GEM Concentrations Research Articles

Growth inhibition of pancreatic cancer by targeted delivery of gemcitabine via fucoidan-coated pH-sensitive liposomes

Fucoidan-coated pH sensitive liposomes were designed for targeted delivery of gemcitabine (FU-GEM PSL) to treat pancreatic cancer (PC). FU-GEM PSL had a particle size of 175.3 ± 4.9 nm, zeta potential of −19.0 ± 3.7 mV, encapsulation efficiency (EE) of 74.05 ± 0.17 %, and drug loading (DL) of 21.27 ± 0.05 %. Cell experiments in vitro showed that FU-GEM PSL could increase the release of GEM and drug concentration, and could inhibit tumor cell proliferation by affecting the cell cycle. FU-GEM PSL entered cells through macropinocytosis and caveolin-mediated endocytosis to exert effects. Meanwhile, the expression of P-selectin was detected in human tissues, demonstrating the feasibility of targeting FU. Moreover, combined with animal experiments in vivo, FU-GEM PSL could inhibit the development of PC. Furthermore, anti-tumor experiments in vivo carried on BALB/c mice indicated that FU-GEM PSL had tumor suppression abilities and safety. Therefore, FU-GEM PSL is a promising formulation for PC therapy.

Effects of nucleoside analogues, lipophilic prodrugs and elaidic acids on core signaling pathways in cancer cells

Objectives Nucleoside analogs such as gemcitabine (GEM; dFdC) and cytarabine (Ara-C) require nucleoside transporters to enter cells, and deficiency in equilibrative nucleoside transporter 1 (ENT1) can lead to resistance to these drugs. To facilitate transport-independent uptake, prodrugs with a fatty acid chain attached to the 5’-position of the ribose group of gemcitabine or cytarabine were developed (CP-4126 and CP-4055, respectively). As antimetabolites can activate cellular survival pathways, we investigated whether the prodrugs or their side-chains had similar or decreased effects. Methods Two cell lines A549 (non-small cell lung cancer) and WiDr (colon cancer cells) were exposed for 2-24hr to IC50 concentrations of GEM, Ara-C, CP-4126, CP4055 and elaidic acid (EA) concentrations corresponding to the CP-4126 and CP-4055 IC50. Cells were harvested and analyzed for proteins in cell survival pathways (p-AKT/AKT, p-ERK/ERK, p-P38/P38, GSK-3β/pGSK-3β) by using Western Blotting. Results All drugs and their derivatives showed time- and cell-line-dependent effects. In A549 cells, GEM, CP-4126 and EA-4126 decreased the p-AKT/AKT ratio at 2 and 24 hr. For the p-ERK/ERK ratio, GEM, EA-4126, Ara-C, CP-4045 and EA-4055 exposure led to an increase after 6 hr in A549 cells. Interestingly, Ara-C, CP-4055 and EA-4055 decreased p-ERK/ERK ratio in WiDr cells after 4 hr. In A549 cells, the p-GSK-3β/GSK-3β ratio decreased after exposure to Ara-C and CP-4055 but in WiDr cells increased after 24 hr. In A549 cells treatment with Ara-C, CP-4055 and EA-4126 decreased the p-P38/P38 after 6 hr. Conclusions The findings suggest that both parent drugs, prodrugs, and the EA chain influence cell survival and signaling pathways.

Spatiotemporal variation and inter-transport of atmospheric speciated mercury between Kaohsiung Harbor and neighboring urban areas

This study investigated the spatiotemporal variation, gas-particle partition, and source resolution of atmospheric speciation mercury (ASM) in Kaohsiung Harbor and neighboring Metro Kaohsiung. Four sampling sites were selected to determine the pollution characteristics and inter-transport of ASM between the port and urban areas. The yearly average GEM, GOM, and PBM concentrations were 7.13 ± 2.2 ng/m3, 331 ± 190 pg/m3, and 532 ± 301 pg/m3, respectively. Notably, GEM emerged as the predominant ASM species (85–94%), primarily originating from anthropogenic emissions from the harbor area and nearby industrial complex. The study revealed a distinct seasonal variation in ASM concentrations in the Kaohsiung Area in the following order: winter > fall > spring > summer. Concerning spatial distribution, ASM concentrations in the port areas were generally higher than those in the urban areas. This disparity was chiefly attributed to the influence of the prevailing winds, local sources, and atmospheric dispersion. Backward trajectory simulation revealed that polluted air masses blown from the northeast in winter and spring, moving along the western in-land part of Taiwan Island, were likely influenced by local sources and long-range transport (LRT). In summer, air pollutants originating from the south were likely transported from the coastal industrial sources. During fall, air masses blown from the western offshore waters transported air pollutants from Kaohsiung Harbor to neighboring Metro Kaohsiung. The results obtained from principle component analysis (PCA) indicated that primary sources in the port areas included ship emissions, vehicular exhausts, and nearby industrial complex, which align with the primary source factors identified by positive matrix factorization (PMF), which were mobile sources and coal-fired industrial boilers. Meanwhile, mobile sources and sulfur-containing fuel/waste combustion were identified as the primary sources in the urban areas.

Unexpectedly high concentrations of atmospheric mercury species in Lhasa, the largest city in the Tibetan Plateau

Abstract. The city of Lhasa is located in the central Tibetan Plateau and is the most densely populated area. As the first continuous monitoring of atmospheric mercury (Hg) species in a city in the Tibetan Plateau, our monitoring in Lhasa showed that the concentrations of gaseous elemental Hg (GEM), gaseous oxidized Hg (GOM), and particle-bound Hg (PBM) during the subsequent Indian summer monsoon (S-ISM) period were 2.73 ± 1.48 ng m−3, 38.4 ± 62.7 pg m−3, and 59.1 ± 181.0 pg m−3, respectively. During the westerly circulation (WEC) period, the GEM, GOM, and PBM concentrations were 2.11 ± 2.09 ng m−3, 35.8 ± 43.3 pg m−3, and 52.9 ± 90.1 pg m−3, respectively. The GOM and PBM concentrations were higher than those of previous monitoring in the Tibetan Plateau and other provincial capitals in China. Typical high-value occurrence processes were studied to investigate random events with high atmospheric Hg concentrations in Lhasa. Combustion events nearby or further away may be the main contributor of the high-concentration events. The lowest GEM concentrations occurred in the afternoon, and persistently high concentrations were observed at night. The changes in GEM concentrations were consistent with the trends of other pollutant concentrations and contradictory to those of the wind speed. The high GEM concentrations at night can be attributed to the lower boundary layer height and lower wind speed. For both GOM and PBM, higher GOM concentrations occurred during the day and PBM during the night. The results of the principal component analysis indicated that local sources and wind speed are important factors influencing atmospheric Hg concentrations in Lhasa. The trajectory simulation showed that the source of the GEM in Lhasa gradually shifted from the south to the west of Lhasa from the S-ISM to the WEC periods, while both the southern and western sources were important in the late WEC period. The concentrations and change patterns of Hg species in Lhasa were significantly different than those at other monitoring sites in the Tibetan Plateau. Monitoring Hg species in Lhasa shows the possible maximum anthropogenic influences in the Tibetan Plateau and demonstrates the dramatic effect of wind on changes in urban atmospheric Hg concentrations.

Internal tree cycling and atmospheric archiving of mercury: examination with concentration and stable isotope analyses

Abstract. Trees predominantly take up mercury (Hg) from the atmosphere via stomatal assimilation of gaseous elemental Hg (GEM). Hg is oxidised in leaves/needles and transported to other tree anatomy including bole wood, where it can be stored long-term. Using Hg associated with growth rings facilitates archiving of historical GEM concentrations. Nonetheless, there are significant knowledge gaps on the cycling of Hg within trees. We investigate Hg archived in tree rings, internal tree Hg cycling, and differences in Hg uptake mechanisms in Norway spruce and European larch sampled within 1 km of a HgCl2-contaminated site using total Hg (THg) and Hg stable isotope analyses. Tree ring samples are indicative of significant increases in THg concentrations (up to 521 µg kg−1) from the background period (BGP; facility closed; 1992–present) to secondary industrial period (2ndIP; no HgCl2 wood treatment; 1962–1992) to primary industrial period (1stIP; active HgCl2 wood treatment; ≈ 1900–1962). Mass-dependent fractionation (MDF) Hg stable isotope data are shifted negative during industrial periods (δ202Hg of 1stIP: −4.32 ± 0.15 ‰, 2ndIP: −4.04 ± 0.32 ‰, BGP: −2.83 ± 0.74 ‰; 1 SD). Even accounting for a ≈ −2.6 ‰ MDF shift associated with stomatal uptake, these data are indicative of emissions derived from industrial activity being enriched in lighter isotopes associated with HgCl2 reduction and Hg0 volatilisation. Similar MDF (δ202Hg: −3.90 ± 0.30 ‰; 1 SD) in bark Hg (137 ± 105 µg kg−1) suggests that stomatal assimilation and downward transport is also the dominant uptake mechanism for bark Hg (reflective of negative stomatal-uptake MDF shift) rather than deposition to bark. THg was enriched in sapwood of all sampled trees across both tree species. This may indicate long-term storage of a fraction of Hg in sapwood or xylem solution. We also observed a small range of odd-isotope mass-independent fractionation (MIF). Differences in Δ199Hg between periods of different industrial activities were significant (Δ199Hg of 1stIP: 0.00 ± 0.03 ‰, 2ndIP: −0.06 ± 0.04 ‰, BGP: −0.13 ± 0.03 ‰; 1 SD), and we suggest MIF signatures are conserved during stomatal assimilation (reflect source MIF signatures). These data advance our understanding of the physiological processing of Hg within trees and provide critical direction to future research into the use of trees as archives for historical atmospheric Hg.

Sustained high atmospheric Hg level in Beijing during wet seasons suggests that anthropogenic pollution is continuing: Identification of potential sources

Gaseous elemental Hg (GEM), particulate bound Hg (PBM), and gaseous oxidized Hg (GOM) were monitored at an urban site in Beijing, China during wet seasons (July–November) of 2021. The mean (± standard deviation) GEM, PBM, and GOM concentrations were 3.45 ± 1.27 ng m−3, 48.2 ± 88.6 pg m−3, and 13.7 ± 55.0 pg m−3, respectively. GEM level was stable (generally 3.0–4.0 ng m−3) and the average concentration was about twice that of the background level in Beijing, while the occasionally very high PBM and GOM concentrations (>1000 pg m−3) suggest pollution events. Moreover, GEM, CO, and NO2 exhibit a conspicuous similar diurnal trend with lower values during daytime compared to nighttime under the combined influence of anthropogenic emissions and meteorological factors, and the significantly positive relationship between them indicates that they had similar or common sources. However, the diurnal pattern of reactive Hg (i.e., RM = PBM + GOM) was not pronounced. Both cluster and potential source contribution function analyses show that southern Beijing, Tianjin, as well as central and east Hebei provinces were the dominant source regions for elevated GEM at this monitoring site. The dominant reason for the elevated GEM level (generally >3.5 ng m−3) during pollution event is that majority of air masses originated from the southern polluted regions of this sampling site and traveled at low heights, while the long-range transport of upper clean air masses and continuous high traveling heights were attributed to the low GEM level (<2.0 ng m−3) during clean event. Positive matrix factorization results reveal that regional transport of coal fired air pollutants and local vehicle emissions were the dominant contributors to elevated GEM level, while RM mainly originated from local sources.

Laser-Induced Forward Transfer Printing on Microneedles for Transdermal Delivery of Gemcitabine.

Cancer treatment with chemotherapeutic drugs remains to be challenging to the physician due to limitations associated with lack of efficacy or high toxicities. Typically, chemotherapeutic drugs are administered intravenously, leading to high drug concentrations that drive efficacy but also lead to known side effects. Delivery of drugs through transdermal microneedles (MNs) has become an important alternative treatment approach. Such delivery options are well suited for chemotherapeutic drugs in which sustained levels would be desirable. In the context of developing a novel approach, laser-induced forward transfer (LIFT) was applied for bioprinting of gemcitabine (Gem) to coat polymethylmethacrylate MNs. Gem, a chemotherapeutic agent used to treat various types of cancer, is a good candidate for MN-assisted transdermal delivery to improve the pharmacokinetics of Gem while reducing efficiency limitations. LIFT bioprinting of Gem for coating of MNs with different drug amounts and successful transdermal delivery in mice is presented in this study. Our approach produced reproducible, accurate, and uniform coatings of the drug on MN arrays, and on in vivo transdermal application of the coated MNs in mice, dose-proportional concentrations of Gem in the plasma of mice was achieved. The developed approach may be extended to several chemotherapeutics and provide advantages for metronomic drug dosing.

A phase I study of first-line L-glutamine (Gln) with gemcitabine (gem) and nab-paclitaxel (nab-p) in advanced pancreatic cancer (GlutaPanc).

TPS636 Background: Cytotoxic chemotherapy remains the preferred first-line treatment for advanced or unresectable pancreatic cancer with combination regimens including 5-fluoruracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), or gem and nab-p. The use and response of second- and third-line therapies remains dismal, thus the optimization of first-line treatment is critical. Our previous work investigating Gln metabolism in pancreatic ductal adenocarcinoma (PDAC) through glutaminase inhibition indicates that Gln deprivation in PDAC increases cancer cell survival and resistance to chemotherapy. However, when PDAC cell were treated with Gln supplementation, there was an increase in PDAC cell death with increasing concentrations of gem. In this present study we aim to test the feasibility and safety of combining L-Gln with gem and nab-p in treatment-naïve patients with unresectable or metastatic PDAC. Methods: This is a single arm, single center, phase I study. The primary objective is to assess the recommended phase II dose (RP2D) of L-Gln in combination with gem and nab-p. The RP2D will be assessed by escalation of overdose control (EWOC), an adaptive Bayesian design, through determination of the maximum tolerated dose (MTD) across 3 doses of gem, nab-p, and L-Gln. The MTD is defined as the dose such that the probability of dose-limiting toxicities (DLTs) at the MTD is θ = 0.33. The first patient will receive 1000 mg/m2 gem, 125 mg/m2 nab-p, and 0.1 g/kg L-Gln and the subsequent doses will be determined by the EWOC algorithm. We plan to enroll a maximum of 16 patients. L-Gln is administered orally BID throughout the 28-day cycle with a one-week lead-in prior to the beginning of the first cycle where gem and nab-p are administered on days 1, 8, and 15 of each cycle. Key inclusion criteria include: advanced or unresectable, histologically confirmed pancreatic cancer that is either new or recurrent (if recurrent, prior neoadjuvant or adjuvant chemotherapy or chemoradiation is allowed but must have been completed &gt;12 months prior to recurrence), ECOG PS ≤ 2 or KP ≥ 60%, and normal organ and marrow function. Secondary objectives are to describe any preliminary evidence of antitumor activity by assessment of objective response rate, progression-free survival, and overall survival. Since October 2020, 3 patients have been screened and 3 enrolled. Clinical trial information: NCT04634539.

Using Passive Air Samplers to Quantify Vertical Gaseous Elemental Mercury Concentration Gradients Within a Forest and Above Soil

AbstractGaseous elemental mercury (GEM), the primary form of mercury (Hg) in the atmosphere, can undergo bidirectional exchange with the Earth's surface, with uptake in growing vegetation constituting the dominant atmospheric deposition process. Whereas direction and magnitude of this exchange can be determined using micrometeorological and chamber techniques, these approaches are complex, costly and labor‐intensive, and often only yield fluxes over relatively short time‐scales at few sites. We demonstrate that an inexpensive and easy‐to‐use passive air sampler can identify and quantify vertical GEM concentration gradients on scales ranging from centimeters to tens of meters over long time periods (up to 1.5 years) and with coarse temporal resolution (monthly to seasonally). Samplers were deployed above clean and contaminated soil and through a deciduous forest canopy at two sites in Southern Ontario. Significant and seasonally variable gradients of GEM concentrations, both increasing and decreasing with height above ground, were observed and can be explained through the influence of factors such as soil contamination, canopy growth, temperature, solar irradiance, and snow cover. At a minimum, the sampler can identify the GEM flux direction, but, when combined with the Modified Bowen Ratio method, can also be used to estimate the evaporative GEM flux from mercury‐contaminated soil. We further demonstrate the application of the approach to contaminated site assessment, using a field in Brescia, Italy, known to contain elevated levels of Hg in soil. By allowing for cost‐effective measurements at multiple sites and over extended time periods, passive sampling complements existing techniques for studying atmosphere‐surface exchange of GEM.

An Integrated Investigation of Atmospheric Gaseous Elemental Mercury Transport and Dispersion Around a Chlor-Alkali Plant in the Ossola Valley (Italian Central Alps).

We present the first assessment of atmospheric pollution by mercury (Hg) in an industrialized area located in the Ossola Valley (Italian Central Alps), in close proximity to the Toce River. The study area suffers from a level of Hg contamination due to a Hg cell chlor-alkali plant operating from 1915 to the end of 2017. We measured gaseous elemental Hg (GEM) levels by means of a portable Hg analyzer during car surveys between autumn 2018 and summer 2020. Moreover, we assessed the long-term dispersion pattern of atmospheric Hg by analyzing the total Hg concentration in samples of lichens collected in the Ossola Valley. High values of GEM concentrations (1112 ng m−3) up to three orders of magnitude higher than the typical terrestrial background concentration in the northern hemisphere were measured in the proximity of the chlor-alkali plant. Hg concentrations in lichens ranged from 142 ng g−1 at sampling sites located north of the chlor-alkali plant to 624 ng g−1 in lichens collected south of the chlor-alkali plant. A north-south gradient of Hg accumulation in lichens along the Ossola Valley channel was observed, highlighting that the area located south of the chlor-alkali plant is more exposed to the dispersion of Hg emitted into the atmosphere from the industrial site. Long-term studies on Hg emission and dispersion in the Ossola Valley are needed to better assess potential impact on ecosystems and human health.

Combination of Gemcitabine and Thymosin alpha 1 exhibit a better anti-tumor effect on nasal natural killer/T-cell lymphoma

BackgroundNasal natural killer/T-cell lymphoma (NNKTL) is an aggressive and poor prognostic malignant tumor along with high-level infection of Epstein-Barr virus (EBV). Gemcitabine (Gem) and Thymosin alpha 1 (Tα1) exert an anti-tumor effect in various cancers. However, the effect of the combination of Gem and Tα1 in NNKTL remains unknown. MethodsSNK6 cells were treated with Gem, Tα1 and Gem plus Tα1 for 48 h. The expression levels of EBV and inflammatory factors were measured by qRT-PCR assay. The effect of Gem and Tα1 on cell viability, proliferation, apoptosis, autophagy was detected by CCK-8, colony formation, flow cytometry, autophagic flux measurement, respectively. Western blot was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT), apoptosis and autophagy. In vivo xenograft models were used to further verify the roles of Gem and Tα1. Tumors were removed for weight measurement, H&E and IHC staining. ResultsWe identified that the half maximal inhibitory concentration (IC50) of Gem and Tα1 was 116.5 μmol/ml and 1.334 μmol/ml. Alone or combined administration of Gem and Tα1 dramatically attenuated the EBV viral load and promoted inflammatory factors expression in SNK6 cells, among which the combination of Gem and Tα1 treatment showed the most significant effect. Besides, combination treatment with Gem and Tα1 markedly inhibited cell growth and EMT progress, and enhanced apoptosis and autophagy. Similarly, Gem combined with Tα1 suppressed tumor growth, promoted apoptosis and autophagy in vivo. Additionally, combination treatment with Gem and Tα1 inhibited PI3K/AKT/mTOR pathway. ConclusionIn summary, combination administration of Gem and Tα1 suppressed the progression of NNKTL in vivo and in vitro. Our study provided an effective therapeutic strategy potentially for the clinical treatment of NNKTL.

Where there is smoke there is mercury: Assessing boreal forest fire mercury emissions using aircraft and highlighting uncertainties associated with upscaling emissions estimates

Abstract. Emissions from biomass burning are an important source of mercury (Hg) to the atmosphere and an integral component of the global Hg biogeochemical cycle. In 2018, measurements of gaseous elemental Hg (GEM) were taken on board a research aircraft along with a series of co-emitted contaminants in the emissions plume of an 88 km2 boreal forest wildfire on the Garson Lake Plain (GLP) in NW Saskatchewan, Canada. A series of four flight tracks were made perpendicular to the plume at increasing distances from the fire, each with three to five passes at different altitudes at each downwind location. The maximum GEM concentration measured on the flight was 2.88 ng m−3, which is ≈ 2.4× background concentration. GEM concentrations were significantly correlated with the co-emitted carbon species (CO, CO2, and CH4). Emissions ratios (ERs) were calculated from measured GEM and carbon co-contaminant data. Using the most correlated (least uncertain) of these ratios (GEM:CO), GEM concentrations were estimated at the higher 0.5 Hz time resolution of the CO measurements, resulting in maximum GEM concentrations and enhancements of 6.76 ng m−3 and ≈ 5.6×, respectively. Extrapolating the estimated maximum 0.5 Hz GEM concentration data from each downwind location back to source, 1 km and 1 m (from fire) concentrations were predicted to be 12.9 and 30.0 ng m−3, or enhancements of ≈ 11× and ≈ 25×, respectively. ERs and emissions factors (EFs) derived from the measured data and literature values were also used to calculate Hg emissions estimates on three spatial scales: (i) the GLP fires themselves, (ii) all boreal forest biomass burning, and (iii) global biomass burning. The most robust estimate was of the GLP fires (21 ± 10 kg of Hg) using calculated EFs that used minimal literature-derived data. Using the Top-down Emission Rate Retrieval Algorithm (TERRA), we were able to determine a similar emission estimate of 22 ± 7 kg of Hg. The elevated uncertainties of the other estimates and high variability between the different methods used in the calculations highlight concerns with some of the assumptions that have been used in calculating Hg biomass burning in the literature. Among these problematic assumptions are variable ERs of contaminants based on vegetation type and fire intensity, differing atmospheric lifetimes of emitted contaminants, the use of only one co-contaminant in emissions estimate calculations, and the paucity of atmospheric Hg species concentration measurements in biomass burning plumes.

Variability in gaseous elemental mercury at Villum Research Station, Station Nord, in North Greenland from 1999 to 2017

Abstract. Mercury is ubiquitous in the atmosphere, and atmospheric transport is an important source for this element in the Arctic. Measurements of gaseous elemental mercury (GEM) have been carried out at Villum Research Station (Villum) at Station Nord, situated in northern Greenland. The measurements cover the period 1999–2017, with a gap in the data for the period 2003–2008 (for a total of 11 years). The measurements were compared with model results from the Danish Eulerian Hemispheric Model (DEHM) that describes the contribution from direct anthropogenic transport, marine emissions and general background concentration. The percentage of time spent over different surfaces was calculated by back-trajectory analysis, and the reaction kinetics were determined by a comparison with ozone. The GEM measurements were analysed for trends, both seasonal and annual. The only significant trends found were negative ones for the winter and autumn months. Comparison of the measurements to simulations using the Danish Eulerian Hemispheric Model (DEHM) indicated that direct transport of anthropogenic emissions of mercury accounts for between 14 % and 17 % of the measured mercury. Analysis of the kinetics of the observed atmospheric mercury depletion events (AMDEs) confirms the results of a previous study at Villum of the competing reactions of GEM and ozone with Br, which suggests that the lifetime of GEM is about a month. However, a GEM lifetime of 12 months gave the best agreement between the model and measurements. The chemical lifetime is shorter, and thus, the apparent lifetime appears to be the result of deposition followed by reduction and re-emission; for this reason, the term “relaxation time” is preferred to “lifetime” for GEM. The relaxation time for GEM causes a delay between emission reductions and the effect on actual concentrations. No significant annual trend was found for the measured concentrations of GEM over the measurement period, despite emission reductions. This is interesting, and together with low direct transport of GEM to Villum as found by the DEHM model, it shows that the dynamics of GEM are very complex. Therefore, in the coming years, intensive measurement networks are needed to describe the global distribution of mercury in the environment as the use of models to predict future levels will still be highly uncertain. The situation is increasingly complex due to global changes that most likely will change the transport patterns of mercury, not only in the atmosphere but also between matrixes.

Prospects for discovery large amber-succinite deposits of in Ukraine

Amber and the deposits are represented by Eocene-Oligocene placers of the coastal-sea and lagoon delta genesis. as practice has shown, they have low industrial grade from 5-10 to 250 g/m3. Few studies have been carried out on the amber of the Dnieper basin. These are the eastern and south-western slopes of the Ukrainian Shield at the juncture of the Dnieper-Donetsk and Black Sea basin.The aim of this work, its scientific and practical significance, is to substantiate the forecast of industrial amber-succinitis placers in Ukraine, which are as good as the Baltic placers, where the concentration of gem per cubic metre is calculated not in grams but in kilograms (up to 2 kg/m3). To carry out this task, the authors conducted expedition work in a number of regions of Ukraine and described sections of boreholes, pits, pits, etc. The authors have processed a large amount of scientific information on the alluvial geology, described and analysed the well sections presented in reports on geological surveys of medium and large scale.The article substantiates the identification and conditions for the accumulation of primary biogenic-sedimentary deposits of the protoamber (primary sources of amber-succinitis placers), age and genesis of placers in the first intermediate reservoirs. The article provides a geological and paleographic analysis of the natural conditions of the Tractor Station and the shallow seas in the Eocene-Early Oligocene. At that time there was an accumulation of tar secretions and their transformation into fossil tars and brand-succinite. The forecast for detection of a new type of buried amber-succinitis placers in Ukraine, which are associated with the remote part of the shelf, fully determines the practical and scientific value of the research conducted by the authors, which is ultimately aimed at improving the quality of amber prospecting and exploration works.Keywords: amber-succinite, prognosis, deposits, fossil resins, placers

Assessing contributions of natural surface and anthropogenic emissions to atmospheric mercury in a fast-developing region of eastern China from 2015 to 2018

Abstract. Mercury (Hg) is a global toxic pollutant that can be released into the atmosphere through anthropogenic and natural sources. The uncertainties in the estimated emission amounts are much larger from natural than anthropogenic sources. A method was developed in the present study to quantify the contributions of natural surface mercury emissions to ambient gaseous elemental mercury (GEM) concentrations through application of positive matrix factorization (PMF) analysis with temperature and NH3 as indicators of GEM emissions from natural surfaces. GEM concentrations were continuously monitored at a 2-hourly resolution at a regional background site in the Yangtze River Delta in eastern China during 2015–2018. Annual average GEM concentrations were in the range of 2.03–3.01 ng m−3, with a strong decreasing trend at a rate of -0.32±0.07 ng m−3 yr−1 from 2015 to 2018, which was mostly caused by reduced anthropogenic emissions since 2013. The estimated contributions from natural surface emissions of mercury to the ambient GEM concentrations were in the range of 1.00–1.13 ng m−3 on annual average, with insignificant interannual changes, but the relative contribution increased significantly from 41 % in 2015 to 57 % in 2018, gradually surpassing those from anthropogenic sources.

Speciated atmospheric mercury during haze and non-haze periods in winter at an urban site in Beijing, China: Pollution characteristics, sources, and causes analyses

Speciated atmospheric mercury (Hg) was measured at an urban site in Beijing, China from February to March 2018. The mean concentrations of gaseous elemental Hg (GEM), gaseous oxidized Hg (GOM), and fine particulate bound mercury (PBM2.5) were 2.81 ± 0.90 ng m−3, 10.7 ± 8.5 pg m−3, and 60.6 ± 43.5 pg m−3, respectively. Reactive Hg (i.e., RM=GOM+PBM2.5) only represented ~2.4% of total atmospheric Hg. The GEM concentration at the monitoring site was 1.7 times higher than the average value in the Northern Hemisphere. In particular, the mean GEM and PBM2.5 concentrations were significantly higher during haze period (hourly average AQI value > 100 for at least consecutive 24 h) (3.65 ± 0.76 ng m−3 and 93.0 ± 37.1 pg m−3) than during non-haze period (2.42 ± 0.73 ng m−3 and 48.5 ± 39.5 pg m−3). One possible explanation is the strong subsidence of air masses during haze period could lead to the accumulation of air pollutants. However, there was no significant difference in GOM concentration between haze and non-haze periods. Although the ozone, relative humidity (RH), and planetary boundary layer (PBL) all followed a clear diurnal cycle, while for RM no distinct diurnal pattern was observed. Additionally, GEM was significantly positively correlated with CO, indicating that they had homogeneous sources; whereas, they were all negatively correlated with wind speed and PBL height. Based on the combination of potential source contribution function and clustering analyses, we found that high atmospheric Hg events during haze days were more likely caused by the domestic sources in the Circum-Bohai-Sea region, while the transboundary transport of the clean air masses originating from Siberia was attributed to the low GEM and PBM2.5 levels during non-haze days.

Atmospheric reactive mercury concentrations in coastal Australia and the Southern Ocean

Mercury (Hg), especially reactive Hg (RM), data from the Southern Hemisphere (SH) are limited. In this study, long-term measurements of both gaseous elemental Hg (GEM) and RM were made at two ground-based monitoring locations in Australia, the Cape Grim Baseline Air Pollution Station (CGBAPS) in Tasmania, and the Macquarie University Automatic Weather Station (MQAWS) in Sydney, New South Wales. Measurements were also made on board the Australian RV Investigator (RVI) during an ocean research voyage to the East Antarctic coast. GEM was measured using the standard Tekran® 2537 series analytical platform, and RM was measured using cation exchange membranes (CEM) in a filter-based sampling method. Overall mean RM concentrations at CGBAPS and MQAWS were 15.9 ± 6.7 pg m−3 and 17.8 ± 6.6 pg m−3, respectively. For the 10-week austral summer period on RVI, mean RM was 23.5 ± 6.7 pg m−3.RM concentrations at CGBAPS were seasonally invariable, while those at MQAWS were significantly different between summer and winter due to seasonal changes in synoptic wind patterns. During the RVI voyage, RM concentrations were relatively enhanced along the Antarctic coast (up to 30 pg m−3) and GEM concentrations were variable (0.2 to 0.9 ng m−3), suggesting periods of enrichment and depletion. Both RM and GEM concentrations were relatively lower while transiting the Southern Ocean farther north of Antarctica. RM concentrations measured in this study were higher in comparison to most other reported measurements of RM in the global marine boundary layer (MBL), especially for remote SH locations. As observations of GEM and RM concentrations inform global ocean-atmosphere model simulations of the atmospheric Hg budget, our results have important implications for understanding of total atmospheric Hg (TAM).

Abstract D050: Enhancing efficacy of modified-gemcitabine nanoparticles in pancreatic PDX model

Abstract Gemcitabine (Gem) is preferred anticancer drug for the treatment of pancreatic cancer (PCa) either alone in debilitated patients or in combination with other drugs in healthy patients, however; the therapeutic concentration of Gem is severally reduced due to rapid metabolism. Due to its short stay in the blood, the maintenance of therapeutic concentrations of Gem requires a continuous parenteral administration leading to severe side effects such as renal and hematological toxicities. This inherent drawback has necessitated novel approach of delivering Gem to improve stability. The objective of this study was to chemically modify Gem and evaluate its anticancer activity against pancreatic cancer cells. Gem was modified by linking 4-amino group of Gem and stearoyl linear acyl derivative to form 4-(N)-stearoyl-gemcitabine (Gem-stearate). Gem-stearate nanoparticle (GSN) was further prepared by mixing lecithin and labrasol solutions until homogenous mixture was formed. Gem-stearate was then added to the mixture and vortexed intermittently until homogenous solution was achieved. The bond between 4-amino group of Gem and stearoyl derivative was confirmed by Nuclear Magnetic Resonance (NMR) and micro-elemental analysis. The particle size of GSN was determined by using a Particle Size Analyze. Patient-derived primary pancreatic cancer cells (CMZ and G46Ca) and MiaPaCa-2 cells were treated with blank nanoparticles and different concentrations of free Gem and GSN for 48 hours and determined the viability by using Resazurin assay. Mice with pre-established tumors (patient-derived xenografts (PDX)) of pancreatic model (G46Ca) were treated with Gem and GSN. Results: Analysis of the H-NMR spectra displayed amide bond single peak of interest was at 11ppm suggesting a bond formation between 4-amino group of Gem and stearoyl derivative. The mass fractions of elements of GSN were found to be (Theory (T) and Found (F)): i) Carbon: 61.23% (T) and 60.97±0.07% (F), ii) Hydrogen: 8.56% (T) and 8.59±0.08% (F), iii) Nitrogen: 7.93 % (T) and 7.52±0.01% (F) and iv) Fluorine:7.17% (T) and 6.94±0.02% (F)). Growth inhibition of GSN-treated CMZ culture (IC50 =21±5μM) was remarkably higher than free Gem treated CMZ culture (IC50 = 62±3 μM). Similar trend of higher GSN inhibitions in G46Ca and MiaPaCa-2 cultures were found (IC50 =46±16 μM; IC50 =27±4 μM) respectively compared with free Gem treated G46Ca and Mia-PaCa-2 culture (IC50 =68±26 μM; IC50 =54±52 μM) respectively. Put together, the anticancer activity of GSN nanoparticle was significantly more effective than free Gem in CMZ, G46Ca and MiaPaCa-2 cultures compared with their corresponding free Gem treated cultures. For the tumor efficacy studies, GSN exhibited significant tumor growth inhibition compared with molar equivalent dose of free Gem. Immunohistostaining showed that GSNs have significant antiproliferative activity in G46Ca tumors. Conclusion: This study reveals that GSN may be a novel approach in delivering an effective and stable Gem to treat pancreatic cancer. Citation Format: Tiara King, Taylor Smith, Kevin Affram, Jose Trevino, Bo Han, Edward Agyare, Andriana Inkoom. Enhancing efficacy of modified-gemcitabine nanoparticles in pancreatic PDX model [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D050.

Characteristics of the air‒sea exchange of gaseous mercury and deposition flux of atmospheric mercury at an island near the boundary of the Bohai Sea and Yellow Sea

The variations of dissolved gaseous mercury (DGM, mainly Hg 0 ), air‒sea exchange of Hg 0 , and deposition of atmospheric mercury were very limited in nearshore regions of North China. Nearly two years measurements of DGM in surface seawater and gaseous elemental mercury (GEM or Hg 0 ) in the atmosphere over the Changdao Island were conducted to elucidate the characteristic of air‒sea exchange of Hg 0 based on meteorological parameters. Simultaneously, the wet deposition fluxes of atmospheric Hg were also calculated based on the precipitation amounts and concentrations of total mercury in precipitation (THg p ). The results show that both DGM and Hg 0 flux exhibit a distinct seasonal pattern with the order of summer (47.7 pg l −1 and 1.46 ng m −2 h −1 ), spring (24.6 pg l −1 and 0.82 ng m −2 h −1 ), fall (21.7 pg l −1 and 0.70 ng m −2 h −1 ), and winter (19.0 pg l −1 and 0.21 ng m −2 h −1 ). However, a striking feature in winter is that the study site and peripheral area sporadically act as a sink of atmospheric Hg 0 as a result of elevated GEM concentrations and low water temperature and solar radiation. The seasonal pattern of saturation was in line with that of DGM. In addition, a distinct diurnal cycle of DGM was observed with maximum concentrations at midday and minimum concentrations in nighttime during the whole study period, especially in summer. These remarkable seasonal and diurnal patterns indicate that the elevated DGM concentration in summer and midday appears mainly a photochemically driven. The mean unfiltered (UTHg) and dissolved (DTHg) seawater THg concentrations were 1.43 ± 0.94 and 0.53 ± 0.19 ng l −1 , respectively. On average, the mean DTHg/UTHg ratio was 0.45 ± 0.16, indicating that less than half of THg was concentrated in DTHg. There was no significant relationships between DGM and DTHg. Seasonal concentrations of THg p were 17.3, 7.4, 7.0, and 27.9 ng l −1 , whereas seasonal wet deposition fluxes were 1.28, 1.31, 0.82, and 0.62 μg m −2 yr −1 for spring, summer, fall, and winter, respectively. Overall, the THg p concentrations varied from 3.9 to 60.1 ng l −1 with a mean value of 16.4 ng l −1 , and the direct wet deposition flux was 4.03 μg m −2 yr −1 , representing approximately 57.4% of the annual evasion flux of Hg 0 (7.02 μg m −2 yr −1 ). • Similar distinct seasonal patterns of DGM, saturation, and Hg 0 flux were observed. • Diurnal DGM cycle was found with the highest values at midday especially in summer. • There were no significant relationships between DGM and DTHg as well as UTHg. • The seasonal patterns of DGM/UTHg and DGM/DTHg were opposite to that of UTHg. • Wet deposition flux of Hg constituted about 57.4% of the emission flux of gaseous Hg.

Gemcitabine Exposure Induces Epigenomic Remodeling in Pancreatic Cancer Cells during Resistance Development

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer‐related deaths in the United States with a devastating overall five‐year survival rate of less than five percent. Chemotherapy is a mainstay for PDAC treatment, with Gemcitabine (Gem) as a part of a first‐line regimen. Although Gem has shown clinical benefit, it possesses limited control over cancer progression, due to the major obstacle of chemoresistance. Consequently, there is an urgent need to further improve our understanding of molecular mechanisms underlying resistance development to identify innovative therapeutic targets. Our laboratory is focused on the use of epigenomic drugs as novel therapeutic approaches. Our experimental design involves developing chemoresistance in patient derived PDAC cells to identify epigenomic alterations and gene expression changes that can participate in the initiation and establishment of resistance to chemotherapeutic agents. Identifying such modifications can provide valid druggable targets to enhance the effect or reverse resistance to anti‐cancer drugs. In the present study, we induced resistance to Gem on a naïve patient‐derived PDAC cell line and evaluated epigenomic landscape remodeling through changes of histone post‐translational modifications. In addition, we characterized phenotypic changes in response to Gem exposure. Using the Incucyte® imaging system, we determined that exposure to increasing concentrations of Gem induced resistance on naïve patient‐derived PDAC cells. Gem resistant cells showed a reduced basal proliferation rate and apoptotic response compared to parental cells, as measured by activation of caspases 3 and 7. Additionally, cells developed morphological changes towards an epithelial state, coincident with the increase of Keratin 17/19 and E‐Cadherin. Moreover, treated cells demonstrated reduced sensitivity to the well‐known DNA damaging agents cisplatin and 5‐Fluorouracil. Evaluation of histone post‐translational modifications on these cells revealed reduction in the global amount of repressive marks (H3K9Me1, 2 and 3; H3K27Me2 and 3), as well as an increase of the activating histone mark H3K27Ac, associated with super enhancers. Furthermore, immunofluorescence‐based microscopy showed re‐distribution of the H3K9Me1 and H3K27Me3 repressive marks from the nuclear periphery to the whole nucleus, suggesting epigenomic remodeling of pancreatic cancer cells in response to the development of Gem resistance. In summary, these data demonstrate that Gem treatment induces chromatin remodeling and that targeting key epigenomic pathways may hold promise for novel strategies toward re‐sensitizing or preventing resistance of pancreatic cancer to chemotherapeutic agents.