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Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field.
Elsevier
2023
The Adverse Outcome Pathway (AOP) framework plays a crucial role in the paradigm shift of toxicity testing towards the development and use of new approach methodologies. AOPs developed for chemicals are in theory applicable to nanomaterials (NMs). However, only subtle efforts have been made to integrate information on NM-induced toxicity into existing AOPs. In a previous study, we identified AOPs in the AOP-Wiki associated with the molecular initiating events (MIEs) and key events (KEs) reported for NMs in scientific literature. In a next step, we analyzed these AOPs and found that mitochondrial toxicity plays a significant role in several of them at the molecular and cellular levels. In this study, we aimed to generate hypothesis-based AOPs related to NM-induced mitochondrial toxicity. This was achieved by integrating science-based information collected on NM-induced mitochondrial toxicity into all existing AOPs in the AOP-Wiki, which already includes mitochondrial toxicity as a MIE/KE. The results showed that several AOPs in the AOP-Wiki related to the lung, liver, cardiovascular and nervous system, with extensively defined KEs and key event relationships (KERs), could be utilized to develop AOPs that are relevant for NMs. Our results also indicate that the majority of the studies included in our literature review were of poor quality, particularly in reporting NM physico-chemical characteristics, and NM-relevant mitochondrial MIEs were scarcely reported. This study highlights the potential role of NM-induced mitochondrial toxicity in human-relevant adverse outcomes and identifies useful AOPs in the AOP-Wiki for the development AOPs that are relevant for NMs.
2023
Method for retrieval of aerosol optical depth from multichannel irradiance measurements
We present, to the best of our knowledge, a new method for retrieval of aerosol optical depth from multichannel irradiance measurements. A radiative transfer model is used to simulate measurements to create the new aerosol optical depth retrieval method. A description of the algorithm, simulations, proof of principle, merits, possible future developments and implementations is provided. As a demonstration, measurements in the New York City area are simulated based on the specific channel configuration of an existing multichannel irradiance instrument. Verification of the method with irradiance measurement data is also provided.
Optical Society of America
2023
2023
2023
Trends in polar ozone loss since 1989: potential sign of recovery in the Arctic ozone column
Ozone depletion over the polar regions is monitored each year by satellite- and ground-based instruments. In this study, the vortex-averaged ozone loss over the last 3 decades is evaluated for both polar regions using the passive ozone tracer of the chemical transport model TOMCAT/SLIMCAT and total ozone observations from Système d'Analyse par Observation Zénithale (SAOZ) ground-based instruments and Multi-Sensor Reanalysis (MSR2). The passive-tracer method allows us to determine the evolution of the daily rate of column ozone destruction and the magnitude of the cumulative column loss at the end of the winter. Three metrics are used in trend analyses that aim to assess the ozone recovery rate over both polar regions: (1) the maximum ozone loss at the end of the winter, (2) the onset day of ozone loss at a specific threshold, and (3) the ozone loss residuals computed from the differences between annual ozone loss and ozone loss values regressed with respect to sunlit volume of polar stratospheric clouds (VPSCs). This latter metric is based on linear and parabolic regressions for ozone loss in the Northern Hemisphere and Southern Hemisphere, respectively. In the Antarctic, metrics 1 and 3 yield trends of −2.3 % and −2.2 % per decade for the 2000–2021 period, significant at 1 and 2 standard deviations (σ), respectively. For metric 2, various thresholds were considered at the total ozone loss values of 20 %, 25 %, 30 %, 35 %, and 40 %, all of them showing a time delay as a function of year in terms of when the threshold is reached. The trends are significant at the 2σ level and vary from 3.5 to 4.2 d per decade between the various thresholds. In the Arctic, metric 1 exhibits large interannual variability, and no significant trend is detected; this result is highly influenced by the record ozone losses in 2011 and 2020. Metric 2 is not applied in the Northern Hemisphere due to the difficulty in finding a threshold value in enough of the winters. Metric 3 provides a negative trend in Arctic ozone loss residuals with respect to the sunlit VPSC fit of −2.00 ± 0.97 (1σ) % per decade, with limited significance at the 2σ level. With such a metric, a potential quantitative detection of ozone recovery in the Arctic springtime lower stratosphere can be made.
2023
2023
2023
Low-cost air quality sensor systems can be deployed at high density, making them a significant candidate of complementary tools for improved air quality assessment. However, they still suffer from poor or unknown data quality. In this paper, we report on a unique dataset including the raw sensor data of quality-controlled sensor networks along with co-located reference data sets. Sensor data are collected using the AirSensEUR sensor system, including sensors to monitor NO, NO2, O3, CO, PM2.5, PM10, PM1, CO2 and meteorological parameters. In total, 85 sensor systems were deployed throughout a year in three European cities (Antwerp, Oslo and Zagreb), resulting in a dataset comprising different meteorological and ambient conditions. The main data collection included two co-location campaigns in different seasons at an Air Quality Monitoring Station (AQMS) in each city and a deployment at various locations in each city (also including locations at other AQMSs). The dataset consists of data files with sensor and reference data, and metadata files with description of locations, deployment dates and description of sensors and reference instruments.
Springer Nature
2023
Low-cost sensors (LCSs) for particulate matter (PM) concentrations have attracted the interest of researchers, supplementing their efforts to quantify PM in higher spatiotemporal resolution. The precision of PM mass concentration measurements from PMS 5003 sensors has been widely documented, though limited information is available regarding their size selectivity and number concentration measurement accuracy. In this work, PMS 5003 sensors, along with a Federal Referral Methods (FRM) sampler (Grimm spectrometer), were deployed across three sites with different atmospheric profiles, an urban (Germanou) and a background (UPat) site in Patras (Greece), and a semi-arid site in Almería (Spain, PSA). The LCSs particle number concentration measurements were investigated for different size bins. Findings for particles with diameter between 0.3 and 10 μm suggest that particle size significantly affected the LCSs’ response. The LCSs could accurately detect number concentrations for particles smaller than 1 μm in the urban (R2 = 0.9) and background sites (R2 = 0.92), while a modest correlation was found with the reference instrument in the semi-arid area (R2 = 0.69). However, their performance was rather poor (R2
MDPI
2023
2023
2023
2023
2023
2023
2023
The 2021 East Asia sandstorm began from the Eastern Gobi desert steppe in Mongolia on March 14, and later spread to northern China and the Korean Peninsula. It was the biggest sandstorm to hit China in a decade, causing severe air pollution and a significant threat to human health. Capturing and predicting such extreme events is critical for society. The Lagrangian particle dispersion model FLEXPART and the associated dust emission model FLEXDUST have been recently developed and applied to simulate global dust cycles. However, how well the model captures Asian dust storm events remains to be explored. In this study, we applied FLEXPART to simulate the recent 2021 East Asia sandstorm, and evaluated its performance comparing with observation and observation-constrained reanalysis datasets, such as the Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2) and CAMS global atmospheric composition forecasts (CAMS-F). We found that the default setting of FLEXDUST substantially underestimates the strength of dust emission and FLEXPART modelled dust concentration in this storm compared to that in MERRA-2 and CAMS-F. An improvement of the parametrization of bare soil fraction, topographical scaling, threshold friction velocity and vertical dust flux scheme based on Kok et al. (Atmospheric Chemistry and Physics, 2014, 14, 13023–13041) in FLEXDUST can reproduce the strength and spatio-temporal pattern of the dust storm comparable to MERRA-2 and CAMS-F. However, it still underestimates the observed spike of dust concentration during the dust storm event over northern China, and requires further improvement in the future. The improved FLEXDUST and FLEXPART perform better than MERRA-2 and CAMS-F in capturing the observed particle size distribution of dust aerosols, highlighting the importance of using more dust size bins and size-dependent parameterization for dust emission, and dry and wet deposition schemes for modelling the Asian dust cycle and its climatic feedbacks.
Frontiers Media S.A.
2023