Sources of Organic Aerosol in China from 2005 to 2019: A Modeling Analysis.

Organic aerosol (OA) is a key component of fine particulate matter (PM2.5) and affects the human health and leads to climate change. With strict control measures for air pollutants during the last decade, the OA concentration in China declined slowly, while its sources remain unclear. In this study, we simulate the primary OA (POA) and secondary OA (SOA) concentrations from 2005 to 2019 with a state-of-the-art air quality model, Community Multiscale Air Quality (CMAQ, version 5.3.2) coupled with a Two-Dimensional Volatility Basis Set (2D-VBS) module, and a long-term emission inventory of full-volatility organic compounds in China and conduct source apportionment and sensitivity analysis. The simulation results show that, from 2005 to 2019, the OA concentration in China decreased from 24.0 to 12.8 µg/m3 with most of the reduction from POA. The OA pollution from residential biomass burning declined 75% from 2005 to 2019, while it is still the major OA source in China. OA pollution from VCP increased by more than 2-fold and became the largest SOA source in China. From 2014 to 2019, the NOx control in China slightly offset the decrease of SOA concentration due to elevated oxidation capacity.

Observation-based sources evolution of non-methane hydrocarbons (NMHCs) in a megacity of China.

Both concentrations and emissions of many air pollutants have been decreasing due to implement of control measures in China, in contrast to the fact that an increase in emissions of non-methane hydrocarbons (NMHCs) has been reported. This study employed seven years continuous NMHCs measurements and the related activities data of Shanghai, a megacity in China, to explore evolution of emissions and effectiveness of air pollution control measures. The mixing ratio of NMHCs showed no statistical interannual changes, of which their compositions exhibited marked changes. This resulted in a decreasing trend of ozone formation potential by 3.8%/year (p < 0.05, the same below), which should be beneficial to ozone pollution mitigation as its production in Shanghai is in the NMHCs-limited regime. Observed alkanes, aromatics and acetylene changed by +3.7%/year, -5.9%/year and -7.4%/year, respectively, and alkenes showed no apparent trend. NMHCs sources were apportioned by a positive matrix factorization model. Accordingly, vehicular emissions (-5.9%/year) and petrochemical industry emissions (-7.1%/year) decreased significantly, but the decrease slowed down; significant reduction in solvent usage (-9.0%/year) appeared after 2010; however, emissions of natural gas (+12.6%/year) and fuel evaporation (with an increasing fraction) became more important. The inconsistency between observations and inventories was found in interannual trend and speciation as well as source contributions, emphasizing the need for further validation in NMHCs emission inventory. Our study confirms the effectiveness of measures targeting mobile and centralized emissions from industrial sources and reveals a need focusing on fugitive emissions, which provided new insights into future air policies in polluted region.

Comparative Assessment of Cooking Emission Contributions to Urban Organic Aerosol Using Online Molecular Tracers and Aerosol Mass Spectrometry Measurements.

Cooking organic aerosol (COA) is an important source of particulate pollutants in urbanized regions. Yet, the diversity and complexity of COA components make direct identification and quantification of COA difficult. In this study, we conducted collocated OA measurements with an aerosol mass spectrometer (AMS) and a thermal desorption aerosol gas chromatography-mass spectrometer (TAG) in Shanghai. Cooking molecular tracers (e.g., C18 fatty acids, azelaic acid) measured by TAG provide unambiguous source information for evaluating the tracer ion (C6H10O+, m/z 98) used for identification and apportionment of COA in AMS analysis. Based on the collocated AMS and TAG measurements, two COA factors, namely, a primary COA (PCOA) and an oxygenated COA (OCOA) produced from rapid oxygenation of freshly emitted PCOA, were identified. Criteria for identifying COA factors from AMS analysis with different oxygenation levels are proposed, i.e., characteristic mass spectra, temporal variations, etc. Furthermore, two positive matrix factorization approaches, namely, AMS-PMF and the molecular marker (MM)-PMF, were compared for COA quantification, where high consistency was found with the contribution of COA to total PM2.5 mass estimated to be 9 ± 7% by AMS-PMF and 6 ± 5% by the MM-PMF. Our study highlights the important impacts of cooking activities on air quality in urban areas. We also demonstrate the advantage of conducting collocated measurements using multiple high time resolution mass spectrometric techniques in advancing our understanding of atmospheric OA chemistry and improving the accuracy of source apportionment.

Ammonia Emission Measurements for Light-Duty Gasoline Vehicles in China and Implications for Emission Modeling.

Motor vehicle ammonia (NH3) emissions have attracted increasing attention for their potential to form secondary aerosols in urban atmospheres. However, vehicle NH3 emission factors (EFs) remain largely unknown due to a lack of measurements. Thus, we conducted detailed measurements of NH3 emissions from 18 Euro 2 to Euro 5 light-duty gasoline vehicles (LDGVs) in Shanghai, China. The distance- and fuel-based NH3 EFs average 29.2 ± 24.1 mg·km-1 and 0.49 ± 0.41 g·kg-1, respectively. The average NH3-to-CO2 ratio is 0.41 ± 0.34 ppbv·ppmv-1. The measurements reveal that NH3 emissions from LDGVs are strongly correlated with both vehicle specific power (VSP) and the modified combustion efficiency (MCE); these relationships were used to predict LDGV NH3 EFs via a newly developed model. The predicted LDGV NH3 EFs under urban and highway driving cycles are 23.3 mg·km-1 and 84.5 mg·km-1, respectively, which are consistent with field measurements. The NH3 EF has decreased by 32% in average since the implementation of vehicle emission control policies in China five years ago. The model presented herein more accurately predicts LDGV NH3 emissions, contributing substantially to the compilation of NH3 emission inventories and prediction of future motor vehicle emissions in China.

Intermediate Volatility Organic Compound Emissions from a Large Cargo Vessel Operated under Real-World Conditions.

Intermediate volatility organic compound (IVOC) emissions from a large cargo vessel were characterized under real-world operating conditions using an on-board measurement system. Test ship fuel-based emission factors (EFs) of total IVOCs were determined for two fuel types and seven operating conditions. The average total IVOC EF was 1003 ± 581 mg·kg-fuel-1, approximately 0.76 and 0.29 times the EFs of primary organic aerosol (POA) emissions from low-sulfur fuel (LSF, 0.38 wt % S) and high-sulfur fuel (HSF, 1.12 wt % S), respectively. The average total IVOC EF from LSF was 2.4 times that from HSF. The average IVOC EF under low engine load (15%) was 0.5-1.6 times higher than those under 36%-74% loads. An unresolved complex mixture (UCM) contributed 86.1 ± 1.9% of the total IVOC emissions. Ship secondary organic aerosol (SOA) production was estimated to be 546.5 ± 284.1 mg·kg-fuel-1; IVOCs contributed 98.9 ± 0.9% of the produced SOA on average. Fuel type was the dominant determinant of ship IVOC emissions, IVOC volatility distributions, and SOA production. The ship emitted more IVOC mass, produced higher proportions of volatile organic components, and produced more SOA mass when fueled with LSF than when fueled with HSF. When reducing ship POA emissions, more attention should be paid to commensurate control of ship SOA formation potential.

An Integrated Source Apportionment Methodology and Its Application over the Yangtze River Delta Region, China.

An integrated source apportionment methodology is developed by amalgamating the receptor-oriented model (ROM) and source-oriented numerical simulations (SOM) together to eliminate the weaknesses of individual SA methods. This approach attempts to apportion and dissect the PM2.5 sources in the Yangtze River Delta region during winter. First, three ROM models (CMB, PMF, ME2) are applied and compared for the preliminary SA results, with information from PM2.5 sampling and lab analysis during the winter seasons. The detailed source category contribution of SOM to PM2.5 is further simulated using the WRF-CAMx model. The two pieces of information from both ROM and SOM are then stitched together to give a comprehensive information on the PM2.5 sources over the region. With the integrated approach, the detailed contributing sources of the ambient PM2.5 at different receptors including rural and urban, coastal and in-land, northern and southern receptors are analyzed. The results are compared with previous data and shows good agreement. This integrative approach is more comprehensive and is able to produce a more profound and detailed understanding between the sources and receptors, compared with single models.

Metavert synergises with standard cytotoxics in human PDAC organoids and is associated with transcriptomic signatures of therapeutic response.

BACKGROUND: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-ß and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics. METHODS: Thirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data. RESULTS: Metavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TSHi samples were enriched for mRNA splicing and DNA repair processes; they were associated with Basal-like tissues but also with GATA6+ve-chemo-naïve samples and were higher following gemcitabine but not FOLFIRINOX treatment. In contrast, Metavert+IR-TSHI samples were enriched for TP53 pathways; they were associated with Classical-like pretreatment samples and with GATA6+ve/KRT17+ve hybrid cell types following FOLFIRINOX, but not gemcitabine treatment, and were unrelated to transcriptional subtypes. CONCLUSIONS: Metavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.

[High-resolution Emission Inventory of Reactive Volatile Organic Compounds from Anthropogenic Sources in the Yangtze River Delta Region].

A high-resolution emission inventory of anthropogenic active volatile organic compounds (VOCs) for the Yangtze River Delta (YRD) region was developed based on the local measurement of 41 cities in the region and the specific 4.4 database of EPA. The emission characteristics and composition of VOCs were analyzed. The ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAP) of VOCs were calculated. The results showed that the total emission of anthropogenic VOCs in the YRD in 2017 was 4.9×106 t. The emission contributions of process sources, industrial solvent sources, mobile sources, domestic sources, storage and transportation sources, agricultural sources, and waste treatment sources were 34.3%, 27.1%, 19.5%, 9.7%, 6.1%, 2.5%, and 0.4%, respectively. Aromatic hydrocarbons and alkanes were the main components of VOCs, accounting for 25% of the total VOCs emissions in the region. The contribution rates of OFP from process sources, industrial solvent sources, mobile sources, and domestic sources were 38.3%, 21.5%, 16.4%, and 13.2%, respectively, and the contribution rates of SOAP were 26.2%, 34.1%, 18.1%, and 17.9%, respectively, which was basically consistent with the main contribution sources of VOCs emissions. The emission characteristics of the key industries in each city were obviously different. The key urban agglomeration of VOCs emission was mainly petrochemical industries and equipment manufacturing, whereas the northern part of the region was mainly wood furniture and other coating industries. The results showed that propylene, m-xylene, p-xylene, and ethylene were the main contribution sources of ozone, whereas toluene, 1,2,4-trimethylene, m-xylene, and p-xylene were the main contribution sources of secondary organic aerosols. In the next stage, the fine management of VOCs can be transformed into the main industries based on chemical reaction activity, which can give priority to the governance of key industries such as the chemical industry, petrochemical, automobile manufacturing, textile, wood, and furniture and can formulate different governance paths according to urban characteristics.

[Spatial and Temporal Distribution Characteristics of Ozone Concentration and Population Health Benefit Assessment in the Yangtze River Delta Region from 2017 to 2020].

In recent years, the ozone (O3) concentration has showed a rising trend in China, becoming second only to PM2.5 as an important factor affecting air quality. To grasp the spatial-temporal variations characteristics of O3 and the associated health impacts during the implementation of the three-year plan on defending the blue sky in the Yangtze River Delta (YRD) region, data collected from 210 monitoring stations in the YRD from 2017 to 2020 were analyzed using the global Moran's index and Getis-Ord Gi* index methods, and the associated health benefits of reduced O3 exposure were evaluated using the health risk and environmental value assessment methods. The results showed that during the study period, the interquartile range (IQR) of the annual average O3 concentration and that of the warm season both presented a declining trend. The average O3 concentrations in both warm and cold seasons showed a similar spatial distribution pattern, with the northern part exhibiting the higher concentrations and the southern part showing the lower concentrations. Furthermore, the O3 concentrations in the warm season were characterized by high O3 concentrations clustering in the northern and central part of the region. The proportion of the population exposure to annual average O3 concentration over 160 µg·m-3 decreased from 72.3% in 2017 to 34.8% in 2020 in the YRD. Although the population-weighted annual mean O3 concentration in the whole YRD region showed a downward trend, some cities in western Anhui province, northern Jiangsu province, and central Jiangsu province showed fluctuations and even an increasing trend. In terms of health benefits, there were 3782 cases (95% CI:2050-5511 cases) of avoided premature deaths associated with reduced O3 concentrations in the warm season in 2020 compared to 2017. The total health benefit was 26198 million yuan (95% CI:14201-38175 million yuan). Compared to the cost of the main O3 precursor emission reduction, the cost-benefits ratio was 1:1.67 to 3.23.

Refining the Treatment of Pancreatic Cancer From Big Data to Improved Individual Survival.

Pancreatic cancer is one of the most lethal cancers worldwide, most notably in Europe and North America. Great strides have been made in combining the most effective conventional therapies to improve survival at least in the short and medium term. The start of treatment can only be made once a diagnosis is made, which at this point, the tumor volume is already very high in the primary cancer and systemically. If caught at the earliest opportunity (in circa 20% patients) surgical resection of the primary followed by combination chemotherapy can achieve 5-year overall survival rates of 30%-50%. A delay in detection of even a few months after symptom onset will result in the tumor having only borderline resectabilty (in 20%-30% of patients), in which case the best survival is achieved by using short-course chemotherapy before tumor resection as well as adjuvant chemotherapy. Once metastases become visible (in 40%-60% of patients), cure is not possible, palliative cytotoxics only being able to prolong life by few months. Even in apparently successful therapy in resected and borderline resectable patients, the recurrence rate is very high. Considerable efforts to understand the nature of pancreatic cancer through large-scale genomics, transcriptomics, and digital profiling, combined with functional preclinical models, using genetically engineered mouse models and patient derived organoids, have identified the critical role of the tumor microenvironment in determining the nature of chemo- and immuno-resistance. This functional understanding has powered fresh and exciting approaches for the treatment of this cancer.

Corrigendum: Clinical impact of molecular subtyping of pancreatic cancer.

[This corrects the article DOI: 10.3389/fcell.2021.743908.].

Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC.

Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to chemotherapy remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) and multiplexed immunofluorescence (n = 122) on chemo-naive and postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) to define the impact of neoadjuvant chemotherapy. Transcriptome analysis combined with high-resolution mapping of whole-tissue sections identified GATA6 (classical), KRT17 (basal-like) and cytochrome P450 3A (CYP3A) coexpressing cells that were preferentially enriched in post-CTX resected samples. The persistence of GATA6hi and KRT17hi cells post-CTX was significantly associated with poor survival after mFOLFIRINOX (mFFX), but not gemcitabine (GEM), treatment. Analysis of organoid models derived from chemo-naive and post-CTX samples demonstrated that CYP3A expression is a predictor of chemotherapy response and that CYP3A-expressing drug detoxification pathways can metabolize the prodrug irinotecan, a constituent of mFFX. These findings identify CYP3A-expressing drug-tolerant cell phenotypes in residual disease that may ultimately inform adjuvant treatment selection.

Responses of nitrogen and sulfur deposition to NH3 emission control in the Yangtze River Delta, China.

NH3 emission control has proven to be of great importance in reducing PM2.5 concentrations in China, while how it affects nitrogen/sulfur (N/S) deposition is still unclear. This study expanded the response surface model method to quantify the responses of N/S deposition to the emission control of precursors (NOx, SO2, NH3, VOCs and primary PM2.5) in the Yangtze River Delta, China. NH3 control was found to have higher efficiency in reducing N/S deposition than NOx and SO2 alone. The reduced N deposition response to NH3 emission control was higher in the northern part of the YRD region, whereas oxidized N deposition decreased sharply in the region with a low N critical load. Synergetic effect was found in reducing N deposition when we controlled the NH3 and NOx emissions simultaneously. Compared with the sum effect of individual NH3 and NOx emission control, the extra benefits from the synergy controls accounted for 4.4% (1.23 kg N·ha-1·yr-1) of the total N deposition, of which 81% came from the oxidized N deposition. The YRD region could receive the largest synergetic effect with a 1:1 ratio of NOx:NH3 emission reduction. The NH3 emission control increases the dry deposition of acid substances and worsens acid rain though it reduces the wet S/oxidized N deposition. These findings highlight the effectiveness of NH3 emission control and suggest a multi-pollutant control strategy for reducing N/S deposition. The response surface model method for deposition also provides a reference for other regions in China and other countries.

[Characteristics and Control Strategies on Summertime Peak Ozone Concentration in Shanghai].

With the continuous development of air pollution control measures, the concentration of PM2.5 in Shanghai has shown a conspicuous downward trend in recent years. However, frequent O3 pollution events have highlighted the urgent need to explore the occurrence patterns of O3 pollution and develop scientific strategies for reducing O3 peaks. This study examines data from July 2017, when the cumulative number of O3 pollution days in 17 cities in the Yangtze River Delta was 165 days, of which Shanghai was the most serious, with an exceedance rate of 64.5%. During this period, the average concentration of NO2 in Shanghai was 27.1 µg·m-3 and volatile organic copunds (VOCs) mixing ratio was 22.5×10-9. By analyzing ozone precursor concentrations and meteorological factors, we determined that these events mainly resulted from a combination of unfavorable meteorological conditions such as high temperature, low humidity, low wind speed, and high precursor emissions. WRF-CMAQ scenario simulations showed that a reduction in precursor emissions in Shanghai alone would have a limited controlling effect on regional O3 pollution. Thus, regional joint control is recommended when widespread pollution events occur. Our analysis shows that if VOCs in Shanghai and nine neighboring cities can be reduced by 30%, the maximum 8-h O3 concentration in Shanghai could be reduced by 7.2%. If the reduction number of these cities rises to 17, the maximum 8-h O3 concentration reduction rate in Shanghai will increase to 7.8%. It is also recommended that the VOCs:NOx reduction ratio should be strictly controlled at more than 3:1, or else the O3 concentration in some areas will increase.

Highly Resolved Dynamic Emissions of Air Pollutants and Greenhouse Gas CO2 during COVID-19 Pandemic in East China.

The unintentional emission reductions caused by the COVID-19 pandemic provides an opportunity to investigate the impact of energy, industry, and transportation activities on air pollutants and CO2 emissions and their synergy. Here, we constructed an approach to estimate city-level high resolution dynamic emissions of both anthropogenic air pollutants and CO2 by introducing dynamic temporal allocation coefficients based on real-time multisource activity data. We first apply this approach to estimate the spatiotemporal evolution of sectoral emissions in eastern China, focusing on the period around the COVID-19 lockdown. Comparisons with observational data show that our approach can well capture the spatiotemporal changes of both short-lived precursors (NOx and NMVOCs) and CO2 emissions. Our results show that air pollutants (SO2, NOx, and NMVOCs) were reduced by up to 31%-53% during the lockdown period accompanied by simultaneous changes of 40% CO2 emissions. The declines in power and heavy industry sectors dominated regional SO2 and CO2 reductions. NOx reductions were mainly attributed to mobile sources, while NMVOCs emission reductions were mainly from light industry sectors. Our findings suggest that differentiated emission control strategies should be implemented for different source categories to achieve coordinated reduction goals.

[Time-Determination and Contribution Analysis of Transport, Retention, and Offshore Backflow to Long-Term Sand-Dust Coupling].

Continuous on-line observation of particulate matter and PM2.5 chemical composition was conducted from October 15th to November 7th 2019 in East China. During the observation period, a wide range of dust-related processes took place. According to supplementary urban air quality assessment affected by dust (hereafter referred to as supplementary provisions), the observations were divided into four stages including pre-dust event, dust Ⅰ, dust Ⅱ, and post-dust event. The dust Ⅰ stage represented the processes of transportation and retention, while the dust Ⅱ stage represented processes of backflow from the sea and scavenging. The start time of the studied dust event was October 29th 08:00-09:00 based on the supplementary provisions, dust tracers, and air quality models; however, disagreements existed between these data sources with respect to the finishing time. The supplementary provisions could not effectively distinguish backflow dust from sea, and results from different dust tracers were variable. The WRF-CMAQ model simulated dust variation trends well but overestimated short-term suspended dust and backflow dust. PM10, PM2.5, and trace element concentrations were much higher during dust events than during non-dust periods, with highest daily concentrations of (234.8±125.5), (76.8±22.5), and (17.54±10.5) µg·m-3, respectively, which occurred on October 29th. During the dust event, concentration of crustal elements were remarkably high in PM2.5. At the same time, secondary ions (SO42-, NO3-, and NH4+) contributed less to PM2.5 mass concentrations. Four major crustal elements (Al, Si, Ca, and Fe) accounted for 23.5% and 13.7% of the mass concentration of PM2.5 and secondary ions accounted for 24.3% and 41.9% during dust Ⅰ and dust Ⅱ stages, respectively. Based on PMF source apportionment, Ca abundance, PM2.5/PM10 in dust sources, and the reconstruction of crustal material, dust particulates accounted for 43.4%-50.0% of PM2.5 and backflow dust accounted for 19.2%-24.7% of PM2.5.

[Characterization of Volatile Organic Compounds (VOCs) Using Mobile Monitoring Around the Industrial Parks in the Yangzte River Delta Region of China].

Volatile organic compounds (VOCs) play important roles in the formation of ozone and fine particles in the troposphere. Industrial parks emit significant amounts of VOCs in China, while few studies have characterized them. In the present study, a mobile platform was employed to measure the levels and composition VOCs around industrial parks in the Yangzte River Delta region. The average concentration of VOCs ranged from 39 µg·m-3 (5% percentile) to 533 µg·m-3 (95% percentile) with an average of 183 µg·m-3, which was three times that of ambient concentrations. Maximum VOC concentrations ranged from 307 µg·m-3 (5% percentile) to 12006 µg·m-3 (95% percentile) with an average of 2812 µg·m-3. The frequency of abnormal peak values was as high as 64% across all the industrial parks, of which toluene (32%), xylene (18%), benzene (9%), and>C9 aromatics (19%) were the most common species. Differences in VOC characteristics were observed among the different types of industrial parks. Specifically, highest concentrations of VOCs were observed in textile industrial parks followed by chemical, painting, and petrochemical industrial parks, and VOC concentrations in electronics industrial parks were the lowest. Importantly, species measured using the mobile platform only contributed~50% of VOCs present in ambient samples, indicating that the concentrations of VOCs in the industrial parks were underestimated overall. These results can inform measures to control VOC pollution in industrial parks in China.

Clinical Impact of Molecular Subtyping of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma is a highly lethal malignancy, which has now become the seventh most common cause of cancer death in the world, with the highest mortality rates in Europe and North America. In the past 30 years, there has been some progress in 5-year survival (rates increasing from 2.5 to 10%), but this is still extremely poor compared to all other common cancer types. Targeted therapies for advanced pancreatic cancer based on actionable mutations have been disappointing, with only 3-5% showing even a short clinical benefit. There is, however, a molecular diversity beyond mutations in genes responsible for producing classical canonical signaling pathways. Pancreatic cancer is almost unique in promoting an excess production of other components of the stroma, resulting in a complex tumor microenvironment that contributes to tumor development, progression, and response to treatment. Various transcriptional subtypes have also been described. Most notably, there is a strong alignment between the Classical/Pancreatic progenitor and Quasi-mesenchymal/Basal-like/Squamous subtype signatures of Moffit, Collinson, Bailey, Puleo, and Chan-Seng-Yue, which have potential clinical impact. Sequencing of epithelial cell populations enriched by laser capture microscopy combined with single-cell RNA sequencing has revealed the potential genomic evolution of pancreatic cancer as being a consequence of a gene expression continuum from mixed Basal-like and Classical cell populations within the same tumor, linked to allelic imbalances in mutant KRAS, with metastatic tumors being more copy number-unstable compared to primary tumors. The Basal-like subtype appears more chemoresistant with reduced survival compared to the Classical subtype. Chemotherapy and/or chemoradiation will also enrich the Basal-like subtype. Squamous/Basal-like programs facilitate immune infiltration compared with the Classical-like programs. The immune infiltrates associated with Basal and Classical type cells are distinct, potentially opening the door to differential strategies. Single-cell and spatial transcriptomics will now allow single cell profiling of tumor and resident immune cell populations that may further advance subtyping. Multiple clinical trials have been launched based on transcriptomic response signatures and molecular subtyping including COMPASS, Precision Promise, ESPAC6/7, PREDICT-PACA, and PASS1. We review several approaches to explore the clinical relevance of molecular profiling to provide optimal bench-to-beside translation with clinical impact.

[Particle Size Distribution of PM Emission from In-use Gasoline and Diesel Vehicles].

Particle size distribution and emission factors from 9 State 3-5 light-duty gasoline vehicles (LDGVs) and 15 State 3-5 heavy-duty diesel vehicles (HDDVs) were tested in this study using a constant volume sampling (CVS) system on a dynamometer. The influences of driving cycles and emission control level on the PM emission factors and particle size distribution were analyzed. The results show that the PM emission factors of the tested LDGVs and HDDVs were (4.1±4.0)×1014 and (5.7±4.3)×1015 kg-1, respectively; the HDDV PM emission factor was (14±7) times less than that of LDGVs. Regarding LDGVs, the PM emission factor under the extra high speed condition was much more than that of the other speed conditions at (5.1±5.0)×1013 km-1, 11.7, 14.1, and 7.3 times more than that under the low, medium, and high speed conditions, respectively. Regarding HDDVs, the emission factor under the high speed condition was 2.5 and 1.4 times that under the low and medium speed conditions, respectively, and was mostly of nuclei-mode particles. At the emission control level of State 3-5, the PM emission factors of LDGVs were (2.7±1.7)×1013, (2.6±1.3)×1013, and (1.6±1.2)×1013 km-1, respectively, and those of HDDVs were (2.2±1.2)×1015, 2.0×1015, and (7.1±2.1)×1014 km-1, respectively. With improvement in emission control level, the particle number emission control of LDGVs and HDDVs generally showed a good downward trend. However, the emission of PM above 110 nm from LDGVs did not improve with the emission control level. Although the quantity emission factor of HDDVs with particle size above 110 nm is relatively low, its harm to the environment cannot be ignored, which should justify necessary attention.

Driving Forces of Changes in Air Quality during the COVID-19 Lockdown Period in the Yangtze River Delta Region, China.

During the COVID-19 lockdown period (from January 23 to February 29, 2020), ambient PM2.5 concentrations in the Yangtze River Delta (YRD) region were observed to be much lower, while the maximum daily 8 h average (MDA8) O3 concentrations became much higher compared to those before the lockdown (from January 1 to 22, 2020). Here, we show that emission reduction is the major driving force for the PM2.5 change, contributing to a PM2.5 decrease by 37% to 55% in the four YRD major cities (i.e., Shanghai, Hangzhou, Nanjing, and Hefei), but the MDA8 O3 increase is driven by both emission reduction (29%-52%) and variation in meteorological conditions (17%- 49%). Among all pollutants, reduction in emissions mainly of primary PM contributes to a PM2.5 decrease by 28% to 46%, and NOx emission reduction contributes 7% to 10%. Although NOx emission reduction dominates the MDA8 O3 increase (38%-59%), volatile organic compounds (VOCs) emission reduction lead to a 5% to 9% MDA8 O3 decrease. Increased O3 promotes secondary aerosol formation and partially offsets the decrease of PM2.5 caused by the primary PM emission reductions. The results demonstrate that more coordinated air pollution control strategies are needed in YRD.