Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the ...lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs,
. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure,
. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting ...PD-L1 expression in liver metastasis of colon cancer.
A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using
F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis.
PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P < 0.05). And liver metastases with high counts of infiltrating cytotoxic T cells showed greater FDG uptake than those with low counts of infiltrating cytotoxic T cells. The SUVmax of liver metastases and the degree of differentiation of metastases were closely related to PD-L1 expression, and were independent risk factors.The combined assessment of SUVmax values and tthe degree of differentiation of metastase can help determine PD-L1 expression in liver metastasis of colon cancer.
FDG uptake in liver metastasis of colon cancer was positively correlated with the PD-L1 expression and the number of cytotoxic T cells infiltration. The joint evaluation of two parameters, SUVmax and degree of differentiation, can predict PD-L1 expression in liver metastases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•A three-dimensional planar hydraulic fracture model is established.•The transition from turbulence to laminar flow in hydraulic fractures is considered.•The frictional behavior in the turbulent flow ...regime was approximated based on the MDR asymptote and Blasius correlation.•The influence of turbulent flow effect on hydraulic fracture is analyzed.
Turbulent flow in fluid-driven fractures exerts important effects on the hydraulic fracture extension, fracture geometry, and proppant transport. Based on linear elastic fracture mechanics, the implicit level set algorithm, laminar flow theory, and turbulent flow theory, this study established planar fracture propagation models of permeable and impermeable reservoirs with consideration the flow regime transition from turbulent to laminar flow when the Reynolds number is larger than the critical Reynolds number. Additionally, the frictional behavior of the fluid in the turbulent flow regime was approximated based on the MDR asymptote and Blasius correlation. The influence of the turbulent flow effect on the hydraulic fracture propagation was theoretically and numerically analyzed. The results reveal that the turbulent flow regime exerts a significant effect within the first few minutes of fracture propagation. Compared with the fully-laminar-flow model, the turbulent-laminar flow model predicted a shorter fracture radius, larger maximum fracture width, and fluid net pressure. This indicates that the fracturing process requires greater pumping power than that predicted by the laminar flow models under the influence of turbulent flow to achieve the desired design parameters. Compared with impermeable rock, the turbulent flow in the fracture is enhanced by fluid leak-off. Slickwater can transition from turbulent to laminar flow at a lower critical Reynolds number compared with pure water. The normalized fracture parameters indicate that the fracture radius corresponding to pure water is smaller, and the maximum width of fracture and maximum net pressure are larger than those of slickwater. The threshold time of turbulent flow for different fracture parameters varies depending on the injected fluid properties and reservoir parameters. Our study contributes toward a deeper understanding of the real physical behavior of hydraulic fracture propagation at large injection rates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Based on fractal geometry theory, the Hagen–Poiseuille law, and the Langmuir adsorption law, this paper established a mathematical model of gas flow in nano-pores of shale, and deduced a new shale ...apparent permeability model. This model considers such flow mechanisms as pore size distribution, tortuosity, slippage effect, Knudsen diffusion, and surface extension of shale matrix. This model is closely related to the pore structure and size parameters of shale, and can better reflect the distribution characteristics of nano-pores in shale. The correctness of the model is verified by comparison with the classical experimental data. Finally, the influences of pressure, temperature, integral shape dimension of pore surface and tortuous fractal dimension on apparent permeability, slip flow, Knudsen diffusion and surface diffusion of shale gas transport mechanism on shale gas transport capacity are analyzed, and gas transport behaviors and rules in multi-scale shale pores are revealed. The proposed model is conducive to a more profound and clear understanding of the flow mechanism of shale gas nanopores.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
AbstractDuring hydraulic fracturing, the filtration of fracturing fluid increases the pore pressure in the vicinity, resulting in pore pressure–induced stress in the reservoir. In order to study the ...evolution of pore pressure–induced stress during fracturing, based on Biot’s theory, a dynamic simulation model of single-fracture or multifracture propagation was established through coupled fluid flow and geomechanics. In the model, the heterogeneity of the reservoir and the influence of pore elasticity of reservoir rock were considered. Further, the finite volume and iterative methods were used to solve the model. The results show that the heterogeneity of reservoir permeability and porosity has a great influence on the distribution of pore pressure–induced stress, and it will make the induced stress distribution more complicated, resulting in local stress prominence. The distribution of pore pressure–induced stress during fracturing is quite different from that of hydraulic fracture opening–induced stress. With the increase of fracturing time, the distribution of pore pressure–induced stress shows a certain regularity, and the minimum horizontal principal stress shows a higher level near the fracture and a lower level on the left and right sides. However, the maximum horizontal principal stress is higher near the fracture and lower at the fracture tip (upper and lower parts of the fracture). Under certain conditions, pore pressure–induced stress will reverse the horizontal principal stress in the local area. Considering the influence of pore elasticity, the pore pressure will increase because of the fracturing fluid filtration, resulting in further increase in reservoir permeability and porosity, which in turn will increase fracturing fluid filtration. Through this study, the distribution of induced stress in the hydraulic fracturing process can be described more accurately, which can provide some guidance for hydraulic fracturing design and theories.
Immunofluorescence is an invaluable technique widely used in cell biology. This technique allows visualization of the subcellular distribution of different target proteins or organelles, by specific ...recognition of the antibody to the endogenous protein itself or to its antigen via the epitope. This technique can be used on tissue sections, cultured cells, or individual cells. Meanwhile, immunofluorescence can also be used in combination with non-antibody fluorescent staining, such as DAPI or fluorescent fusion proteins, e.g., GFP or YFP, etc.Autophagy is a catabolic pathway in which dysfunctional organelles and cellular components are degraded via lysosomes. During this process, cytoplasmic LC3 translocates to autophagosomal membranes. Therefore, cells undergoing autophagy can be identified by visualizing fluorescently labeled LC3 or other autophagy markers. Immunofluorescence is an important part of autophagy detection methods even if observation of the formation of autophagosome by transmission electron microscopy has become a gold standard for characterizing autophagy.By observing the immunofluorescence staining of some key autophagy proteins, we can intuitively evaluate the levels of autophagy in samples. Herein, this protocol describes the predominant method used for the research of autophagy, which mainly focuses on the immunofluorescence staining of cellular LC3, P62, and ULK1 in response to normoxia and hypoxia, by presenting the detailed materials required and methodology.
In this paper, a novel porous media permeability model is established by using particle model, capillary bundle model and fractal theory. The three-dimensional irregular spatial characteristics ...composed of two ideal particles are considered in the model. Compared with previous models, the results of our model are closer to the experimental data. The results show that the tortuosity fractal dimension is negatively correlated with porosity, while the pore area fractal dimension is positively correlated with porosity; The permeability is negatively correlated with the tortuosity fractal dimension and positively correlated with the integral fractal dimension of pore surface and particle radius. When the tortuosity fractal dimension is close to 1 and the pore area fractal dimension is close to 2, the faster the permeability changes, the greater the impact. Different particle arrangement has great influence on porous media permeability. When the porosity is close to 0 and close to 1, the greater the difference coefficient is, the more the permeability of different arrangement is affected. In addition, the larger the particle radius is, the greater the permeability difference coefficient will be, and the greater the permeability difference will be for different particle arrangements. With the increase of fractal dimension, the permeability difference coefficient first decreases and then increases. When the pore area fractal dimension approaches 2, the permeability difference coefficient changes faster and reaches the minimum value, and when the tortuosity fractal dimension approaches 1, the permeability difference coefficient changes faster and reaches the minimum value. Our research is helpful to further understand the connotation of medium transmission in porous media.
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The ultra-low-permeability shale gas reservoir has a lot of well-developed natural fractures. It has been proven that hydraulic fracture growth pattern is usually a complex network fracture rather ...than conventional single planar fractures by micro-seismic monitoring, which can be explained as the shear and tensile failure of natural fractures or creation of new cracks due to the increase in reservoir pore pressure caused by fluid injection during the process of hydraulic fracturing. In order to simulate the network fracture growth, a mathematical model was established based on full tensor permeability, continuum method and fluid mass conservation equation. Firstly, the governing equation of fluid diffusivity based on permeability tensor was solved to obtain the reservoir pressure distribution. Then Mohr–Coulomb shear failure criterion and tensile failure criterion were used to decide whether the rock failed or not in any block on the basis of the calculated reservoir pressure. The grid-block permeability was modified according to the change of fracture aperture once any type of rock failure criterion was met within a grid block. Finally, the stimulated reservoir volume (SRV) zone was represented by an enhancement permeability zone. After calibrating the numerical solution of the model with the field micro-seismic information, a sensitivity study was performed to analyze the effects of some factors including initial reservoir pressure, injection fluid volume, natural fracture azimuth angle and horizontal stress difference on the SRV (shape, size, bandwidth and length). The results show that the SRV size increases with the increasing initial pore reservoir and injection fluid volume, but decreases with the increase in the horizontal principal stress difference and natural fracture azimuth angle. The SRV shape is always similar for different initial pore reservoir and injection fluid volume. The SRV is observed to become shorter in length and wider in bandwidth with the decrease in natural fracture azimuth angle and horizontal principal stress difference.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The first fractured shale gas well of China was constructed in 2010. After 10 years of development, China has become the second country that possesses the core technology of shale gas development ...around the world, realized the shale gas fracturing techniques from zero to one and from lagging to partially leading, and constructed the fracturing theory and technology system suitable for middle–shallow marine shale gas exploitation. In order to provide beneficial guidance for the efficient exploitation of shale gas in China in the future, this paper comprehensively reviews development history and status of domestic fundamental theories, optimized design methods, fluid systems, tools and technologies of shale gas fracturing and summarizes the research results in fundamental theories and optimized design methods, such as fracturing sweet-spot cognition, fracture network propagation simulation and control, rock hydration and flowback control, and SRV (stimulated reservoir volume) evaluation and characterization. The development and application of slick-water fracturing fluid system and new fracturing fluid with little or no water is discussed. The development and independent research & development level of multi-stage fracturing tools are evaluated, including drillable composite plug, soluble plug, large-diameter plug and casing cementing sleeve. The implementation situations of field technologies and processes are illustrated, including the early conventional multi-stage multi-cluster fracturing and the current “dense cluster” fracturing and temporary plugging fracturing. Based on this, the current challenges to domestic shale gas fracturing technologies are analyzed systematically, and the development direction of related technologies is forecast. In conclusion, it is necessary for China to continuously research the fracturing theories, technologies and methods suitable for domestic deep and ultra-deep marine shale gas, terrestrial shale gas and transitional shale gas to facilitate the future efficient development of shale gas in China.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Spontaneous imbibition behavior of fracturing fluid retained in reservoirs is considered to be one of the important mechanisms of spontaneous oil–water displacement in tight reservoirs. However, the ...mechanism of imbibition displacement in oil-wet rocks remains unclear. Inspired by the principle of the Marangoni effect, a mathematical model of oil displacement driven by an interfacial tension gradient in an oil-wet capillary tube was established, and the effects of osmotic pressure and hydraulic mechanical dispersion were coupled in the model. The results show that the key component of this mechanism is the breakdown of the initial capillary equilibrium state due to the diffusion of solute, which changes the pressure distribution in the capillary and drives the water to drive oil out of the pores. This can explain the spontaneous imbibition of low-salinity fracturing fluid into the oil-wet tight sample and displace oil without any external force, despite its low permeability. In addition, the related factors were analyzed, including initial concentration, contact angle, solute type, osmotic behavior, and size of the capillary. The results show that for an oil wet reservoir with high salinity, the connate water interfacial tension gradient plays an important role in oil displacement, and the coupling effect of osmotic pressure and hydromechanical dispersion considerably improves recovery. This can provide new insight into the mechanism of spontaneous imbibition of fracturing fluid.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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