► The Lungu giant Ordovician condensate represents a mix of early oil and late gas. ► Gas from oil cracking resulted in gas washing of the reservoir. ► The condensate pool contains dry gas, heavy ...oil, abundant aromatics and high wax.
The Lunnan Lower Uplift in the Tarim Basin, NW China contains a composite petroleum system with mainly biodegraded heavy oil in the west, normal oil in the center and gas condensate in the east. Twenty-three gas samples and 37 oil samples taken from three major hydrocarbon bearing intervals in the Lunnan lower bulge were analyzed for their stable carbon isotopes and molecular biomarkers. On the basis of their isotopic compositions, biomarkers, especially diamondoids, and integrating the physical properties of the hydrocarbons including densities, GOR and PVT relationships, it has been concluded that the recently discovered deep (6500
m) eastern Lungu giant Ordovician gas condensate pool with an estimated reserve of 723 million bbl oil equivalent is a secondary hydrocarbon accumulation derived from the mixing of an early formed oil and a late formed gas. The extremely dry gases with a gas dryness of >0.98 were derived from thermal cracking of crude oils and charged to an existing oil reservoir causing extensive gas washing and secondary alteration. Compared with most of the hydrocarbons in the Lunnan area, the gas from the eastern Lungu gas condensate pool has a heavier carbon isotopic composition, higher dryness and a higher maturity level. The unique physical, chemical and isotopic compositions of the gas condensate are believed to be a direct result of gas flushing of an early formed eastern Lungu oil pool by a late formed dry gas from oil cracking. The eastern Lungu gas condensate pool is presently characterized by containing “dry gas, heavy oil, abundant aromatics and high wax”.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Therapeutics targeting osteoclasts are commonly used treatments for bone metastasis; however, whether and how osteoclasts regulate premetastatic niche and bone tropism are largely unknown. In this ...study, we report that osteoclast precursors (OPs) can function as a premetastatic niche component that facilitates breast cancer (BCa) bone metastasis at early stages. At the molecular level, unbiased GPCR ligand/agonist screening in BCa cells suggested that R-spondin 2 (RSPO2) and RANKL, through interaction with their receptor LGR4, promoted osteoclastic premetastatic niche formation and enhanced BCa bone metastasis. This was achieved by RSPO2/RANKL-LGR4 signal modulating the WNT inhibitor DKK1 through Gαq and β-catenin signaling. DKK1 directly facilitated OP recruitment through suppression of its receptor LDL receptor-related protein 5 (LRP5) but not LRP6, upregulating Rnasek expression via inhibition of canonical WNT signaling. In clinical samples, RSPO2, LGR4, and DKK1 expression showed a positive correlation with BCa bone metastasis. Furthermore, soluble LGR4 extracellular domain (ECD) protein, acting as a decoy receptor for RSPO2 and RANKL, significantly alleviated bone metastasis and osteolytic lesions in a mouse bone metastasis model. These findings provide unique insights into the functional role of OPs as key components of the premetastatic niche for BCa bone metastasis and identify RSPO2/RANKL-LGR4 signaling as a promising target for inhibiting BCa bone metastasis.
Siamese trackers demonstrated high performance in object tracking due to their balance between accuracy and speed. Unlike classification-based CNNs, deep similarity networks are specifically designed ...to address the image similarity problem and thus are inherently more appropriate for the tracking task. However, Siamese trackers mainly use the last convolutional layers for similarity analysis and target search, which restricts their performance. In this paper, we argue that using a single convolutional layer as feature representation is not an optimal choice in a deep similarity framework. We present a Multiple Features-Siamese Tracker (MFST), a novel tracking algorithm exploiting several hierarchical feature maps for robust tracking. Since convolutional layers provide several abstraction levels in characterizing an object, fusing hierarchical features allows to obtain a richer and more efficient representation of the target. Moreover, we handle the target appearance variations by calibrating the deep features extracted from two different CNN models. Based on this advanced feature representation, our method achieves high tracking accuracy, while outperforming the standard siamese tracker on object tracking benchmarks.The source code and trained models are available at
https://github.com/zhenxili96/MFST
.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Large to middle-scale thrust structures are important reservoir plays for coal-derived hydrocarbons in the foreland basins of NW China, with both gas and some accompanying oil. In the Dabei Gas Field ...of the Kuqa Thrust, however, the oil and gas pools are vertically distributed in a quite unique way: (1) liquid oil and some dissolved gas are present in the Dawanqi Anticline with the reservoir at 300–700 m depth, forming the only oil field in the Kuqa Thrust; (2) gas and minor accompanying oil are found in the deep reservoir of the Dabei-1 and Dabei-2 thrust traps around 5000–6000 m depth; (3) an extremely dry gas pool is found in the Dabei-3 thrust trap where the depth of the reservoir is over 7000 m. Geochemical data suggest that the hydrocarbons in the Dawanqi Anticline and the Dabei thrust traps originated from a similar source, i.e. the underlying Jurassic coal measures, with some contribution from Jurassic lacustrine shales. The Jurassic source rocks did not start to generate oil until the Miocene (around the Kangcun Stage), and extended into the Pliocene (the Kuche Stage) with the main gas generation period in the Pliocene (the Kuche Stage) and the Quaternary. Because the traps formed relatively early, the Dabei-1 and Dabei-2 thrusts could trap some of the early generated oils, but most of the early charged oil was redistributed to the shallower Dawanqi Anticline during the Kuche Stage. The Dabei-3 thrust trap formed concurrently with major gas generation and thus could not trap liquid hydrocarbons. The difference in the vertical distribution of the hydrocarbon accumulations in the Dabei Gas Field resulted from a complex interplay of source variability, structural evolution of the basin and thermal maturation.
► The unique vertical distribution of hydrocarbon has been described and discussed. ► Three types of oils have been identified based on geochemistry data. ► Hydrocarbon charge history has been rebuilt based on basin modeling. ► GC × GC-TOFMS method has been used to detect PAH and diamondoid hydrocarbons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is ...essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.
Transforming growth factor beta (TGFβ), which is implicated in metastasis to various organs in breast cancer, is a potential target for new antitumor metastasis drugs.
To identify specific inhibitors ...of TGFβ receptor 1 (TGFβR1) in breast cancer metastasis, a virtual library of more than 400000 different compounds was screened by molecular docking modeling and confirmed with Smad-binding element luciferase and TGFβR1 kinase assays. Affymetrix GeneChip expression analysis of mRNA levels and real-time polymerase chain reaction were performed to determine expression changes of TGFβ-mediated, metastasis-associated genes in breast cancer cells after treatment with the small-molecule inhibitor YR-290. YR-290 was also examined for its effects on breast cancer migration, invasion, and metastasis using transwell and epithelial-to-mesenchymal transition (EMT) assays in vitro and three different mouse (BALB/c and NU/NU nude) models (n = 10 per group). Kaplan-Meier analyses were used to assess survival. All statistical tests were two-sided.
YR-290 interacted with the kinase domain of TGFβR1, abrogated kinase activity (half maximal inhibitory concentration = 137nM, 95% confidence interval = 126.4 to 147.6nM) and inhibited the TGFβ-mediated downstream signaling pathway and metastasis-associated genes in breast cancer cells. YR-290 inhibited TGFβ-modulated breast cancer cell migration and invasion. In tumor metastasis mouse models, YR-290 almost completely blocked cancer metastasis. Numbers of lung tumor nodules of mice treated with 1mg/kg and 5mg/kg YR-290 were reduced by 74.93% (95% confidence interval = 61.45% to 88.41%) and 94.93% (95% confidence interval = 82.13% to 100%), respectively, compared with control mice. Treatment with YR-290 also statistically significantly prolonged the survival of tumor-bearing mice.
YR-290 is a novel inhibitor of tumor metastasis that works by blocking TGFβ signaling pathways.
Highlights ► Nitidine Chloride inhibits breast cancer cells migration and invasion. ► NC reduces protrusion formation and proteolytic activity of MMP-9 and MMP-2. ► PDGF induced signaling and AP-1 ...transcriptional activity was decreased by NC. ► NC could have potential as a novel anti-metastasis drug to breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•MiR-126-5p was expressed at low level in GCT.•MMP-13 is consistently and highly expressed by the GCTSCs in GCT.•MiR-126-5p could negatively regulate MMP-13 expression.•MiR-126-5p can regulate OC ...differentiation and osteolysis formation in GCT.
Giant cell tumor (GCT) of bone is an aggressive skeletal tumor characterized by localized bone resorption. Matrix metalloproteinase-13 (MMP-13) is the principal proteinase expressed by the stromal cells of GCT (GCTSCs) and also considered to play a crucial role in formation of the osteolytic lesion in GCT. However, the exact mechanism of the regulation of MMP-13 expression in GCTSCs was unknown. In this study, we identified miR-126-5p was significantly downregulated in GCTSCs and affect osteoclast (OC) differentiation and bone resorption by repressing MMP-13 expression at the post-transcriptional level. Thus, our studies show that miR-126-5p plays an important physiological role in multinucleated giant cell formation and osteolytic lesion in GCT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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