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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]

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]

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]

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]

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]

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]

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]

• 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]