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Increasing oil production is crucial for multilayer co-production. When there are significant differences in the permeability of each layer, an interlayer contradiction arises that can impact the recovery efficiency. After a number of tests and the establishment of a mathematical model, the effects of permeability contrast on oil production for water flooding were revealed. In the meantime, the developed mathematical model was solved using the Buckley–Lever seepage equation. Ultimately, the accuracy of the established model was confirmed by comparing the simulated outcomes of the mathematical model with the experimental results. The findings indicate that when permeability contrast increases, the production ratio of the high-permeability layer will improve. This is primarily due to the low-permeability layer’s production contribution rate decreasing. The accuracy of the established model is ensured by an error of less than 5% between the results of the experiment and the simulation. When the permeability contrast is less than three, the low-permeability layer can be effectively used for three-layer commingled production. However, when the permeability contrast exceeds six, the production coefficient of the low-permeability layer will be less than 5%, which has a significant impact on the layer’s development.

Understanding and manipulating geological pore structures is of paramount importance for geo-energy productions and underground energy storages in porous media. Nevertheless, research emphases for long time have been focused on understanding the pore configurations, while few work conducted to modify and restructure the porous media. This study deploys ultrasonic treatments on typical geological in-situ core samples, with follow-up processes of high-pressure mercury injections and nitrogen adsorptions and interpretations from nuclear magnetic resonance and x-ray diffraction. The core permeability and porosity are found to increase by 8.3 mD, from 4.1 to 12.4 mD, and by 0.95%, from 14.03% to 14.98%, respectively. Meanwhile, the number and size of the micro- and mesopore are increased with progressing of ultrasonic treatment, while those of the macropore decrease, which finally increase the permeability and porosity. The increase of micro- and mesopore number, from x-ray diffraction results, is attributed to the migration and precipitation of clay minerals caused through ultrasonic wave. The relocation of clay minerals also helps to improve the pore-throat connectivity and modify the micro-scale heterogeneity. Basically, this study reveals the characterizations of geological pore reconfigurations post-ultrasonic treatments and interprets the associated mechanisms, which provides guidance to manipulate the geological pores and be of benefit for further porous media use in science and engineering.

CO2 flooding can effectively enhance the recovery of low-permeability reservoirs and realize CO2 geological storage. During the displacement process, the minimum miscible pressure (MMP) of CO2 and oil is an important parameter that affects the displacement effect and storage efficiency. However, the microscopic pore-throat structure of low-permeability reservoirs has significant influences on the fluids and phase behaviors. This paper presented a method to determine the miscible state of CO2 flooding based on the microscopic pore-throat structure. Firstly, a physic model was established to quantitatively characterize the microscopic pore-throat structure. Secondly, taking into consideration the P-R equation of state, the gas-liquid equilibrium in the narrow pore-throat was calculated. On this basis, a MMP prediction model was established correspongdingly by considering the multi-stage contact and mass transfer of CO2-oil. Finally, the results obtained by the proposed model were compared with the experimental results of CO2 flooding, and then the model was applied to the actual reservoir to predict plane distribution of MMP. The curves of MMP distribution and pressure drawdown between wells were combined to determine the position of miscible front and non-miscible area at different production stages. The results have shown that the MMP of core sample calculated by the model was 20.3 MPa, which was comparable to that of CO2 flooding experiment, e.g., 20 MPa, and thus indicatesd a high accuracy of the model. The MMP in the well control area of the Y29-101 well group was 19.8 MPa. During the unsteady flow stage, the miscible-phase front was 430 m from the injection well, while it was 310 m from the injection well during the stable flow stage. This method can accurately determine the specific phase distribution of CO2-oil in the formation, which is of great significance to promote the development of CO2 flooding and storage technology, improve the recovery of low permeability reservoirs, ensure energy supply and reduce carbon emission.

At present, the main development mode of “horizontal well + volume fracturing” is adopted in a tight glutenite reservoir. Due to the existence of conglomerate, the seepage characteristics are more complex, and the production capacity after volume fracturing is difficult to predict. In order to solve this problem, a dual media unstable seepage model was established for matrix seepage and discrete fracture network seepage when considering the trigger pressure gradient. By considering the Poisson's ratio of stress sensitivity in an innovative way, the coupling model of permeability and stress is improved, and the production prediction model of volume fracturing horizontal well in a tight glutenite reservoir based on the fluid-solid coupling effect is formed. The finite element method is used to numerically solve the model, and the fitting verification of the model is carried out; the impact of stress sensitivity, producing pressure difference, fracture length, number of fracture clusters and fracture flow capacity conductivity on productivity is analyzed, which has certain guiding significance for the efficient development of volume fracturing in a tight glutenite reservoir.

Low-salinity water (LSW) and CO2 could be combined to perform better in a hydrocarbon reservoir due to their synergistic advantages for enhanced oil recovery (EOR); however, its microscopic recovery mechanisms have not been well understood due to the nature of these two fluids and their physical reactions in the presence of reservoir fluids and porous media. In this work, well-designed and integrated experiments have been performed for the first time to characterize the in-situ formation of micro-dispersions and identify their EOR roles during a LSW-alternating-CO2 (CO2-LSWAG) process under various conditions. Firstly, by measuring water concentration and performing the Fourier transform infrared spectroscopy (FT-IR) analysis, the in-situ formation of micro-dispersions induced by polar and acidic materials was identified. Then, displacement experiments combining with nuclear magnetic resonance (NMR) analysis were performed with two crude oil samples, during which wettability, interfacial tension (IFT), CO2 dissolution, and CO2 diffusion were quantified. During a CO2-LSWAG process, the in-situ formed micro-dispersions dictate the oil recovery, while the presence of clay minerals, electrical double-layer (EDL) expansion and multiple ion exchange (MIE) are found to contribute less. Such formed micro-dispersions are induced by CO2 via diffusion to mobilize the CO2-diluted oil, alter the rock wettability towards more water-wet, and minimize the density contrast between crude oil and water. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a common complication of diabetes and has become the leading cause of end-stage kidney disease. The pathogenesis of DKD is complicated, and oxidative stress is considered as a core of DKD onset. High glucose can lead to increased production of reactive oxygen species (ROS) via the polyol, PKC, AGE/RAGE and hexosamine pathways, resulting in enhanced oxidative stress response. In this way, pathways such as PI3K/Akt, TGF-β1/p38-MAPK and NF-κB are activated, inducing endothelial cell apoptosis, inflammation, autophagy and fibrosis that cause histologic and functional abnormalities of the kidney and finally result in kidney injury. Presently, the treatment for DKD remains an unresolved issue. Traditional Chinese medicine (TCM) has unique advantages for DKD prevention and treatment attributed to its multi-target, multi-component, and multi-pathway characteristics. Numerous studies have proved that Chinese herbs (e.g., Golden Thread, Kudzuvine Root, Tripterygium glycosides, and Ginseng) and patent medicines (e.g., Shenshuaining Tablet, Compound Rhizoma Coptidis Capsule, and Zishen Tongluo Granule) are effective for DKD treatment. The present review described the role of oxidative stress in DKD pathogenesis and the effect of TCM intervention for DKD prevention and treatment, in an attempt to provide evidence for clinical practice. [ABSTRACT FROM AUTHOR]

KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium–calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether KB-R7943 modulates acid-sensing ion channels (ASICs), a group of proton-gated cation channels implicated in the pathophysiology of various neurological disorders, using the whole-cell patch clamp techniques. Our data show that KB-R7943 irreversibly inhibits homomeric ASIC1a channels heterologously expressed in Chinese Hamster Ovary (CHO) cells in a use- and concentration-dependent manner. It also reversibly inhibits homomeric ASIC2a and ASIC3 channels in CHO cells. Both the transient and sustained current components of ASIC3 are inhibited. Furthermore, KB-R7943 inhibits ASICs in primary cultured peripheral and central neurons. It inhibits the ASIC-like currents in mouse dorsal root ganglion (DRG) neurons and the ASIC1a-like currents in mouse cortical neurons. The inhibition of the ASIC1a-like current is use-dependent and unrelated to its effect on NCX since neither of the other two well-characterized NCX inhibitors, including SEA0400 and SN-6, shows an effect on ASIC. Our data also suggest that the isothiourea group, which is lacking in other structurally related analogs that do not affect ASIC1a-like current, may serve as a critical functional group. In summary, we characterize KB-R7943 as a new ASIC inhibitor. It provides a novel pharmacological tool for the investigation of the functions of ASICs and could serve as a lead compound for developing small-molecule drugs for treating ASIC-related disorders. [ABSTRACT FROM AUTHOR]

Recently, a multiwell-pad-production (MWPP) scheme has been the center of attention as a promising technology to improve shale-gas (SG) recovery. However, the increasing possibility of multiwell pressure interference (MWPI) in the MWPP scheme severely distorts flow regimes, which strongly challenges the traditional pressure-transient analysis methods that focus on single multifractured horizontal wells (SMFHWs) without MWPI. Therefore, a methodology to identify pressure-transient response of the MWPP scheme with and without MWPI is urgent. To fill this gap, a new semianalytical pressure-transient model of the MWPP scheme is established by use of superposition theory, Gauss elimination, and the Stehfest numerical algorithm. Type curves are generated, and flow regimes are identified by considering MWPI. Finally, a sensitivity analysis is conducted. Our results show that there are good agreements between our proposed model and numerical simulation; moreover, our semianalytical approach also demonstrates a promising calculation speed compared with numerical simulation. Some expected flow regimes are significantly distorted by MWPI. In addition, well rate determines the distortion of pressure curves, whereas fracture length, well spacing, and fracture spacing determine when the MWPI occurs. The smaller the gas rate, the more severely flow regimes are distorted. As the well spacing increases, fracture length decreases, fracture spacing decreases, and the occurrence of MWPI occurs later. The stress-sensitivity coefficient has little to no influence on the occurrence of MWPI. Similar to the concept of the dual-porosity model, three new flow regimes--the single-well flow regime, MWPI flow regime, and MWPP flow regime--are artificially defined to systematically characterize the flow regimes of the MWPP scheme. This work offers some additional insights on pressure-transient response for the MWPP scheme in the SG reservoir, which can provide considerable guidance for fracture-properties estimation and well-pattern optimization for the MWPP scheme. [ABSTRACT FROM AUTHOR]

The detection of interacting behavior between the hydraulic fracture (HF) and the natural fracture (NF) is of significance to accurately and efficiently characterize an underground complex-fracture system induced by hydraulic-fracturing technology. This work develops a semianalytical pressure-transient model in the Laplace domain to detect interacting behavior between HF and NF depending on pressure-transient characteristics. Our results have shown that no matter what the flow state (compressible or incompressible flow) within a hydraulically induced fracture system, we can easily detect interacting behavior between HF and NF depending on whether the "dip" shape occurs at the formation radial-flow regime. Referring to sensitivity analysis, distance between NF and well, horizontal distance between NF and HF, and NF length are the three most sensitive factors to detect fracture-interacting behavior. Depending on interference analysis, although the pressure-transient characteristics of a pseudosteady-state dual-porosity model can interfere with our proposed methodology, the difference between our model and a pseudosteady-state dual-porosity system lies in whether the value of the horizontal line of dimensionless pressure derivative is equal to 0.5 at the formation radial-flow regime. Our work obtains some innovative insights into detecting fracture-interacting behavior, and the valuable results can provide significant guidance for refracturing operations and fracture detection in an underground fracture system. [ABSTRACT FROM AUTHOR]

Background Neuroactive steroids represent promising candidates for the treatment of neurological disorders. Our previous studies identified an endogenous steroid cholestane-3 β, 5 α, 6 β-triol (Triol) as a novel neuroprotectant. Aim We aimed to identify a potent candidate for stroke treatment through a screening of Triol analogs. Methods Hypoxia- and glutamate-induced neuronal injury models in vitro, middle cerebral artery occlusion ( MCAO)-induced cerebral ischemia model in vivo, fluorescein diacetate ( FDA) for alive and propidium iodide ( PI) for dead staining, LDH assay, and calcium imaging techniques were used. Results 24-keto-cholest-5-en-3 β, 19-diol (Diol) showed the most potent neuroprotective effect among the screened structurally related compounds. FDA and PI staining showed that Diol concentration dependently increased the survival rate of cerebellar granule neurons ( CGNs) challenged with glutamate or hypoxia, with an effective threshold concentration of 2.5 μM. Consistently, the quantitative LDH release assay showed the same concentration-dependent protection in both models. Diol, at 10 μM, potently decreased glutamate- and hypoxia-induced LDH release from 51.6 to 18.2% and 62.1 to 21.7%, respectively, which values are close to the normal LDH release (~16-18%). Moreover, we found Diol effectively decreased MCAO-induced infarction volume in mice from ~23% to 7%, at a dose of 6 mg/kg. We further explored the underlying mechanism and found that Diol attenuated NMDA-induced intracellular calcium ([Ca2+]i) increase in cortical neurons, suggesting a negative modulatory effect on NMDA receptor. Conclusion Taken together, we identified Diol as a potent neuroprotectant. It may represent a novel and promising neuroprotectant for stroke intervention. [ABSTRACT FROM AUTHOR]

Background: Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7- mediated intracellular Zn2+ accumulation may represent a promising strategy in the treatment of stroke. Aims: To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. Methods: Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn2+ imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn2+ accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. Results: (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn2+ accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn2+ toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. Conclusion: Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. [ABSTRACT FROM AUTHOR]

In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, including synaptic transmission, cerebral ischemia, epilepsy, brain trauma, and tissue inflammation. Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems. Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASIC1a activation in acidosis-mediated brain injury, small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the colon. The aim of the present study was to explore the effects of leonurine (YMJ) on inflammation and intestinal microflora in colonic tissues of a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Mice were randomly divided into control (n=5), DSS (n=5, treated with DSS) and DSS+YMJ (n=5, treated with DSS and YMJ) groups. Body weight was recorded, disease activity index (DAI) was calculated, and colon histopathology was evaluated using hematoxylin and eosin staining. Serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β levels were examined using ELISA. Expression levels of nuclear factor-κB (p65) and phosphorylated (p)-p65 were evaluated via western blotting. 16S ribosomal RNA was extracted from mouse feces. Composition or abundance changes of intestinal microflora were analyzed. The results indicated that YMJ treatment (DSS+YMJ group) significantly increased body weight, reduced DAI scores and increased colon length in UC mouse models compared with those in the DSS group (P<0.05). YMJ significantly reduced inflammatory infiltration, significantly decreased serum TNF-α, IL-6 and IL-1β levels (P<0.05) and significantly downregulated the p-p65/p65 ratio compared with the DSS group (P<0.05). YMJ increased the quantity of the intestinal flora and improved intestinal microflora diversity in the mice of the DSS group. Specifically, YMJ partly regulated intestinal microflora in feces, including a reduction of Bifidobacterium, and an increase in Parasutterella and Ackermania. In conclusion, YMJ improved disease outcomes of the UC mice, reduced the levels of serum inflammatory factors and increased the ratio of beneficial bacteria in the intestinal tract. [ABSTRACT FROM AUTHOR]

Abstract Background Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated. Results We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells. Conclusion These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.

To analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from hospitalized patients of all ages in Zhongjiang county, Sichuan province, where the young children have just begun to vaccinate the PCV13 in private sector. Serotypes were determined for 387 isolates of S. pneumoniae by Quellung reaction. Antibiotic susceptibility was tested with the E-test or disc diffusion method. The most common serotypes were type 19F and confirmed for 88 isolates (22.7%), followed by 19A (15.0%), 6B (7.8%), 16F (7.8%), 23F (7.0%) and 15A (4.4%). The coverage rates of PCV13 and PPSV23 were 63.3% and 65.1%. With the increase of age, the proportion of PCV13 types decreased significantly, from 71.3% (<2 years old) to 41.9% (≥60 years old). The intermediate rate and resistance rate of the isolates to oral penicillin were 48.6% and 45.2%, respectively. The resistance rate of erythromycin was high (94.4%). The PCV13 isolates was more resistant to penicillin than the non-PCV13 ones. The PCV13 coverage rate in pediatric isolates was higher than those in adult isolates. The adults, especially the elderly, may be the reservoir of non-PCV13 types. It is necessary to investigate the serotype distribution of S. pneumoniae based on all age population to assess potential epidemics of non-vaccine serotype associated with PCVs administration. [ABSTRACT FROM AUTHOR]