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Abstract Phosphodiesterase-5 (PDE5) inhibitors have shown promise as anti-cancer agents in malignancies. However, their specific effects on gastric cancer (GC) and the underlying mechanisms remain elusive. Our aim was to investigate this by combining evidence from population-based studies with data obtained from in vivo and in vitro experiments. By combing a couple of nationwide Swedish registers, GC patients who received PDE5 inhibitors were compared to matched controls while adjusting for confounding factors. The anti-tumor effect and mechanism of the PDE5 inhibitor sildenafil were evaluated via using tumor cells, patient-derived tumor organoids and xenograft animal models in GC. A total of 161 Swedish GC patients from a nationwide population-based cohort who received post-diagnostic PDE5 inhibitors demonstrated lower cancer-specific mortality compared to the controls (HR = 0.66, 95% CI = 0.47-0.92, P = 0.016). Functionally, the PDE5 inhibitor sildenafil exhibited the suppressive ability to prevent oncogenic growth in GC. Mechanistically, sildenafil restrained GC growth by directly activating PKG through PDE5 inhibition for regulating c-MYC expression via its phosphorylation and ubiquitination degradation, thereby suppressing c-MYC stability for IL-6 transcription within the downstream IL-6/JAK/STAT3 signalling pathway. The PDE5 inhibitor sildenafil may serve as a promising adjuvant for GC therapy if further randomized clinical trials confirm its efficacy.

Abstract Background Gastric cancer poses a significant global health challenge. We aim to use period analysis to assess the changes in gastric cancer treatment at our center over the past 15 years. This study reflects the current state of gastric cancer treatment at our center and provides valuable data to support clinical advancements. Method We used period analysis to evaluate the survival status of 3915 patients with gastric cancer at Nanfang Hospital, Southern Medical University, over a 15-year period spaning from 2008 to 2022. The 5-year relative survival rates were analyzed. Result Our findings indicate that the 5-year relative survival rate at our center from 2018 to 2022 is 71.4%. From 2018 to 2022, the 5-year relative survival rates for patients aged

Polarization camera based on CMOS sensor and nano wire-grid technology have found widespread applications in medical diagnostics, remote sensing and industrial inspection. However, the limited filtering properties of wire-grid polarizers and the small field-of-view provided by conventional microlens restrict the energy efficiency of these systems while also increasing their cost, size and weight. In this study, we propose an innovative approach that integrates focusing and splitting of polarization states into a single-layer all-dielectric metasurface. This metasurface enables full-Stokes polarization imaging for a wide field-of-view conical light. The design of the metasurface utilizes a phase compensation method to effectively focus orthogonal polarized conical light onto the central pixel of the CMOS sensor. Theoretical analysis demonstrates that this metasurface can accurately detect full-Stokes parameters within ±20° incident cone angles with an average efficiency reaching 83.0%. The angle can be extended to ±90° with an average efficiency exceeding 80%. We fabricated a three super-pixel metasurface prototype, and experimental measurements reveal its ability to efficiently focus and split three pairs of orthogonal polarization states under ±11° conical angle incidence with an average focusing efficiency of 68.1%. This study presents a promising solution for achieving wide field-of-view and high-efficiency polarization detection in integrated CMOS systems.

To explore the impact of environmental factors on soil organic carbon (SOC) with machine learning (ML) model is of great significance for mitigating climate change and soil carbon sequestration and emission reduction. However, the traditional ML model is limited by the hyperparameter adjustment of artificially trial-and-error experimentation and the inexplicability of fitting process, and the precision and performance of ML model cannot be fully utilized. For the end, this study developed a tree-structured Parzen estimator-extreme gradient boosting (TPE-XGBoost) method based on SHapley additive explanations (SHAP) analysis to analyze the response of climate, human activities, soil properties and terrain for SOC (0-200cm) in different land use types of China. The results of descriptive statistics described the order of SOC content: forest land > grassland > cultivated land > unused land. With the increase of soil depth, the SOC content of all land types decreased continuously, and the values indicate a left-skewed non-normal distribution. The fitting accuracy (R2) of TPE-XGBoost model for SOC content was greater than 0.8. At the depth of 0-5cm, the prediction accuracy of cultivated land (R2 = 0.96), grassland (R2 = 0.93), forest land (R2 = 0.95) and unused land (R2 = 0.95) was the highest. The result of SHAP analysis showed that the factors that contributed the most to the fitting accuracy of cultivated land, grassland, forest land and unused land in all depths were temperature, soil pH, temperature and elevation. From surface to deep soil, the mean SHAP value showed a downward trend, indicating that the driving force of environmental factors on the content of SOC gradually weakened. The individual explanations of the variance partitioning (VP) analysis of climate, terrain, and soil property for cultivated land (0-200cm), forest land (30-60cm), and unused land (0-200cm) was as high as 0.32, 0.17, and 0.16, respectively, which indicated that these environmental factors had a high response to SOC content. It is found that the appropriate temperature not only promotes plant roots to obtain nutrients, but also interacts with soil pH on microorganisms, thereby increasing the SOC content. The results confirm that the TPE-XGBoost model based on SHAP analysis can reliably explain the nonlinear driving effect of environmental factors on the SOC, which provides credible decision support for accounting carbon budget and carbon sequestration in large-scale regions.

Antiferromagnetic Weyl semimetal Mn3Sn exhibiting strong magneto-optical Kerr effect (MOKE) due to non-zero Berry curvature is attractive for spintronic and photonic device applications. Despite many reports on the anisotropic anomalous Hall effect (AHE), so far, there have been few studies on its anisotropic optical properties. In this work, we experimentally characterized the anisotropic optical and magneto-optical (MO) properties of Mn3Sn(20)/MgO(110) and Mn3Sn(0001)/Al2O3(0001) epitaxial films using ellipsometry in the wavelength range from 300 to 1690 nm. By measuring the Mueller matrix of magnetized Mn3Sn, the anisotropic permittivity tensor is determined using the 4 × 4 transfer matrix method. Temperature dependent MOKE measurement confirmed the origin of the anisotropic MO effect to the non-zero Berry curvature of the chiral magnetic phase. The measured permittivity also agrees well with first-principles calculations. The anisotropic optical and MO properties determined in this work can be useful for Mn3Sn based spintronic device characterization and photonic device development.

The accurate prediction of the spatial variability for soil water content (SWC) in farmland is essential for water resource management and sustainable agricultural development. However, natural factors introduce uncertainty and result in poor alignment when predicting farmland SWC, leading to low accuracy. To address this, this study introduced a novel indicator: landscape indices. These indices include the largest patch index (LPI), edge density (ED), aggregation index (AI), patch cohesion index (COH), contagion index (CON), landscape division index (DIV), percentage of like adjacencies (PLA), Shannon evenness index (SHEI), and Shannon diversity index (SHDI). A Bayesian optimization–deep forest (BO–DF) model was developed to leverage these indices for predicting the spatial variability of SWC. Statistical analysis revealed that landscape indices exhibited skewed distributions and weak linear correlations with SWC (r < 0.2). Despite this, incorporating landscape index variables into the BO–DF model significantly improved prediction accuracy, with R2 increasing by 35.85%. This model demonstrated a robust nonlinear fitting capability for the spatial variability of SWC. Spatial mapping of SWC using the BO–DF model indicated that high-value areas were predominantly located in the eastern and southern regions of the Yellow River Delta in China. Furthermore, the SHapley additive explanation (SHAP) analysis highlighted that landscape indices were key drivers in predicting SWC. These findings underscore the potential of landscape indices as valuable variables for spatial SWC prediction, supporting regional strategies for sustainable agricultural development.

As coal resource development progresses deeper underground, the increasing depth of mine shafts poses significant challenges to the safety and stability of traditional shaft construction methods, further compounding operational difficulties. In this context, cast-in-situ concrete shaft walls in a slurry environment have emerged as an effective solution. The strength of these shaft walls is a crucial parameter for assessing their safety. To explore this, experiments were conducted on slurry preparation and mortar casting (used here as a substitute for concrete) under three different conditions: slurry environment, pure water environment, and dry environment. The cast specimens underwent compressive, tensile, shear, and microscopic observation tests to analyze the strength development patterns of the mortar specimens in these varied casting environments. The study yielded several key findings: As the casting environment becomes more complex, the strength of the mortar specimens gradually decreases. Specifically, specimens cast in a slurry environment exhibit strengths approximately 15% to 20% lower than those cast in a dry environment, although both environments show similar trends in strength development over time. Across all casting environments, the initial strength loss of the specimens is significant, while the rate of strength loss decreases in the later stages; the strength loss is minimal in specimens cast in a pure water environment and reaches its maximum in those cast in a slurry environment. Additionally, in specimens cast in a slurry environment, air void diameter tends to polarize, and the distribution of air void is denser compared to the other two environments. In conclusion, cast-in-situ mortar in a slurry environment exhibits the lowest strength and the greatest strength loss compared to specimens cast in dry and pure water environments. Nonetheless, the strength development trends over time remain similar across all conditions, providing theoretical and technical support for the construction of shaft walls in slurry environments.

In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at −18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to β-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.

Abstract Phosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.

The spatial prediction of soil CO2 flux is of great significance for assessing regional climate change and high-quality agricultural development. Using a single satellite to predict soil CO2 flux is limited by climatic conditions and land cover, resulting in low prediction accuracy. To this end, this study proposed a strategy of multi-source spectral satellite coordination and selected seven optical satellite remote sensing data sources (i.e., GF1-WFV, GF6-WFV, GF4-PMI, CB04-MUX, HJ2A-CCD, Sentinel 2-L2A, and Landsat 8-OLI) to extract auxiliary variables (i.e., vegetation indices and soil texture features). We developed a tree-structured Parzen estimator (TPE)-optimized extreme gradient boosting (XGBoost) model for the prediction and spatial mapping of soil CO2 flux. SHapley additive explanation (SHAP) was used to analyze the driving effects of auxiliary variables on soil CO2 flux. A scatter matrix correlation analysis showed that the distributions of auxiliary variables and soil CO2 flux were skewed, and the linear correlations between them (r < 0.2) were generally weak. Compared with single-satellite variables, the TPE-XGBoost model based on multiple-satellite variables significantly improved the prediction accuracy (RMSE = 3.23 kg C ha−1 d−1, R2 = 0.73), showing a stronger fitting ability for the spatial variability of soil CO2 flux. The spatial mapping results of soil CO2 flux based on the TPE-XGBoost model revealed that the high-flux areas were mainly concentrated in eastern and northern farmlands. The SHAP analysis revealed that PC2 and the TCARI of Sentinel 2-L2A and the TVI of HJ2A-CCD had significant positive driving effects on the prediction accuracy of soil CO2 flux. The above results indicate that the integration of multiple-satellite data can enhance the reliability and accuracy of spatial predictions of soil CO2 flux, thereby supporting regional agricultural sustainable development and climate change response strategies.

Dynamic compaction is a method of ground reinforcement that uses the huge impact energy of a free-falling hammer to compact the soil. This study presents a DC method for strengthening coral reef foundations in the reclamation area of remote sea islands. Pilot tests were performed to obtain the design parameters before official DC operation. The standard penetration test (SPT), shallow plate-load test (PLT), and deformation investigation were conducted in two improvement regions (A1 and A2) with varying tamping energies. During the deformation test, the depth of the tamping crater for the first two points’ tamping and the third full tamping was observed at two distinct sites. The allowable ground bearing capacity at two disparate field sites was at least 360 kPa. The reinforcement depths were 3.5 and 3.2 m in the A1 and A2 zones, respectively. The DC process was numerically analyzed by the two-dimensional particle flow code, PFC2D. It indicated that the reinforcement effect and effective reinforcement depth were consistent with the field data. The coral sand particles at the bottom of the crater were primarily broken down in the initial stage, and the particle-crushing zone gradually developed toward both sides of the crater. The force chain developed similarly at the three tamping energies (800, 1500, and 2000 kJ), and the impact stress wave propagated along the sand particles primarily in the vertical direction.

Monitoring and evaluation of soil ecological environments are very important to ensure saline–alkali soil health and the safety of agricultural products. It is of foremost importance to, within a regional ecological risk-reduction strategy, develop a useful online system for soil ecological assessment and prediction to prevent people from suffering the threat of sudden disasters. However, the traditional manual or empirical parameter adjustment causes the mismatch of the hyperparameters of the model, which cannot meet the urgent need for high-performance prediction of soil properties using multi-dimensional data in the WebGIS system. To this end, this study aims to develop a saline–alkali soil ecological monitoring system for real-time monitoring of soil ecology in the Yellow River Delta, China. The system applied advanced web-based GIS, including front-end and back-end technology stack, cross-platform deployment of machine learning models, and a database embedded in multi-source environmental variables. The system adopts a five-layer architecture and integrates functions such as data statistical analysis, soil health assessment, soil salt prediction, and data management. The system visually displays the statistical results of air quality, vegetation index, and soil properties in the study area. It provides users with ecological risk assessment functions to analyze heavy metal pollution in the soil. Specially, the system introduces a tree-structured Parzan estimator (TPE)-optimized machine learning model to achieve accurate prediction of soil salinity. The TPE–RF model had the highest prediction accuracy (R2 = 94.48%) in the testing set in comparison with the TPE–GBDT model, which exhibited a strong nonlinear relationship between environmental variables and soil salinity. The system developed in this study can provide accurate saline–alkali soil information and health assessment results for government agencies and farmers, which is of great significance for agricultural production and saline–alkali soil ecological protection.

Artificial ground freezing is an effective method for underground constructions in deep alluvium. To study the compressive strength of frozen soil under high ground pressure and high hydraulic pressure, it is necessary to understand the mechanical behaviour of ice that is formed under triaxial compressive stress. A low-temperature triaxial test system was developed and used to study both formation and deformation of columnar ice under hydrostatic pressure. Cylindrical ice specimens 125 mm in height and 61.8 mm in diameter were prepared and tested under constant strain rates. At a strain rate of 5 × 10−5 s−1, the peak axial stress showed a linear increase as the confining pressure increased from 2 to 30 MPa, while the peak deviatoric stress exhibited a slight decrease. At a confining pressure of 30 MPa, the peak deviatoric stress showed a logarithmic increase with the strain rate increasing from 5 × 10−6 to 5 × 10−4 s−1, and the failure strain nearly doubled. A power law relationship between the time to failure and the strain rate was also observed. In this study, each test consistently demonstrated a ductile failure mode, with a noticeable reduction in cracking as the confining pressure increased. Due to the effect of the high confining pressure, crack propagation was suppressed, and an apparent recrystallization after peak stress was observed.

Abstract In situ stress and groundwater have important effects on the deformation and stability of deep underground rock masses. Therefore, it is extremely important to study the mechanical properties and permeability evolutionary processes of rocks under hydromechanical (HM) coupling. The purpose of this study was to investigate the mechanical properties and permeability evolution of sandstone using triaxial compression tests under different confining and seepage pressures. The test results show that the confining pressure can increase the strength of sandstone, whereas the seepage pressure has the opposite effect. The initial and maximum permeabilities were positively correlated with seepage pressure and negatively correlated with confining pressure. The confining and seepage pressures had little effect on the change in initial permeability. As a common parameter of acoustic emission (AE), cumulative AE counts can intuitively reflect the permeability evolutionary process in the sandstone failure process. A permeability evolutionary early warning model for the sandstone failure process under HM coupling is proposed. The results are helpful for understanding the influence of in situ stress and seepage pressure on deep sandstone and the permeability evolutionary mechanism, and they can be used to provide early warning of water inrush disasters in deep underground structures.

The technology for freezing shaft sinking is widely used for shafts to pass through deep, unstable alluvia with the continuous exploitation of mineral resources. Due to the technique using the sectional excavation and shaft lining construction adopted in deep alluvia, the radial stress at the inner edge of a frozen wall is incompletely unloaded. In this paper, a mechanical model was established for a frozen wall with its inner edge radially incompletely unloaded. A parameter, α, expressing the degree of being unloaded was introduced, and then a new method of designing and calculating the thickness of the frozen wall was proposed. The range of parameter α was estimated based on the frozen wall–shaft lining interaction forces from field data from a given project. The results indicate that the range of α can be chosen to be from 0.05 to 0.15 in deep alluvia. The design thickness of the frozen wall can be reduced by at least 5% for the frozen wall with the inner edge radially incompletely unloaded. The design thickness is significantly influenced by the strength and elastic modulus of the frozen soil and the elastic modulus of the surrounding unfrozen alluvium. The design and calculation method of frozen wall thickness can provide new ideas for guiding the design of frozen walls in deep alluvia.

Optical gyromagnetic properties are not observed in natural or metamaterials to date. Here, the authors experimentally demonstrated optical gyromagnetic properties in a magneto-plasmonic metamaterial, realizing the long-sought bi-gyrotropic medium.

Abstract Background High Blood Urea Nitrogen (BUN) and high Serum Creatinine (SCr) levels are risk factors for Coronary Artery Disease (CAD). However, the relationship between the Blood Urea Nitrogen to Creatinine (BUN/SCr) ratio (UCR) and the risk of CAD in patients living with new-onset diabetes is unclear. This study aimed to examine the relationship between blood UCR and the risk of CAD in patients living with new-onset type 2 diabetes mellitus (T2DM). Methods We analyzed the data from the cohort of 12,299 patients living with type 2 diabetes mellitus. Primary endpoints were the events of CAD. The ANOVA test (continuous indicators) and χ2 test (categorical indicators) were used to assess the differences of baseline characteristics across the groups of UCR. In order to understand the correlation between variables, we performed correlation analysis on variables that have significant differences between CAD group and non-CAD group. Multivariate-adjusted Cox proportional hazard regression models were applied to estimate the association of the blood UCR with the risk of CAD in patients living with T2DM. The Kaplan–Meier survival function plotting and the log-rank test were used to evaluate the event-free survival according to the groups of UCR. The restricted cubic spline model was used to show the adjusted association between blood UCR and risk of CAD in patients living with T2DM. Results During a median follow-up of 2.66 years, 1173 CAD were recorded with an event rate of 28.49 events per 1000 person-years. In multivariate-adjusted Cox regression models, elevated blood urea nitrogen to creatinine ratio (UCR) was associated with higher risk of CAD in patients living with T2DM [hazard ratio (HR), 1.782; 95% confidence interval (CI), 1.237–2.567]. The Kaplan–Meier survival curves indicated that the high group of UCR tended to have a lower event-free survival than the low group and medium group. There was a nonlinear trend toward increasing risk of CAD across the groups of UCR. And cubic spline function graph suggested that the influence of UCR level on HR for CAD increased significantly at UCR levels above 6.67. Conclusions An elevated UCR was significantly associated with an increased risk for CAD in patients living with T2DM.

Objectives: To present a case series of modified transjugular intrahepatic portosystemic shunts (TIPS) and percutaneous transhepatic intrahepatic portosystemic shunts (PTIPS) in cirrhotic patients with variceal bleeding (VB). In addition, the scientific literature pertaining to PTIPS was reviewed. Methods: This retrospective clinical case series included six cirrhotic patients with VB who were treated with PTIPS after the failure of endoscopic band ligation or endoscopic injection sclerotherapy combined with vasoactive drugs. The treatment was conducted between January 2017 and June 2019 at a single institution. Three patients suffered from severe atrophy of the right or left lobar of the liver as well as the main right or left branch of the portal vein. The remaining three patients showed severe atrophy of the whole liver and portal vein, resulting in widening of the liver fissure. A paired t-test was used to compare the changes in portal pressure gradient between before and after the PTIPS operation. The rebleeding rate, treatment efficacy, complications, and technical success rate were all assessed during follow-up. Results: All six PTIPS procedures were performed successfully, with no severe procedural-related complications observed. None of the patients experienced VB during a mean follow-up of 22.8 (range, 18.0–28.0) months. The mean portosystemic pressure gradient decreased from 28.3 ​± ​4.3 ​mmHg pre-procedure to 12.3 ​± ​2.6 ​mmHg immediately post-procedure (P ​

Purpose: We aimed to compare treatment efficacy, safety and material cost between tissue gel and coil regarding variceal embolization during transjugular intrahepatic portosystemic shunt (TIPS).Materials & Methods: This retrospective study including cirrhotic patients with variceal bleeding treated with TIPS combined with variceal embolization between January 2016 and August 2017. Patients were divided into three groups according to embolic agents used in variceal embolization: tissue gel group (Group A), combination group (Group B), and coil group (Group C). The primary endpoint was 1-year rebleeding rate after TIPS creation. The secondary endpoints included shunt dysfunction, overt hepatic encephalopathy, liver function, and embolic agents-related expense. Results: A total of 60 patients (30, 10, and 20 in Group A, B, and C) were included. Variceal rebleeding occurred in 3 (10%), 0 (0%), and 4 (20%) patients within one year after TIPS creation in Group A, B, and C, respectively. Stent dysfunction occurred in 2 (3.3%) patients and 9 (15.0%) patients experienced overt hepatic encephalopathy. No significant differences were observed between three groups regarding primary and secondary endpoints except embolic agents-related expense, with a significantly lower cost in Group A when compared to the other two groups. Stent dysfunction occurred in two patients, with one patient in Group A developed acute occlusion caused by thrombus and another patient in Group C underwent stent stenosis during follow-up. Conclusions: Compares to coil alone or combines with coil, tissue gel has similar treatment efficacy and safety, but with significantly lower cost for variceal bleeding during TIPS.

Study of the compressive strength and damage constitutive model of frozen sand has an important significance for construction design and prevention-control of soil destabilization damage in frozen soil engineering. In this paper, a new triaxial apparatus was used to carry out a series of triaxial compression tests of frozen sand under different confining pressure and strain rate, based on which a segmental strength criterion is established to describe the damage of microelement strength of frozen sand. Assuming that the microelement strength of frozen sand obeys the Weibull distribution, a statistical damage constitutive model of frozen sand is established by statistics and continuous medium mechanics. Based on the test data, the model parameters were calculated and the relationship between the strength distribution parameters, the strain rate, and the confining pressure was obtained. Finally, the calculated values of the damage constitutive model are compared with the experimental values, and it is found that the model can simulate the stress-strain process curve of frozen sand well and can reflect the transition of the curve from elasto-plasticity to strain-hardening when the strain rate increases from low to high. The results of this study have an important significance in engineering construction of cold regions and artificial ground freezing projects.

A similarity experiment study is conducted to investigate the evolution characteristics of temperature field and frozen wall closure judgment criteria for the inclined shaft, under inclined holes freezing condition using an adjustable-angle freeze sinking analogous instrument. The changes of temperature and frozen wall thickness with the freezing time in the inclined shaft section, are recorded in real time, and the water pressure of axial and radial hydrological holes are measured. The results demonstrate that the soil temperature change can be divided into three stages under the conditions of salt-water temperature of -32°C and flow rate of 3.18 m/s: rapid cooling before reaching the freezing point, slow cooling in the process of freezing latent heat release, and accelerated cooling and stabilization after freezing latent heat release. The distance from the freezing pipe is the main factor affecting the freezing wall temperature. Affected by the arched arrangement of frozen pipes, the freezing speed in the position of arch crown and arch baseline is slower than the position of wall corner and base plate. A new judgment criterion of frozen wall closure based on the water pressure of the axial hydrological pipe is recommended. In all, this paper has an enlightenment significance for understanding the evolution of the soil temperature field, and predicting the frozen wall closure time in applications of the inclined holes freezing method for the inclined shaft.

The vertical additional force induced by the drainage consolidation settlement of the topsoil is one of the main factors for shaft wall fracture. To date, the number of aquifers of topsoil rises with the depth increasing of shaft, which would lead to a more serious additional force effect. Thus, studying the vertical additional force law of the shaft when drainage settlement occurs in its surrounding topsoil containing multiaquifers is of great significance to predicting the shaft stress and guarantying shaft safety. In this study, mechanical analysis of the topsoil with the shaft crossing multiaquifer was carried out, and the settlement of each aquifer and aquiclude was calculated by separating the single-slope drainage consolidation and the double-slope drainage consolidation. Then, the calculation model of vertical additional force was established due to the settlement caused by the reaction of the additional force on the topsoil containing multiaquifers, and the calculation model of shaft wall stress was also developed. Verification of this model was conducted by comparing the filed measurement data of the shaft wall strain and the theoretical data calculated by the stress model. Finally, the effect laws of drainage velocity, central aquifer thickness, location, and number on the additional force were obtained and analysed. This paper is expected to provide theoretical support for predicting the additional force and shaft wall stress during its service time.

The paths of a two-phase flow are usually non-linear and discontinuous in the production of shale gas development. To research the influence mechanism between shale gas and water, several integer two-phase flow models have been studied but few analytical solutions have been obtained on shale gas and water pressure. This study first developed a local fractional mathematical model for gas and water two-phase flow in shale gas production. The model thus created considers the effects of capillary pressure, the fractal dimension of the flow pipe, and the discontinuity of the flow path. Second, the local fractional traveling wave method and variational iteration method were applied to this model for the development of iterative analytical solutions. Both shale gas and water pressure were analytically derived. Third, the depressurization process of the shale gas and water was analyzed, and a parametric study was conducted to explore the impacts of fractional dimension, entry capillary pressure, and travel wave velocity on shale gas pressure. Finally, our conclusions are drawn, based on the results of these studies.

Rock properties (e.g., brittleness, fracture toughness, hardness, compressive strength and tensile strength), cutting parameters (e.g., cutting depth, attack angle, wedge angle, cutting velocity) and confining stress are closely related to rock fragmentation behaviors in the design and application of excavation and mining machinery. To investigate the influence mechanism of those factors on rock fragmentation, a series of linear cutting numerical tests were conducted using the discrete element method. Numerical models with different rock mechanical parameters were calibrated by changing the cohesion strength-to-tensile strength ratio of the linear parallel bond model in PFC2D. The effects of cutting parameters on rock fragmentation were studied using orthogonal test and range analysis. The numerical results indicated that the strength ratio had a dominant effect on the specific energy and that the cutting depth and attack angle had a dominant effect on the mean cutting force. The cutting velocity significantly influenced the specific energy, and a higher cutting velocity should be adopted in actual rock cutting. In addition, a cutting force prediction model was proposed that considered factors such as the compressive strength, wedge angle, attack angle and cutting depth. Moreover, the introduction of more rock mechanical parameters into the evaluation indicators can reflect a greater number of fragmentation characteristics.

The asymmetric temperature field is one of the main factors inducing the cracking of the inner shaft lining during freezing-shaft sinking. The evolution equation for the thermophysical and mechanical properties of shaft lining concrete during construction period is the basis for revealing the cracking mechanism. In this study, several experiments were conducted to reveal the evolution of the temperature field, thermal conductivity, specific heat capacity, compressive strength, tensile strength, and elastic modulus of shaft lining concrete with age and lining thickness within the first 7 d after pouring. Results show that the shaft lining concrete temperature curve after pouring can be divided into five stages: induction, slow heating, rapid heating, rapid cooling, and slow cooling. Thermal conductivity and specific heat capacity reached the maximum on Day 1 and gradually decreased with an increase in age. The compressive strength, tensile strength and elastic modulus significantly increased with age. With an increase in thickness, the shaft lining concrete at the same age improved its three mechanical parameters. Finally, the evolution equation for these thermophysical and mechanical parameters with age within the first 7 d after pouring was fitted based on experimental data. This study is expected to provide a thermophysical and mechanical basis for studying the cracking mechanism of the inner shaft lining.

The in-situ combustion–explosion fracturing technology in shale reservoirs can promote continuous fracture expansion with a radial detonation wave first converging into a shock wave and then decaying into an elastic wave. The transformation scale of the shale reservoir is determined by the range of wave propagation during combustion–explosion. As wave propagation paths are usually tortuous and fractal, the previous integer wave models are not competent to describe the wave propagation and estimate the impact range of the combustion–explosion fracturing process. This study develops two fractional wave propagation models and seeks analytical solutions. Firstly, a novel fractional wave model of rotation angle is proposed to describe the process of detonation waves converting into shock waves in a bifurcated structure. The radial displacement gradient of the detonation wave is represented by the internal expansion and rotation deformation of the shale. Secondly, another fractional wave propagation model of radial displacement is proposed to show the process of a shock wave decaying into an elastic wave. Thirdly, the proposed models are analytically solved through the fractional variable separation method and variational iteration method, respectively. Analytical solutions for rotation angle and radial displacement with fractal time and space are obtained. Finally, the impacts of the branching parameter of the detonation wave converge bifurcation system, aggregation order of detonation compression wave, and different types of explosives on the rotation angle of the shock wave are investigated. The propagation mechanism of the primary wave (P-wave) with time and space is analyzed. The analytical solutions can well describe the wave propagation process in fractured shales. The proposed fractional wave propagation models can promote the research of wave propagation in the combustion–explosion fracturing process of shale reservoirs.

Heat treatment on shale reservoirs can promote the development of secondary fractures in a matrix on the basis of hydraulic fracturing, forming multi-scale gas–water seepage channels and strengthening the gas desorption. Experimental evidence shows that heat treatment can enhance gas recovery in the same mining life. Heat treatment on a shale gas reservoir is a multi-physical and multi-phase coupling process. However, how the thermal stimulation interacts with nonlinear two-phase flow in heterogeneous shale volume fracturing has not been clear. In this paper, a fully coupled THGM model for heating-enhanced shale-gas recovery in heterogeneous shale reservoirs is proposed. First, the governing equations are formulated for the shale-reservoir deformation involving both gas adsorption and thermal expansion, the permeability evolution model for the cracking process of fractured shale, the gas–water two-phase continuity equation considering the effects of gas solubility and the heat transfer equation for heat conduction and convection. The interactions among stress, temperature and seepage in a heterogeneous shale reservoir were studied. Secondly, a test on shale permeability after 50 °C temperature treatment was conducted. The evolution of temperature, capillary pressure, water and gas saturation and the permeability of shale during the heat treatment of the reservoir were numerically analyzed. Finally, the gas production from a shale gas reservoir was numerically simulated with this THGM model. The numerical results indicated that the thermal-induced fracturing, gas desorption and separation from water make predominant contributions to the evolution of permeability. The heat treatment can enhance cumulative gas production by 58.7% after 27.4 years of heat injection through promoting gas desorption and matrix diffusion.

Renal cell carcinoma (RCC) is responsible for most cases of the kidney cancer. Previous research showed that low serum levels of cholesterol level positively correlate with poorer RCC-specific survival outcomes. However, the underlying mechanisms and functional significance of the role of cholesterol in the development of RCC remain obscure. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) plays a pivotal role in RCC development as it is the key rate-limiting enzyme of the cholesterol biosynthetic pathway. In this study, we demonstrated that the inhibition of HMGCR could accelerate the development of RCC tumors by lactate accumulation and angiogenesis in animal models. We identified that the inhibition of HMGCR led to an increase in glycolysis via the regulated HSP90 expression levels, thus maintaining the levels of a glycolysis rate-limiting enzyme, pyruvate kinase M2 (PKM2). Based on these findings, we reversed the HMGCR inhibition-induced tumor growth acceleration in RCC xenograft mice by suppressing glycolysis. Furthermore, the coadministration of Shikonin, a potent PKM2 inhibitor, reverted the tumor development induced by the HMGCR signaling pathway.

The mechanical characteristics of high-pressure frozen ice are a basis for the design of deep underground frozen walls, the drilling of thick permafrost and ice sheets, and the probing of extraterrestrial ice. The continuous control of the sample stress state from freezing to testing is essential for the experimental study of in situ mechanical response of high-pressure frozen ice. In the context, we developed a preparation technique for freezing pressurized water into a standard cylindrical ice sample in a triaxial cell. Through theoretical analysis, a cylindrical water sample with precise dimensions and strong sealing was fabricated using heat shrinkable tubing, sectional end caps, and an assembly cylinder. A mounting device was designed to insert the water sample into the triaxial cell without deformation. In order to deal with the lateral surface irregular of the resulting ice sample caused by freezing expansion, we proposed a pressurization method in which the volume of the confining medium is controlled to restrict the radial deformation of the sample, and the axial pressure on the sample is kept constant; thus, the freezing expansion will develop along the height direction through releasing the expansion pressure. Based on the analysis of sample deformation and finite element numerical simulations, the control method of the temperature fields of the sample and the confining medium was obtained, and the standard cylindrical ice sample which satisfies the geometric accuracy requirements was produced. The comparison of ice samples frozen by different freezing methods showed that the control of the confining medium mean temperature and the sample unidirectional freezing is necessary to improve the dimensional precision of the ice sample.

In this study, a test technique that enables continuous control of the sample stress state from freezing to testing is proposed to investigate the influence of freezing pressure on the mechanical properties of ice under uniaxial compression. In this method, the water is frozen into the standard cylindrical ice specimen under high hydraulic pressure in a triaxial pressure chamber, and then, the temperature field and stress field of the ice specimens are adjusted to the initial state of the test; finally, an in situ mechanical test is conducted in the triaxial chamber. The uniaxial compression test of ice specimens with temperature of −20°C and freezing pressure of 0.5–30 MPa is performed in the strain rate range of 5 × 10−5−1.5 × 10−6 s−1. The results show that, as the freezing pressure increases, the ductile-to-brittle transition zone of the ice specimen during failure moves to the low strain rate range, and the failure mode of the specimen changes from shear failure to splitting failure. Further, the brittleness index of the ice specimen first increases, then decreases, and then again increases with the increase in freezing pressure. The brittleness index reaches the maximum (minimum) when the freezing pressure is 30 MPa (20 MPa). The peak stress of the ice specimen also increases first, then decreases, and then increases with the increase in freezing pressure. The maximum value is also at the freezing pressure of 30 MPa, but the minimum value is obtained at the freezing pressure of 0.5 MPa. The failure strain of the ice specimen first decreases and then increases with the increase in freezing pressure, and the maximum (minimum) value is achieved at the freezing pressure of 0.5 MPa (10 MPa). When the ice specimen exhibits brittle failure, the relationships between the residual stress and the freezing pressure and between the peak stress and freezing pressure are the same, but when the ice specimen exhibits ductile failure, there is no obvious relationship between the residual stress and the freezing pressure.

Using the coda wave interferometry (CWI) method to obtain the ultrasonic coda wave characteristics of loaded concrete is an important method to evaluate the mechanical response of concrete. In this paper, the ultrasonic coda wave characteristics of C40–C70 concrete specimens (four strengths of concrete) under uniaxial compression were tested by laboratory experiments. Furthermore, to clarify the relationship between the internal damage process of concrete and the change rate of coda wave velocity, an ultrasonic coda wave discrete element simulation model combined with digital image processing technology was established. The results show that the coda wave is very sensitive to small changes in the compressive damage to concrete, and the change in coda wave velocity can correspond to the development process of concrete damage. This research is conducive to a better understanding of the complex material behavior of compressive concrete and proves the feasibility of ultrasonic field simulation and processing by using numerical simulation images of concrete damage.

To prevent serious shaft deflection disasters under asymmetric mining conditions, it is urgent to solve the problem of designing shaft protection rock pillar (SPRP) sizes in thick soil and thin rock strata. In this paper, based on the parallel mining model and the perpendicular mining model, a dynamic prediction model that can describe the horizontal movement of the shaft was established by the probability integration method and the Knothe time function. Next, according to the measured data of the shaft deflection in the Guotun Coal Mine, a back analysis was used to calculate the prediction parameters that were suitable for the deep soil strata. Based on the mining model, the variation law of the horizontal deflection displacement of the shaft and SPRP size was obtained. The results showed that the final displacements of the shaft under the two ideal mining models were equal, while the parallel mining model was superior to the perpendicular mining model at the initial stage of mining. The horizontal displacement of the shaft head had a nonlinear negative correlation with the SPRP, and the SPRP size in thick soil and thin rock strata calculated by the parallel mining model was more reasonable. For the Guotun Coal Mine, when the soil movement angle was 57.8% of the actual value, the horizontal displacement of the main shaft head was reduced by 87%. The results have important theoretical and practical value in preventing shaft deflection in thick soil and thin rock strata.

To solve the leakage problem of concrete cracking and seepage in the freezing shaft lining of deep topsoil, it is proposed to use hybrid fibers and micro expansion high-performance concrete. Based on the normal concrete mix ratio of the frozen shaft lining, the orthogonal test method was used to investigate the effect of the water-to-binder ratio, the amount of expansion agent, the amount of polyvinyl alcohol fiber and the amount of imitation steel fiber on the compressive strength and splitting tensile strength of fiber hybrid and micro expansion high performance concrete. Comprehensive balance determines that the best mix ratio of this test is water: cement: NF-F: expansion agent: polyvinyl alcohol fiber: polypropylene imitation steel fiber: sand: basalt gravel =166.112:410:130:32.8:1.092:5:615.992:1 095.096. The crack resistance test results show that the fiber hybrid and expansion agent composite concrete has excellent crack resistance.