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Purpose Our study was to investigate the correlation between 18F-FDG uptake in HCC and tumor PD-L1 expression in HCC, and assess the value of 18F-FDG PET/CT imaging for predicting PD-L1 expression in HCC. Methods A total of 102 patients with confirmed HCC were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of HCC lesions were assessed using 18F-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 Results The SUVmax of HCC primary tumors was higher in patients with poorly differentiated HCC, large tumor size, portal vein tumor thrombus, lymph node and distant metastases, and death. The SUVmax of HCC are correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. PD-L1 expression was significantly correlated with tumor SUVmax, tumor differentiation, tumor size, portal vein tumor thrombosis, and patient survival status and infiltrating M2 macrophages. Further, our results confirmed that SUVmax, portal vein tumor thrombosis, and the number of infiltrating M2 macrophages were closely related to PD-L1 expression and were independent risk factors by multivariate analysis. The combined assessment of SUVmax values and the presence of portal vein tumor thrombosis by 18F-FDG PET/CT imaging can help determine PD-L1 expression in HCC. Conclusions FDG uptake in HCC was positively correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. The combined use of SUVmax and portal vein tumor thrombosis by PET/CT imaging assess the PD-L1 expression better in HCC. These findings also provide a basis for clinical studies to assess the immune status of tumors by PET/CT.

Perforation is the key to the successful implementation of hydraulic fracturing, and the study of perforation parameters is of great significance for reservoir reconstruction and oil and gas exploitation. A finite element model is established to simulate multi-hole fractures' initiation and propagation based on the global embedded cohesive zone model. In the model, the reservoir is considered a dense, low-permeability porous elastic medium, wherein the coupling effect of fluid and geomechanics during fracturing is considered. The KGD analytical solution is consistent with the simulation results, verifying the cohesive zone model's accuracy. The results show that there are four competitive modes for multi-hole crack initiation. Firstly, the cracks open initially and remain open; secondly, the hole is open but not cracked; thirdly, the initial initiation extends and then closes; finally, the initial crack did not start in the late crack. With the increase of perforation density, the perforation initiation rate and average fracture pressure gradually decrease, and the fracture complexity in the near-wellbore area increases. With the increase of displacement and viscosity, the initial crack rate, the number of main cracks and microcracks formed in the hole tend to increase, while horizontal stress difference has an inversely proportional trend. In the presence of multiple perforating holes, the crack propagation presents a change from complex to simple, and the number of cracks presents a change from more to less. The expansion mode is formed with 2–4 main cracks and micro-cracks as auxiliary.

The study on induced stress of hydraulic fracturing is an important part of hydraulic fracturing design, temporary plugging and steering fracturing design, and completion design in oil and gas development. Based on fracture continuum method (FCM), cohesive unit method, and finite volume method (FVM), the propagation behavior of multiple hydraulic fractures (HFs) in fractured‐porous media reservoir is simulated from the perspective of fluid and geological stress coupling. The influence of natural fractures (NFs) on stress distribution and stress inversion sensitive factors are studied. NFs in the model are equivalent to physical models controlled by tension and shear bonds. The proposed model can deal with any number of NFs, which greatly improves the computational efficiency of the model. Then PKN analytic solution and Abaqus software results were used to verify the correctness of our model. The results show that the NF will make the reservoir stress show strong heterogeneity after fracturing, and the prominent feature is the regional stress mutation. The sudden change of stress shows the sudden increase or decrease in stress; with the increase in the initial stress difference, the stress inversion becomes more difficult. When the stress difference exceeds 3 MPa, the stress inversion area is almost 0. The stress interference increases with the decrease in cluster spacing. The stress inversion region between HFs decreases, while the external stress inversion region increases; Biot coefficient has great influence on stress and stress inversion. With the decrease in Biot coefficient, stress inversion region will decrease obviously. When the Biot coefficient is 0.4, there is no stress inversion area in the whole reservoir. Poisson's ratio has little influence on stress inversion. When Poisson's ratio changes between 0.1 and 0.3, the change range of stress is within 1 MPa, and the stress inversion area is almost unchanged. Our results can be helpful for understanding the stress distribution after hydraulic fracturing in fractured‐porous media.

Energy deprivation activates the cellular energy sensor AMP-activated protein kinase (AMPK), which in turn induces macroautophagy/autophagy. The mitochondrial-associated ER membrane (MAM) plays a key role in mitochondrial division and autophagy, and the mitochondrial fusion protein MFN2 (mitofusin 2) tethers the MAM, but the mechanism by which AMPK and MFN2 regulate autophagy in response to energy stress remains unclear. Here, we found that energy stress not only triggers mitochondrial fission and autophagy, but more importantly increases the number of MAMs, a process that requires AMPK. Interestingly, under energy stress, considerable amounts of AMPK translocate from cytosol to the MAM and the mitochondrion as mitochondrial fission occurs. Unexpectedly, AMPK interacts directly with MFN2. The autophagic ability of mouse embryonic fibroblasts (MEFs) lacking MFN2 (mfn2(−/-)) is significantly attenuated in response to energy stress as compared to wild-type MEFs (WT MEFs), while re-expression of MFN2 in mfn2(−/-) cells rescues the autophagy defects of these cells. The abundance of MAMs is also greatly reduced in MFN2-deficient cells. Functional experiments show that the oxygen consumption rate and the glycolytic function of cells lacking MFN2 but not MFN1 are obviously attenuated, and MFN2 is important for cell survival under energy stress. In conclusion, our study establishes the molecular link between the energy sensor AMPK and the MAM tether MFN2, and reveals the important role of AMPK and MFN2 in energy stress-induced autophagy and MAM dynamics. Abbreviations: ACTB, actin beta; AMPK, AMP-activated protein kinase; BECN1, beclin 1; CANX, calnexin; ER, endoplasmic reticulum; HRP, horseradish peroxidase; EM, electron microscopy; FL, full-length; KD, kinase dead, KO, knockout; MAb, monoclonal antibody; MAMs, mitochondria-associated membranes; MAP1LC3/LC3B, microtubule associated protein 1 light chain 3; MFN2, mitofusin 2; OPA1, OPA1 mitochondrial dynamin like GTPase; PAb, polyclonal antibody; PtdIns3K, class III phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; SD, standard deviation; TEM, transmission electron microscopy; TOMM20, translocase of outer mitochondrial membrane 20; ULK1, unc-51 like autophagy activating kinase 1; MEF, mouse embryonic fibroblast; WT, wildtype

Attribute to the hydraulic fracturing technology, China has carried out commercial development of the low permeability and tight gas reservoirs in Sulige Gasfield, Ordos Basin. However, the practice indicates that the gas well with hydraulic fracturing performs rapid decline rate, which generally repeated fracturing technology is often adopted to enhance the economic benefits of gas field development. Therefore, the reservoir physical properties, pressure system, fluid properties, and formation parameters of fracturing engineering, such as rock characteristic parameters and original in-situ stress, are respectively summarized. Furthermore, compared with traditional hydraulic fracturing, the theory of refracturing and the simulation of crack extension are studied. This study starts from the geological characteristics, gas reservoir properties and rock physical properties of the main layer. Firstly, based on the theory of rock elasticity, the problem of crack induced stress field is analyzed. Then, combined with the rock media and mechanical environment around the initial artificial crack, the mathematical model of the induced stress field of the initial artificial crack is established. Meanwhile, the semi-inverse solution is applied to solve the mathematical model. Finally, the analytical formula of crack induced stress is obtained, by introducing Fourier transform, complex variable and Bessel function integral formula. Taking a fractured gas well in Sulige Gasfield as an example, only single-phase gas flowing is considered and depletion constant pressure production is adopted. The results show that: (a) The induced stress is mainly related to the net pressure on the crack wall, in which the induced stress in the direction of the original horizontal principal stress increases with the net pressure. (b) Through the simulation of tight gas reservoir performance, we found that the change of production induced stress is great with the longer production time, the lower bottom-hole flowing pressure and the more variable anisotropy of reservoir permeability. (c) The area of in-situ stress reorientation is also greater, and the new crack gets easy to change direction. (d) This simulation can help engineers realize that the initial artificial crack induced stress and gas well production induced stress all change the initial in-situ stress, thence, the new crack of refracturing will not fracture along the direction of the old crack. In this case, the Orientation-Angle and Extension-Length are recalculated, after calculating the current stress state in the direction of the original principal stress, and production time, bottom hole production pressure and others that affect the new crack are analyzed. More importantly, this research could be applied for other similar refracturing wells with vertical cracks in tight gas reservoirs worldwide and provides a research basis for the afterward study of the description of volumetric crack.

Network traffic flows contain a large number of correlated and redundant features that significantly degrade the performance of data-driven network anomaly detection. In this paper, we propose a novel clustering and ranking-based feature selection scheme, termed as CBFS, to reduce redundant features in network traffic, which can greatly improve the efficiency and accuracy of feature-based network anomaly detection. Our proposed CBFS scheme first calculates the distance between feature vectors, merges these feature vectors into different clusters, and selects the center of each cluster as a representative feature vector. The proposed CBFS scheme then integrates the information gain and gain rate of features to further streamline the number of features on the basis of clustering generation. Finally, the proposed CBFS scheme applies the decision-tree-based classifier to the generated subset of features so that the abnormal traffic flows are detected. The experimental results show that our proposed CBFS scheme is effective in reducing feature dimensions across different datasets. The proposed CBFS scheme can achieve feature reduction rates of 20% to 70%, and cost-performance of up to 70% as compared to benchmarking methods.

Among investigations on the mechanics of energy accumulation via well shut-in to increase oil production, reservoir imbibition is deemed effective. However, another element, i.e., the coupling effect of fluid flow and geomechanics has always been underrated in production. Hence, this is discussed herein based on seepage mechanics, elastic mechanics, and Biot pore elastic theory. Further, an integral mechanical coupling numerical model is established from staged fracturing on a horizontal well to analyze well shut-in and production, to simulate stress variation during the shut-in period and the impact of shut-in time on oil production. The model considers the coupling effect of oil and water flow, and geomechanics on the stress distribution of reservoir adjacent to hydraulic cracks during fracturing, well shut-in, and production. From the study of reservoir stress and physical parameters in different shut-down times, it is found that reservoir stress and physical parameters demonstrate some regular changes. The pore pressure and saturation demonstrate pressure diffusion and oil phase saturation recovery with increasing well shut-in time. Owing to pressure diffusion, horizontal maximum principal stress, and horizontal minimum principal stress, the shear stress and stress difference demonstrate high complexity. Meanwhile, permeability and porosity exhibit a complex distribution subject to effective stress; the characteristic parameters of reservoir rock based on construction parameters (total injection volume, injection rate, and shut-in time) affect the subsequent production considerably. The correlation curves drawn upon a simulated experiment that reflect the construction parameters against cumulative oil production indicate that cumulative oil production is in direct proportion to shut-in time and in reverse proportion to injection rate. The optimum shut-in time is correlated positively with both the total injection volume and injection rate.

With the rapid increase in the exploitation of shale reservoirs in the Sichuan province of China, the demand for long horizontal wells for contacting reservoirs has also significantly expanded. With increasing horizontal sections, the coiled tubing (CT) penetration depth and efficiency of the surface weight transferred to the weight-on-bit (WOB) downhole are limited by the friction between the CT and wellbore. Plug milling with CT has become less efficient, and the final bridge plugs close to the bottom cannot be removed. Therefore, an experiment is conducted to study the effects of the pump rate on the vibration amplitude of the axial and radial directions, vibration frequency, and pressure difference. An improved tubing force analysis model is used to study the effect of a vibrator with different pump rates and friction coefficients on the CT surface weight, maximum set-down force, maximum pickup force, CT lockup depth, and maximum WOB of different plugs in well wx202 of the Wei Yuan shale block. The calculated data exhibit strong agreement with the real-time data collected from previous CT operations. The simulated results are used to solve the problems faced when milling the final four plugs at the end of a long horizontal section in well wx202. The results indicate that the amplitude variation in the radial vibration at both ends of the hydraulic oscillator is greater than that in the axial direction under the same pump rate. The optimized flow rate for the vibrator is 8.33 L/s. The use of a vibrator can greatly reduce the friction and transfer that are sufficient for a WOB downhole.

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophago-some and then delivered to lysosome for destruction. Recently, tremen-dous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or au-tophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

Background To evaluate the value of preablative stimulated thyroglobulin (ps-Tg) before the first radioactive ablation iodine (RAI) treatment to predict the postoperative metastasis of DTC. Methods A total of 235 DTC patients, who underwent total thyroidectomy and neck lymph node dissection, were enrolled. On the basis of the presence or absence of metastasis, all patients were divided into metastasis (M1) and non-metastasis (M0) groups. Besides, the patients in the M1 group were further divided into two subgroups according to sites of metastasis. These groups included cervical lymph node metastasis and distant metastasis groups. Subsequently, the level of serum ps-Tg was measured 3 - 4 days before the first RAI ablation treatment, whereas 131I whole-body imaging and SPECT/CT tomography were performed 5 - 7 days after radio ablation. Subsequently, the Mann Whitney U test was used to compare the different levels of ps-Tg between the two groups. Additionally, the relationship between ps-Tg and the metastasis of DTC was analyzed through correlation analysis, regression analysis, and the ROC curve. Results The ps-Tg level in the M1 group was higher than that in the M0 group. Further analysis discovered that the ps-Tg in the distant metastasis group was higher than that in the cervical lymph node metastasis and non-metastasis groups. Also, the ps-Tg level was positively correlated with distant metastasis (r = 0.599, p = 0.000). Besides, the results of multivariate logistic regression analysis outlined that the level of ps-Tg was an independent risk factor for the development of distant metastasis (OR = 1.008, p = 0.018). Subsequently, the results from the ROC analysis also showed a good diagnostic performance for ps-Tg in treating distant metastasis (AUC = 0.964, p = 0.000), and the optimal cutoff value was 61.87 ng/mL. Conclusions The ps-Tg in patients with DTC before the first RAI ablation treatment is an independent risk factor and a meaningful indicator in predicting postoperative distant metastasis.

This paper presents our vision of on-the-wall tangible interaction. We envision a future where tangible interaction can be extended from conventional horizontal surfaces to vertical surfaces; indoor vertical areas such as walls, windows, and ceilings can be used for dynamic and direct physical manipulation. We first discuss the unique properties that vertical surfaces may offer for tangible interaction and the interaction scenarios they imbue. We then propose two potential paths for realizing on-the-wall interaction and the technical challenges we face. We follow with one prototype called Climbot. We showcase how Climbot can be used as an on-the-wall tangible user interface for dynamic lighting and as a wall switch controller. We conclude with a discussion of future work.

We propose Auth+Track, a novel authentication model that aims to reduce redundant authentication in everyday smartphone usage. By sparse authentication and continuous tracking of the user’s status, Auth+Track eliminates the “gap” authentication between fragmented sessions and enables “Authentication Free when User is Around”. To instantiate the Auth+Track model, we present PanoTrack, a prototype that integrates body and near field hand information for user tracking. We install a fisheye camera on the top of the phone to achieve a panoramic vision that can capture both user’s body and on-screen hands. Based on the captured video stream, we develop an algorithm to extract 1) features for user tracking, including body keypoints and their temporal and spatial association, near field hand status, and 2) features for user identity assignment. The results of our user studies validate the feasibility of PanoTrack and demonstrate that Auth+Track not only improves the authentication efficiency but also enhances user experiences with better usability.

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, etc. 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, etc. 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.

We prove that certain crystabelline deformation rings of two dimensional residual representations of $$\mathrm {Gal}(\overline{\mathbb {Q}}_p/\mathbb {Q}_p)$$ are Cohen–Macaulay. As a consequence, this allows to improve Kisin’s $$R[1/p]=\mathbb {T}[1/p]$$ theorem to an $$R=\mathbb {T}$$ theorem.

Let $p$ be a prime and $L$ be a finite extension of $\mathbb{Q}_p$. We study the ordinary parts of $\mathrm{GL}_2(L)$-representations arised in the mod $p$ cohomology of Shimura curves attached to indefinite division algebras which splits at a finite place above $p$. The main tool of the proof is a theorem of Emerton \cite{Em3}.

The fracture propagation in hydraulic fracturing is described as a nonlinear problem dynamic boundary. Due to the limitation of mesh refinement, it is difficult to obtain the real crack propagation path using conventional numerical methods. Meshless methods (MMs) are an effective method to eliminate the dependence on the computational grid in the simulation of fracture propagation. In this paper, a hydraulic fracture propagation model is established based on the element-free Galerkin (EFG) method by introducing jump and branch enrichment functions. Based on the proposed method, three types of fracturing technology are investigated. The results reveal that the stress interference between fractures has an important impact on the propagation path. For the codirectional fracturing simultaneously, fractures propagate in a repel direction. However, the new fracture is attracted and eventually trapped by the adjacent fracture in the sequential fracturing case. For the opposite simultaneous fracturing in multiwells, two fractures with a certain lateral spacing will deflect toward each other. The effect of stress shadow should be used rationally in the optimization of construction parameters; for the single well multistage fracturing, the stage spacing should be out of stress inversion area, while for the simultaneous fracturing of multiple wells, stress inversion zones should be used to maximize communication between natural fractures. Overall, this study establishes a novel and effective approach of using MM to simulate the propagation of hydraulic fractures, which can serve as a useful reference for understanding the mechanism of hydraulic fracture propagation under various conditions.

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.

Artificial intelligence (AI) is enabling the automated analysis of large amounts of image/video data, boosting the speed of multimedia data processing remarkably. Meanwhile, Image Quality Assessment (IQA) plays an important role in developing automatic analysis methods. To ensure the effectiveness of AI, images in multimedia applications should be considered for visual examination by both human and machine. Therefore, it is significant to understand the differences between human's and AI's perception of semantic distortion. However, little work has been done due to the lack of data from human on the semantic level. In this paper, we first propose a semantic database (SID) based on the surveillance scenarios, by collecting subjective average recognition rates of 3 semantic targets (face, pedestrian, license plate) with 3 types of distortion (JPEG Compression, BPG Compression, Motion Blur). Then, we present a detailed analysis of how human and AI perceive semantic distortion differently. Experimental results show that AI is stronger in tolerance to distortion than human beings on average, while weaker at generalization and stability. It is also implied in the experiments that existing IQA methods are not effective enough at judging the semantic distortion.

Proppant distribution has great influence on well performance. It's necessary to investigate the mechanism of proppant distribution in fracturing treatment. This paper presents a new coupled model of fracture propagation with proppant transport. The model considers the coupling of sand settling, proppant bed build-up and wash-out, fluid velocity, and fluid filtration in extending fracture. The finite difference method combined with boundary element method are used to make the model quickly solved. Two different moving mesh systems are used to facilitate the moving boundary. The solutions are validated against published experimental data. The effect of fluid viscosity, injection rate, fluid filtration, injection proppant concentration and particle size on proppant distribution in fracture is studied. According to the study, proppant settling has great influence on the proppant bed balance height and proppant concentration. Fracture length and width decreases with the increase of the fluid leak-off coefficient, increases with the increase of the injection rate. The transport distance of proppant increases with the increasing injection rate, fluid viscosity and injection proppant concentration, and decreases with the increasing particle size. Fluid leak-off has less effect on equilibrium height of proppant bed and proppant migration distance.

A number of reports have been focusing on chemical compositions and functional properties of essential oils isolated from mint. However, there is little data available on the biological activities of non-volatile constituents. In this study, the antibacterial (against 2 gram-positive bacterial strains: Staphylococcus aureus and Bacillus cereus; 2 gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa), antifungal (against Candida albicans, Colletotrichum gloeosporioides and Penicillium polonicum) and cytotoxic (against Human Embryonic Kidney 293 cell line) activities of three non-volatile extracts (Extracts 1 to 3) from the leaves and stems of mint were evaluated. Extract 1 showed significant antibacterial activity against gram-positive pathogens S. aureus and B. cereus, with an inhibition zone of 12.60 and 12.08 mm, respectively. The minimal inhibitory concentration (MIC) of extract 1 against S. aureus was 0.94 mg/ml. On the other hand, it exhibited low cytotoxic activity against normal Human Embryonic Kidney 293 cell line (CI50 nearly 30 mg/ml), which suggested that Extract 1 could be a potential and safe antibacterial agent. Nevertheless, the tested gram-negative bacteria and pathogenic fungi were not susceptible towards Extracts 2 and 3. Key words: Mint, antibacterial activity, antifungal activity, cytotoxicity.

Highly-deviated well are applied for effectively developing WCH9 gas field with deep buried and low permeability, and the payzone are candidates for hydraulic fracturing by evaluation of gas reservoir. Therefore, fracture initiation pressure is a key parameter for design of hydraulic fracturing treatment. Firstly, a series of experiments were completed by core sample from target formation, Young's modulus is about 13GPa and Poisson's ratio is 0.286 at a confining pressure of 40MPa, horizontal principal stress is 78 MPa and 63 MPa, and in-situ stress profiles were interpreted by logging data. Then, the formation rock is regarded as isotropic linear elastic material, thus total stresses distribution on the deviated wellbore wall was determined by stress superposition principle, in which in-situ stress redistribution around the deviated wellbore, fluid pressure acted on the borehole wall and filtration stress are taken into account when fracturing fluid was injected into wellbore. Further, prediction model of fracture initiation pressure was established by applying criterion of maximum tensile stress and effective stress transformation. Lastly, according to the borehole trajectory, in-situ stress and other parameters from payzone of WCH9 block, fracturing initiation pressure varied with Deviation angle and azimuth angle were computed by numerical simulation method, these results provide a basis for optimization design of hydraulic fracturing technology parameters.

Perforation is the key to the successful implementation of hydraulic fracturing. The research on perforation mechanism is of great significance to perforation planning, completion design, hydraulic fracturing design, and proppant migration analysis. In this paper, a finite element model for simulating crack initiation and propagation in the presence of multiple perforations is established based on the global embedded cohesive zone model (CZM). The reservoir is considered as a dense, low-permeability porous elastic medium, and the coupling between fluid flow and geomechanics, as well as the back-stress effect, are considered. The Blanton's (1982) criteria were used to verify the accuracy of the global embedded CZM. Then five cases are used to discuss the effects of perforation density, horizontal stress difference (HSD) on fracture initiation, propagation, and fracture complexity. The results show: There are four competitive fracture initiation modes for multiple perforations: First, fracture initiation at an early stage and keeping on; Second, hole deformed but not cracked; Third, fracture initiation first and then close; Fourth, at the beginning, there is no fracture initiation, initiation later. With the increase of perforation density, affected by the decrease of flow distribution, increase of friction and stress interference, the initiation rate of perforations gradually decreases, and the fracture pressure shows a tendency of decreasing first and then increasing. When multiple perforations exist, the crack propagation changes from complex to simple, and the number of cracks changes from more to less. Finally, the expansion mode is formed with 2–3 main cracks as the main and micro cracks as the auxiliary. The increase of perforation density can increase the complexity of fractures around the wellbore, and is beneficial to the diversion of fractures and the expansion of the impact range of fractures. However, it can also cause distortion and deformation of the fracture wall and decrease of fracture opening near the wellbore, which can lead to difficulty in proppant migration. Under low HSD, under the influence of stress inversion, connected horizontal cracks are easy to form between holes, and the fractures are easier to turn and more complicated. Under high HSD, disconnected horizontal micro-cracks can be formed between holes, and the main fractures tend to develop into simple straight fractures. The results of our research have important practical guiding significance for the development of perforation plan, hydraulic fracturing design and proppant migration analysis.

Spontaneous imbibition behavior gained popularity several decades ago which led to widely exploited application in fractured reservoirs. Recently the imbibition behavior of unconventional reservoirs has attracted a good number of researchers and field engineers to pay attention and research more on how to enhance recovery through imbibition behavior. Despite the numerous studies that have been conducted in this area, it is still controversial whether spontaneous imbibition behavior is applicable on reservoir stimulation especially for shale reservoir. In this paper, the recent works on the spontaneous imbibition behavior in unconventional reservoirs particularly for shale has been reviewed. This paper is divided into four main sections, the first section presents the review of the research progress in wettability, the imbibition scale model, and the pore-throat structure with regard to the capillary force and its related influencing factors. Moreover, the shortcomings of current research methods are presented. The second section involves the water–rock interaction examination including the ion exchange between the fracture fluid and reservoir as well as the evolution of the rock physical properties during well shut-in. The third section presents the review of the numerical simulation methods that have been used to study imbibition in the recent years focusing on the flow characteristics at the micro scale. In the final section, the future research directions from the current conducted researches have been suggested. Our research proposes that the thermal-hydro-mechanical-chemistry multi-field coupling effect should be considered in numerical simulations. It can provide a basis and reference for quantifying the effect of imbibition stimulation during the shut-in time.

Non-planar fractures often occur in directional well fracturing and old well refracturing, which has great influence on fracture parameters and well production. To better understand the mechanism of non-planar fracture propagation, the mathematical model of non-plane fracture propagation is established based on the coupling of rock deformation and fluid flow in fracture. The coupled model is solved by a combination of the displacement discontinuity method and finite difference method, and the whole numerical calculations are carried out by MATLAB-developed program. The accuracy of the model is verified by comparing the calculated results with existing models and published experiment. The effect of perforation angles, horizontal stress differences and injection rates on fracture extension trajectory, fracture width, injection pressure and pressure distribution in fracture is investigated. The model is also employed to explore the influence of injection rate and perforation angles on fracture propagation path in the Mahu block, Xinjiang province, China. The results indicate that the coupled model has a good agreement with the published experiment data. Fracture turning distance increases with the increasing injection rate. Perforating in the direction of maximum principal stress and low injection rate is beneficial to reduce the injection pressure. Fracture width near wellbore decreases with the increasing perforation angle and differential stress, and increase with the increasing injection rate. Injection pressure increases with the increasing perforation angle, differential stress and injection rate. In the non-planar fracture propagation process, fracture width first increases and then decreases gradually. With the growing differential stress, perforation angle and injection rate has less influence on fracture turning. In the formation with high differential stress, it is difficult to achieve long fracture turning distance.

Refracturing, temporary plugging, and infilling well design play an important role in the development of reservoirs. The prediction of stress distribution can provide the basic guiding theory for the design and implementation of these techniques. In this paper, a fully-coupled three-dimensional production model based on the finite element method (FEM) and fracture continuum method (FCM) for naturally fractured reservoirs is presented to study the effects of fluid consumption on the reservoir stress. Furthermore, the effects of natural fractures on the stress re-distribution and stress re-orientation are also studied. The model also considers the influence of natural fractures on the permeability, and the effect of the effective stress on natural fracture openings, pore-elastic deformation, and fluid consumption. An analytical solution model and Eclipse were used for the comparison, which verifies the accuracy of the model results. Based on two cases of one cluster of fractures and three clusters of non-planar fractures, the research results revealed that natural fractures have a significant influence on the surrounding drainage, stress distribution, and stress re-orientation during the development. Under the influence of natural fractures, the production of the fluid along the direction of natural fractures is significantly easier, and it is highly probably that the insufficient consumption area is perpendicular to the direction of natural fractures. Compared with the conventional model, the stress distribution in the proposed model is deflected to a certain extent under the flow mode dominated by natural fractures, which is significantly prominent in the non-planar fracture model. Due to the effect of natural cracks, the absolute values of the stress, displacement, and stress difference in this model are relatively larger than those in the conventional model. Moreover, the re-orientation angles of the maximum principal stress are significantly different. After considering the natural cracks, there was an increase in the change in re-orientation and the re-orientation range. The research findings reported in this paper can be used to predict the initiation, extension, and steering process of temporary plugging fracturing fractures and refracturing fractures in fractured reservoirs.

The aim of the study involves examining the effect of heavy oil viscosity on fracture geometry in detail by establishing a heavy oil fracturing model and conventional fracturing model based on thermal–hydraulic–mechanical (THM) coupled theory, Walther viscosity model, and K–D–R temperature model. We consider viscosity and density within the heavy oil fracturing model as functions of pressure and temperature while that as constants within the conventional fracturing model. A heavy oil production well is set as an example to analyze the differences between the two models to account for the thermo-poro-elastic effect. The results show that temperature exhibits the most significant influence on the heavy oil viscosity while the influence of pressure is the least. In addition, a cooling area with a width of 0–1 m and varied length is generated near the fracture. The heavy oil viscosity increases sharply in this area, thereby indicating an area of viscosity increment. The heavy oil viscosity increases faster and is closer to wellbore, and a high viscosity increment reduces the mobility of the heavy oil and prevents the fracturing fluid from entering into the reservoir. The special viscosity distribution results in significant differences in pore pressure, oil saturation, and changing trends between these two models. In the heavy oil reservoir fracturing model, the thermal effect completely exceeds the influence of pore elasticity, and the values of the fracture length, width, and static pressure exceed those calculated in the conventional fracturing model. Thus, a comparison of the measured values indicates that the results obtained by considering viscosity as a function of temperature and pressure are more accurate. Therefore, the results of this study are expected to provide good guidelines for the design of heavy oil fracturing.

Gymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3-I (LC3-I)/LC3-II in MIN-6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase β-1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase-3 under the high glucose stress. The inhibition of apoptosis and caspase-3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet β cells MIN-6. Our data suggested that GA I-induced autophagy protected MIN-6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR.

Background: Laccases, copper-based polyphenol oxidases, played vital roles in lignin and humus degradation as well as fruiting body formation and stress response. Sixteen putative laccase genes (Lacc1-Lacc16) were reported in the genome of white-rot fungus Ganoderma lucidum. Members in this multi-gene family usually had close inter-relationships and may vary in the roles contributing to functions. Identifying the interactions among multiple genes and thus the conjoined consequence to an activity was essential for systematically unraveling the molecular mechanisms of laccase and improving laccase activity. Methods: In this study, multivariate statistical analysis was applied to track the relationship between thetranscriptional level of laccase genes and the total enzymatic activities. We outlined and compared the interaction networks among the transcriptional levels of 16 laccase genes and associations with the total enzymatic activities with or without copper ion (Cu 2+ ). Results: A multi-gene interaction network among the sixteen genes and laccase activity was constructed to figure out the changes induced by Cu 2+ . The interaction network showed that the enzyme activity was the result of interactions among genes, and these interactions might vary with the presence of Cu 2+ , subsequently leading to the alteration of enzyme activity. Some genes always kept relation with enzyme activity (positive or negative, Lacc13, Lacc10), some were irrelevant (Lacc1, Lacc6), while another some were inconsistent (Lacc3, Lacc8, Lacc14 and Lacc15). Discussion: Network-based methods were applied to identify key functional genes and to outline associations among genes and phenotype in laccase multi-gene family. This is an exploratory strategy to describe the transcriptional complexity of laccase and its relevant responses to Cu 2+ stress. The identified key functional genes associated with laccase activity (e.g. Lacc10, Lacc13) and the associations among genes and activity will benefit for the regulation of enzyme activity.

Semantic information is important in video encryption. However, existing image quality assessment (IQA) methods, such as the peak signal to noise ratio (PSNR), are still widely applied to measure the encryption security. Generally, these traditional IQA methods aim to evaluate the image quality from the perspective of visual signal rather than semantic information. In this paper, we propose a novel semantic-level full-reference image quality assessment (FR-IQA) method named Semantic Distortion Measurement (SDM) to measure the degree of semantic distortion for video encryption. Then, based on a semantic saliency dataset, we verify that the proposed SDM method outperforms state-of-the-art algorithms. Furthermore, we construct a Region Of Semantic Saliency (ROSS) video encryption system to demonstrate the effectiveness of our proposed SDM method in the practical application.

Special nanoscale storage mechanisms and pore radii create complex shale gas transport mechanisms. Shale gas reservoir production performance evaluations are challenging due to difficulties associated with microcosmic flow mechanisms, such as Knudsen diffusion, surface diffusion, adsorption and desorption. A thorough understanding of the effects of these transport mechanisms on shale gas production can help to develop new and improved shale gas production prediction models. This paper derives a unified apparent permeability equation based on the Knudsen number and four flow regimes, incorporating viscous, slip, transition and free molecule flows. The new apparent-permeability model also considers the surface diffusion, adsorption layer and tortuous diffusion path. Fully coupled differential equations were developed for a hydraulic fracture and matrix system based on these microcosmic transport mechanisms and using the finite difference method. A sensitivity analysis was performed to investigate the impacts of several parameters on production, including the nanopore radii, Langmuir parameters and bottom-hole flow pressure. The simulation results demonstrate that the microcosmic flow mechanisms significantly impact shale gas production. Gas production increases as the Langmuir parameters increase, but the rate of the increase decreases over time. Knudsen diffusion and surface diffusion become more prominent as the pore radius and reservoir pressure decrease. The adsorption layer cannot be ignored at sufficiently small pore radii.

Based on the impact of the stress perturbation effect created by simultaneous propagation of multiple fractures in the process of simultaneous hydraulic fracturing, a thorough research on the mechanism and adaptation of simultaneous fracturing of double horizontal wells in ultra-low permeability sandstone reservoirs was conducted by taking two adjacent horizontal wells (well Yangping-1 and well Yangping-2 located in Longdong area of China Changqing Oilfield) as field test wells. And simultaneous fracturing optimal design of two adjacent horizontal wells was finished and employed in field test. Micro-seismic monitoring analysis of fracture propagation during the stimulation treatment shows that hydraulic fractures present a pattern of complicated network expansion, and the well test data after fracturing show that the daily production of well Yangping-1 and well Yangping-2 reach 105.8 t/d and 87.6 t/d, which are approximately 9.4 times and 7.8 times the daily production of a fractured vertical well in the same area, respectively. Field test reflects that simultaneous hydraulic fracturing of two adjacent horizontal wells can enlarge the expansion area of hydraulic fractures to obtain a lager drainage area and realize the full stimulation of ultra-low permeability sandstone reservoirs in China Changqing oilfield. Therefore, simultaneous fracturing of two adjacent horizontal wells provides a good opportunity in stimulation techniques for the efficient development of ultra-low permeability reservoirs in China Changqing oilfield, and it has great popularization value and can provide a new avenue for the application of stimulation techniques in ultra-low permeability reservoirs in China.

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.

Organosulfur compounds (OSCs) are the bioactive components of garlic. Some OSCs have apoptotic or autophagy-inducing effects. Autophagy plays roles in both cytoprotection and apoptosis-related cell death, and the interaction between autophagy and apoptosis is important in the modulation of immune responses. The mechanism of an OSC-mediated effect via the interaction of autophagy and apoptosis is unknown. In this study, the effects of five OSC compounds on autophagy in the macrophage cell line RAW264.7 and primary macrophages were investigated. We found that S-allylcysteine (SAC), diallyl disulde (DADS) and diallyl tetrasulfide (DTS) treatment increased the number of autophagosomes of RAW264.7 cells, inhibited the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K/S6K1) which is a substrate of mammalian target of rapamycin (mTOR), and significantly enhanced autophagy flux. The induction of autophagy by SAC, DADS and DTS was inhibited by stably knocking down the expression of autophagy-related gene 5 (ATG5) with short hairpin RNA (shRNA). Further experiments confirmed that SAC, DADS and DTS also induced apoptosis in RAW264.7 cells. The induction of apoptosis and Caspase 3 activity by SAC, DADS and DTS were increased by stably knocking down of ATG5 expression with shRNA in RAW264.7 cells or treating with 5 mM 3-MA in primary macrophages. Our results suggest that SAC, DADS and DTS induce both autophagy and apoptosis. The autophagy induction protects macrophages from apoptosis by inhibiting mTOR phosphorylation activity to maintain the mass of immune cells.

Xiaokeping (XKP), a prescribed Traditional Chinese Medicine (TCM), has been used to treat patients with type Ⅱ diabetes mellitus for many years; however, the molecular mechanism of its effects is unknown. As the only insulin producer, the pancreatic β cell plays an important role in diabetes. Whether XKP influences the viability of pancreatic β cells remains to be substantiated. In the present study, autophagy/apoptosis analyses were used to evaluate the therapeutic effect of XKP on pancreatic β-cells induced by high glucose levels and to investigate a potential causal molecular mechanism of XKP effect on the cells. The pancreatic β-cell lines MIN-6 were divided into four groups: control, high glucose (33.3 mmol/L), high glucose with XKP, high glucose with XKP and 3-Methyladenine (3-MA). Immunofluorescence assay was employed to determine autophagosome formation and flow cytometry was used to determine apoptotic rates of the β cells by the detecting expression of autophagy- and apoptosis-related proteins. High glucose increased the apoptotic rate of β-cells from 5.37% to 23.24%; however addition of XKP mitigated the rate at 10.92%. Data indicate that autophagy of β-cells was induced by XKP via the mammalian target of rapamycin (mTOR) pathway. Where the autophagy inhibitor 3-MA was added, the apoptotic rate was 23.94%, similar to the high glucose group rate. The results suggest a potential cytoprotective effect of XKP from high glucose toxicity by its induction of autophagy which may be linked to mTOR-mediated autophagy.

We prove a new upper bound for the dimension of the space of cohomological automorphic forms of fixed level and growing parallel weight on $\mathrm{GL}_2$ over a number field which is not totally real, improving the one obtained by Marshall. The main tool of the proof is the mod $p$ representation theory of $\mathrm{GL}_2(\mathbb{Q}_p)$ as started by Barthel-Livne and Breuil, and developed by Paskunas., Final version

In this study, we investigated the biological function of pyruvate kinase M2 (PKM2) and its regulation by deregulated microRNAs (miRNAs) in thyroid cancer (TC). The mRNA and protein expression of PKM2 was examined by quantitative reverse transcription PCR and western blot. The biological role of PKM2 was demonstrated through small interfering RNA-mediated knockdown experiments. The regulation of PKM2 by miR-148a and miR-326 was confirmed by western blot, dual luciferase activity assays, and rescue experiments. PKM2 was overexpressed in TC tissues and cell lines. The knockdown of PKM2 in TC cells suppressed cell proliferation, reduced colony formation, and inhibited cell invasion and migration significantly. Luciferase reporter assays revealed that PKM2 is a direct target of two tumor-suppressive miRNAs, miR-148a and miR-326. Re-expressed PKM2 rescued the anticancer effects of miR-148a. Taken together, these data strongly suggest that, apart from gene amplification and mutation, the activation of PKM2 in TC is partly due to the down-regulation of the tumor-suppressive miRNAs miR-148a and miR-326. Thus, PKM2 is overexpressed and plays an oncogenic role in thyroid carcinogenesis.

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.

We prove the Breuil-Mezard conjecture for split non-scalar residual representations of Gal(Qp/Qp) by local methods. Combined with the cases previously proved in [18] and [24], this completes the proof of the conjecture (when p>3). As a consequence, the local restriction in the proof of the Fontaine-Mazur conjecture in [18] is removed., Final version. To appear in Ann. Scient. de l'E.N.S