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Abstract Background Circular RNAs (circRNAs) have been reported to be involved in the initiation and development of cancers. The aim of this study was to determine the role of a circRNA, circ_0020123, in the development of non‐small cell lung cancer (NSCLC). Methods The expression of circ_0020123, microRNA‐146a‐5p (miR‐146a‐5p), and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) mRNA was detected by quantitative real‐time PCR (qPCR). Western blot was used to determine the protein levels of cyclin D1, Bax, MMP‐9, and EIF4G2. Cell proliferation was assessed by cell counting kit‐8 (CCK‐8) assay and colony formation assay. Flow cytometry assay was applied to determine cell cycle apoptosis. Cell migration and invasion were assessed using transwell assay. The potential relationship between miR‐146a‐5p and circ_0020123 or EIF4G2 was ascertained by dual‐luciferase reporter assay and RIP assay. The role of circ_0020123 in vivo was explored by xenograft assay. Results Circ_0020123 was upregulated in NSCLC, and circ_0020123 knockdown repressed proliferation, migration, and invasion of NSCLC cells. Circ_0020123 targeted miR‐146a‐5p, and miR‐146a‐5p inhibitor reversed the effects of circ_0020123 knockdown on NSCLC cells. In addition, miR‐146a‐5p suppressed cell proliferation, migration, and invasion by targeting EIF4G2. Moreover, the antitumor role of circ_0020123 knockdown was verified in vivo. Conclusion Knockdown of circ_0020123 inhibited NSCLC cell progression and tumor growth by targeting the miR‐146a‐5p/EIF4G2 axis.

The proficient application of multistage fracturing methods enhances the status of the Duvernay shale formation as a highly esteemed shale reservoir on a global scale. Nevertheless, the challenge is in accurately characterizing unconventional fracture behavior and predicting shale productivity due to the complex distributions of natural fractures, pre-existing faults, and reservoir heterogeneity. The present study puts forth a Geo-Engineering approach to comprehensively investigate the Duvernay shale reservoir in the vicinity of Crooked Lake. To begin with, on the basis of the experimental results and well-logging interpretations, a high-quality petrophysical and geomechanical model is constructed. Subsequently, the establishment of an unconventional fracture model (UFM) takes into account the heterogeneity of the reservoir and the interactions between hydraulic fractures and pre-existing natural fractures/faults and is further validated by 18,040 microseismic events. Finally, the analysis of well productivity is conducted by numerical simulations, revealing that the agreement between the simulated and observed production magnitudes exceeds 89%. This paper will guide the efficient development of increasingly important unconventional shale resources.

BackgroundLung squamous cell carcinoma (LUSC) is a devastating and difficult-to-treat type of lung cancer, and the prognosis of LUSC is the worst. The functional roles of focal adhesion-related genes were explored in LUSC based on data from The Cancer Genome Atlas (TCGA).MethodsRNA sequencing data and clinical characteristics of LUSC patients in TCGA-LUSC were obtained from the TCGA database. Through systematic analysis, we screened the prognostic genes and determined the focal adhesion-related pathways closely associated with LUSC.ResultsWe identified 444 prognostic genes and focal adhesion-related pathways intimately associated with LUSC. According to the focal adhesion-related genes, TCGA-LUSC patients were well divided into two groups: the low-risk group (G1) and the high-risk group (G2). A differential expression analysis identified 44 differentially expressed genes (DEGs) upregulated in the low-risk G1 group and 379 DEGs upregulated in the high-risk G2 group. The upregulated DEGs in the G1 group were primarily related to tyrosine metabolism, steroid hormone biosynthesis, retinol metabolism, platinum drug resistance, pentose and glucuronate interconversions, and metabolism of xenobiotics by cytochrome P450, while the downregulated DEGs in the G1 group were primarily related to ECM-receptor interaction, focal adhesion, proteoglycans in cancer, small cell lung cancer, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. The immune activity of the G1 group was lower than that of the G2 group, and the half-maximal inhibitory concentration (IC50) of five chemotherapy drugs (i.e., gemcitabine, methotrexate, vinorelbine, paclitaxel, and cisplatin) was significantly different between the G1 and G2 groups. Furthermore, a 10-gene prognostic model was constructed to predict the prognosis for LUSC patients: ITGA3, VAV2, FLNC, FLT4, HGF, MYL2, ITGB1, PDGFRA, CCND2, and PPP1CB.ConclusionThe status of focal adhesion-related genes has a close relationship with tumor classification and immunity in LUSC patients. A novel focal adhesion-related signature had good prognostic and predictive performance for LUSC. Our findings may provide new insight into the diagnosis and treatment of LUSC.

Abstract The recent remarkable increase in induced seismicity in Western Canada has been largely attributed to hydraulic fracturing in unconventional reservoirs. The nucleation of large magnitude events has been demonstrated to be closely linked to site-specific geological and operational factors. A mitigation strategy of fracturing-induced seismicity concerning both factors has not been well investigated. In this paper, a comprehensive investigation of risk mitigations from induced seismicity is conducted based on the formation overpressure, distance to Precambrian basement, proximity to faults, fracturing job size and safe hydraulic fracture-fault distance. It is found that the middle-south region near Crooked Lake is an optimal region for fracturing operations with low formation pressure, a great distance to the basement and relatively fewer pre-existing faults. A field case study suggests that fracturing operations of three new horizontal wells are successful with low magnitude induced events and with high production performance, demonstrating the applicability of a comprehensive approach of seismicity risk mitigations. Such an approach can be applied to other field cases to mitigate the potential fracturing-induced seismicity in unconventional reservoirs.

In the development of unconventional shale resources, production forecasts are fraught with uncertainty, especially in the absence of a full, multi-data study of reservoir characterization. To forecast Duvernay shale gas production in the vicinity of Fox Creek, Alberta, the multi-scale experimental findings are thoroughly evaluated. The relationship between shale gas production and reservoir parameters is assessed using multiple linear regression (MLR). Three hundred and five core samples from fifteen wells were later examined using the MLR technique to discover the fundamental controlling characteristics of shale potential. Quartz, clay, and calcite were found to comprise the bulk of the Duvernay shale. The average values for the effective porosity and permeability were 3.96% and 137.2 nD, respectively, whereas the average amount of total organic carbon (TOC) was 3.86%. The examined Duvernay shale was predominantly deposited in a gas-generating timeframe. As input parameters, the MLR method calculated the components governing shale productivity, including the production index (PI), gas saturation (Sg), clay content (Vcl), effective porosity (F), total organic carbon (TOC), brittleness index (BI), and brittle mineral content (BMC) (BMC). Shale gas output was accurately predicted using the MLR-based prediction model. This research may be extended to other shale reservoirs to aid in the selection of optimal well sites, resulting in the effective development of shale resources.

Abstract Historically, the Duvernay East Shale Basin had been regarded as a seismicity‐quiescent region. However, an ML 4.18‐magnitude earthquake on 04/03/2019 was triggered due to hydraulic fracturing of two horizontal wells. The physical mechanism and controlling factors of this large‐magnitude earthquake are not well understood. In this work, the coupled modeling of the ML 4.18 case is conducted to quantify the poroelastic effects during fluid injection and to reveal the triggering mechanism of this earthquake cluster. Additional simulations of tested cases with different hydraulic, geomechanical, and operational parameters are also conducted to quantify the effects of these factors on hydraulically induced seismicity. It is found that the hydraulic fractures of two wells propagated within the Duvernay formation and connected with the inferred fault. The increase in pore pressure reduced the shear stress of the fault and caused the fault slip. The hydraulically induced seismicity is susceptible to the low permeable injection layer and high‐permeable fault, less rigid fault with low‐Biot's coefficient, large fluid injection, and proximity of hydraulic fracturing‐fault distance. Enlarging the distance between the stimulated well and seismogenic fault is the first‐order choice to mitigate seismic risks. Under the proximity of well‐fault distance, reducing the fracturing size job would be an effective approach to reduce the expected magnitude of hydraulically induced seismicity.

An integrated hydraulic fracturing followed by waterflooding was conducted in a heterogeneous sandstone formation in the Northern Shanxi Slop of Ordos Basin in Western China. Water breakthrough quickly occurred, and the underlying mechanism of water breakthrough has not been well understood. Such mechanism needs to be investigated comprehensively from the spatial connectivity of multilayer sand bodies and characterization of hydraulic-natural fracture networks. Here, an integrated approach is proposed to tap the remaining oil in the individual sand layer during the late-stage development of tight sandstone reservoirs. A case study is utilized to demonstrate the applicability of the integrated method. It is found that the six sand layers could be further divided within the target oil layers. These sand layers have a variety of physical and mechanical properties, leading to the asymmetric spatial distribution of hydraulic fractures after performing the integrated fracturing of whole oil layers. The spatial difference of sand bodies conforms to the features of the multiperiod superimposed channel in the sedimentary environment of fan delta front. The natural fractures were generated from the tectonic movement in the Mesozoic period with a dominant orientation of approximately NE 67°. The asymmetric hydraulic fractures propagated and connected with the preexisting natural fractures, forming the intricate natural-hydraulic fracture networks. The water breakthrough pattern in each sand layer is primarily ascribed to the spatial distribution of the hydraulic-natural fracture networks and sedimentary microfacies. The refracturing operations based on the remaining oil distribution in sand layers are proven to be effective in further developing the formation. The average oil production of related wells increased from 0.61 t/d to 2.18 t/d. This practical development strategy provides insights for further development of likewise heterogeneous tight sandstone reservoirs.

Heart failure (HF) is a heterogeneous clinical syndrome with a variety of causes, risk factors, and pathology. Clinically, only brain natriuretic peptide (BNP) or its precursor N-terminus proBNP (NTproBNP) has been validated for HF diagnosis, but they are also affected by other conditions, such as female gender, renal disease, and acute coronary syndromes, and false low levels in the setting of obesity or flash pulmonary edema. In addition, there is no one biomarker which could encompass all heart failure phenotypes. Advances in bioinformatics have provided us with large databases that characterize the complex genetic and epigenetic changes associated with human diseases. The use of data mining strategies on public access databases to identify previously unknown disease markers is an innovative approach to identify potential biomarkers or even new therapeutic targets in complex diseases such as heart failure (HF). In this study, we analyzed the genomic and transcription data of HF peripheral blood mononuclear cell (PBMC) samples obtained from the Gene Expression Omnibus data sets using Omicsbean online database (http://www.omicsbean.cn/) and found that the prostaglandin-endoperoxide synthase 2 (PTGS2), also named as cyclooxygenase-2 (COX-2), as well as its related micro RNAs including miR-1297 and miR-4649-3p might be used as potential biomarkers for non-ischemic heart failure. Our result showed that plasma COX-2 and miR-4649-3p were significantly up-regulated, whereas the plasma miR-1297 was significantly decreased, and miR-4649-3p displayed high predictive power for non-ischemic heart failure.

Abstract Background Drug-eluting balloons (DEB) have significant value for treating coronary artery disease (CAD). However, the merits of using DEB versus drug-eluting stents (DES) to treat CAD remain controversial. Herein, we conducted a meta-analysis to compare the safety and efficacy of DEB and DES for treatment of CAD. Methods We searched MEDLINE, EMBASE, and CENTRAL databases for eligible trials comparing DEB with DES for treatment of CAD. The primary endpoint was major adverse cardiac events (MACE); the secondary endpoints included in-lesion late lumen loss (LLL), binary restenosis (BR), myocardial infarction (MI), target lesion revascularization (TLR) and mortality. Results Twenty-three trials with a total of 2712 patients were included. There were no significant differences in the primary endpoint of MACE between the DEB and DES groups (Risk Ratio (RR) 1.19; 95% confidence interval (CI) (0.87, 1.63); P = 0.27), or in the clinical outcomes of each of MACE’s components, including TLR, MI and mortality. However, efficacy was significantly different between the DEB and DES groups, especially when we compared DEB to second-generation DES: in-lesion LLL (Mean Difference (MD) 0.11; (0.01, 0.22); P = 0.03); binary restenosis (RR 1.46; (1.00, 2.13); P = 0.05). Conclusions DEB is equivalent to DES in terms of safety for managing CAD, and DEB may be considered as an alternative choice for treatment of CAD.

Hypertension is a significant global public health problem and recognized as an important risk factor for cardiovascular diseases. This study was designed to assess the current prevalence of hypertension and to explore risk factors associated with hypertension by urban and rural status to guide the prevention and control of hypertension in Jilin province.A multi-stage stratified random cluster sampling method was used to obtain data on hypertension, which was investigated by physical examination and face-to-face questionnaire in July 2014-December 2015. Sample data were analyzed by complex weighted statistical analysis to estimate blood pressure levels and prevalence of hypertension in the province. Multivariable logistic regression analysis was used to identify factors influencing hypertension rates.The prevalence of hypertension was significantly higher in rural areas than urban areas (25.93% versus 22.73%, respectively). The rates of hypertension known (46.7% versus 38.1%, respectively), control (13.7% versus 5.0%, respectively), and controlled among treated subjects (38.3% versus 17.5%, respectively) were higher in urban areas than in rural areas (all p < 0.001), while the treatment rate was not statistically significantly different between urban and rural areas (35.9% versus 28.4%, respectively). After adjusting for demographic covariates, hypertension prevalence in rural areas was still significantly greater than in urban areas (adjusted OR = 1.22; 95%CI: 1.10, 1.36; p < 0.001). Common risk factors for hypertension among urban and rural residents included older age; male; married; employed; less education; overweight/obese; greater abdominal waist circumference; family history of hypertension, stroke, or coronary heart disease; current smoker; alcohol consumption; higher visceral adiposity index; and higher body fat percentage.This study identified an increased risk for hypertension in rural regions of Jilin province, suggesting that rural hypertension screening and treatment guidelines should receive greater attention.

Based on the dynamic characteristics of water-flooding in ultra-low permeability oilfields, the concept of dynamic fracture is proposed and its formation mechanism and impacts on oilfield development are discussed. Dynamic fractures refer to the new-generated fracture channels when bottom hole pressure exceeds rock breakdown pressure and propagation pressure, or the effective fracture channels generated when the originally closed or filled natural fractures are reactivated, due to high pressure in near wellbore area of injection well in a long term water injection of the ultra-low permeability reservoir. Dynamic fractures, controlled by the current stress field, constantly extend toward the direction of the oil well with the rise of the injected water volume and bottom hole pressure, until connecting with the oil well hydraulic fractures. The analysis of the sealed coring well groups L76-60 and L88-40 located in the same block in the JA Oilfield, Changqing Oilfield, NW China shows that the dynamic fractures changed the seepage characteristics of water displacing oil in the ultra-low permeability reservoir, greatly aggravated the reservoir heterogeneity, which led to the reduction of profile producing degree and the distribution of remaining oil on both sides of the fractures in continuous or discontinuous belts. The generation and propagation of dynamic fractures are closely related to water injection pressure, injection-production ratio, oil and water well stimulation measures. When the porosity-permeability condition of the matrix allows effective oil displacement, high pressure water injection or oil and water well stimulation measures should be avoided as far as possible. Key words: dynamic fracture, ultra-low permeability reservoir, development geological attribute, formation mechanism, water-flooding swept volume

Chitin deacetylase (CDA) is a chitin degradation enzyme that catalyzes the conversion of chitin to chitosan by the deacetylation of N-acetyl-D-glucosamine residues, playing an important role in the high-value utilization of waste chitin. The shells of shrimp and crab are rich in chitin, and mangroves are usually recognized as an active habitat to shrimp and crab. In the present study, a CDA-producing bacterium, strain TCI-16, was isolated and screened from the mangrove soil. Strain TCI-16 was identified and named as Bacillus aryabhattai TCI-16, and the maximum CDA activity in fermentation broth reached 120.35 ± 2.40 U/mL at 36 h of cultivation. Furthermore, the complete genome analysis of B. aryabhattai TCI-16 revealed the chitin-degrading enzyme system at genetic level, in which a total of 13 putative genes were associated with carbohydrate esterase 4 (CE4) family enzymes, including one gene coding CDA, seven genes encoding polysaccharide deacetylases, and five genes encoding peptidoglycan-N-acetyl glucosamine deacetylases. Amino acid sequence analysis showed that the predicted CDA of B. aryabhattai TCI-16 was composed of 236 amino acid residues with a molecular weight of 27.3 kDa, which possessed a conserved CDA active like the known CDAs. However, the CDA of B. aryabhattai TCI-16 showed low homology (approximately 30%) with other microbial CDAs, and its phylogenetic tree belonged to a separate clade in bacteria, suggesting a high probability in structural novelty. In conclusion, the present study indicated that the novel CDA produced by B. aryabhattai TCI-16 might be a promising option for bioconversion of chitin to the value-added chitosan.

By using equipment such as time-lapse cameras and 3D laser scanners, this study conducted flume simulation experiments to obtain topographic elevation, the amount of sediment increment, sedimentary cross sections, and other related data and diagrams. Quantitative software was then utilized for sedimentological analysis to clarify the depositional evolution, architecture, and depositional model of lobate shallow-water deltas. The research results show that under the influence of hydraulic conditions and main distributary channels, lobate shallow-water deltas primarily undergo three evolution stages: initial channel formation, distributary channel system formation, and continuous stable evolution stage. The architecture elements of lobate shallow-water deltas can be divided into distributary channels dominated by channel deposition, proximal river mouth bars, transitional bars, and distal bars. The lateral composition and downstream deposition of the river-bar combination are the main structural units of the shallow water delta. The proximal profile distributary channels exist in the form of thick channel sand bodies with multiple repetitive intercalation cycles, and thick proximal bar deposits form on both sides of the distributary channels. The bifurcation of distributary channels in the middle profile leads to a reduction in channel scale, while large-scale proximal bars still develop on both sides of the channel. In the distal profile, a substantial river mouth bar complex is formed at the break of the delta front slope, and with the gradual progradation of the delta, the river mouth bar deposition zone becomes flattened. Based on the insights of the flume simulation experiments, a sedimentary model for lobate shallow-water delta was established. [ABSTRACT FROM AUTHOR]

The intricate interplay between biomechanical and biochemical pathways in modulating morphogenesis is an interesting research topic. How biomechanical force regulates epithelial cell tubulogenesis remains poorly understood. Here, we established a model of tubulogenesis by culturing renal proximal tubular epithelial cells on a collagen gel while manipulating contractile force. Epithelial cells were dynamically self-organized into tubule-like structures by augmentation of cell protrusions and cell-cell association. Reduction and asymmetric distribution of phosphorylated myosin light chain 2, the actomyosin contractility, in cells grown on soft matrix preceded tube connection. Notably, reducing matrix stiffness via sonication of collagen fibrils and inhibiting actomyosin contractility with blebbistatin promoted tubulogenesis, whereas inhibition of cytoskeleton polymerization suppressed it. CXC chemokine ligand 1 (CXCL1) expression was transcriptionally upregulated in cells undergoing tubulogenesis. Additionally, inhibiting actomyosin contractility facilitated CXCL1 polarization and cell protrusions preceding tube formation. Conversely, inhibiting the CXCL1-CXC receptor 1 pathway hindered cell protrusions and tubulogenesis. Mechanical property asymmetry with cell-collagen fibril interaction patterns at cell protrusions and along the tube structure supported the association of anisotropic contraction with tube formation. Furthermore, suppressing the mechanosensing machinery of integrin subunit beta 1 reduced CXCL1 expression, collagen remodeling, and impaired tubulogenesis. In summary, symmetry breaking of cell contractility on a soft collagen gel promotes CXCL1 polarization at cell protrusions which in turn facilitates cell-cell association and thus tubule connection. [ABSTRACT FROM AUTHOR]