Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides. Erastin, the ferroptosis activator, binds to voltage-dependent ...anion channels VDAC2 and VDCA3, but treatment with erastin can result in the degradation of the channels. Here, the authors show that Nedd4 is induced following erastin treatment, which leads to the ubiquitination and subsequent degradation of the channels. Depletion of Nedd4 limits the protein degradation of VDAC2/3, which increases the sensitivity of cancer cells to erastin. By understanding the molecular mechanism of erastin-induced cellular resistance, we can discover how cells adapt to new molecules to maintain homeostasis. Furthermore, erastin-induced resistance mediated by FOXM1-Nedd4-VDAC2/3 negative feedback loop provides an initial framework for creating avenues to overcome the drug resistance of ferroptosis activators.
Coalbed methane extraction suffers from low permeability, and liquid nitrogen treatment has been suggested as one of the methods to address this issue. This study thus investigates cryogenic liquid ...N2 fracturing of a bituminous coal at pore scale through 3D X-ray micro-computed tomography. The μ-CT results clearly demonstrate that freezing the coal with liquid nitrogen increases the porosity by over 11% and creates fracture planes with large apertures originating from the pre-existing cleats in the rock. The images also suggest connection establishment of the cleat network with originally isolated pores and micro-cleats following the freezing, thereby increasing pore network connectivity. Furthermore, SEM images of the frozen sample highlights the appearance of continuous wide conductive fractures with the maximum aperture size of 9 μm. The analysis of mechanical properties through Nano-indentation technique shows a decrease of up to 25% in the indentation modulus due to increase in the compressibility of the cracked rock. Moreover, as the main purpose of this fracturing treatment, the permeability evolution of the coal is examined computationally and experimentally. Lattice Boltzmann simulations on the μ-CT images highlight two-fold enhancement in permeability measure of the treated rock. Additionally, the outcome of core flooding tests shows 2.5 times increase in the permeability measure after liquid nitrogen exposure. This study thus provides a visual understanding of fracturing mechanism associated with liquid nitrogen treatment of a coal, and quantifies the pore structure and permeability evolution of the rock.
•Pore-scale analysis of porosity and permeability evolution of a bituminous coal through liquid nitrogen fracturing.•In-situ micro-scale morphological alteration of the coal rock treated with liquid nitrogen through micro computed tomography.•Inspecting the mechanical properties alteration of the rock due to the fracturing damage using Nano-indentation technique.•Examining the surface morphological alteration of the coal frozen with liquid nitrogen via SEM.•Experimentally and numerically measuring the permeability enhancement through the treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy maintains homeostasis and is induced upon stress. Yet, its mechanistic interaction with oncogenic signaling remains elusive. Here, we show that in BRAF
-melanoma, autophagy is induced by ...BRAF inhibitor (BRAFi), as part of a transcriptional program coordinating lysosome biogenesis/function, mediated by the TFEB transcription factor. TFEB is phosphorylated and thus inactivated by BRAF
via its downstream ERK independently of mTORC1. BRAFi disrupts TFEB phosphorylation, allowing its nuclear translocation, which is synergized by increased phosphorylation/inactivation of the ZKSCAN3 transcriptional repressor by JNK2/p38-MAPK. Blockade of BRAFi-induced transcriptional activation of autophagy-lysosomal function in melanoma xenografts causes enhanced tumor progression, EMT-transdifferentiation, metastatic dissemination, and chemoresistance, which is associated with elevated TGF-β levels and enhanced TGF-β signaling. Inhibition of TGF-β signaling restores tumor differentiation and drug responsiveness in melanoma cells. Thus, the "BRAF-TFEB-autophagy-lysosome" axis represents an intrinsic regulatory pathway in BRAF-mutant melanoma, coupling BRAF signaling with TGF-β signaling to drive tumor progression and chemoresistance.
Fundamental understanding of pore‐scale methane hydrate dissociation in porous media is important to evaluate submarine slope stability and potential utilization of methane resources. In this paper, ...a general pore‐scale framework based on the lattice Boltzmann (LB) method is established for reactive transport coupled with nonisothermal multiple physicochemical processes in porous media. The framework combines the gas hydrate dissociation kinetic model, the single‐phase flow LB model, the mass transport LB model, and the conjugate heat transfer LB model. The pore‐scale framework is validated by several benchmark problems and then employed to investigate the endothermic dissociation process of methane hydrate with pore‐filling and grain‐coating habits in porous media. The methane hydrate endothermic dissociation behavior coupled with nonlinear nonisothermal multiple physicochemical processes involving intrinsic dissociation dynamics, gas flow, mass transport, phase change heat transfer, and conjugate heat transfer is well captured by the framework. The phase change of methane hydrate dissociation and pore structure evolution for different pore habits of hydrate are well depicted, and some insights about the dissociation front advancement and temperature distributions are also obtained. In addition, the effects of temperature field, inlet temperature, and inlet pressure on methane hydrate dissociation are investigated. The pore‐scale methane hydrate dissociation helps to advance our understanding of permeability‐saturation variation relation for continuum models.
Key Points
A pore‐scale lattice Boltzmann model for reactive transport in porous media is established
Methane hydrate dissociation induced dissociation front evolution and variation of transport properties in porous media are studied
Effects of temperature and pressure on pore‐scale dissociation process of pore‐filling and grain‐coating methane hydrates are emphasized
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ferroptosis is a recently recognized form of regulated cell death driven by lipid‐based reactive oxygen species (ROS) accumulation. However, the molecular mechanisms of ferroptosis regulation are ...still largely unknown. Here we identified a novel miRNA, miR‐9, as an important regulator of ferroptosis by directly targeting GOT1 in melanoma cells. Overexpression of miR‐9 suppressed GOT1 by directly binding to its 3′‐UTR, which subsequently reduced erastin‐ and RSL3‐induced ferroptosis. Conversely, suppression of miR‐9 increased the sensitivity of melanoma cells to erastin and RSL3. Importantly, anti‐miR‐9 mediated lipid ROS accumulation and ferroptotic cell death could be abrogated by inhibiting glutaminolysis process. Taken together, our findings demonstrate that miR‐9 regulates ferroptosis by targeting GOT1 in melanoma cells, illustrating the important role of miRNA in ferroptosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fluid flow in nanoscale organic pores is known to be affected by fluid transport mechanisms and properties within confined pore space. The flow of gas and water shows notably different ...characteristics compared with conventional continuum modeling approach. A pore network flow model is developed and implemented in this work. A 3‐D organic pore network model is constructed from 3‐D image that is reconstructed from 2‐D shale SEM image of organic‐rich sample. The 3‐D pore network model is assumed to be gas‐wet and to contain initially gas‐filled pores only, and the flow model is concerned with drainage process. Gas flow considers a full range of gas transport mechanisms, including viscous flow, Knudsen diffusion, surface diffusion, ad/desorption, and gas PVT and viscosity using a modified van der Waals' EoS and a correlation for natural gas, respectively. The influences of slip length, contact angle, and gas adsorption layer on water flow are considered. Surface tension considers the pore size and temperature effects. Invasion percolation is applied to calculate gas‐water relative permeability. The results indicate that the influences of pore pressure and temperature on water phase relative permeabilities are negligible while gas phase relative permeabilities are relatively larger in higher temperatures and lower pore pressures. Gas phase relative permeability increases while water phase relative permeability decreases with the shrinkage of pore size. This can be attributed to the fact that gas adsorption layer decreases the effective flow area of the water phase and surface diffusion capacity for adsorbed gas is enhanced in small pore size.
Key Points
A multiphase pore network flow model is proposed to study gas‐water flow pattern in nanoporous organic matter
Effects of slip length, contact angle, flow area on water flow are considered and gas flow accounts for full range of transport mechanisms
Water relative permeabilities decrease and gas relative permeabilities increase with the decrease of pore size
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Direct pore-scale modelling of two-phase flow in three-dimensional porous media by VOF method.•The evolution of remaining oil was investigated by considering wettability, viscous force and capillary ...number.•Phase circulation phenomenon was simulated and two circulation patterns were found which can be interconverted.•Preferred conditions for improving the oil recovery rate was discussed in detail.
Characterizing the trapped phase in porous media is essential for many engineering applications, such as enhanced oil recovery, nuclear storage, and geological sequestration of CO2. This study aims to study the distribution, evolution, and influencing factors of the remaining oil in the process of water flooding at the pore scale. The single-connected pore space model was established by reconstructing the real micron CT scanned images of carbonate rocks. The VOF (volume of fluid) method using FSF (filtered surface force) formulation was adopted on OpenFOAM platform to simulate the oil-water two-phase flow process at the pore scale. Different wettability and capillary number were considered in the model. The accuracy of the model was proved by comparing with previous experimental results. The results showed that in the process of water flooding, the complex pore structure would lead to the generation of remaining oil, and the phase circulation phenomenon can be observed in the remaining oil and presents two distribution forms: co-current driven flow and lid-cavity driven flow. It also revealed that the phase recirculation increases the viscous dissipation. Further research also showed that the two forms of recirculation could be transferred by changing the wettability and that a higher capillary number was more beneficial for reducing the remaining oil saturation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Digital core simulation technology, as an emerging numerical simulation method, has gradually come to play a significant role in the study of petrophysical properties. By using this numerical ...simulation method, the influence of micro factors on seepage properties of reservoir rock is taken into consideration, making up the shortcomings of the traditional physical experiment. Three-dimensional core images are reconstructed by a computed tomography scanning technique. Different sizes of the sub-region were simulated by three methods including the direct computation of Navier-Stokes equations, the simulation of the pore network model, and the lattice Boltzmann method. The permeability computed by each simulation was compared. After comparison between these three methods, the results of the direct computation method based on Navier-Stokes equations were found to be higher than the other two methods. The pore network model simulation has an obvious advantage on the computation speed and the simulation area. The lattice Boltzmann method shows the low efficiency due to the time-consuming process. At last, the permeability calculated by the three methods is matched by the Kozeny-Carman equation. A more accurate formula can be obtained by a series of numerical simulations, which can be applied to marco-scale simulation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•A nanoscale multiphase pore network transport model is proposed.•Multiphase transport in dual wettability nanoporous shale is studied.•Effects of slip length, contact angle, flow area on water flow ...are considered.•Gas flow accounts for multiple transport mechanisms.
Fluid transport in nanoporous shale is known to be affected by the nanoscale fluid transport mechanisms, surface wettability and heterogeneous pore structure. The pores of shale are believed to be dual surface wettability with gas-wet organic pores and water-wet inorganic pores. Investigation on the nanoscale multiphase transport behavior in dual surface wettability nanoporous shale has practical implication in understanding inject water distribution during injected water flow in and flow back process. In this study, we propose a nanoscale gas and water multiphase pore network transport model to study nanoscale confined gas and water transport behavior in dual wettability nanoporous shale. A 3-D shale pore network model is constructed from 3-D image that is reconstructed from 2-D shale SEM image of organic-rich sample. Water transport considers the boundary slip length determined by the contact angle. Bulk gas transport in inorganic pores considers slip effect while bulk gas transport and surface diffusion for adsorbed gas are both considered in organic pores. Injected water flow in process is modeled by water displacing gas process while injected water flow back process is modeled by gas displacing water process. Gas and water relative permeabilities during injected water flow in and flow back process at different TOC volumes and inorganic pore contact angle are analyzed in detail and are compared with relative permeabilities without nanoscale transport mechanisms. Study results reveal that nanoscale gas and water relative permeabilities are influenced by the total organic carbon (TOC) in volumes and inorganic pore water contact angle while nanoscale transport mechanisms influence on the relative permeabilities can be neglected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Due to the multi-scale pore size and complex gas-bound water distribution, it is challenging to accurately predict gas transport property in shale. Given the known heterogeneities, single-resolution ...pore-scale imaging is not reliable for representative pore structure characterization. In this study, the image-based shale multi-scale pore network model (MPNM) is proposed and the impacts of pore structure and relative humidity (RH) on gas transport are analyzed in detail. 3D binary images are constructed by the multiple-point statistics method from a section of low-resolution SEM image which covers the large-scale pore structure and fine-scale SEM images with the same physical size at high resolution. The maximal ball fitting method is applied to extract large-scale pore network model (LPNM) and fine-scale pore network models (FPNMs) from the 3D binary images, respectively. MPNM is obtained by merging the LPNM and FPNMs based on the proposed procedure. The confined gas-bound water distribution at different RH is calculated considering the disjoining pressure resulting from van der Waals force, electric double-layer interactions and structural force. Gas slippage in irregular pores is considered for gas transport. Pore structure parameters and gas permeabilities are calculated based on the MPNM, LPNM and FPNMs. Study results indicate that the gas permeability of MPNM is more close to the laboratory pressure pulse decay measured gas permeability of studied sample. Gas permeability decreases with the increasing RH and drops to zero at average pore radius less than 12 nm and RH larger than 0.7.
Article Highlights
The image-based shale multi scale pore network model (MPNM) is proposed based on low resolution and high resolution SEM images.
Permeability of MPNM is more close to the laboratory measured permeability compared with that of fine scale and large scale pore network.
Gas permeability drops to zero at average pore radius less than 12 nm and relative humidity larger than 0.7.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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