satellite, and/or model), the spatiotemporal resolutions, and the algorithms used to fuse data sources. Implications: Fine particulate matter (PM2.5) has large impacts on human morbidity and mortality. Even though the methods for generating the PM2.5 exposure estimates have been significantly improved in recent years, there is a lack of review articles that document PM2.5 exposure datasets that are publicly available and easily accessible by the health and air quality communities. In this article, we discuss the main methods that generate PM2.5 data, compare several publicly available datasets, and show the applications of various data fusion approaches. Guidance to access and critique these datasets are provided for stakeholders in public health sectors. [ABSTRACT FROM AUTHOR]

Determining effective strategies for mitigating surface ozone (O3) pollution requires knowledge of the relative ambient concentrations of its precursors, NO x, and VOCs. The space-based tropospheric column ratio of formaldehyde to NO2 (FNR) has been used as an indicator to identify NO x-limited versus NO x-saturated O3 formation regimes. Quantitative use of this indicator ratio is subject to three major uncertainties: (1) the split between NO x-limited and NO x-saturated conditions may shift in space and time, (2) the ratio of the vertically integrated column may not represent the near-surface environment, and (3) satellite products contain errors. We use the GEOS-Chem global chemical transport model to evaluate the quantitative utility of FNR observed from the Ozone Monitoring Instrument over three northern midlatitude source regions. We find that FNR in the model surface layer is a robust predictor of the simulated near-surface O3 production regime. Extending this surface-based predictor to a column-based FNR requires accounting for differences in the HCHO and NO2 vertical profiles. We compare four combinations of two OMI HCHO and NO2 retrievals with modeled FNR. The spatial and temporal correlations between the modeled and satellite-derived FNR vary with the choice of NO2 product, while the mean offset depends on the choice of HCHO product. Space-based FNR indicates that the spring transition to NO x-limited regimes has shifted at least a month earlier over major cities (e.g., New York, London, and Seoul) between 2005 and 2015. This increase in NO x sensitivity implies that NO x emission controls will improve O3 air quality more now than it would have a decade ago. [ABSTRACT FROM AUTHOR]

ABSTRACT Water vapour, an important greenhouse gas in the atmosphere, is crucial for hydrological, atmospheric, and meteorological processes. This study first compared five precipitable water vapour ( PWV) products from multi-sensors including radiosonde, AERosol RObotic NETwork ( AERONET) sunphotometer, Global Positioning System ( GPS) and MODerate resolution Imaging Spectroradiometer ( MODIS), and then characterized the spatial and temporal trends of PWV in mainland China. Intercomparison results indicate good agreements among PWV products with correlation coefficients ranging from 0.775 to 0.937. As for spatial analysis, 13 years of MODIS MOD05 products were investigated and the spatial distribution of PWV is closely correlated with the topography, e.g. latitude and altitude, in mainland China. A monotonically increasing annual trend was detected in some radiosonde sites in China between 1976 and 1999, but a decreasing trend was observed between 2000 and 2012. Analysis of the differences in PWV between weekdays and weekends indicated a marked weekend effect, suggesting the influence of anthropogenic activities. Diurnal variations in PWV were also studied from 1999 to 2009 using GPS data. A pronounced diurnal cycle of PWV was observed in most of the sites during summer and spring seasons. [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]

Nonrigid multimodal image registration remains a challenging task in medical image processing and analysis. The structural representation (SR)-based registration methods have attracted much attention recently. However, the existing SR methods cannot provide satisfactory registration accuracy due to the utilization of hand-designed features for structural representation. To address this problem, the structural representation method based on the improved version of the simple deep learning network named PCANet is proposed for medical image registration. In the proposed method, PCANet is firstly trained on numerous medical images to learn convolution kernels for this network. Then, a pair of input medical images to be registered is processed by the learned PCANet. The features extracted by various layers in the PCANet are fused to produce multilevel features. The structural representation images are constructed for two input images based on nonlinear transformation of these multilevel features. The Euclidean distance between structural representation images is calculated and used as the similarity metrics. The objective function defined by the similarity metrics is optimized by L-BFGS method to obtain parameters of the free-form deformation (FFD) model. Extensive experiments on simulated and real multimodal image datasets show that compared with the state-of-the-art registration methods, such as modality-independent neighborhood descriptor (MIND), normalized mutual information (NMI), Weber local descriptor (WLD), and the sum of squared differences on entropy images (ESSD), the proposed method provides better registration performance in terms of target registration error (TRE) and subjective human vision. [ABSTRACT FROM AUTHOR]

State-of-the-art Tb-to-Eu energy transfer (TEET) efficiency (>90%) under ultralow Eu3+ proportion (<6%) has been achieved in Eu/Tb bimetallic lanthanide coordination polymers (LnCPs). The yellow-light-emitting sample as sensor exhibits micromolar l -phenylalanine (l -Phe) in water and serum via obvious yellow-to-green luminometric behavior, meanwhile nanomolar-level detection limits are determined in terms of an updated Stern-Volmer equation with high selectivity and competitiveness. Excited-state inter-ligand photon transfer (ESILPT) greatly contributes to superior TEET property and outstanding luminometric behavior. This work opens a window for developing sensitive and stable visualization sensing, being of values on monitoring biochemical markers. [Display omitted] • State-of-the-art TEET efficiency (>90%) under ultralow Eu3+ proportion (<6%) has been achieved. • Colorimetric sensing is exhibited toward l -phenylalanine (l -Phe) in water and serum. • Excited-state inter-ligand photon transfer greatly contributes to superior TEET property and outstanding luminometric behavior. [ABSTRACT FROM AUTHOR]

Qualification and quantification of trace organic contaminants necessitates development of highly efficient sensing system, where excited-state inter-ligand proton transfer (ESILPT) provides a feasible pathway to construct efficient chemo-sensors. Herein, a strategically synthesized lanthanide complex, Eu(DBM) 3 (MeOH) 3 (briefly as Eu-DBM-MeOH; DBM = dibenzoylmethane), features two-step ESILPT processes, along with modification on molecular structure and energy band. As a result, Eu-DBM-MeOH exhibits excellent photophysical properties with characteristic luminescence of Eu3+ ion. Benefiting from these merits, the Eu-DBM-MeOH complex acts as ultra-sensitive chemo-sensor toward nanomolar-level nitrofuran antibiotics (nitrofurazone and nitrofurantoin) in water, by disrupting ESILPT processes. Combining the advantages on photophysical property and luminescent sensitivity, ESILPT-active compounds are expected to widen and deepen the research on complex-based luminophores, being potentially useful in trace detection and biological imaging. Nanomolar determination toward nitrofuran antibiotics in water has been realized by disrupting ESILPT process in a luminescent lanthanide complex. [Display omitted] • State-of-the-art sensitivity toward nitrofuran antibiotics in water has been realized. • ESILPT serves as photoluminescence and sensing mechanism. [ABSTRACT FROM AUTHOR]

The frequency of wildfires in the western United States has escalated in recent decades. Here we examine the impacts of wildfires on ground-level ozone (O 3 ) precursors and the O 3 -NO x -VOC chemistry from the source to downwind urban areas. We use satellite retrievals of nitrogen dioxide (NO 2 ) and formaldehyde (HCHO, an indicator of VOC) from the Tropospheric Monitoring Instrument (TROPOMI) to track the evolution of O 3 precursors from wildfires over California from 2018 to 2020. We improved these satellite retrievals by updating the a priori profiles and explicitly accounting for the effects of smoke aerosols. TROPOMI observations reveal that the extensive and intense fire smoke in 2020 led to an overall increase in statewide annual average HCHO and NO 2 columns by 16% and 9%. The increase in the level of NO 2 offsets the anthropogenic NO x emission reduction from the COVID-19 lockdown. The enhancement of NO 2 within fire plumes is concentrated near the regions actively burning, whereas the enhancement of HCHO is far-reaching, extending from the source regions to urban areas downwind due to the secondary production of HCHO from longer-lived VOCs such as ethene. Consequently, a larger increase in NO x occurs in NO x -limited source regions, while a greater increase in HCHO occurs in VOC-limited urban areas, both contributing to more efficient O 3 production.

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., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

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.)

Objective: Urinary tract infection (UTI) is an inflammatory response of the urothelium to bacterial invasion and is a common complication in patients with cutaneous ureterostomy (CU). For such patients, accurate and efficient identification of pathogens remains a challenge. The aim of this study included exploring utility of metagenomic next-generation sequencing (mNGS) in assisting microbiological diagnosis of UTI among patients undergoing CU, identifying promising cytokine or microorganism biomarkers, revealing microbiome diversity change and compare virulence factors (VFs) and antibiotic resistance genes (ARGs) after infection., Methods: We performed a case-control study of 50 consecutive CU patients from December 2020 to January 2021. According to the clinical diagnostic criteria, samples were divided into infected group and uninfected group and difference of urine culture, cytokines, microorganism, ARGs and VFs were compared between the two groups., Results: Inflammatory responses were more serious in infected group, as evidenced by a significant increase in IFN-α (p=0.031), IL-1β (0.023) and IL-6 (p=0.018). Clinical culture shows that there is higher positive rate in infected group for most clinical pathogens like Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida auris etc. and the top three pathogens with positive frequencies were E. coli , K. pneumoniae , and Enterococcus faecalis. Benchmarking clinical culture, the total sensitivity is 91.4% and specificity is 76.3% for mNGS. As for mNGS, there was no significant difference in microbiome α- diversity between infected and uninfected group. Three species biomarkers including Citrobacter freundii, Klebsiella oxytoca , and Enterobacter cloacae are enriched in infected group based on Lefse. E. cloacae were significantly correlated with IL-6 and IL-10. K. oxytoca were significantly correlated with IL-1β. Besides, the unweighted gene number and weighted gene abundance of VFs or ARGs are significantly higher in infected group. Notablely, ARGs belonging to fluoroquinolones, betalatmas, fosfomycin, phenicol, phenolic compound abundance is significantly higher in infected group which may have bad effect on clinical treatment for patients., Conclusion: mNGS, along with urine culture, will provide comprehensive and efficient reference for the diagnosis of UTI in patients with CU and allow us to monitor microbial changes in urine of these patients. Moreover, cytokines ( IL-6, IL-1β , and IFN-a ) or microorganisms like C. freundii, K. oxytoca or E. cloacae are promising biomarkers for building effective UTI diagnostic model of patients with CU and seriously the VFs and ARGs abundance increase in infected group may play bad effect on clinical treatment., Competing Interests: JG was employed by Genskey Medical Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Yuan, Gao, Liu, Jin, Tang and Cao.)

Effective and long-term treatment is required for controlling chronic Hepatitis B Virus (HBV) infection. Natural killer (NK) cells are antiviral innate lymphocytes and represent an essential arm of current immunotherapy. In chronic HBV (CHB), NK cells display altered changes in phenotypes and functions, but preserve antiviral activity, especially for cytolytic activity. On the other hand, NK cells might also cause liver injury in the disease. NK -based immunotherapy, including adoptive NK cell therapy and NK -based checkpoint inhibition, could potentially exploit the antiviral aspect of NK cells for controlling CHB infection while preventing liver tissue damage. Here, we review recent progress in NK cell biology under the context of CHB infection, and discuss potential NK -based immunotherapy strategies for the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin and Bi.)

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).)

Urban ozone (O 3 ) formation can be limited by NO x , VOCs, or both, complicating the design of effective O 3 abatement plans. A satellite-retrieved ratio of formaldehyde to NO 2 (HCHO/NO 2 ), developed from theory and modeling, has previously been used to indicate O 3 formation chemistry. Here, we connect this space-based indicator to spatiotemporal variations in O 3 recorded by on-the-ground monitors over major U.S. cities. High-O 3 events vary nonlinearly with OMI HCHO and NO 2 , and the transition from VOC-limited to NO x -limited O 3 formation regimes occurs at higher HCHO/NO 2 value (3 to 4) than previously determined from models, with slight intercity variations. To extend satellite records back to 1996, we develop an approach to harmonize observations from GOME and SCIAMACHY that accounts for differences in spatial resolution and overpass time. Two-decade (1996-2016) multisatellite HCHO/NO 2 captures the timing and location of the transition from VOC-limited to NO x -limited O 3 production regimes in major U.S. cities, which aligns with the observed long-term changes in urban-rural gradient of O 3 and the reversal of O 3 weekend effect. Our findings suggest promise for applying space-based HCHO/NO 2 to interpret local O 3 chemistry, particularly with the new-generation satellite instruments that offer finer spatial and temporal resolution.

Fine particulate matter (PM 2.5 ) is a well-established risk factor for public health. To support both health risk assessment and epidemiological studies, data are needed on spatial and temporal patterns of PM 2.5 exposures. This review article surveys publicly available exposure datasets for surface PM 2.5 mass concentrations over the contiguous U.S., summarizes their applications and limitations, and provides suggestions on future research needs. The complex landscape of satellite instruments, model capabilities, monitor networks, and data synthesis methods offers opportunities for research development, but would benefit from guidance for new users. Guidance is provided to access publicly available PM 2.5 datasets, to explain and compare different approaches for dataset generation, and to identify sources of uncertainties associated with various types of datasets. Three main sources used to create PM 2.5 exposure data are ground-based measurements (especially regulatory monitoring), satellite retrievals (especially aerosol optical depth, AOD), and atmospheric chemistry models. We find inconsistencies among several publicly available PM 2.5 estimates, highlighting uncertainties in the exposure datasets that are often overlooked in health effects analyses. Major differences among PM 2.5 estimates emerge from the choice of data (ground-based, satellite, and/or model), the spatiotemporal resolutions, and the algorithms used to fuse data sources. Implications : Fine particulate matter (PM 2.5 ) has large impacts on human morbidity and mortality. Even though the methods for generating the PM 2.5 exposure estimates have been significantly improved in recent years, there is a lack of review articles that document PM 2.5 exposure datasets that are publicly available and easily accessible by the health and air quality communities. In this article, we discuss the main methods that generate PM 2.5 data, compare several publicly available datasets, and show the applications of various data fusion approaches. Guidance to access and critique these datasets are provided for stakeholders in public health sectors.

Determining effective strategies for mitigating surface ozone (O 3 ) pollution requires knowledge of the relative ambient concentrations of its precursors, NO x , and VOCs. The space-based tropospheric column ratio of formaldehyde to NO 2 (FNR) has been used as an indicator to identify NO x -limited versus NO x -saturated O 3 formation regimes. Quantitative use of this indicator ratio is subject to three major uncertainties: (1) the split between NO x -limited and NO x -saturated conditions may shift in space and time, (2) the ratio of the vertically integrated column may not represent the near-surface environment, and (3) satellite products contain errors. We use the GEOS-Chem global chemical transport model to evaluate the quantitative utility of FNR observed from the Ozone Monitoring Instrument over three northern midlatitude source regions. We find that FNR in the model surface layer is a robust predictor of the simulated near-surface O 3 production regime. Extending this surface-based predictor to a column-based FNR requires accounting for differences in the HCHO and NO 2 vertical profiles. We compare four combinations of two OMI HCHO and NO 2 retrievals with modeled FNR. The spatial and temporal correlations between the modeled and satellite-derived FNR vary with the choice of NO 2 product, while the mean offset depends on the choice of HCHO product. Space-based FNR indicates that the spring transition to NO x -limited regimes has shifted at least a month earlier over major cities (e.g., New York, London, and Seoul) between 2005 and 2015. This increase in NO x sensitivity implies that NO x emission controls will improve O 3 air quality more now than it would have a decade ago.