Search

Effects of long intergenic non-coding RNA (lincRNA)-p21 on the proliferation, migration and invasion ability of HepG2 liver cancer cells were assessed to explore the underlying mechanism. The lincRNA-p21 small interfering RNA (siRNA) lentivirus vector was constructed, transfected and screened to obtain a stable cell line, which constituted the experimental group. At the same time, the empty virus vector was transfected as the control group. The messenger RNA (mRNA) expression of lincRNA-p21 in cells was detected via reverse transcription-polymerase chain reaction (RT-PCR). The proliferation ability of cells was detected via Cell Counting kit-8 (CCK-8) assay. Transwell chamber experiment was used to observe cell migration and invasion ability. Compared with that in the control group, the mRNA expression level of lincRNA-p21 in cells in the experimental group was obviously decreased (p<0.05). Results of CCK-8 showed that the proliferation ability of liver cancer cells was remarkably higher than that in the control group after knockout of lincRNA-p21 (p<0.05). Results of the Transwell chamber experiment revealed that the invasion and migration ability of HepG2 cells in experimental group was markedly higher than that in control group (p<0.05). When lincRNA-p21 was inhibited, the proliferation, invasion and migration ability of HepG2 cells were significantly enhanced, and the apoptosis rate was significantly decreased. Thus, lincRNA-p21 on the surface may play an inhibitory role in the occurrence, development and metastasis of liver cancer. [ABSTRACT FROM AUTHOR]

The differential expression of microRNAs (miRNAs) in plasma of pancreatic cancer (PC) patients may act as a diagnostic biomarker. A four-stage study was performed to identify plasma miRNAs with potential in detecting PC. Exiqon panels (20 PC vs. 10 normal controls (NCs)) were applied in the screening phase to obtain miRNA profiling. The identified miRNAs were further assessed in the training (40 PC vs. 40 NCs) and testing stages (112 PC vs. 116 NCs) with qRT-PCR assays. A six-miRNA signature including up-regulated miR-122-5p, miR-125b-5p, miR-192-5p, miR-193b-3p, miR-221-3p and miR-27b-3p was identified. The signature could accurately discriminate PC patients from NCs with areas under the receiver operating characteristic curve of 0.848, 0.833 and 0.937 for the training, testing and the external validation stage (41 PC vs. 50 NCs), respectively. The multivariate Cox regression analyses showed that down-regulated plasma miR-125b-5p could predict worse OS independent from late tumor stage and high CA19-9. All the six miRNAs except miR-122-5p showed high expression levels in PC tissues than those in matched normal tissues. MiR-122-5p and miR-193b-3p were up-regulated, while miR-221-3p was down-regulated in plasma exosomes from PC patients. Bioinformatics analysis demonstrated that the miRNAs might involve in several molecular pathways closely related with PC such as p53 signaling pathway, pancreatic cancer, TGF-beta signaling pathway and so on. In conclusion, we identified a six-miRNA signature in plasma which could act as a non-invasive biomarker in diagnosis and prognosis of PC. Plasma miR-125b-5p might act as an independent biomarker in predicting OS of PC patients. [ABSTRACT FROM AUTHOR]

An estimated trillions of cubic meters of natural gas have recently been discovered in the Sinian dolomite reservoirs in the Sichuan Basin, China. The 20–26 m thick reservoirs were found in deep structural–lithologic traps of 5000–5500 m deep. The Sinian gas is thought to have been derived mainly from the Sinian source rocks, and partly from the Cambrian source rocks. The gas is thermally matured, with a dryness ratio (C 1 /∑C 1–4 ) of 0.997–0.9998, C 2 H 6 content <0.2%, and H 2 S content of 0.5–2.75%. The stable carbon isotope compositions (δ 13 C) of CH 4 and C 2 H 6 are similar in all the reservoirs, with values of −33.5‰ to −31.5‰ and −36.0‰ to −27.0‰ (PDB), respectively. The Sinian gas reservoirs are believed to have been accumulated by the following processes: initial paleo-oil accumulated during the Silurian–Devonian; gas accumulation after oil cracking of the paleo-oil accumulations during the Jurassic–Early Cretaceous; and the current gas accumulations formed by paleo-gas remigration and adjustment since the Late Cretaceous. This new gas accumulation model is consistent with large-scale gas accumulations for deeply buried paleocratonic basins worldwide, in which the source rocks initially underwent thermal oil generation from kerogen, followed by gas generation via oil cracking. The gas discovery in the Sinian dolomite reservoirs has led to a new wave of hydrocarbon gas exploration in the ancient cratonic basin containing the mostly thermally matured source rocks in China. We conducted a series of geochemical analyses of the H 2 S in the gases. The sulfur isotope compositions (δ 34 S) of gypsum, H 2 S, and secondary pyrite sampled from the Sinian Dengying Formation showed that H 2 S was generated by a moderate thermochemical sulfate reduction (TSR) during the Jurassic–Early Cretaceous periods. TSR was terminated by the depletion of SO 4 2− in the formation water, resulting in a modest H 2 S content of 5–10% in the natural gases. Because the dolomites are rich in cations, a large quantity of H 2 S may have been bound to form metal sulfides. We infer that H 2 S contents of 0.8–10% are present widely in the deeply buried Sinian reservoirs. Therefore, measures should be taken to prevent H 2 S-related accidents during gas exploration in the deep strata. [ABSTRACT FROM AUTHOR]

Background: This research explored the effects of vinorelbine combined with oxaliplatin on non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC cells were treated with vinorelbine, oxaliplatin, and insulin-like growth factor-1 (IGF-1; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway activator), and transfected with ATP-binding cassette subfamily G member 2 (ABCG2) overexpression plasmid and silenced ABCG2 (siABCG2). Cell viability was detected by cell counting kit-8 assay, cell migration and invasion by the transwell assay, and cell apoptosis by flow cytometry. Levels of ABCG2, PI3K, phosphorylation (p)-PI3K, AKT, and p-AKT were evaluated through qRT-PCR and western blot. Results: Co-treatment with vinorelbine and oxaliplatin exerted synergistic effects in suppressing the proliferation, migration, invasion, and the phosphorylation of PI3K and AKT, and inhibiting ABCG2 expression while inducing apoptosis in NSCLC cells. Overexpression of ABCG2 reversed these effects on proliferation, migration, invasion, and apoptosis, while not affecting the PI3K/AKT pathway in NSCLC cells. IGF-1 inhibited the synergistic effect of vinorelbine and oxaliplatin on the NSCLC cells. Moreover, siABCG2 reversed the effects of IGF-1 on ABCG2 expression, and other cellular functions mentioned above in NSCLC cells receiving the co-treatment. Conclusion: A combination of vinorelbine with oxaliplatin represses the proliferation, migration, and invasion of NSCLC cells, and facilitates apoptosis via inhibition of the PI3K/AKT/ABCG2 axis. [ABSTRACT FROM AUTHOR]

Abstract: Patients with advanced hepatocellular carcinoma (HCC) have shown to benefit from tamoxifen treatment. The mechanisms of tamoxifen effects in HCC, however, are not yet clearly understood. The PI3K/Akt/mTOR signal pathway is involved in cell proliferation, tumorigenesis, and apoptosis. Over-expression of survivin has played an important role in leading to antiapoptosis. The current study investigated changes in mTOR pathway and survivin expression in hepatocarcinoma cell line HepG2 treated with tamoxifen. We detected apoptosis of hepatocarcinoma cells by flow cytometry assay. Survivin transcription level and p70S6k was demonstrated by PCR, dual-luciferase reporter assay and western blot analysis respectively. Our results are showed as follows: tamoxifen leads to apoptosis of the cells, and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6 kinase. Twenty micromoles tamoxifen treatment signifcantly depresses transcription of survivin mRNA. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Our results suggest that tamoxifen down-regulate survivin expression in HepG2 cells is mediated by transcriptional and posttranscriptional level via PI3K/Akt/mTOR pathway to induce apoptosis. [Copyright &y& Elsevier]

Abstract: Pyrolysis was carried out in anhydrous closed system (gold tubes) under a constant pressure of 50MPa to discuss the differences of gas generation mechanism between crude oil and its asphaltenes. Yields and carbon isotopic composition of gaseous hydrocarbons were determined. The results show that the yield curves of gaseous hydrocarbons generated from crude oil have analogy change trends with that of asphaltenes correspondingly. The yield of methane generated from asphaltene cracking is 50% of that of oil cracking when oil and asphaltene cracked completely. The relation of δ 13C1 < δ 13C2 < δ 13C3 exists in the whole process of pyrolysis, and the δ 13C value of methane, ethane and propane generated from oil is more than that of asphaltene correspondingly. Kinetic parameters of gaseous hydrocarbon generation for crude oil and asphaltene were obtained by kinetic calculation, and the result can be extrapolated to geological conditions. [Copyright &y& Elsevier]

Oil cracking gas plays an important role in the resources of natural gas in the basins with high and over mature marine source rocks in China. The prediction of the oil cracking gas resources becomes necessary and urgent in the gas exploration in these basins. A marine crude oil sample was pyrolyzed using sealed gold tubes system. The pyrolysates including gas, liquid and solid were quantitatively analyzed. Based on the pyrolysis data and kinetic calculation, the yield correlativity among gas, liquid and solid products was regressed with high correlative coefficients to establish a prediction model suitable for the resource estimation of oil cracking gas. The verification formula for this model was also established on the principle of mass conservation. The affecting factors and the application preconditions of this prediction model were discussed. This model would enlighten and provide some new ideas for the resource assessment of natural gas in the high and over mature marine carbonate source rock areas in China. It is expected to be valuable in gas exploration. [ABSTRACT FROM AUTHOR]

Background: MicroRNA (miRNA) which can act as post-transcriptional regulators of mRNAs via base-pairing with complementary sequences within mRNAs is involved in processes of the complex interaction between immune system and tumors. In this research, we elucidated the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation and survival data. Results: We conducted the analysis of differential miRNA/mRNA expression profile by GEO, TCGA and GTEx databases and the correlation between miRNA and targeted mRNA by miRTarBase and TarBase. Then we detected using qRT-PCR and validated the diagnostic value of miRNA-mRNA regulator pairs by the ROC, calibration curve and DCA. Phenotypic hallmarks of regulatory pairs including tumor-infiltrating lymphocytes, tumor microenvironment, tumor mutation burden, global methylation and gene mutation were also described. The expression levels of miRNAs and target mRNAs were detected in 80 paired colon tissue samples. Ultimately, we picked up two pivotal regulatory pairs (miR-139-5p/ STC1 and miR-20a-5p/ FGL2) and verified the diagnostic value of the complex model which is the combination of 4 signatures above-mentioned in 3 testing GEO datasets and an external validation cohort. Conclusions: We found that 2 miRNAs by targeting 2 metastasis-related mRNAs were correlated with tumor-infiltrating macrophages, HRAS, and BRAF gene mutation status. Our results established the diagnostic model containing 2 miRNAs and their respective targeted mRNAs to distinguish CRCs and normal controls and displayed their complex roles in CRC pathogenesis especially tumor immunity. [ABSTRACT FROM AUTHOR]

The article discusses a study to describe geochronological data for the contact relation between the Changcheng System and underlying Paleo-proterozoic through detrital zircon uranium-lead geochronology of the fine-grain quartz siltstone in the Zhaojiazhuang Formation in China. Topics discussed include sampling of the detrital zircon, oscillatory zoned structures of magmatic zircons, and the minimum concordant age of detrital zircon in the Zhaojiazhuang Formation.

Non-small-cell lung cancer (NSCLC) predominates lung cancer with a striking percentage of 85%. Eupafolin is documented to possess anti-tumor efficacy, which prompts efforts to uncover its impacts on the pathology of diseases including cancers. Focal adhesion kinase (FAK)-mediated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) has been found to be associated with several carcinomas. Nevertheless, how eupafolin exerts its effects in NSCLC and whether FAK/PI3K/AKT is related to the corresponding mechanism remain unclear. Thus, the relevant experiments were carried out with NSCLC cells treated with eupafolin and/or LY294002 at first. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing, and transwell assays were used to assess cell viability, proliferation, migration, and invasion, respectively. Western blot assay was performed to measure the relative protein expressions of phosphorylated (p)-FAK/FAK, p-PI3K/PI3K, p-AKT/AKT, matrix metalloproteinase 9 (MMP9), and ras homolog gene family member A (RhoA), and to determine transfection efficiency. From experimental results, it was found that eupafolin inhibited the viability, proliferation, migration, and invasion of NSCLC cells, and inactivated the FAK/PI3K/AKT pathway by downregulating the ratios of p-FAK/FAK, p-PI3K/PI3K, and p-AKT/AKT and the expressions of MMP9 and RhoA. On the contrary, overexpressed FAK upregulated the expressions of FAK, MMP9, and RhoA and the ratios of p-PI3K/PI3K and p-AKT/AKT, and promoted cell proliferation, migration, and invasion. LY294002, conversely, could partly reverse the effects of FAK on the aforementioned aspects of NSCLC cells. Collectively, it was verified in our study that eupafolin regulates the proliferation, migration, and invasion of NSCLC cells by downregulating MMP9 and RhoA expressions via the FAK/PI3K/AKT axis, which may provide a promising avenue for cancer therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: MicroRNAs regulating mRNA expression by targeting at mRNAs is known constructive in tumor occurrence, immune escape, and metastasis. OBJECTIVE: This research aims at finding negatively regulatory miRNA-mRNA pairs in esophageal squamous cell carcinoma (ESCC). METHODS: GENE expression data of The Cancer Genome Atlas (TCGA) and GEO database were employed in differently expressed RNA and miRNA (DE-miRNAs/DE-mRNAs) screening. Function analysis was conducted with DAVID-mirPath. MiRNA-mRNA axes were identified by MiRTarBase and TarBase and verified in esophageal specimen by real-time reverse transcription polymerase chain reaction (RT-qPCR). Receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA) were applied in miRNA-mRNA pairs predictive value estimation. Interactions between miRNA-mRNA regulatory pairs and immune features were analyzed using CIBERSORT. RESULTS: Combining TCGA database, 4 miRNA and 10 mRNA GEO datasets, totally 26 DE-miRNAs (13 up and 13 down) and 114 DE-mRNAs (64 up and 50 down) were considered significant. MiRTarBase and TarBase identified 37 reverse regulation miRNA-mRNA pairs, 14 of which had been observed in esophageal tissue or cell line. Through analysis of RT-qPCR outcome, miR-106b-5p/KIAA0232 signature was chosen as characteristic pair of ESCC. ROC and DCA verified the predictive value of model containing miRNA-mRNA axis in ESCC. Via affecting mast cells, miR-106b-5p/KIAA0232 may contribute to tumor microenvironment. CONCLUSIONS: The diagnostic model of miRNA-mRNA pair in ESCC was established. Their complex role in ESCC pathogenesis especially tumor immunity was partly disclosed. [ABSTRACT FROM AUTHOR]

The Mesoproterozoic Hongshuizhuang Formation in Jixian, northern China, is a hydrocarbon source unit containing abundant organic matter. We investigated the mechanisms controlling this organic matter accumulation by analyzing the sedimentology and geochemistry of the Qinghe section, in the Kuancheng region of northern China. Trace element geochemistry suggests that organic matter accumulation was controlled primarily by marine productivity, which was the main determinant of redox conditions. Elevated marine productivity and consequent anoxic-sulfidic bottom water conditions were coincident with accumulation of the organic-rich (TOC > 1.0%) lower part of the Hongshuizhuang Formation. Deposition of the organic-lean upper Hongshuizhuang Formation appears to have been coeval with diminished productivity and a transition to oxic-suboxic redox conditions. Enhanced organic matter accumulation in the lower Hongshuizhuang Formation was promoted by a warm, humid paleoclimate and submarine hydrothermal activity. Average Rb/Sr ratios (3.42) and negative carbon isotope excursion reflect a warm climate, likely caused by the release of volcanogenic CO 2 . Warm conditions would have promoted continental weathering, and increased the flux of nutrients into the oceans, enhancing marine productivity. An increased supply of nutrients and enhanced marine productivity would have depleted oxygen in the bottom water environment and favored the proliferation of sulfate-reducing bacteria, leading to anoxic-sulfidic conditions. The relative stability of δ 13 C carb values suggests that organic matter enrichment in the Hongshuizhuang Formation reflects changes in surface water productivity and redox conditions, caused by climate-induced sea-level fluctuations. Shale-normalized rare earth element (REE) distributions show a depletion in light REEs and enrichment in heavy REEs, positive Eu anomalies, and mean Y/Ho and Ba/Sr ratios of 33.2 and 9.91, respectively, suggesting that deposition of the Hangshuizhuang Formation was accompanied by submarine hydrothermal activity. [ABSTRACT FROM AUTHOR]

Background. The whole tumor microenvironment (TME) infiltration features monitored by integrated roles of different RNA N6-methyladenosine (m6A) regulators remain elusive. Our study is aimed at exploring the association between m6A modification patterns, TME cell-infiltrating levels, and patients' prognosis in stomach adenocarcinoma (STAD) patients. Methods. Consensus clustering was performed based on the integrated analyses of 17 m6A regulators and 229 m6A-related hallmark genes in STAD (The Cancer Genome Atlas (TCGA) cohort, n = 443 ; Gene Expression Omnibus (GEO) GSE57303, n = 70 , GSE62254 n = 300 , and GSE84437 n = 433). A m6ASig scoring system was calculated by the principal component analysis (PCA), and its prognostic value was validated in an independent dataset GES15459. Results. Three m6A clusters were identified among 1246 STAD patients, which had significant overall survival (OS) differences and demonstrated different TME immune cell infiltration and biological behaviors. According to the m6ASig score, which was generated from the m6A-related hallmark genes, STAD patients were divided into the high-m6ASig group (n = 585) and low-m6ASig group (n = 586). Patients in the high-m6ASig group had a notably prolonged OS and higher immune cell infiltration. Moreover, patients with higher m6ASig score were associated with higher microsatellite instability (MSI); higher PD-L1, CTLA4, and ERBB2 expressions; and greater tumor mutation burden (TMB). Patients with higher m6ASig score demonstrated a better immune response and drug sensitivity. Conclusion. Our m6ASig scoring system could characterize TME immune cell infiltration, thus predict patient's prognosis and immunotherapy and chemotherapy efficacy, offering a novel tool for the individualized therapeutic implications for STAD patients. [ABSTRACT FROM AUTHOR]

Mild oxidative degradation was used to release the aliphatic hydrocarbons occluded inside the macromolecular structure of solid bitumens collected from Sinian carbonate reservoir, Sichuan basin, SW China. In contrast to the adsorbed aliphatic hydrocarbons extracted from the solid bitumens, the mild oxidative products showed unaltered n -alkanes distributions, which had been trapped within the macromolecular structure of the bitumens and protected from biodegradation processes. These observations are quite informative and suggest that at least, two phases of hydrocarbon charging to the Sinian reservoirs might have occurred. The occluded hydrocarbons seem to represent the first phase of hydrocarbon charge while the adsorbed and biodegraded hydrocarbons correspond to the second phase of hydrocarbon charge. However, terpane and sterane distributions in both fractions were preserved and similar, and the carbon isotope analysis results obtained in this work along with the previous geological information, corroborates the idea that Sinian reservoirs hydrocarbons have been sourced from the black shale of Lower Cambrian Qiongzhusi Formation. This study reveals the geochemical significance of adsorbed/occluded aliphatic hydrocarbons in understanding the charging history of oil into reservoirs. [ABSTRACT FROM AUTHOR]

BACKGROUND: MicroRNAs (miRNAs) capable of post-transcriptionally regulating mRNA expression are essential to tumor occurrence and progression. OBJECTIVE: This study aims to find negatively regulatory miRNA-mRNA pairs in prostate adenocarcinoma (PRAD). METHODS: Combining The Cancer Genome Atlas (TCGA) RNA-Seq data with Gene Expression Omnibus (GEO) mRNA/miRNA expression profiles, differently expressed miRNA/mRNA (DE-miRNAs/DE-mRNAs) were identified. MiRNA-mRNA pairs were screened by miRTarBase and TarBase, databases collecting experimentally confirmed miRNA-mRNA pairs, and verified in 30 paired prostate specimens by real-time reverse transcription polymerase chain reaction (RT-qPCR). The diagnostic values of miRNA-mRNA pairs were measured by receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA). DAVID-mirPath database and Connectivity Map were employed in GO/KEGG analysis and compounds research. Interactions between miRNA-mRNA pairs and phenotypic features were analyzed with correlation heatmap in hiplot. RESULTS: Based on TCGA RNA-Seq data, 22 miRNA and 14 mRNA GEO datasets, 67 (20 down and 47 up) miRNAs and 351 (139 up and 212 down) mRNAs were selected. After screening from 2 databases, 8 miRNA (up)-mRNA (down) and 7 miRNA (down)-mRNA (up) pairs were identified with Pearson's correlation in TCGA. By external validation, miR-221-3p (down)/GALNT3 (up) and miR-20a-5p (up)/FRMD6 (down) were chosen. The model combing 4 signatures possessed better diagnostic value. These two miRNA-mRNA pairs were significantly connected with immune cells fraction and tumor immune microenvironment. CONCLUSIONS: The diagnostic model containing 2 negatively regulatory miRNA-mRNA pairs was established to distinguish PRADs from normal controls. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis. Patients and methods: MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study. Results: After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity. Conclusions: The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several studies have demonstrated that microRNAs (miRNAs) and target mRNAs are associated with different frequencies of microsatellite instability. OBJECTIVE: The study aimed to elucidate the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of microsatellite instability in colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation, and survival data. METHODS: Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened out and then the miRNA-mRNA regulatory pairs were identified through two databases. We verified that the expression levels were detected in 40 microsatellite instable (MSI) and 40 microsatellite stable (MSS) CRC samples and used the logistic regression and the Cox regression method to evaluate the diagnostic and prognostic value of negative regulatory pairs respectively. RESULTS: The best diagnostic model that combines miR-31-5p, PLAGL2, miR-361-5p, and RAB27B, which were associated with immune microenvironment, tumor mutation burden (TMB), and overall DNA methylation, could significantly predict microsatellite instability in colon tissues. MiR-31-5p and RAB27B could also predict the overall survival of MSS CRCs. CONCLUSION: This study generated a predictive model of the combination of miRNAs and mRNAs to distinguish MSI versus MSS CRCs and elaborated their potential molecular mechanisms and biological functions. [ABSTRACT FROM AUTHOR]

An increasing number of studies have highlighted the biological significance of neutrophil activation and polarization in tumor progression. However, the characterization of tumor-associated neutrophils (TANs) is inadequately investigated. Patients' expression profiles were obtained from TCGA, GEO, and IMvigor210 databases. Six algorithms were used to assess immune cell infiltration. RNA sequencing was conducted to evaluate the differentially expressed genes between induced N1- and N2-like neutrophils. A TAN-associated risk score (TRS) model was established using a combination of weighted gene co-expression network analysis (WGCNA) and RNA-seq data and further assessed in pan-cancer. A clinical cohort of 117 GC patients was enrolled to assess the role of TANs in GC via immunohistochemistry (IHC). A TRS signature was built with 10 TAN-related genes (TRGs) and most TRGs were highly abundant in the TANs of the GC microenvironment. The TRS model could accurately predict patients' prognosis, as well as their responses to chemotherapy and immunotherapy. The TRS was positively correlated with pro-tumor immune cells and exhibited negative relationship with anti-tumor immune cells. Additional functional analyses revealed that the signature was positively related to pro-tumor and immunosuppression pathways, such as the hypoxia pathway, across pan-cancer. Furthermore, our clinical cohort demonstrated TANs as an independent prognostic factor for GC patients. This study constructed and confirmed the value of a novel TRS model for prognostic prediction of GC and pan-cancer. Further evaluation of TRS and TANs will help strengthen the understanding of the tumor microenvironment and guide more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Reef and oolitic gas reservoirs in the Permian Changxing and Triassic Feixianguan formations have been discovered in both the Luojiazhai-Puguang and Longgang areas of the Sichuan Basin, but the accumulation scale, abundance and distribution patterns differ greatly. In fact, the two areas have more differences than they have similarities. Similarities include: (1) the lithology, properties and types of porosity of the reef and oolitic reservoirs are primarily consistent in the two areas; (2) well-developed regional caprocks that seal the fluid system; and (3) accumulation process histories, with liquid hydrocarbon charging at an early stage, cracking into gas at a high to over-mature stage, adjustment of gas reservoirs at an uplifting stage, and final reservoir generation at a late stage. Differences include: (1) gas accumulations in the Luojiazhai-Puguang area that are dominated by oil-type cracked gas, with multiple and sufficient gas sources, contrasting with gas accumulations in the Longgang area that are dominated by coal-sourced gas with insufficient gas sources; (2) heterogeneity and horizontal diversity of reservoirs in the Longgang area that are stronger than in the Luojiazhai-Puguang area; and (3) the development of deep and large faults in the Luojiazhai-Puguang area that link source, reservoir and migration pathways, contrasting with poorly developed faults in Longgang area, where laterally variable fractures are the major migration pathway. Because of these differences, abundant large-scale structurally-controlled gas accumulations are developed in the Luojiazhai-Puguang area, whereas lithology plays a more important role in gas accumulation in the Longgang area where accumulations are smaller-scale and have lower gas-bearing abundance. We suggest that future exploration for reef and oolitic gas accumulations should be strengthened in NE Sichuan and NW Sichuan Jiulongshan. In particular, the transitional zone between Longgang and Kaijiang-Liangping Bay has the best potential for new discoveries. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We sought to determine whether paeoniflorin enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relationship between this apoptosis and NF-κB activation. Methods: Paeoniflorin was diluted to different concentrations and added to gastric carcinoma cells (SGC-7901) at different times. Western blot was used to test the expression of NF-κB in nuclear and IκBα, p-IκBα, IKKα in cytoplasm. Further, the intranuclear expression of NF-κB was confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell apoptosis of gastric carcinoma cells was estimated by flow cytometry. Results: Paeoniflorin revealed dramatic inhibition of NF-κB activity in the nuclei of the cells. The inhibition pattern of NF-κB was exhibited in a time- and dose-dependent manner, which was confirmed by Western blot and ELISA. Decreased nuclear translocation of NF-κB induced by paeoniflorin was found by preventing IκBα phosphorylation. Moreover, 5-fluorouracil-induced cell apoptosis was promoted by paeoniflorin in gastric carcinoma cells. Conclusions: Paeoniflorin can inhibit NF-κB activity of SGC-7901 cells, and enhance 5-fluorouracil-induced apoptosis of gastric carcinoma cells. [Copyright &y& Elsevier]

Objectives: Head and neck cancers are aggressive epithelial tumours that are recognised as being particularly challenging to treat. Here, we report the targeted DNA profiling and the prevalence of neurotrophic-tropomyosin receptor tyrosine kinase gene (NTRK) aberrations in Chinese patients with head and neck cancers.Methods: Samples of 127 patients with head and neck cancer were retrospectively analysed. Profiling was performed by next-generation sequencing of the 1021-gene panel with tumour tissue and matched peripheral blood control samples.Results: This study was inspired by the outcome benefit of a parotid cancer patient harbouring ETV6-NTRK3 fusion, who received crizotinib treatment and achieved a 2-year progression-free survival. Genomic profiling of 127 patients with head and neck cancers indicated that TP53 is the most frequently mutated gene both in our cohort and in The Cancer Genome Atlas (TCGA) database. A higher prevalence of NTRK genetic aberrations (7.9%, 10/127), including NTRK fusion (3.1%) and mutation, was observed in our population than in TCGA. The most common fusion was the ETV6-NTRK3. Compared to the NTRK-wt group, the NTRK aberration group had more APC and PTPRD aberrations (p < 0.05). NTRK fusion was also associated with lower tumour mutation burden (TMB) (p < 0.05). TP53 and LRP1B mutations were significantly associated with higher TMB (both p < 0.01), which may be potential markers of immunotherapy.Conclusions: This is the first study to report targeted DNA profiling of Chinese patients with head and neck cancers. As NTRK genetic aberrations are more common in this Chinese population, the efficacy of NTRK inhibitors should be studied further. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. [ABSTRACT FROM AUTHOR]

Background: The recommended phase 2 dose (RP2D) of pamiparib, an investigational PARP1/2 inhibitor, was established as 60 mg twice daily (BID) in a first‐in‐human (FIH) study (NCT02361723). Methods: Chinese patients with advanced non‐mucinous high‐grade ovarian cancer (HGOC) or triple‐negative breast cancer (TNBC) whose disease either progressed despite standard therapy, or for which there is no standard therapy were enrolled in the dose‐escalation (DE) portion of a phase 1/2 study (NCT03333915). The primary endpoint was safety/tolerability; secondary objectives were pharmacokinetics and antitumor activity. BRCA1/2 mutation status was retrospectively evaluated. Results: Nine HGOC and six TNBC patients (N = 15; n = 4, 20 mg; n = 4, 40 mg; n = 7, 60 mg) were enrolled; as of 30 September 2019, one HGOC patient remained on treatment. Seven patients (n = 5, HGOC; n = 2, TNBC) had germline BRCA1/2 mutation (gBRCAmut); all HGOC patients were resistant/refractory to platinum. Asthenia and nausea (n = 12 each) were the most common treatment‐related adverse events (TRAEs). Decreased hemoglobin was the most common grade 3 TRAE (n = 3); no grade ≥4 AEs were observed. No dose‐limiting toxicities (DLTs) were reported. Pamiparib plasma exposure was similar to exposure observed in the FIH study after a single‐dose administration, albeit slightly higher at steady state. Among 13 RECIST‐evaluable patients, two with HGOC (gBRCAmut, n = 1) achieved a confirmed partial response and six with HGOC (gBRCAmut, n = 4) achieved stable disease; all TNBC RECIST‐evaluable patients (n = 5) reported progressive disease. Conclusions: Pamiparib was generally well tolerated in Chinese patients, with durable responses observed in patients with HGOC. Based on these results, pamiparib 60 mg BID was confirmed as the RP2D. [ABSTRACT FROM AUTHOR]

We report a case of a 68-year-old man diagnosed with pulmonary pleomorphic carcinoma who showed partial response after a single treatment with camrelizumab (PD1 monoclonal antibody). The patient's tumor was positive for programmed cell death ligand 1 (PD-L1) and progressed rapidly after a course of chemotherapy. Fortunately, the tumors dramatically shrank after one cycle of camrelizumab, an anti-programmed cell death-1 (PD-1) antibody developed by Chinese Hengrui Medicine. In conclusion, camrelizumab may be a good treatment option, especially in tumors that express PD-L1. [ABSTRACT FROM AUTHOR]

With acceleration of "oil exploration near the source" in the petroleum industry, black shales (BS) play an increasingly important role in oil and gas exploration. Meso-Neoproterozoic BS are well developed in the North China Craton (NCC), China, many of which are identified as potential hydrocarbon source rocks. Although BS from the Mesoproterozoic Era has been widely investigated, few studies were focused on the Neoproterozoic BS so far. Based on petrology and geochemistry analysis, the sedimentary environment, provenance and organic matter accumulation of two BS layers in the Tonian Baishugou Formation from Sujiacun section, Luonan Area, southern NCC were investigated. It suggests that the lower BS (LB) was deposited in a shallow and non-stratified cratonic-interior sea environment with unstable dysoxic or suboxic conditions. The seawater salinity increased from brackish to marine facies conditions due to the decrease of runoff caused by climate cooling. The Upper BS (UB) was deposited in an open paleomarine environment with stable suboxic conditions and brackish salinity in continuously humid and hot paleoclimate. Both BS were derived from granitoids formed by the ca.2.5 Ga collisional-thermal events in the NCC. The OM accumulation rate of UB is higher than that of UB while LB records lower OM loss rate. On these bases, two developmental modes for the BS from the Baishugou Formation were established. • Two black shale (BS) layers dated to Tonian from North China Craton are studied. • The paleoclimate and paleoredox condition for two BS layers are very different. • The ca. 2.5 Ga felsic rock is the main source rock for the two BS. • Proxies based on Ba bio indicate higher accumulation rate for organic matter of UB. • Stable suboxic condition for UB resulted in higher primary productivity. [ABSTRACT FROM AUTHOR]

Purpose: Anlotinib is a novel oral multi-targeted receptor tyrosine kinase inhibitor, which selectively inhibits VEGFR2/3, FGFR1-4, PDGFR α/β, c-kit, and Ret. It shows antitumor effect in patients with advanced refractory solid tumors. The detailed absorption, metabolism, and excretion pathways of anlotinib have not yet been fully investigated.Methods: Six male patients were enrolled and divided into two groups. Group A (containing two patients) received 14.15 mg/80 µCi/subject [14C]-anlotinib hydrochloride. Group B (containing four patients) received 14.15 mg/120 µCi/subject [14C]-anlotinib hydrochloride. The blood, urine, and feces of all the six patients after orally administration of [14C]-anlotinib were collected. The absorption, metabolism, and excretion of [14C]-anlotinib were investigated, and the efficacy and safety of anlotinib were evaluated.Results: In plasma, the average time to peak concentration (Tmax) of total radioactivity was 4.42 h and the average peak concentration (Cmax) of total radioactivity was 18.80 ng Eq./g. The average values of AUC0-last, AUC0-∞, and MRT0-t were 4071 h.ng Eq./g, 13,555 h.ng Eq./g, and 125 h, respectively. The average recovery of total radioactivity (TRA) in urine and feces was 62.03%, accounting for 48.52% and 13.51% in feces and urine of the total dosage, respectively. The parent drug, a carboxylic metabolite (M30), and mono-oxidation products (M46/M66) were major drug-related components in human plasma. Oxidative metabolism played the major role in drug clearance in human. The major metabolic pathways include oxidative deamination to M2, mono-oxidation to M1, and the formation of M30. Adverse events occurred in five patients and severe adverse events (SAE) occurred in one. Tumor response were evaluated as stable disease (SD) in three, partial response (PR) in one, and progressive disease (PD) in one of the patients, respectively.Conclusions: Anlotinib had a good pharmacokinetic profile with rapid absorption, long half-life, and extensive hepatic metabolism. The adverse events and efficacy were as expected. [ABSTRACT FROM AUTHOR]

Long intergenic non-coding RNA for kinase activation (LINK-A) has been characterized as an oncogenic long non-coding (lnc)RNA in triple-negative breast cancer and ovarian carcinoma, but its involvement in other malignancies remains elusive. In the present study, it was determined that the plasma levels of LINK-A lncRNA and Rho-associated protein kinase 1 (ROCK1) were significantly increased in patients with pancreatic adenocarcinoma compared with those in healthy controls. The plasma levels of LINK-A lncRNA were positively correlated with the plasma levels of ROCK1 in pancreatic adenocarcinoma patients, but not in healthy controls. Silencing of LINK-A led to inhibition of pancreatic adenocarcinoma cell proliferation, migration and invasion. Simultaneous overexpression of ROCK1 attenuated the inhibitory effect of LINK-A silencing on cancer cell proliferation, migration and invasion. Overexpression of LINK-A lncRNA led to upregulation of ROCK1 expression, while overexpression of ROCK1 had no significant effect on LINK-A lncRNA expression. It may therefore be concluded that LINK-A lncRNA may have a role in pancreatic adenocarcinoma, at least in part, by promoting ROCK1 expression. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) have become reliable sources of non‐invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). Methods: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan‐Meier curves using log‐rank tests. Results: We identified a 7‐miRNA signature including let‐7b‐5p, miR‐140‐3p, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, miR‐20b‐5p, and miR‐205‐5p in plasma for NPC diagnosis after four‐stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, and miR‐205‐5p were consistently up‐regulated while let‐7b‐5p and miR‐140‐3p were significantly down‐regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma‐derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. Conclusion: We identified a 7‐miRNA signature in plasma as promising non‐invasive biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four‐phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT‐PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) whose expression levels were significantly different between BC patients and NCs. A 5‐miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver‐operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma‐derived exosome samples from 32 BC patients vs 32 NCs. Let‐7b‐5p was contrarily down‐regulated in BC tissue. In exosomes samples, only miR‐122‐5p was significantly up‐regulated as in plasma for BC patients. In conclusion, we identified a 5‐miRNA plasma panel (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) that could serve as a promising biomarker for BC detection. [ABSTRACT FROM AUTHOR]

A large number of primary oil and gas reservoirs have been discovered in Proterozoic strata all over the globe. Proterozoic sequences are widely distributed in China, and the discovery of large Sinian-aged gas reservoirs in the Sichuan Basin and Mesoproterozoic liquid oil seepages in North China shows that attention should be paid to the exploration potential of Proterozoic strata. In this paper, the main controlling factors of Proterozoic source rocks are discussed. Principally, active atmospheric circulation and astronomical cycles may have driven intense upwelling and runoff to provide nutrients; oxygenated oceanic surface waters could have provided suitable environments for the organisms to thrive; volcanic activity and terrestrial weathering caused by continental break-up would have injected large amounts of nutrients into the ocean, leading to persistent blooms of marine organisms; and extensive anoxic deep waters may have created ideal conditions for the preservation of organic matter. Additionally, the appearance of eukaryotes resulted in diversified hydrocarbon parent material, which effectively improved the generation potential for oil and gas. Through the comparison of Formations across different cratons, seven sets of Proterozoic organic-rich source rocks have been recognized in China, which mainly developed during interglacial periods and are also comparable worldwide. The Hongshuizhuang and Xiamaling Formations in North China have already been identified previously as Mesoproterozoic source rocks. The early Proterozoic Changchengian System is highly promising as a potential source rock in the Ordos Basin. In the Upper Yangtze area, the Neoproterozoic Datangpo and Doushantuo Formations are extensively distributed, and represent the major source rocks for Sinian gas reservoirs in the Sichuan Basin. Moreover, the Nanhuan System may contain abundant shales with high organic matter contents in the Tarim Basin, although this possibility still needs to be verified. Indeed, all three cratons may contain source rocks of Proterozoic strata; thus, these strata represent major exploration targets worthy of great attention. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection. Highlights • We investigated plasma miRNA profiles of CRC in a four-stage process and present a seven-miRNA signature in discriminating CRC. • We found that miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were significantly up-regulated in CRC tissues. • We found that miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. • We discovered that plasma miR-26a-5p was only up-regulated in colon cancer patients but not in rectal cancer. • We found none of the seven miRNAs demonstrated significant different expression in patients with stage III + IV compared to those with stage I + II. • We found that no difference of the above seven plasma miRNA between left-sided and right-sided CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Circulating microRNAs (miRNAs) have been implicated as novel biomarkers for various types of cancers. The aim of the study is to identify serum miRNAs with potential in detecting gastric cardia adenocarcinoma (GCA). METHODS: A three-phase study was designed with 102 GCA patients and 84 cancer-free controls. In the screening phase (3 GCA pools vs. 1 normal control (NC) pool), a total of 35 miRNAs were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel. Subsequently, these miRNAs were further assessed by qRT-PCR in the training phase (30 GCAs vs. 30 NCs) and testing phase (72 GCAs vs. 54 NCs). Finally, the expression levels of the identified miRNAs were assessed in GCA tissues and exosomes. RESULTS: Five up-regulated miRNAs (miR-200a-3p, miR-296-5p, miR-132-3p, miR-485-3p and miR-22-5p) were identified in serum of the GCA patients compared with NCs. The areas under the receiver operating characteristic curve (AUCs) of the five-miRNA panel were 0.766 and 0.724 for the training and testing phases, respectively. In addition, miR-200a-3p, miR-296-5p, miR-485-3p and miR-22-5p were significantly up-regulated in GCA tissues. However, none of the miRNAs in the exosomes showed different expression between GCA patients and NCs. CONCLUSIONS: We identified a five-miRNA panel in peripheral serum samples as a non-invasive biomarker in detection of GCA. [ABSTRACT FROM AUTHOR]

Abstract: Dysregulated microRNAs (miRNAs) in the plasma of patients with lung squamous cell carcinoma (LSCC) might serve as biomarkers for LSCC diagnosis. The expression of miRNAs was performed using quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) on the basis of Exiqon panels in the initial screening phase including three male LSCC pool samples and one normal control (NC) pool sample (per 10 samples were pooled as one pool sample). After the training (32 LSCC vs. 31 NCs), the testing (55 LSCC vs. 55 NCs), and the external validation (15 LSCC vs. 15 NCs) stages via qRT‐PCR, a four‐miRNA signature (miR‐181a‐5p, miR‐21‐5p, miR‐106a‐5p, and miR‐93‐5p) was identified for LSCC detection. Areas under the receiver operating characteristic (ROC) curve (AUC) of the four‐miRNA panel for the training, the testing, and the external validation phases were 0.795, 0.827, and 0.914, respectively. Then, the four miRNAs were explored in LSCC tissue samples (23 LSCC vs. 23 NCs), and their expression was significantly up‐regulated. However, none of the four miRNAs found significantly up‐regulated in plasma exosomes expect miR‐93‐5p with borderline significance (16 LSCC vs. 16 NCs). In summary, our study established a four‐miRNA peripheral plasma signature, which contributed to diagnosing male LSCC patients in China to a certain degree. [ABSTRACT FROM AUTHOR]

The tectonic evolution and Paleoposition of the North China Craton (NCC) in the Columbia supercontinent during Mesoproterozoic is still not well constrained owing to scarce outcrops of the Mesoproterozoic geological records. Here we present detailed U-Pb geochronological study on detrital zircons and trace elemental geochemistry of the Mesoproterozoic meta-sedimentary rocks from the Sanxiatian Formation, the upper Huade Group, in the northern NCC. The youngest cluster of detrital zircons from the Sanxiatian Formation has U-Pb age peak at ∼1357 Ma, which constrains the deposition of the Sanxiatian Formation after ∼1400 Ma. We suggest a stratigraphic correlation among the Sanxiatian, Baiyinbaolage, Liuhongwan and Xiamaling formations, all of which were deposited simultaneously in the northern NCC. The small portion of ∼2530 Ma zircons possibly corresponds with the growth of juvenile crust in the NCC at the late Neoarchean. The distinct ∼1850 Ma population may have originated from the syn-and post- tectonic granites distributed in the Trans-North China Orogen (TNCO), which is related with the collision between the Western and Eastern blocks in the NCC. The ∼1750–∼1600 Ma zircon populations were also sourced from the NCC and are possibly characterized by the post-collisional magmatic events after the amalgamation of the NCC. The zircon clusters younger than 1600 Ma with peaks at ∼1575 Ma and ∼1357 Ma, were interpreted as exotic sources, while the latter possibly related with the final breakup of the supercontinent Columbia. With the compilation of the detrital zircon dataset from the North India, the West Australia, the North Australia, the Siberia blocks and the northwestern Laurentia, the final fragmentation of the supercontinent Columbia is suggested to be characterized by the separation between the NCC, the Australia or the India blocks during the late Mesoproterozoic. [ABSTRACT FROM AUTHOR]

We looked for differentially expressed MicroRNAs (miRNAs) in Immunoglobulin A nephropathy (IgAN). Forty-eight miRNAs were identified through the initial screening phase (2 IgAN pools vs. 1 normal control (NC) pool) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V 1 .M). By qRT-PCR, these miRNAs were further assessed in the training (32 IgAN VS. 31 NCs) and testing stages (51 IgAN VS. 51 NCs). The renal pathological lesions of patients with IgAN were evaluated according to Lee's grading system. We discovered a plasma miRNA signature including four up-regulated miRNAs (miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p) and the areas under the receiver operating characteristic (ROC) curve (AUC) were 0.80 and 0.76 for the training and testing stage, respectively. The expression of the four miRNAs in IgAN grade I–II subgroups (according to Lee's grading system) was obviously higher than that in IgAN grade III-V ( P  < .05). In summary, the plasma e xpression of miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425-3p were up-regulated in patients with IgAN, especially the early-stage disease. Further studies are needed to explore the roles of the four miRNAs in the pathogenesis and progression of IgAN. [ABSTRACT FROM AUTHOR]

Background The altered expression of circulating miRNAs has been discovered in many autoimmune diseases (ADs). With rare existing research, it is still unclear in Hashimoto's thyroiditis (HT). We detected plasma miRNA expression of HT patients in this three-stage designed study. Methods Differently expressed miRNAs (4 HT pools vs. 1 normal control pool) were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use- PCR-Human- panel-I + II-V1.M) in the initial discovery stage. These miRNAs were then confirmed in the training stage and further validated in the testing stage using qRT-PCR with 64 (32 HT vs. 32 NCs) and 136 samples (68 HT vs. 68 NCs), respectively. Results A total of 10 miRNAs showed differential expression through the training stage. For further validation in the testing stage, expression of 6 miRNAs ( miR - 205 , miR - 20a - 3p , miR - 375 , miR - 296 , miR - 451 , miR - 500a ) were consistent with those in the training stage. Combination results showed that these 6 miRNAs were significantly up-regulated in peripheral plasma of HT patients compared with normal controls ( P < 0 . 05 ). In addition, the six-miRNA signature was evaluated to be a potential diagnostic marker of HT. The areas under the receiver operating characteristic curve of the signature were 0.80, 0.75 and 0.69 for the training, testing and the combined stages, respectively. Three miRNAs were associated with TSH levels in HT patients ( miR - 451 , P = 0.043; miR - 375 , P = 0.043; miR - 500a , P = 0.043). Additionally, miR - 20a - 3p was related with TgAb level ( P = 0.046). Conclusions We identified a miRNA signature including six dysregulated plasma miRNAs which could act as a diagnostic marker in plasma of HT, providing more evidence and better understanding for the association between circulating miRNAs and autoimmune diseases. [ABSTRACT FROM AUTHOR]

In order to evaluate rare earth elements (REEs) as a potential proxy for solid bitumen classification, we employed traditional correlation approaches, such as carbon isotopes and V/(V + Ni) ratios, to infer the source rocks of Sinian-Cambrian reservoir solid bitumens in the Sichuan Basin and analyse solid bitumens for their REE compositions by inductively coupled plasma-mass spectrometry. Our data suggested that Sinian-Cambrian reservoir solid bitumens were primarily sourced from the lower Cambrian shales deposited under anoxic-euxinic conditions. REE and their associated parameters seemed to be more sensitive to classify solid bitumens than traditional correlation approaches. REE concentrations played a dominant role and fractionation degree between light and heavy REE and played a secondary role in solid bitumen classification. REE concentration and pattern in solid bitumens might be controlled by two processes, including inheritance from source rocks and water-rock interaction. The major factor controlling REE concentrations in solid bitumens was the type of organic matter of source rocks. Authigenic minerals in solid bitumens formed by water-rock interaction appeared to have little influence on REE compositions of solid bitumens because of their trace contents. Overall, REE could be used as a novel complementary approach to solid bitumen classification in complicated petroleum systems. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The metastasis of gastric cancer, one of the most common tumors, has a molecular mechanism that is still largely unclear. Here we investigated the role of possible tumor-suppressor miR-1296-5p in the cell migration and invasion of ERBB2-positive gastric cancer. It found that miR-1296-5p was significantly down-regulated in gastric cancer tissues. Moreover, it was down-regulated in lymph node metastatic gastric cancer tissues compared with non-metastatic gastric cancer tissues. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in SNU-216 and NUGC-4 gastric cancer cells suggested that ERBB2 was the target gene of miR-1296-5p. Overexpressed miR-1296-5p reduced its target protein level and Rac1 activation, and inhibited the migration and invasion of SNU-216 and NUGC-4 gastric cancer cells. MiR-1296-5p was down-regulated in ERBB2-positive gastric cancer tissues compared with ERBB2-negative gastric cancer tissues. In ERBB2-positive gastric cancers, the miR-1296-5p expression was suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples. The migration and invasion of gastric cancer cells was inhibited by miR-1296-5p overexpression or herceptin treatment, and rescued by the overexpression of constitutively active Rac1-Q61L or ERBB2. Taken together, our findings first suggest that miR-1296-5p might be involved in the regulation on the migration and invasion of human gastric cancer cells at least in part via targeting ERBB2/Rac1 signaling pathway. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) have been used as promising diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). We performed miRNA expression profiling using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panels from three ESCC pools and one normal control (NC) pool samples. Using qRT-PCR, identified serum miRNAs were further confirmed in training (32 ESCC vs. 32 NCs) and testing stages (108 ESCC vs. 96 NCs). Consequently, five serum miRNAs (miR-20b-5p, miR-28-3p, miR-192-5p, miR-223-3p, and miR-296-5p) were significantly overexpressed in ESCC compared with NCs. The diagnostic value of the 5-miRNA signature was validated by an external cohort (60 ESCC vs. 60 NCs). The areas under the receiver operating characteristic curve (ROC) of the 5-miRNA signature were 0.753, 0.763, and 0.966 for the training, testing, and the external validation stages, respectively. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes. MiR-20b-5p, miR-28-3p, and miR-192-5p were significantly upregulated in ESCC tissues, while miR-296-5p was overexpressed in ESCC serum exosomes. In conclusion, we identified a 5-miRNA signature in serum for the detection of ESCC. [ABSTRACT FROM AUTHOR]

In order to understand redox variations and organic matter accumulation on the Yangtze carbonate platform during the Late Ediacaran–Early Cambrian, petrological and geochemical studies of several wells were carried out in this work. Our data suggest that depositional environments were dominated by oxidizing bottom water conditions during the late Ediacaran, and evolved to anoxic conditions, triggered by blooms of microbial organisms in surface waters during the earliest Cambrian. Subsequently, massive release of H 2 S derived from both anaerobic recycling of organic matter and, probably, hydrothermal venting promoted a sulfidic ocean. The discovery of a Ni-Mo sulfide ore layer in the basal Cambrian implies that such a sulfidic condition spread onto the Yangtze carbonate platform interior during the late Cambrian Stage 2. Further, transgressive flooding led to widespread black shale deposition and persistently anoxic conditions, as indicated by geochemical proxies. During the late Ediacaran to earliest Cambrian, local and widespread phosphogenesis indicates that organic matter accumulation was intimately associated with microbial (especially cyanobacterial) blooms driven by phosphorus cycling. The organic matter accumulations in early Cambrian black shales, however, were in connection with anoxic bottom water conditions and intermittent replenishment of recycled organic phosphorus to surface waters. [ABSTRACT FROM AUTHOR]

On the basis of the results of simulation experiments, now we better understand the contribution of high carbon number hydrocarbons to diamondoid generation during thermal pyrolysis of crude oil and its sub-fractions (saturated, aromatic, resin, and asphalene fractions). However, little is known about the effect of volatile components in oil on diamondoid generation and diamondoid indices due to the lack of attention to these components in experiments. In this study, the effect of volatile components in oil on diamondoid generation and maturity indices was investigated by the pyrolysis simulation experiments on a normal crude oil from the HD23 well of the Tarim Basin and its residual oil after artificial volatilization, combined with quantitative analysis of diamondoids. The results indicate that the volatile components (≤ nC) in oil have an obvious contribution to the generation of adamantanes, which occurs mainly in the early stage of oil cracking (Easy R<1.0%), and influences the variations in maturity indices of adamantanes; but they have no obvious effect on the generation and maturity indices of diamantanes. Therefore, some secondary alterations e.g., migration, gas washing, and biodegradation, which may result in the loss of light hydrocarbons in oil under actual geological conditions, could affect the identification of adamantanes generated during the late-stage cracking of crude oil, and further influence the practical application of adamantane indices. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that Smad4 (DPC4) plays a fundamental role in the development and prognosis of several types of cancer. The objective of this study was to conduct a meta-analysis to evaluate whether the loss of Smad4 staining could serve as a prognostic marker. Methods: A comprehensive meta-analysis was conducted using major useful databases to determine the relationship between the immunohistochemical detection of Smad4 and the survival of patients with various cancers. We used hazard ratios (HRs) with 95% confidence interval (CIs) as the effect estimation to evaluate the association of Smad4 with overall survival (OS), cancer-specific survival (CSS) or recurrence-free survival (RFS). The relationship between the clinical characteristics of patients and Smad4 was also evaluated using the odds ratio (OR). Results: A total of 7570 patients from 26 studies were included in the analysis. The pooled results showed that loss of Smad4 staining was a negative predictor of OS with an HR of 1.97 (95% CI: 1.55–2.51; Pheterogeneity<0.001) and CSS/RFS (HR = 1.81; 95% CI: 1.30–2.54; Pheterogeneity<0.001). In addition, loss of Smad4 staining was more likely to be found in older (OR = 1.69, 95% CI: 1.09–2.61; Pheterogeneity = 0.648) colorectal cancer patients with a late tumor stage (OR = 2.31, 95% CI: 1.71–3.10; Pheterogeneity = 0.218) and in gastric cancer patients with lymph node metastasis (OR = 2.11, 95% CI: 1.03–4.34; Pheterogeneity = 0.038). Conclusion: Based on these results, our meta-analysis provided evidence that loss of Smad4 staining could act as an unfavorable biomarker in the prognosis of various cancers and should be used as a powerful tool in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Recently, more and more studies investigated the association of inflammation parameters such as the Platelet Lymphocyte Ratio (PLR) and the prognosis of various cancers. However, the prognostic role of PLR in cancer remains controversial. Methods: We conducted a meta-analysis of published studies to evaluate the prognostic value of PLR in various cancers. In order to investigate the association between PLR and overall survival (OS), the hazard ratio (HR) and its 95% confidence interval (CI) were calculated. Results: A total of 13964 patients from 26 studies were included in the analysis. The summary results showed that elevated PLR was a negative predictor for OS with HR of 1.60 (95%CI: 1.35–1.90; Pheterogeneity <0.001). Subgroup analysis revealed that increased PLR was a negative prognostic marker in patients with gastric cancer (HR = 1.35, 95%CI: 0.80–2.25, Pheterogeneity = 0.011), colorectal cancer (HR = 1.65, 95%CI: 1.33–2.05, Pheterogeneity = 0.995), hepatocellular carcinoma (HR = 3.07, 95% CI: 2.04–4.62, Pheterogeneity = 0.133), ovarian cancer (HR = 1.57, 95%CI: 1.07–2.31, Pheterogeneity = 0.641) and non-small cell lung cancer (NSCLC) (HR = 1.85, 95% CI: 1.42–2.41, Pheterogeneity = 0.451) except for pancreatic cancer (HR = 1.00, 95%CI: 0.92–1.09, Pheterogeneity = 0.388). Conclusion: The meta-analysis demonstrated that PLR could act as a significant biomarker in the prognosis of various cancers. [ABSTRACT FROM AUTHOR]

Reef-bank of Sichuan (四川) basin have been explored along the platform margin belt on both sides of the Kaijiang (开江)-Liangping (梁平) trough for a long time. Correspondingly, a series of major breakthroughs have been obtained and a number of large oil and gas fields have been found. After the breakthroughs of Kaijiang-Liangping trough, how reef-bank exploration will proceed? Is there another 'Kaijiang-Liangping trough' in Sichuan basin? Previous research shows that Sichuan basin underwent intracratonic rift and basement fault activities in Late Permian, developing a paleogeography framework of 'three uplifts and three depressions' under the background of the regional large ramp, including Exi (鄂西)-Chengkou (城口) trough, Kaijiang-Liangping trough and Yanting (盐 亭)-Tongnan (潼南) trough. Based on sedimentology and tectonics dynamics analysis, data of drillings, outcrops and seismic, Yanting-Tongnan trough has been discovered in central Sichuan basin in our study which distributes from Mianzhu (绵竹), Jiangyou (江油) in western Sichuan basin through Nanchong (南充) to Guang'an (广安), as long as about 210 km, extending in NW-SE nearly paralleling to Kaijiang-Liangping trough, opening to the sea north-westward, and gradually pinchout to the east platform. Similar to Kaijiang-Liangping trough, another platform margin reef belt distributes along a U-shape belt around Yanting-Tongnan trough, which is expected to become another natural gas accumulation zone after the platform margin around Kaijiang-Liangping trough. The discovery of Yanting-Tongnan trough expands favorable reef exploration area from original 2×10 km on both sides of Kaijiang-Liangping trough to more than 6×10 km in Yanting-Tongnan trough platform margin belt and Kaijiang-Liangping platform margin belt, greatly enlarging the reef exploration field. But compared to Kaijiang-Liangping trough, Yanting-Tongnan trough is relatively shallower and smaller, and the scale and quality of reef-bank reservoirs in its margin belt is a little poor relatively. Therefore, much research should be done timely such as comparative study of two troughs, detailed research of formation and evolution of the trough, regularity of reef migration, meticulous depiction of reef-bank reservoir size and distribution in order to obtain major breakthroughs around the Yanting-Tongnan trough. [ABSTRACT FROM AUTHOR]

Purpose: MicroRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. We aimed to investigate the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. Methods: miRNA Quantitative real-time PCR was used to detect the different miRNA expression levels between drug resistant and parental cancer cells. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to test the drug-resistant phenotype changes in cancer cells via over or downregulation of miRNAs. Dual-luciferase activity assay was used to verify the target genes of miRNAs. Western blot analysis and apoptosis assay were used to elucidate the mechanism of miRNAs on modulating drug resistance in cancer cells. Results: miR-200bc/429 cluster was downregulated, while BCL2 and XIAP were upregulated in both MDR SGC7901/VCR (vincristine) and A549/CDDP (cisplatin) cells, compared with the parental SGC7901 and A549 cells, respectively. Overexpression of miR-200bc/429 cluster sensitized SGC7901/VCR and A549/CDDP cells to anti-cancer drugs, respectively. Both BCL2 and XIAP 3′-UTR reporters constructed in MDR cells suggested that BCL2 and XIAP were the common target genes of the miR-200bc/429 cluster. Enforced miR-200bc/429 cluster expression reduced BCL2 and XIAP protein level and sensitized both MDR cells to VCR-induced and CDDP-induced apoptosis, respectively. Conclusions: Our findings first suggest that miR-200bc/429 cluster could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part by modulation of apoptosis via targeting BCL2 and XIAP. [ABSTRACT FROM AUTHOR]

• Three lamination types are distinguished in the Upper Ediacaran botryoidal dolostones in Western Yangtze Platform. • EPS and filaments are documented in botryoidal laminae which were previously believed to be abiogenic origin. • Different microbial mineralization types are recognized in different botryoidal laminae. Botryoidal dolostones are abundant in the Second Member of the Upper Ediacaran Dengying Formation in the Western Yangtze Platform. Although they have been extensively discussed as important host rocks for giant gas reservoirs, there is no consensus on the microbial impact on mineralization processes in the botryoidal laminations. Typical botryoidal laminations were studied under optical microscopes and scanning electron microscopes (SEMs) to investigate their origin. There are three macroscopic morphological types of botryoidal lamination: stromatoid lamination, cavity-lining lamination, and spherical-encrusting lamination. These three types of lamination are composed of fibrous and bladed crystals growing perpendicular to the botryoidal laminae, which have hitherto been implicitly considered to be from abiogenic chemical precipitation. There are many lines of new evidence that demonstrate microbial activities in the interbedded dark and bright laminae constituting the laminations. In the dark laminae, euhedral dolomite rhombs are observed sticking to linear and tubular filaments, or wrapped in sheets of extracellular polymeric substances (EPS) with dolomite crystal sizes of generally <5 μm. The bright laminae are dominated by coarser dolomites and connected by radial sheaths and trichomes with dolomite crystal sizes of primarily around 10 μm. Different species of bacteria, which are closely related to the macroscopic morphology of the laminations, are present in both the bright and dark laminae. The results are useful in understanding the origin and formation mechanisms of the Neoproterozoic botryoidal dolostones. The new findings may also shed new light on the occurrence and evolution of early life on Earth in the Precambrian Era. [ABSTRACT FROM AUTHOR]

The Meso-Neoproterozoic period, sometimes referred to as the 'boring billion' or 'Earth's middle age', spans the interval between the formation of the Columbia and Rodina supercontinents. It is regarded as a stable era of the Earth. However, from a global perspective, there are many intensive events of mafic volcanism, dyke intrusions and formation of rift basins recorded in different cratons during this period. This paper focuses on rift basins that developed in three cratons in China (North China, South China and Tarim cratons), because large-scale primary gasfields, as one of the deep resources, have been discovered recently in rocks of Meso-Neoproterozoic age. The formation mechanisms and tectonic settings of these rift basins as the targets of Deep Earth are discussed, based on the restoration of global positions of the three cratons by pre-existing paleomagnetic data and plate reconstruction. We recognise that the rift basins of the North China Craton are related to extrusion tectonics in the southwest Ordos Block or are pull-apart basins along the northern and southern sides of the Ordos Block. The rift basins of the South China Craton are derived from mantle lithospheric delamination of the Jiangnan Orogen in the eastern South China Craton or subduction retreat and backarc opening in the western South China Craton, respectively. The rift basins of the Tarim Craton originated from the backarc opening along the margin of the Supercontinent Rodinia. [ABSTRACT FROM AUTHOR]

Altered energy metabolism is a hallmark of tumors aiming at supplying necessary nutrients for tumorigenesis and development. These redirected metabolic pathways associated with carbohydrate, lipid and amino acid are orchestrated not only by carcinogenic proteins but by non-coding RNAs. Among them, circular RNA (circRNA), as a kind of novel identified non-coding RNAs, has become the focus of attention. Through binding with corresponding microRNAs or directly contacting proteins, circRNA plays a primarily important role in regulating cellular metabolism. Herein, we analyze the emerging findings and select circRNAs contributing to mutant glycolysis, lipogenesis and lipolysis, glutam inolysis, and oxidative respiration to deepen the understanding about the cancer metabolic regulatory network. In addition, we also discuss the possibility of circRNAs exerting their functions via exosomes and cancer stem cells. Owing to their unique structures and wide impacts, circRNAs may help reap huge fruits in developing clinical treatments targeting cancer metabolism. [ABSTRACT FROM AUTHOR]