Based on the drilling, logging, experimental and testing data of Well PD1, a shallow normal-pressure shale gas well in the Laochangping anticline in southeastern Sichuan Basin, the shallow shale gas ...reservoirs of the Ordovician Wufeng Formation to Silurian Longmaxi Formation (Wufeng–Longmaxi) were investigated in terms of geological characteristics, occurrence mechanism, and adsorption-desorption characteristics, to reveal the enrichment laws and high-yield mechanism of shallow normal-pressure shale gas in complex structure areas. First, the shallow shale gas reservoirs are similar to the medium–deep shale gas reservoirs in static indicators such as high-quality shale thickness, geochemistry, physical properties and mineral composition, but the former is geologically characterized by low formation pressure coefficient, low gas content, high proportion of adsorbed gas, low in-situ stress, and big difference between principal stresses. Second, shallow shales in the complex structure areas have the gas occurrence characteristics including low total gas content (1.1–4.8 m3/t), high adsorbed gas content (2.5–2.8 m3/t), low sensitive desorption pressure (1.7–2.5 MPa), and good self-sealing. Third, the adsorbed gas enrichment of shales is mainly controlled by organic matter abundance, formation temperature and formation pressure: the higher the organic matter abundance and formation pressure, the lower the formation temperature and the higher the adsorption capacity, which is more beneficial for the adsorbed gas occurrence. Fourth, the shallow normal-pressure shale gas corresponds to low sensitive desorption pressure. The adsorbed gas can be rapidly desorbed and recovered when the flowing pressure is reduced below the sensitive desorption pressure. Fifth, the exploration breakthrough of Well PD1 demonstrates that the shallow complex structure areas with adsorbed gas in dominance can form large-scale shale reservoirs, and confirms the good exploration potential of shallow normal-pressure shale gas in the margin of the Sichuan Basin.
Sirtuin 1 (SIRT1), an NAD
-dependent deacetylase, is a key regulator of cellular metabolism. Recent genome-wide association studies identified genetic variants of SIRT1 linked to major depressive ...disorders. SIRT1 is widely expressed in the brain; however, neuronal substrates that mediate SIRT1 action on depressive behaviors remain largely unknown. Here we show that selective deletion of SIRT1 in forebrain excitatory neurons causes depression-like phenotypes in male but not female mice. AAV-Cre-mediated SIRT1 knockdown in the medial prefrontal cortex (mPFC) of adult male mice induces depressive-like behaviors. Whole-cell patch-clamp recordings demonstrate that loss of SIRT1 decreases intrinsic excitability and spontaneous excitatory synaptic transmission in layer V pyramidal neurons in the prelimbic mPFC. Consistent with neuronal hypoexcitability, SIRT1 knockout reduces mitochondrial density and expression levels of genes involved in mitochondrial biogenesis and dynamics in the prelimbic mPFC. When a SIRT1 activator (SRT2104) is injected into the mPFC or lateral ventricle of wild-type mice, it reverses chronic unpredictable stress-induced anhedonia and behavioral despair, indicating an antidepressant-like effect. These results suggest that SIRT1 in mPFC excitatory neurons is required for normal neuronal excitability and synaptic transmission and regulates depression-related behaviors in a sex-specific manner.
In this paper, we study the Cauchy problem for the one-dimensional Euler-Poisson (or hydrodynamic) model for semiconductors, where the energy equation is replaced by a pressure-density relation. ...First, the existence of global entropy solutions is proved by using the vanishing artificial viscosity method, where, a special flux approximate is introduced to ensure the uniform boundedness of the electric field E and the a-priori L∞ estimate, 0<2δ≤ρε,δ≤M(t),|uε,δ|≤M(t), where M(t) could tend to infinity as the time t tends to infinity, on the viscosity-flux approximate solutions (ρε,δ,uε,δ); Second, the compensated compactness theory is applied to prove the pointwise convergence of (ρε,δ,uε,δ) as ε,δ go to zero, and that the limit (ρ(x,t),u(x,t)) is a global entropy solution; Third, a technique, to apply the maximum principle to the combination of the Riemann invariants and ∫−∞xρε,δ(x,t)−2δdx, deduces the uniform L∞ estimate, 0<2δ≤ρε,δ≤M,|uε,δ|≤M, independent of the time t and ε,δ; Finally, as a by-product, the known compactness framework 14,29 is applied to show the relaxation limit, as the relation time τ and ε,δ go to zero, for general pressure P(ρ).
Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired ...drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival. Knockdown DUSP6 inhibited GC proliferation, migration, invasion and induced apoptosis. (E/Z)-BCI hydrochloride (BCI), a DUSP6 small molecule inhibitor, increased the activity of ERK but interestingly decreased the expression of ERK response genes in BGC823, SGC7901 and CDDP-resistant SGC7901/DDP cells. BCI also caused cell death through the DNA damage response (DDR) pathway. Moreover, BCI inhibited cell proliferation, migration and invasion in a receptor-independent manner and enhanced CDDP cytotoxicity at pharmacological concentrations in the GC cells. In vivo experiments further showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models. In summary, our findings indicated that disruption of DUSP6 by BCI enhanced CDDP-induced cell death and apoptosis in GC may partly through ERK and DDR pathways. Thus, this study suggests that DUSP6 is a potential prognostic biomarker and a promising target for GC therapy.
•DUSP6 was overexpressed and promote proliferation, metastasis and predict poor prognosis in GC.•BCI inhibited cell proliferation, migration and invasion and enhanced CDDP cytotoxicity in GC through DUSP6.•In vivo experiments showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models.•BCI enhanced CDDP-induced cell death and apoptosis may partly through ERK and DDR pathways in GC.
The secularization paradigm suggests that economic development should lead to the decline of clerical influence in politics. However, this suggestion is challenged by the fact that there is ...widespread support for clerics who try to transform politics according to religious precepts in many developed societies. In order to address this question, the present study examines how national economic development moderates the relationship between individual-level religiosity and attitudes towards clerical influence in politics, using the fourth and fifth waves of the World Values Survey data from 54 national samples. Multilevel regression models show that, first, religious individuals are more likely to support clerics’ political influence than nonreligious individuals. Moreover, the effects of individual religiosity in this regard depend on the economic context. In less developed societies, there is no significant difference between religious and nonreligious individuals regarding their attitudes toward clerical influence in politics. However, religious individuals become more supportive of clerical influence in politics in more developed countries.
Leptin is an adipocyte-derived hormone with pleiotropic functions affecting appetite and mood. While leptin's role in the regulation of appetite has been extensively studied in hypothalamic neurons, ...its function in the hippocampus, where it regulates mood-related behaviors, is poorly understood. Here, we show that the leptin receptor (LepRb) colocalizes with brain-derived neurotrophic factor (BDNF), a key player in the pathophysiology of major depression and the action of antidepressants, in the dentate gyrus of the hippocampus. Leptin treatment increases, whereas deficiency of leptin or leptin receptors decreases, total Bdnf mRNA levels, with distinct expression profiles of specific exons, in the hippocampus. Epigenetic analyses reveal that histone modifications, but not DNA methylation, underlie exon-specific transcription of the Bdnf gene induced by leptin. This is mediated by stimulation of AKT signaling, which in turn activates histone acetyltransferase p300 (p300 HAT), leading to changes in histone H3 acetylation and methylation at specific Bdnf promoters. Furthermore, deletion of Bdnf in the dentate gyrus, or specifically in LepRb-expressing neurons, abolishes the antidepressant-like effects of leptin. These findings indicate that leptin, acting via an AKT-p300 HAT epigenetic cascade, induces exon-specific Bdnf expression, which in turn is indispensable for leptin-induced antidepressant-like effects.
Galectins are involved in the regulation of divergent physiological and pathological processes and are increasingly recognized to play important roles in a number of diseases. However, a simple and ...effective way in assessing galectin-ligand interactions is lacking. Our examination of the sequence of all 12 human galectin members reveals the presence of one or more tryptophan residues in the carbohydrate-recognition domains of each galectin. This led us to investigate the possibility that alteration of the galectin intrinsic tryptophan fluorescence could be used in determining the strength of galectin-ligand interactions. One representative member from each of the three subtype galectins, galectin-2 (proto-), galectin-3 (chimera-) and galectin-4 (tandem repeat-type), was selected and analysed for galectin interaction with three ligands of different affinities: galactose, lactose and N-acetyl-lactosamine using tryptophan fluorescence spectroscopy (TFS) and, as a comparison, isothermal titration calorimetry (ITC). Good agreement between TFS and ITC measurements were revealed in ligand bindings of all galectin members. Moreover, TFS detected very weak galectin binding where ITC could not reliably do so. The reliability of TFS in determining galectin-ligand interactions was further validated by analysis of galectin-3 interaction with a semisynthetic ligand, F3. Thus, TFS can be used as a simple, sensitive and reliable way to determine galectin-ligand interactions and also as a drug-discovery platform in developing galectin-targeted therapeutic drugs.
Astragaloside IV (AsIV), an active ingredient isolated from traditional Chinese medicine astragalus membranaceus, is beneficial to cardiovascular health. This study aimed to characterize the ...functional role of AsIV against adriamycin (ADR)-induced cardiomyopathy. Here, healthy rats were treated with ADR and/or AsIV for 35 days. We found that AsIV protected the rats against ADR-induced cardiomyopathy characterized by myocardial fibrosis and cardiac dysfunction. Meanwhile, ADR increased type I and III collagens, TGF-β, NOX2, and NOX4 expression and SMAD2/3 activity in the left ventricles of rats, while those effects were countered by AsIV through suppressing oxidative stress. Moreover, ADR was found to promote cardiac ferroptosis, whereas administration of AsIV attenuated the process via activating Nrf2 signaling pathway and the subsequent GPx4 expression increasing. These results suggest that AsIV might play a protective role against ADR-induced myocardial fibrosis, which may partly attribute to its anti-ferroptotic action by enhancing Nrf2 signaling.
Theory and Application of Multiphase Lattice Boltzmann Methods presents a comprehensive review of all popular multiphase Lattice Boltzmann Methods developed thus far and is aimed at researchers and ...practitioners within relevant Earth Science disciplines as well as Petroleum, Chemical, Mechanical and Geological Engineering. Clearly structured throughout, this book will be an invaluable reference on the current state of all popular multiphase Lattice Boltzmann Methods (LBMs). The advantages and disadvantages of each model are presented in an accessible manner to enable the reader to choose the model most suitable for the problems they are interested in. The book is targeted at graduate students and researchers who plan to investigate multiphase flows using LBMs. Throughout the text most of the popular multiphase LBMs are analyzed both theoretically and through numerical simulation. The authors present many of the mathematical derivations of the models in greater detail than is currently found in the existing literature. The approach to understanding and classifying the various models is principally based on simulation compared against analytical and observational results and discovery of undesirable terms in the derived macroscopic equations and sometimes their correction. A repository of FORTRAN codes for multiphase LBM models is also provided.
Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through ...screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.
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