Neddylation, a post-translational modification that adds an ubiquitin-like protein NEDD8 to substrate proteins, modulates many important biological processes, including tumorigenesis. The process of ...protein neddylation is overactivated in multiple human cancers, providing a sound rationale for its targeting as an attractive anticancer therapeutic strategy, as evidence by the development of NEDD8-activating enzyme (NAE) inhibitor MLN4924 (also known as pevonedistat). Neddylation inhibition by MLN4924 exerts significantly anticancer effects mainly by triggering cell apoptosis, senescence and autophagy. Recently, intensive evidences reveal that inhibition of neddylation pathway, in addition to acting on tumor cells, also influences the functions of multiple important components of the tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts (CAFs), cancer-associated endothelial cells (CAEs) and some factors, all of which are crucial for tumorigenesis. Here, we briefly summarize the latest progresses in this field to clarify the roles of neddylation in the TME, thus highlighting the overall anticancer efficacy of neddylaton inhibition.
Preexisting discontinuities, such as joints and beddings, are widely distributed in unconventional reservoirs. During fluid injection, hydraulic fractures strongly interact with preexisting ...discontinuities, leading to great uncertainty in prediction of fracture geometry. To investigate how preexisting discontinuities affect fracture complexity, numerical simulations are carried out using the distinct element method. A discrete fracture network (DFN) model for a shale reservoir in the southeastern Ordos basin, China is built. Four cubic models, including the (1) rock matrix model, (2) bedding model, (3) joint model and (4) bedding and joint model, are extracted from the DFN model and then are used for numerical simulations. The results indicate that preexisting discontinuities strongly influence fracture complexity: they impose a barrier for fracture growth in most cases, and thus result in a smaller fracture area and a higher fluid pressure for fracture extension. However, the roles that joints and beddings play in fracture complexity differ. Compared with the bedding model, the joint model causes a less complex fracture geometry under the same injection condition, suggesting that the joints play a more significant role in reducing fracture complexity.
•A 3D DFN model coupling different kinds of preexisting discontinuities is built.•Interaction between hydraulic fractures and preexisting discontinuities is modeled.•Influence of preexisting discontinuities on fracturing complexity is discussed.•Results show that joints play a significant role in reducing fracture complexity.
Outcrops and core observations show that sandy and tuffaceous laminas and natural fractures are well developed in the continental shale gas reservoir. This study reports the distribution of laminas ...and natural fracture networks at different scales, in cases of outcrops, wells and cores from Yanchang Formation, southern Ordos Basin. Firstly, based on two-dimensional fracture field investigations, a 3-D joint network model of the study area was built using the Monte Carlo simulation method. Then the laminations were identified from macroscopic scales to microscopic scales with multiple probe techniques. Statistical analysis of multi-scale layer thickness suggested that the average thickness of layers at multiple scales showed a fractal feature, and that the layer thickness at each scale followed with an exponential probability distribution, whose exponential coefficient was −3.38, −1.91, −1.65, −1.21, corresponding to meter scale, decimeter scale, centimeter scale and millimeter scale respectively. The fitting curves indicated that the majority of laminas at each scale were relatively thin, and the thicker the layer, the less the number of layers contained in shale. Finally, the lamination models were constructed and superposed over the joint network model to generate 3-D geological structure models at various scales. The models were validated by reproducing fracture and lamina parameters fairly close to those obtained from realistic geological bodies in the study area. The findings of this work could provide a more reliable geological model for the numerical simulation and physical model test of hydraulic fracturing in shale gas reservoir.
•Multi-scale 3D real geological model of the strata was established using Monte-Carlo simulation technique. It's the first time to establish the 3D geological strata model considering the fracture network and lamina in multi-scales.•In accordance to the probability distribution analysis, all the lamina thickness at studied scales are revealed to obey an exponential probability distribution.•The validation results suggest that the multi-scale laminas and natural fracture networks coincide with the outcrops and core samples in the study area. This result can be a good guide for the study of outcrops substitute for the several thousand meters depth strata.
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•The guided filter exhibited remarkable effectiveness in reducing data sparsity and enhancing data usability for downstream analysis.•The phase extraction method enabled the ...measurement of major phase proportions, including unreacted precursors, reaction products, and pores.•Classification of different reaction products was achieved by utilizing Mg/Al ratios as thresholds, with validity confirmed using the element ratios and shortest distance function.•The proposed analysis framework offers both visual and quantitative insights into the microstructure evolution of alkaline-activated cementitious systems.
Accurately quantifying the proportions and distributions of reaction products is crucial for interpreting reaction mechanisms and microstructure evolution in alkaline activated fly ash/slag pastes. However, existing techniques are limited in their ability to provide a comprehensive and visual analysis. This paper presents a versatile energy dispersive X-ray spectroscopy (EDS) mapping analysis that enables image enhancement, phase extraction, and component classification in the alkaline-activated materials (AAMs) -irrespective of the nature and quality of element mappings. The proposed methodology effectively removes the detection noise that inherently existed in EDS mappings, subsequently reinforcing the accuracy of the clustering analysis. The phase extraction procedure allows for obtaining the proportion of pores, reaction products, and unreacted solid precursors (SPs). Moreover, the component classification procedure enables further categorization of the reaction products and unreacted SPs. By analyzing the element ratios and shortest distances, the chemical compositions and spatial distributions of various reaction products could be revealed. Through the application of different analysis schemes, a consistent tendency was obtained, validating the practicability and reliability of this methodology.
Tuff rock is highly heterogeneous due to volcanic activity, hydrothermal alteration, and weathering. It is difficult to explain the deterioration mechanisms of the weathered rocks merely based on ...mineralogical and chemical parameters. It has been reported that subtle weathering can modify pore structure and subsequently affect the rock mechanical behavior of tuffs. In this work, the pore characteristics in slightly weathered tuffs and fresh tuffs are systematically analyzed based on Nuclear Magnetic Resonance (NMR) and Mercury Intrusion Porosimetry (MIP) tests. Additionally, meso-level uniaxial compression tests were conducted on the tuff samples by utilizing the MTI–LM (miniature tensile instrument–light microscope) system to detect the crack propagation and deformation process. The results demonstrated that additional mesopore (10–50 nm) increases with pore throat expansion during weathering, and the change of pore structure influences the tuff failure mode. Specifically, for the slightly weathered tuff, crack initiates in the altered minerals or matrix and results in shear failure. However, as for the fresh tuff, crack usually initiates in the intact and fresh minerals and matrix, and eventually leads to tensile failure. Therefore, we propose that tuff pore property can serve as potential indicator of the micro-mechanism of substantial macro-deterioration due to weathering.
•Revealing increase of mesopores and expansion of pore throats in tuff during weathering.•Pore throats become more homogeneous as weathering proceeds.•Pore properties changes indicate macro-deterioration of tuff during weathering.
•An economic and environmental approach has been established to optimize the recycled aggregate concrete (RAC) performance.•Numerical simulations is an effective approach to show agreeable results ...with the chloride ion migration tests.•Strong relationship between mechanical and durability properties of the treated RAC has been found.•The proposed RCA treatment method offers the possibility of using 100% RCA in concrete.
Disposal of construction and demolition wastes (C&DW) has been deemed as a major concern all over the world due to their disposal crisis that often adversely affect the environment. Several efforts are being made to recycle and manage such wastes for using them in the different building materials production. Using recycled concrete aggregate (RCA) as a partial or full substitution for normal aggregate (NA) in cement concrete is becoming a desirable solution to handle the huge amount of (C&DW). However, RCA possesses relatively higher porosity due to the adhered mortar, which often impedes its application in the construction industries. This paper proposes an economic and environmental approach to optimize the recycled aggregate concrete (RAC) performance. Outcomes showed that the modified RAC exhibited better mechanical strength and higher chloride ion migration resistance than untreated RAC. Compared with normal concrete (NAC), the loss in compressive strength was between 4.5 and 18%, flexural strength 3–18.5%, and elastic modulus 8–22% for the modified RAC at 28-days age. The numerical simulation model to analyze the chloride migration process for the treated RAC showed a good convention with the experimental test results. X-μCT images demonstrated that the untreated RCA sample has larger pores and air voids than the treated RCA samples. The proposed strengthening technique improved the micro-structure of the ITZ for RAC, making it denser and reduced the micro-cracks when compared with the untreated RAC. This technique provides the possibility to use 100% RCA in concrete and address the long-term environmental, waste disposal, and economic goals.
This paper optimizes the 2D Wadell roundness calculation of particles based on digital image processing methods. An algorithm for grouping corner key points is proposed to distinguish each ...independent corner. Additionally, the cyclic midpoint filtering method is introduced for corner dealiasing, aiming to mitigate aliasing issues effectively. The relationships between the number of corner pixels (m), the central angle of the corner (α) and the parameter of the dealiasing degree (n) are established. The Krumbein chart and a sandstone thin section image were used as examples to calculate the 2D Wadell roundness. A set of regular shapes is calculated, and the error of this method is discussed. When α ≥ 30°, the maximum error of Wadell roundness for regular shapes is 5.21%; when 12° ≤ α < 30°, the maximum error increases. By applying interpolation to increase the corner pixels to the minimum number (m
) within the allowable range of error, based on the α-m
relational expression obtained in this study, the error of the corner circle can be minimized. The results indicate that as the value of m increases, the optimal range interval for n also widens. Additionally, a higher value of α leads to a lower dependence on m. The study's results can be applied to dealiasing and shape analysis of complex closed contours.
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