Application of interpolation methodology with dynamical constraint to the suspended particulate matter in the Liaodong Bay

IntroductionSuspended Particulate Matter (SPM) influences the primary production and the distributions of pollutants in the ocean. Besides, the regulation mechanisms of SPM in the Liaodong Bay were complicated.MethodTo analyze the distributions and influencing factors of SPM, based on the adjoint assimilation method, an interpolation method with dynamical constraint was established in the Liaodong Bay.ResultIn two ideal experiments, the cost function, Mean Absolute Error (MAE) and Normalized Mean Error (NME) all had reduced by more than 90%, which proved the accuracy of the interpolation method. Based on conventional observations of SPM, the distributions of dynamically constrained, Kriging and radial basis function (RBF) interpolations in March, May, August and October of 2015 were obtained.DiscussionThe cross-validation was carried out to compare the dynamically constrained interpolation and the unconstrained interpolations. Among seven unconstrained interpolation methods, the averaged MAE of RBF interpolation was the lowest, which was 10.976 mg/L. The averaged MAE of dynamically constrained interpolation was 7.703 mg/L, reduced by 29.8% compared with the RBF interpolation. It was indicated that RBF interpolation was the most accurate among the seven unconstrained interpolations and dynamically constrained interpolation was more accurate than unconstrained interpolations at the observation stations. The distributions of dynamically constrained and RBF interpolations were compared with Korean Geostationary Ocean Color Imager (GOCI) satellite-derived distributions of SPM concentrations in the Liaodong Bay. Fully considering the influences of the hydrodynamic processes, the dynamically constrained interpolation provided distributions more consistent with the satellite-derived distributions. However, due to the lack of observations in some areas and ignoring the influences of currents, some high values of SPM concentration were not captured by the distributions of RBF interpolation. Moreover, in accordance with the results of dynamically constrained interpolation, it was found that the SPM concentrations in the bay were affected by the SPM discharge from the Liao River Basin

Intestinal Microbiome-Metabolome Responses to Essential Oils in Piglets

This study investigated the effects of dietary essential oils (EOs) on intestinal microbial composition and metabolic profiles in weaned piglets. The piglets were fed the same basal diet supplemented with EOs (EO) or without EOs (Con) in the current study. The results showed that the body weight gain was significantly increased, while the diarrhea incidence was significantly reduced in the EO group. In addition, EOs could modify the intestinal microbial composition of weaned piglets. The relative abundances of some beneficial bacterial species such as Bacilli, Lactobacillales, Streptococcaceae, and Veillonellaceae were significantly increased in the EO group. Metabolomics analysis indicated that protein biosynthesis, amino acid metabolism, and lipid metabolism were enriched in the EO group. And correlation analysis demonstrated that some gut bacterial genera were highly correlated with altered gut microbiota-related metabolites. Taken together, this study indicated that dietary EOs not only altered microbial composition and function but modulated the microbial metabolic profiles in the colon, which might help us understand EOs’ beneficial effects on intestinal health of weaned piglets

Investigations into how best to target FGFR2 mutant endometrial cancer

Endometrial cancer (EC) is the fourth most common cancer in women in developed countries, such as North America, Europe and Australia. Patients with low-grade, early-stage disease usually have a favourable survival rate. However, patients that present at an advanced stage of disease have an average survival of only 12 months. Current treatments for these patients are radiation and chemotherapy, which offer limited clinical benefit. There is no efficient treatment for advanced EC. Improved therapeutic approaches are needed for the treatment of recurrent and metastatic endometrial cancer. Recent advances in cancer biology have resulted in the development of molecular targeted therapies. The Fibroblast Growth Factors Receptor (FGFR) family and their ligands (fibroblast growth factors, FGFs) regulate a broad spectrum of physiological processes as well as tissue patterning and organogenesis during embryogenesis. Abnormally activated FGFRs have been identified in various cancers and are emerging as potential therapeutic targets. The Pollock laboratory and other groups have demonstrated that 10-20% of endometrioid ECs carry FGFR2 mutations that may be a novel therapeutic target in endometrial carcinoma. Preclinical studies show that inhibition of FGFR can inhibit EC cell growth in vitro. However, FGFR inhibitors are not as efficient at inhibiting tumour growth in vivo. We aim to find a way to improve the efficacy of FGFR inhibition in cancer treatment. About 90% of EC patients harbour genetic aberrations in the components of the PI3K/AKT pathway which indicates this signalling pathway plays an important role in the development of EC. Work from our lab demonstrates that inhibition of FGFR results in abrogation of MAPK activation in sensitive EC cells, however, the PI3K/AKT signalling pathway remains unaffected. PI3K/AKT signalling plays a vital role in cancer cell proliferation and survival, furthermore crosstalk between the MAPK and PI3K/AKT signalling pathways is associated with resistance to targeted therapies. Thus, the first aim of this study was to examine whether combination of the FGFR inhibitor (BGJ398) with various different PI3K inhibitors was synergistic in FGFRi sensitive EC cells. We present data that the combination of the pan-FGFR inhibitor (BGJ398) with pan-PI3K inhibitors (GDC-0941, BKM120) or a p110α-selective PI3K inhibitor (BYL719) was synergistic in inhibiting cell growth. Significantly more cell death and inhibition of long-term cell survival was observed in the combination treatments compared to each of the single drug treatments. Importantly, these effects could also be observed at lower concentrations. This study is the first to indicate that partial inhibition of the PI3K signalling pathway could significantly increase cell death when combined with the FGFR inhibitor BGJ398 in FGFR2 mutant EC cells. These data provide evidence that sub-therapeutic doses of PI3K inhibitors could enhance the efficacy of anti-FGFR therapies and a combination therapy may represent a superior therapeutic treatment in FGFR2 mutant EC patients. The in vivo work (conducted by Dr Vanessa Bonazzi) shows that the combination of BGJ398 and GDC-0941 and BYL719 resulted in tumour regression, while single drug treatment only slowed tumour growth. Interestingly, BYL719 alone resulted in increased tumour growth in tumour xenografts of AN3CA but not JHUEM2. In the first results chapter we further investigated the mechanism of enhanced cell death from the combination of BGJ398 and PI3K inhibitors. The activation of ERK and AKT has been inhibited by the combination of BGJ398 and PI3K inhibitors. However, the combination of the MEK inhibitor trametinib and the PI3K inhibitors induced less cell death than inhibition of the FGFR and PI3K signalling pathways. BGJ398 but not trametinib or GDC-0941 inhibited the activity of PLCγ1. We have also found trametinib up-regulated PLCγ1 activity, which is a novel finding in the field. We next employed several pharmacological inhibitors to investigate whether PLCγ1 is involved in the cell death observed following the combination of BGJ398 and GDC-0941 treatment. As there is no PLCγ1 inhibitor available currently, we used two different pan-PLC inhibitors, manoalide and U73122. Co-inhibition of the MAPK, PI3K/AKT and PLC signalling recapitulated cell growth inhibition seen with the combination of FGFR and PI3K inhibitor in both cell lines. Cell death induced by the combination of PLC inhibitors with trametinib and GDC0941 was similar as the combination BGJ398 and GDC0941 in AN3CA, but significantly less than the combination BGJ398 and GDC0941 in JHUEM2. Unfortunately, Western blotting was unable to show inhibition of PLCγ1 bringing into question whether these PLC inhibitors inhibited PLC function sufficiently, and whether the phenotypic effects of manoalide and U73122 when added to the trametinib and GDC0941 combination are due to inhibition of PLCγ1. The second results chapter reports efforts to identify the mechanism of intrinsic resistance to FGFR inhibition in EC cell lines carrying FGFR2 activating mutations but showing intrinsic resistance to FGFR inhibition (EI, EN1078D, and MFE319) with comparisons to the two sensitive EC cell lines (JHUEM2 and AN3CA). We have observed sustained activation of ERK in the resistant cells after treatment with an FGFR inhibitor, while ERK was inhibited in the sensitive cells. Inhibition of the MAPK signalling pathway could not sensitise the resistant cells to FGFR inhibition. Although several other receptor tyrosine kinases (RTKs) were hyperactivated in these cells, pharmacological inhibition did not show they were reliant on these RTKs. Co-inhibition of these kinases did not sensitise these cells to BGJ398. Knockdown of FGFR2 by shRNA in the sensitive cells induced moderate cell death, but limited cell death in the resistant cells. Interestingly, co-inhibition of the MAPK, PI3K/AKT and PLC signalling pathways has induced markedly less cell growth inhibition in the resistant cells compared to the sensitive cells, suggesting the resistant cells are less dependent on these central signalling pathways than the sensitive cells. Western blotting results showed that FGFR2 expression was considerably lower in the resistant cells than in the sensitive cells. Based on these results we have concluded that FGFR2 mutation status is not the only factor that determines sensitivity to FGFR inhibition, high expression of mutant FGFR2 is also important. This is a novel finding in the field and one which could guide patient select criteria in future clinical trials. Lastly, we show that FGFR2 knockdown in medium containing 10% FBS has little impact on downstream ERK phosphorylation whereas pan FGFR inhibition with BGJ398 could totally abrogate ERK phosphorylation. In cells grown overnight in serum starved conditions, FGFR2 knockdown did reduce downstream ERK phosphorylation but not to the same extent as pan FGFR inhibition in full growth medium. These data suggest that inhibition of FGFR2 alone is insufficient and that inhibition of multiple FGFRs will be more effective as a cancer treatment

Thermal alteration of biomarkers in the presence of elemental sulfur and sulfur-bearing minerals during hydrous and anhydrous pyrolysis

Although elemental sulfur and sulfur-bearing minerals are not the main constituents of sedimentary rock, they are still important for the formation and destruction of biomarkers. In this study, a bitumen of Sichuan Basin mudstone with abundant biomarkers was separately pyrolyzed (under both hydrous and anhydrous conditions) with elemental sulfur (S degrees) and sulfur-bearing minerals (including pyrite, ferrous sulfate, and ferric sulfate) at various temperatures (300, 330 and 350 degrees C). The results show that the effects of different forms of sulfur on the evolution of biomarkers vary. Pyrite (FeS2) had only a slight influence on the characteristics of the biomarkers during anhydrous and hydrous pyrolysis. On the other hand, the presence of S, ferrous sulfate (FeSO4) and ferric sulfate (Fe-2(SO4)(3)) promoted the thermal cracking of the biomarkers and changed the biomarker distributions under anhydrous conditions. The extent of biomarker thermal alterations decreased in the following order: S degrees > Fe-2(SO4)(3) > FeSO4 > FeS2. Additionally, the presence of water seemed to promote the effects of the sulfur additive on the changes in biomarker compositions, but this did not change their raking in terms of influence. The elemental sulfur alteration of the biomarkers increased with pyrolysis temperature (simulated maturity) and the abundance of elemental sulfur in the sample. The results obtained offer new insights into how biomarkers evolve when elemental sulfur and sulfur-bearing minerals are present. (C) 2018 Elsevier Ltd. All rights reserved

Formation and evolution of the Ediacaran to Lower Cambrian black shales in the Yangtze Platform, South China

Black shales in the Ediacaran Doushantuo Formation (predominantly from Member II, IV and equivalent strata) and the Lower Cambrian Niutitang Formation (or equivalents) occur widely in the Yangtze Platform, South China. These black shales could provide sufficient hydrocarbons for the petroleum system in this region. However, biomarker parameters have proven invalid in the assessment of petroleum resources because of the high thermal maturity. Therefore, it is necessary to study the characteristics and formation mechanisms of these two black shales. This study analyzed redox-sensitive elements, total organic carbon (TOC) contents, and carbon isotopic compositions of organic matter in four continuous sedimentary successions including the two investigated shales in the Yangtze Platform (namely Jiulongwan on the inner shelf, Songlin in an intra-shelf lagoon, Dongkanshang on the upper slope, and Fengtan in the basin). Combined with other previously reported five sections, the redox conditions of sedimentary waters and marine paleoproductivity of the Ediacaran to Lower Cambrian black shales in the Yangtze Platform were discussed and compared. The results showed that the redox conditions of the Early Cambrian in the study area were similar to those of the Ediacaran Doushantuo period, which were oxic-suboxic at surface water, and anoxic in the deep with the occurrence of euxinic conditions. However, the euxinic conditions in the deep waters were distributed more widely in the Early Cambrian than in the Ediacaran period. The source of organic matter in the Doushantuo Formation was dominated by algae in the shallow-water platform and the shelf-margin areas, while chemoautotrophic/methanotrophic biomass may also have contributed in the intra-shelf lagoon and deep-water basin areas. In contrast, the organic matter of the Niutitang Formation was mainly contributed by the chemoautotrophic/methanotrophic biomass, with a minor contribution by photosynthetic algae and cyanobacteria. During the Doushantuo period, the input of terrigenous clastic materials was low, resulting in the enrichment of organic matter and formation of organic-rich black shale in the Yangtze Platform over a long geological time period. Compared to the Doushantuo period, the shorter sedimentation time and the higher deposition rate during the Early Cambrian produced a thicker and higher-quality Niutitang Formation source rock widely distributed in the Yangtze Platform

MicroRNA Profiling of Red Blood Cells for Lung Cancer Diagnosis

Background: Despite extensive endeavors to establish cell-free circulating biomarkers for lung cancer diagnosis, clinical adoption remains elusive. Noteworthy, emergent evidence suggests the pivotal roles of red blood cells (RBCs) and their derivatives in tumorigenesis, illuminating potential avenues for diagnostic advancements using blood cell-derived microRNAs (miRNAs). Methods: We executed microarray analyses on three principal blood cell types—RBCs, peripheral blood mononuclear cells (PBMCs), and neutrophils—encompassing 26 lung cancer patients and 26 healthy controls. Validation was performed using droplet digital PCR within an additional cohort comprising 42 lung cancer and 39 control cases. Results: Our investigation unearthed distinct miRNA profiles associated with lung cancer across all examined blood cell types. Intriguingly, RBC-miRNAs emerged as potential novel biomarkers for lung cancer, an observation yet to be documented. Importantly, integrating miRNAs from disparate blood cell types yielded a superior diagnostic accuracy for lung cancer over individual cell-type miRNAs. Subsequently, we formulated three diagnostic panels, adeptly discerning non-small cell lung cancer, adenocarcinoma, and squamous cell carcinoma, maintaining consistency across various disease stages. Conclusion: RBC-derived molecules introduce novel cancer biomarkers, and exploiting miRNA profiles across varied blood cell types unveils a promising frontier for lung cancer’s early detection and histological classification

Utilizing MiSeq Sequencing to Detect Circulating microRNAs in Plasma for Improved Lung Cancer Diagnosis

Non-small cell lung cancer (NSCLC) is a major contributor to cancer-related deaths, but early detection can reduce mortality. NSCLC comprises mainly adenocarcinoma (AC) and squamous cell carcinoma (SCC). Circulating microRNAs (miRNAs) in plasma have emerged as promising biomarkers for NSCLC. However, existing techniques for analyzing miRNAs have limitations, such as restricted target detection and time-consuming procedures. The MiSeqDx System has been shown to overcome these limitations, making it a promising tool for routine clinical settings. We investigated whether the MiSeqDx could profile cell-free circulating miRNAs in plasma and diagnose NSCLC. We sequenced RNA from the plasma of patients with AC and SCC and from cancer-free smokers using the MiSeqDx to profile and compare miRNA expressions. The MiSeqDx exhibits high speed and accuracy when globally analyzing plasma miRNAs. The entire workflow, encompassing RNA to data analysis, was completed in under three days. We also identified panels of plasma miRNA biomarkers that can diagnose NSCLC with 67% sensitivity and 68% specificity, and detect SCC with 90% sensitivity and 94% specificity, respectively. This study is the first to demonstrate that rapid profiling of plasma miRNAs using the MiSeqDx has the potential to offer a straightforward and effective method for the early detection and classification of NSCLC

The effects of minerals on oil cracking in confined pyrolysis experiments

Abstract Confined pyrolysis experiments of oil in the presence and absence of minerals were conducted to reveal the effects of minerals on the oil cracking process. The results indicated that the methane generation rates decreased in the following order: oil alone > oil with clastic minerals > oil with carbonate minerals > oil with clay minerals, and the yields of C2-5 decreased in the order: oil with clay minerals > oil with carbonate minerals > oil with clastic minerals > oil alone. That means these minerals inhibited the cracking of C2-5 into methane. The inhibiting effect were decreased in the order: clay minerals > carbonate minerals > clastic minerals. Meanwhile, the ratios of i-C4/n-C4 decreased in the order: oil with clay minerals > oil with carbonate minerals > oil with clastic minerals > oil alone. That means the efficiencies of isomerization catalysed by minerals were decreased in the order: clay minerals > carbonate minerals > clastic minerals. Meanwhile, the ratios of C2H4/C2H6 increased with the order: oil with clay minerals < oil with carbonate minerals < oil with clastic minerals < oil alone. The hydrogenation rates of olefins increased in the following order: clay minerals < carbonate minerals < clastic minerals. The extent of enrichment12C for the generated methane and ethane increased in the order: clastic minerals < carbonate minerals < clay minerals. Such carbon isotopic fractionation during methane and ethane formation was probably induced by the catalytic effect of mineral surface on the terminal methyl group of hydrocarbons. The study of minerals effects on oil cracking may enhance our understanding on the evolution of petroleum reservoirs

Exogenous Fecal Microbiota Transplantation from Local Adult Pigs to Crossbred Newborn Piglets

This study was conducted to investigate the effect of exogenous fecal microbiota transplantation on gut bacterial community structure, gut barrier and growth performance in recipient piglets. Twelve litters of Duroc × Landrace × Yorkshire piglets of the same birth and parity were weighed and divided into two groups. One group (recipient piglets) was inoculated orally with fecal microbiota suspension of healthy adult Jinhua pigs daily from day 1 to day 11. The other (control) was given orally the same volume of sterile physiological saline at the same time. The experiment lasted 27 days. The results showed that the relative abundance of Firmicutes, Prevotellaceae, Lachnospiraceae, Ruminococcus, Prevotella, and Oscillospira in the colon of recipient piglets was increased. Proteobacteria, Fusobacteriaceae, Clostridiaceae, Pasteuriaceae, Alcaligenaceae, Bacteroidaceae, Veillonellaceae, Sutterella, Escherichia, and Bacteroides in the colon of recipient piglets were decreased. An average daily weight gain of recipient piglets was increased, and diarrhea incidence of the recipient was decreased during the trial. Intestinal morphology and tight junction barrier of recipient piglets were improved. The optical density of sIgA+ cells, the number of goblet cells and relative expressions of MUC2 in the intestinal mucosa of recipient piglets were enhanced. Protein expressions of β-defensin 2 and mRNA expressions of TLR2 and TLR4 in the intestinal mucosa of recipient piglets were also increased. These findings supported that the exogenous fecal microbiota had significant effects on animal’s growth performance, intestinal barrier function, and innate immune via modulating the composition of the gut microbiota