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Summary Uniform proppant distribution in a cluster and a stage with multiple clusters is a primary objective to optimize fracturing parameters and improve the production from each cluster. Because fracturing slurry is typically pumped at high pressure and rate in fields, it is a big challenge to study proppant transport behavior and distribution characteristics through laboratory experiments. There is still a lack of an effective model to quantitatively evaluate proppant distribution based on an actual wellbore configuration. The objective is to propose a novel method to accurately evaluate the distribution uniformity and quickly optimize fracturing parameters based on field conditions. This paper conducts particle transport experiments in a horizontal pipe with six holes at the helical distribution. A 3D numerical model coupling of the computational fluid dynamics (CFD) and discrete element method (DEM) is used to study proppant distribution. Proppant distribution is quantitatively evaluated by the proppant transport efficiency (E) and normalized standard deviation (NSD). The effects of 10 parameters are investigated. An artificial neural network (ANN) model is developed to predict proppant distribution in a cluster. The results identify that proppant distribution among perforations is generally toe-biased in a horizontal wellbore due to a high pumping rate. Proppants with large inertia easily miss the heel-side holes and are suspended to the toe side. The complex vorticity flow carries them to the toe-side perforation regardless of hole orientation. Fluid distribution can significantly change proppant distribution regardless of fluid velocity. The heel-biased fluid distribution leads to the same bias of proppant, and the downward perforations receive more proppants. Proppant transport reaches equilibrium quickly, and the distribution is hard to change unless the injection condition varies. It is a good choice to increase fluid viscosity, add perforation sealers, and inject small mesh proppant, especially for the low density. The ANN model trained by extensive experimental and numerical samples can accurately evaluate proppant distribution uniformity. The study provides an efficient way to optimize injection parameter design and achieve real-time optimization coupled with the fiber-optic downhole diagnostic. It can be a crucial part of artificial intelligence hydraulic fracturing.

Summary Understanding proppant transport and distribution in hydraulic fractures is crucial to designing and optimizing hydraulic fracturing treatments in the field. The actual fracture surfaces are typically rough and form a tortuous pathway, significantly affecting proppant migration. However, many rough models are very small in size, and some have only one rough surface. Thus, it is inadequate to display proppant transport behaviors and placement laws. This study proposed a novel method to develop large-scale rough panels reproduced from actual hydraulic fractures. A large transparent slot (2×0.3 m) was successfully constructed to simulate a shear fracture with 5 mm relative displacement of two matched surfaces. Six kinds of proppants were selected to study the effects of particle density and size. Four types of slickwater were prepared to achieve viscous diversity. A high-resolution particle image velocimetry (PIV) system detected the instantaneous velocity and vector fields in the rough pathway to understand particle transport behaviors. The specific parametric study includes a quantitative analysis of the proppant bed profile, equilibrium height, coverage area, injection pressure, and volumes of proppant settled in the slot and outlet tank. Also, five tests are carried out in the smooth slot, which has the same size as the rough slot. The test results demonstrate that the narrow rough fracture would significantly hinder particle transport, especially in the horizontal direction. The proppant bed is higher and closer to the inlet than that in the smooth model. Particles mixed with highly viscous slickwater easily aggregate in the two-sided rough model and gradually form finger-like regions at the lower part of the inlet. The unstable flow and vortices can disperse aggregated particles and avoid particle clogging. Proppants injected at the high volume fraction are prone to settle quickly and build up a higher bed contact with the inlet, leading to more considerable injection pressure. Perforation blockage often occurred in the rough model, and the near-wellbore screenout was induced as the bed blocked all perforations. Enhancing the fluid carrying capacity and using smaller proppant help avoid perforation blockage and improve far-field fracture conductivity. Two correlations were developed to predict the equilibrium height and coverage area of the proppant bed. The experimental results and laws provide novel understandings that can help optimize hydraulic fracturing design and treatment by rationally selecting proppant and fracturing fluid to improve the productivity in tight reservoirs.

Summary Hydraulic fracturing is recognized as the primary stimulating technique to enhance recovery in unconventional reservoirs. Connecting natural fractures and filling proppant are crucial elements to achieve the effective development of the reservoirs. Many studies have investigated the interaction characteristics between hydraulic fracture and natural fracture and proppant transport in complex fracture systems. However, few studies show how natural fracture affects proppant migration and placement. In this work, we experimentally explore proppant transport in an irregular, nonplanar fracture containing hydraulic fractures and a natural fracture. The objective is to identify the influence of natural fractures on proppant transport and placement. In this paper, proppant transport in a nonplanar fracture with bends is studied experimentally by a laboratory size slot, and the bending section represents a natural fracture. A high-resolution particle image velocimetry (PIV) system is used to detect the instantaneous velocity field in the complex pathway to understand particle transport behaviors. Proppant placement is quantitatively evaluated by the proppant coverage area as the proppant bed reaches the equilibrium state. Also, the effects of natural fracture width and height, intersection angle with hydraulic fracture, and relative location with the inlet on proppant placement are investigated. The results identify that the natural fracture would significantly increase the complexity of proppant transport and lead to a discontinuous and irregular proppant bed in the complex fracture. The vorticity flow appears around the bend and resuspends deposited proppants through the bending section. The small natural fracture width and height increase flow erosion and are not conducive to proppant settlement, resulting in no proppant. The more the bending angle, the lower the coverage area and bed height. When the natural fracture is close to the inlet, a depleted region without proppants would be formed around the wellbore. The multiple linear regression method developed two reliable models expressed by four normalized parameters to predict the bed coverage areas. The experimental results and laws provide ways to quantitatively analyze natural fracture characteristics' effect on proppant transport and placement in unconventional reservoirs and fissured formations.

Particle transport in a vertical nonplanar fracture is a typical but poorly understood element in hydraulic fracturing. Particle-fluid flow in a nonplanar fracture with a narrowing width is investigated experimentally by a laboratory-scale slot, and the relevant transport mechanisms are compared with that in the planar slot. The effects of fluid flow rate, particle density, particle size, and particle volume fraction on particle distribution are investigated. The results indicate that the narrowing width complicates the slurry flow and lowers the bed coverage area. The vortex flow appears at the contraction of the cross-section as the bed grows to a threshold height and resuspends more particles further into the slot. An irregular bed with a descending stepped surface is formed due to non-uniform placement. Smaller size sands injected at a high flow rate and a low particle volume fraction build up a smaller bed. Larger and denser particles would reverse the trend. A rational model expressed by four dimensionless numbers is developed by the linear regression method to predict the coverage percentage of the particle bed. The model and experimental results provide directions to quantitatively evaluate the particle transport and distribution in a nonplanar fracture.

Summary Proppant placement plays a crucial role in maintaining the conductivity of fractures after a hydraulic fracturing treatment. The process involves the transport of particles by fluid flow in complex fractures. Many studies have focused on proppant transport and distribution in the fracture with a constant aperture, but relatively few studies have investigated the proppant-fluid flow in a vertical fracture with a contracted aperture. In this work, we examine experimentally proppant transport in a fracture with a contracted aperture. The objective is to evaluate the distribution of particle beds in the contracted fracture at different flow conditions. In this paper, particle-fluid flow in the contracted fracture is studied experimentally by a laboratory size slot. A planar slot with a constant width is used to benchmark the experimental results, and a published correlation validates the bed equilibrium heights in the planar slot. Six types of particles are chosen to simulate the effects of particle density and size. The proppant distribution is evaluated by the bed height when the bed reaches the equilibrium states. The effects of fluid velocity, fluid viscosity, particle density, particle size, and particle volume fraction on particle distribution are investigated. The results confirm that the proppant particle-fluid flow in the contracted slot is more complicated than that in the planar slot. The phenomena of particle vortices and resuspension were observed at the contraction of the cross-section. The shape on the top of the bed is like a descending stair in which the height gradually decreases in the length direction. The bed height in the contracted slot is lower and more irregular than that in the planar slot at the same flow conditions. Smaller sands injected at a high flow rate and fluid viscosity can form a lower bed. The trend would be reversed by using denser particles and high particle volume fraction. A reliable model expressed by four dimensionless numbers is developed by the linear regression method for predicting the bed equilibrium height. The model and experimental results provide directions to quantitatively evaluate the particle transport and distribution in a fracture with a contracted aperture.

Chinese Pharmacopoeia is an important part of drug standards in China, and it is also a legal basis that must be strictly followed in drug development, production, operation, application, and management. The information on prescriptions, preparation methods, properties, identification, inspection, content determination, functions and indications, usage and dosage, precautions, specifications, and storage of Chinese patent medicine preparations included in the Chinese Pharmacopoeia(Vol.Ⅰ) was clarified. Thequot;Preparation Methodquot; section describes the preparation process of Chinese patent medicine from decoction pieces to finished preparations in detail and specifies the preparation production methods and parameters, which has a good guiding and standardizing effect on the production of Chinese patent medicine in China. The present study summarized the preparation methods of Chinese patent medicine preparations and single drug preparations contained in the Chinese Pharmacopoeia(2020 edition, Vol.Ⅰ) in stages and analyzed the common preparation methods and technical parameters of Chinese patent medicine preparations, which is helpful to understand the current situation of Chinese patent medicine production technology in China and can provide references for the development of new Chinese medicine, the transformation of large varieties of Chinese patent medicine, and the optimization of preparation process of Chinese patent medicine in the market.

Usage of shale gas as an energy source offers additional reassurance if fossil fuels become depleted. Because the shale reservoir is buried deep, the formation has the characteristic of high ground...

Knowing of gas shale permeability reduction is vital for gas production from shale gas reservoirs stimulated by multistage hydraulic fracturing. However, the role of shale matrix permeability reduc...

Purpose Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. Methods The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. Results TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1-induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. Conclusion The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.

Shale gas is a promising energy source offering additional energy security over concerns of fossil fuel depletion. Injecting CO2 into depleted shale gas reservoirs might provide a feasible solution for CO2 storage and enhanced gas recovery. However, shale strain caused by the CO2 injection as well as CO2 sequestration in the reservoir needs to be considered during shale gas production. For this purpose, this paper examines the adsorption capacities, CO2-induced swelling, and He-induced strain of shales at 0-16 MPa and 35-75 °C. The maximum excess adsorption at different temperatures correlated with the bulk phase density: as the CO2 temperature increased, the maximum excess adsorption density decreased. The density of the adsorbed phase, obtained using the Dubinin-Radushkevich model, was used to fit the excess adsorption data. At low pressure, the CO2-induced strain on shale was caused by the gas adsorption, whereas at high pressure, it was caused by gas pressure. The absolute adsorption linearly correlated with the adsorption-induced strain.

The shale of the Lower Silurian Longmaxi Formation is an important gas-producing layer for shale gas development in southern China. This set of shale reservoir characteristics and shale gas development potential provide an important foundation for shale gas development. This study takes wellblock XN111 in the Sichuan Basin, China, as an example and uses X-ray diffraction (XRD), scanning electron microscopy (SEM), isothermal adsorption, and other techniques to analyze the shale reservoir characteristics of the Lower Silurian Longmaxi Formation. The results show that the Lower Silurian Longmaxi Formation was deposited in a deep-water shelf environment. During this period, carbonaceous shale and siliceous shale characterized by a high brittle mineral content ( quartz > 40 wt . % , carbonate mineral > 10 wt . % ) and a low clay mineral content (

Background: Dendrobium catenatum is a kind of precious Traditional Chinese Medicine, and possesses unique developmental programs and epiphytic lifestyle. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are responsible for maintenance of histone acetylation homeostasis, and they are widely involved in developmental regulation and stress responses via remodeling chromatin structure, but their biological functions in orchid plants remain largely unknown.Results: Here we identified 8 HAT genes and 14 HDAC genes from D. catenatum genome. We carried out phylogenetic construction, gene structure and domain architecture analysis of these D. catenatum HAT/HDAC (DcHAT/DcHDAC) proteins using the well-defined homologs from the model plants Arabidopsis thaliana and Oryza sativa as references. DcHAT proteins can be classified into four families: GNAT family (3 members), MYST family (2), CBP family (2), and TAFII250 family (1), and DcHDAC proteins can be grouped into three families: RPD3/HDA1 family (10), SIR2 family (2), and HD2 family (2), in accordance with previously described classification. Cis-acting element analysis indicated that the promoter regions of DcHAT/DcHDAC genes contain diverse stress-responsive elements. Subcellular localization predictions suggested that DcHAT/DcHDAC proteins might be localized in nucleus or/and cytoplasm. Spatiotemporal expression profiling showed that DcHAT/DcHDAC genes generally exhibit either universal or specific expression pattern in different tissues and organs. Finally, stress response assay suggested drought treatment significantly represses the expression of DcHAG1 and DcHDA14, cold exposure evidently influences the expression of DcHAG1 and DcHDT1, and heat shock has a broad impact on the expression of DcHAT/DcHDAC genes.Conclusions: In this study, we reveal the identification and expression profiles of DcHATs and DcHDACs in epiphytic orchid plant D. catenatum, indicating their roles in the regulation of both long-term developmental programs and short-term stress responses. This study provides a foundation for in-depth functional excavation of HATs/HDACs associated with dynamic histone acetylation levels in orchids.

Purpose Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. Methods The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. Results TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1-induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. Conclusion The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.

Particle-fluid flow in complex fractures plays a crucial role in the stimulation of unconventional reservoirs. In this paper, particle transport experiments were conducted in a vertical, nonplanar slot with two 90° bends and a straight slot. The corresponding simulation model was performed by a 3D coupled method of computational fluid dynamics (CFD) and discrete element method (DEM), which was calibrated and validated against experimental results. The effects of bending angle, fluid velocity and viscosity, particle density on particle placement are analyzed based on the experimental and simulation results. The studies reveal that the particle-fluid flow pattern is more complicated in the nonplanar slot than that of the straight slot. An irregular particle bed with two depressions around two bends would be formed. With the reduction of bending angle, the particle bed height and covered area decrease, while the sizes of the two depressions increase. The complicated flow induced by the bend increases the fluidization layer height. The high fluid velocity and viscosity can effectively suspend the low-density particles through two bends deeper into the complex fracture. A regression model with dimensionless numbers is developed for predicting the percentage of covered area. This study provides fundamental insight into understanding particle-fluid flow in a nonplanar fracture.

At present, the stimulation technique involving soaking after fracturing of shale gas reservoirs has received increasing attention. In this study, gas-water displacement experiments were carried out to simulate the contact state between the fracturing fluid and the shale during the soaking stage after hydraulic fracturing of the shale gas reservoir. By using low-field nuclear magnetic resonance to dynamically monitor the occurrence state of the methane in shale cores, the changes in the masses of the methane in different occurrence states were calculated. Furthermore, the displacement of the adsorbed methane in the shale by the fracturing fluid was studied. In addition, the influences of the fracturing fluid's salinity and the shale clay content and type on the displacement process were also analyzed. The results of this study show that the fracturing fluid has a stronger adsorption on clay minerals than that of methane, so it can replace the adsorbed methane in the shale. Compared with pure fracturing fluid solution, the high salinity fracturing fluid solution containing cations has a stronger adsorption on the clay minerals in the shale, and thus, it has a stronger displacement ability. The mineral composition of the shale reservoir also has an important influence on the displacement efficiency. The higher the content of clay minerals with high adsorption capacities, the more adsorbed methane is replaced. The results of this study are important for gaining a better understanding of the stimulation technique involving soaking after fracturing of shale gas reservoirs and for optimizing the design of soaking.

Hsp40s or DnaJ/J-proteins are evolutionarily conserved in all organisms as co-chaperones of molecular chaperone HSP70s that mainly participate in maintaining cellular protein homeostasis, such as protein folding, assembly, stabilization, and translocation under normal conditions as well as refolding and degradation under environmental stresses. It has been reported that Arabidopsis J-proteins are classified into four classes (types A–D) according to domain organization, but their phylogenetic relationships are unknown. Here, we identified 129 J-proteins in the world-wide popular vegetable Brassica oleracea, a close relative of the model plant Arabidopsis, and also revised the information of Arabidopsis J-proteins based on the latest online bioresources. According to phylogenetic analysis with domain organization and gene structure as references, the J-proteins from Arabidopsis and B. oleracea were classified into 15 main clades (I–XV) separated by a number of undefined small branches with remote relationship. Based on the number of members, they respectively belong to multigene clades, oligo-gene clades, and mono-gene clades. The J-protein genes from different clades may function together or separately to constitute a complicated regulatory network. This study provides a constructive viewpoint for J-protein classification and an informative platform for further functional dissection and resistant genes discovery related to genetic improvement of crop plants.

After multistage hydraulic fracturing, it is essential to understand the effect of fracturing fluids trapped in shale gas reservoirs on the shale-well. To address the effect of cleanup additive as a major composition of slickwater fracking fluids on methane desorption after hydraulic fracturing, we performed a series of experiments, including X-ray to obtain the mineralogical composition of the gas shale sample, low-pressure nitrogen adsorption to obtain pore size distribution, and series of adsorption and desorption tests. We compared the effect of different methane densities of adsorbed phase on methane absolute adsorption and results demonstrate that the methane adsorption is significantly undervalued. The methane adsorption isotherm and desorption isotherms before and after cleanup additive treatment were well fit by Freundlich model. Furthermore, we compared the desorption isotherms, desorption efficiency, free gas content as well as cumulative gas production before and after treatment. These findings indicate that cleanup additive treatment results in the decrease of adsorption capacity and the increase of adsorption intensity. There exists an intersection between two curves of desorption efficiency before and after treatment. Cleanup additive significantly translates adsorbed phase into free phase to improve free gas content, and increases cumulative gas production. These results can be very helpful for reserves evaluation, knowledge of the role of cleanup additive both increasing slickwater flowback and improving gas recovery.

Effective particle placement in complex fractures plays a crucial role in unconventional reservoirs. Non-planar fracture geometry poses a challenge to assess particle placement. Compared to the straight slot, particle-fluid flow in a curved fracture has not been fully understood. In this paper, particle-fluid flow in curved fractures is studied experimentally by laboratory size slots. The experimental results are compared with the published data, and they are consistent. After validation, the effect of bending angle, fluid velocity, particle size, particle density, and particle volume fraction on particle distribution is investigated. The results show that particle-fluid flow mechanisms in the curved slot are more complicated than that of the straight slot. With the decrease of the bending angle, the height and coverage area of the bed decrease. The flow redirection around the bend induces particle vortices, which change the transport mechanism from fluidization to resuspension. Although the bending section has a hindering effect on particle transport, resuspension promotes particles to flow through the bending section further into the slot and avoid bridging at the bend. The fluid velocity and particle size are two crucial factors impacting particle placement, and an irregular bed with two depressions would be formed in the curved slots. A correlation is developed for predicting the normalized coverage area. This study provides fundamental insight into understanding particle-fluid flow in a curved fracture.