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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]

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]

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]

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]

Drug resistance of cancer cells can be regulated by the dysregulated miRNAs, and sustained NFκB activation also plays an important role in tumor resistance to chemotherapy. Here, we sought to investigate whether there was a correlation between miR-20a and the NFκB pathway to clarify the effects that miR-20a exerted on gastric cancer (GC) chemoresistance. We found that miR-20a was significantly upregulated in GC plasma and tissue samples. In addition, it was upregulated in GC plasma and tissues from patients with cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP). And the upregulation of miR-20a was concurrent with the downregulation of NFKBIB (also known as IκBβ) as well as upregulation of p65, livin, and survivin. The luciferase activity suggested that NFKBIB was the direct target gene of miR-20a. Transfection of miR-20a inhibitor could increase NFKBIB level; downregulate the expression of p65, livin, and survivin; and lead to a higher proportion of apoptotic cells in SGC7901/DDP cells. Conversely, ectopic expression of miR-20a dramatically decreased the expression of NFKBIB; increased the expression of p65, livin, and survivin; and resulted in a decrease in the apoptosis induced by DDP in SGC7901 cells. Taken together, our findings suggested that miR-20a could promote activation of the NFκB pathway and downstream targets livin and survivin by targeting NFKBIB, which potentially contributed to GC chemoresistance. [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]

MicroRNAs (miRNAs) are short non-coding RNA molecules, which posttranscriptionally regulate genes expression and play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. Here, we investigated the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines. We found that miR-497 was downregulated in both multidrug-resistant human gastric cancer cell line SGC7901/vincristine (VCR) and multidrug-resistant human lung cancer cell line A549/cisplatin (CDDP) and the downregulation of miR-497 was concurrent with the upregulation of BCL2 protein, compared with the parental SGC7901 and A549 cell lines, respectively. In vitro drug sensitivity assay demonstrated that overexpression of miR-497 sensitized SGC7901/VCR and A549/CDDP cells to anticancer drugs, respectively. The luciferase activity of BCL2 3′-untranslated region-based reporter constructed in SGC7901/VCR and A549/CDDP cells suggested that BCL2 was the direct target gene of miR-497. Enforced miR-497 expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively. Taken together, our findings first suggested that has-miR-497 could play a role in both gastric and lung cancer cell lines at least in part by modulation of apoptosis via targeting BCL2. [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]

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]

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]

The differential expression of microRNAs (miRNAs) in plasma of gastric cancer (GC) patients may serve as a diagnostic biomarker. A total of 33 miRNAs were identified through the initial screening phase (3 GC 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-V1.M). By qRT-PCR, these miRNAs were further assessed in training (30 GC VS. 30 NCs) and testing stages (71 GC VS. 61 NCs). We discovered a plasma miRNA signature including five up-regulated miRNAs (miR-185, miR-20a, miR-210, miR-25 and miR-92b), and this signature was evaluated to be a potential diagnostic marker of GC. The areas under the receiver operating characteristic curve of the signature were 0.86, 0.74 and 0.87 for the training, testing and the external validation stages (32 GC VS. 18 NCs), respectively. The five miRNAs were consistently dysregulated in GC tissues (n = 30). Moreover, miR-185 was decreased while miR-20a, miR-210 and miR-92b were increased in arterial plasma (n = 38). However, none of the miRNAs in the exosomes showed different expression between 10 GC patients and 10 NCs. In conclusion, we identified a five-miRNA signature in the peripheral plasma which could serve as a non-invasive biomarker in detection of GC. [ABSTRACT FROM AUTHOR]