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Objective To identify small molecule inhibitors of APC-mutant colon cancer and provide lead compounds for targeted therapy of colon cancer. MethodsAPC-mutant colon cancer cell lines that stably express 7*Tcf-GFP/SV40-Cherry (7TGC) dual fluorescence reporter system was constructed for small-molecule inhibitor screening. Cell viability, colony formation, EdU incorporation, and xenograft tumor assay were used to evaluate the inhibitory effect of these inhibitors on APC-mutant colon cancer in vitro and in vivo. Western blot and co-immunoprecipitation assays were used to explore the molecular mechanism. ResultsFour small molecules that inhibited Wnt activity in APC-mutant colon cancer cells were discovered. Shikonin exhibited significant inhibition of cell viability and proliferation while inducing apoptosis of APC-mutant colon cancer cells. Xenograft tumor assay demonstrated that shikonin significantly reduced tumor growth in vivo. Furthermore, Western blot and co-immunoprecipitation assays revealed that shikonin markedly decreased β-catenin levels. ConclusionShikonin effectively inhibits Wnt activity and suppresses tumor growth in APC-mutant colon cancer.

Abstract Background Although numerous studies have indicated that activated pyroptosis can enhance the efficacy of antitumour therapy in several tumours, the precise mechanism of pyroptosis in colorectal cancer (CRC) remains unclear. Methods Pyroptosis in CRC cells treated with antitumour agents was assessed using various techniques, including Western blotting, lactate dehydrogenase release assay and microscopy analysis. To uncover the epigenetic mechanisms that regulate NLRP3, chromatin changes and NLRP3 promoter histone modifications were assessed using Assay for Transposase‐Accessible Chromatin using sequencing and RNA sequencing. Chromatin immunoprecipitation‒quantitative polymerase chain reaction was used to investigate the NLRP3 transcriptional regulatory mechanism. Additionally, xenograft and patient‐derived xenograft models were constructed to validate the effects of the drug combinations. Results As the core molecule of the inflammasome, NLRP3 expression was silenced in CRC, thereby limiting gasdermin D (GSDMD)‐mediated pyroptosis. Supplementation with NLRP3 can rescue pyroptosis induced by antitumour therapy. Overexpression of HDAC2 in CRC silences NLRP3 via epigenetic regulation. Mechanistically, HDAC2 suppressed chromatin accessibility by eliminating H3K27 acetylation. HDAC2 knockout promotes H3K27ac‐mediated recruitment of the BRD4‐p‐P65 complex to enhance NLRP3 transcription. Inhibiting HDAC2 by Santacruzamate A in combination with classic antitumour agents (5‐fluorouracil or regorafenib) in CRC xenograft‐bearing animals markedly activated pyroptosis and achieved a significant therapeutic effect. Clinically, HDAC2 is inversely correlated with H3K27ac/p‐P65/NLRP3 and is a prognostic factor for CRC patients. Conclusion Collectively, our data revealed a crucial role for HDAC2 in inhibiting NLRP3/GSDMD‐mediated pyroptosis in CRC cells and highlighted HDAC2 as a potential therapeutic target for antitumour therapy. Highlights Silencing of NLRP3 limits the GSDMD‐dependent pyroptosis in colorectal cancer. HDAC2‐mediated histone deacetylation leads to epigenetic silencing of NLRP3. HDAC2 suppresses the NLRP3 transcription by inhibiting the formation of H3K27ac/BRD4/p‐P65 complex. Targeting HDAC2 activates pyroptosis and enhances therapeutic effect.

The miscibility of flue gas and different types of light oils is investigated through slender-tube miscible displacement experiment at high temperature and high pressure. Under the conditions of high temperature and high pressure, the miscible displacement of flue gas and light oil is possible. At the same temperature, there is a linear relationship between oil displacement efficiency and pressure. At the same pressure, the oil displacement efficiency increases gently and then rapidly to more than 90% to achieve miscible displacement with the increase of temperature. The rapid increase of oil displacement efficiency is closely related to the process that the light components of oil transit in phase state due to distillation with the rise of temperature. Moreover, at the same pressure, the lighter the oil, the lower the minimum miscibility temperature between flue gas and oil, which allows easier miscibility and ultimately better performance of thermal miscible flooding by air injection. The miscibility between flue gas and light oil at high temperature and high pressure is more typically characterized by phase transition at high temperature in supercritical state, and it is different from the contact extraction miscibility of CO2 under conventional high pressure conditions.

The accurate prediction of carbon dioxide (CO2) emissions in the building industry can provide data support and theoretical insights for sustainable development. This study proposes a hybrid model for predicting CO2 emissions that combines a multi-strategy improved particle swarm optimization (MSPSO) algorithm with a long short-term memory (LSTM) model. Firstly, the particle swarm optimization (PSO) algorithm is enhanced by combining tent chaotic mapping, mutation for the least-fit particles, and a random perturbation strategy. Subsequently, the performance of the MSPSO algorithm is evaluated using a set of 23 internationally recognized test functions. Finally, the predictive performance of the MSPSO-LSTM hybrid model is assessed using data from the building industry in the Yangtze River Delta region as a case study. The results indicate that the coefficient of determination (R2) of the model reaches 0.9677, which is more than 10% higher than that of BP, LSTM, and CNN non-hybrid models and demonstrates significant advantages over PSO-LSTM, GWO-LSTM, and WOA-LSTM hybrid models. Additionally, the mean square error (MSE) of the model is 2445.6866 Mt, and the mean absolute error (MAE) is 4.1010 Mt, both significantly lower than those of the BP, LSTM, and CNN non-hybrid models. Overall, the MSPSO-LSTM hybrid model demonstrates high predictive accuracy for CO2 emissions in the building industry, offering robust support for the sustainable development of the industry.

Abstract Although immunogenic cell death (ICD) inducers evidently enhance the effectiveness of immunotherapy, their potential is increasingly restricted by the development of apoptosis resistance in tumor cells, poor immunogenicity, and low T‐cell immune responsiveness. In this study, for the first time, piezoelectrically catalyzed Mg2+‐doped hydroxyapatite (Mg‐HAP) nanoparticles, which are coated with a mesoporous silica layer and loaded with ONC201 as an agonist to specifically target the death receptor DR5 on tumor cells, ultimately developing an Mg‐HAP@MS/ONC201 nanoparticle (MHMO NP) system, are engineered. Owing to its excellent piezoelectric properties, MHMO facilitates the release of a significant amount of reactive oxygen species and Ca2+ within tumor cells, effectively promoting the upregulation of DR5 expression and inducing tumor cell necroptosis to ultimately overcome apoptosis resistance. Concurrently, Mg2+ released in the tumor microenvironment promotes CD8+ T receptor activation in response to the antitumor immune reaction induced by ICD. Using RNA‐seq analysis, it is elucidated that MHMO can activate the NF‐κB pathway under piezoelectric catalysis, thus inducing M1‐type macrophage polarization. In summary, a dual‐targeting therapy system that targets both tumor cells and the tumor microenvironment under piezoelectric catalysis is designed. This system holds substantial potential for advancements in tumor immunotherapy.

PurposeThe objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer’s disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients.MethodsIn this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients.ResultsThe ADD group exhibited significant cognitive impairment compared to the ADND group (p

In order to improve the oil recovery of mid-deep heavy oil reservoirs, this study investigates the efficiency of enhanced oil recovery and the mechanisms of oil displacement in mid-deep heavy oil reservoirs using different injected gases (N2, CH4, CO2) and development approaches (gas flooding and gas huff-n-puff) through a series of experiments. These experiments include high-pressure physical properties tests of crude oil after gas injection, displacement efficiency tests of gas injection, and displacement efficiency tests of gas huff-n-puff. The results indicate that for mid-deep heavy oil reservoirs, the preferred optimal injection gas is CO2, with gas huff-n-puff being the most effective development method. Furthermore, a numerical simulation study was conducted to explore the adaptability parameters of CO2 huff-n-puff development in different well patterns, encompassing variables such as the amount of gas injected per cycle, crude oil viscosity, reservoir permeability, and oil layer thickness.

Abstract Background Multitarget tyrosine kinase inhibitors (mTKIs) such as Regorafenib and Sorafenib have already been approved for the treatment of many solid tumours. However, the efficacy of mTKIs in colorectal cancer (CRC) is limited; the underlined mechanism remains largely elusive. Our study was aimed to find out the resistance mechanism of mTKIs in CRC. Methods RNA sequencing was used to identify the expression of Activin A receptor-like type 1 (ACVRL1) under the treatment of mTKIs. Gain/loss-of-function experiments were performed to assess the biological function of ACVRL1 in resistance to mTKIs. The underlying mechanisms of ACVRL1-mediated mTKI resistance were investigated by using liquid chromatography-mass spectrometry assays (LC-MS), co-immunoprecipitation assays (Co-IP), chromatin immunoprecipitation assays, ubiquitination assays, dual luciferase reporter assays, etc. Results RNA sequencing identified the activation of ACVRL1 under the treatment of mTKIs in CRC cells. ACVRL1 knockdown and overexpression significantly affects the sensitivity of CRC cells to mTKIs both in vitro and vivo. Mechanistically, we found the β-catenin/TCF-1-KCNQ1OT1/miR-7-5p axis mediated the activation of ACVRL1. Furthermore, LC-MS assays indicated the interaction between ACVRL1 and glutathione peroxidase 2(GPX2) protein. IP assay defined ACVRL1 truncation (282–503aa) could be responsible for interacting with GPX2, and rescue experiments with ACVRL1 truncations confirmed the importance of this interaction in driving mTKI resistance. Co-IP assays confirmed that ACVRL1 associates with ubiquitin-specific peptidase 15(USP15) which directly deubiquinates GPX2 at the K187(K, lysine) site, leading to the accumulation of GPX2 protein. Rescue experiments performed with the lysine mutants in GPX2 CRISPR knockout cell model confirmed the importance of GPX2 K187 mutant. As a result, the increased ROS clearance and decreased cell apoptosis eventually lead to mTKI resistance in CRC. Conclusions Our results demonstrate that the Wnt/β-catenin/KCNQ1OT1/miR-7-5p/ACVRL1/GPX2 biological axis plays a vital role in CRC, targeting which may be an effective approach for overcoming mTKI resistance.

Soil environmental issues in the red bed region are increasingly conspicuous, underscoring the critical importance of assessing soil quality for the region’s sustainable development and ecosystem security. This study examines six distinct land use types of soils—agricultural land (AL), woodland (WL), shrubland (SL), grassland (GL), bare rock land (BRL), and red bed erosion land (REL)—in the Nanxiong Basin of northern Guangdong Province. This area typifies red bed desertification in South China. Principal component analysis (PCA) was employed to establish a minimum data set (MDS) for calculating the soil quality index (SQI), evaluating soil quality, analyzing influencing factors, and providing suggestions for ecological restoration in desertification areas. The study findings indicate that a minimal data set comprising soil organic matter (SOM), pH, available phosphorus (AP), exchangeable calcium (Ca2+), and available copper (A-Cu) is most suitable for evaluating soil quality in the red bed desertification areas of the humid region in South China. Additionally, we emphasize that exchangeable salt ions and available trace elements should be pivotal considerations in assessing soil quality within desertification areas. Regarding comprehensive soil quality indicators across various land use types, the red bed erosion soils exhibited the lowest quality, followed by those in bare rock areas and forest land. Within the minimal data set, Ca2+ and pH contributed the most to overall soil quality, underscoring the significance of parent rock mineral composition in the red bed desertification areas. Moreover, the combined effects of SOM, A-Cu, and AP on soil quality indicate that anthropogenic land management and use, including fertilization methods and vegetation types, are crucial factors influencing soil quality. Our research holds significant implications for the scientific assessment, application, and enhancement of soil quality in desertification areas.

We present the discovery of three pulsars in the globular cluster (GC) M15 (NGC 7078) by the Five-hundred-meter Aperture Spherical Radio Telescope. PSR J2129+1210J (M15J) is a millisecond pulsar with a spin period of 11.84 ms and a dispersion measure of 66.68 pc cm ^−3 . Both PSR J2129+1210K and L (M15K and L) are long-period pulsars with spin periods of 1928 ms and 3961 ms, respectively. M15L is the GC pulsar with the longest spin period known. We update the timing solutions of M15A to M15H. As predicted by A. Ridolfi et al., the flux density of M15C keeps decreasing, and the latest detection in our data set was on 2022 December 20. We have also detected M15I’s signal for the first time since its discovery. Current timing suggests that it is an isolated pulsar.

We present the scintillation velocity measurements of FRB 20201124A from the Five-hundred-meter Aperture Spherical radio Telescope observations, which reveal an annual variation. This annual variation is further supported by changes detected in the scintillation arc as observed from the secondary spectrum. We attribute the annual velocity variation to the presence of a moderately anisotropic scattering screen located at a distance of 0.4 ± 0.1 kpc from Earth. Our results prove that the scintillation of this fast radio burst (FRB) is mainly caused by material close to Earth on a Galactic scale. However, scintillation observations of other FRBs may expose their surrounding environment or uncover possible orbital motion if scintillation is caused by materials in their host galaxy.

By combining the Fermi catalog and the single-lined spectroscopic binaries of Gaia Data Release 3 (DR3), we report a new candidate redback millisecond pulsar binary, which is recommended as a target for radio telescopes to detect pulsed signals. Using TESS data in the T band spanning over 4 yr, we find a period of ∼4.13 days, which is consistent with the radial velocity solution of the Gaia DR3 and optical spectroscopy from the LAMOST telescope. The light curve in the T band reveals periodic modulation of low amplitude that is a characteristic feature of the heating of the photosphere of a nondegenerate low-mass stellar companion by the pulsar wind. The nondegenerate companion is a bright ( G = 11.96), slightly metal-poor ([Fe/H] = − 0.55), G-type main-sequence star ( T _eff = 5891 K; $\mathrm{log}g=4.07;$ R = 1.356 R _⊙ ). This orbital period of 4.13 days would be the longest one for known redback candidates, which could hardly be understood for its formation in the standard recycling scenario due to its large Roche-lobe radius (≫the radius of the G-type main-sequence star). It is proposed here that this candidate redback millisecond pulsar binary could be created via accretion-induced collapse of an oxygen–neon–magnesium white dwarf.

Neural radiance fields (NeRFs) leverage a neural representation to encode scenes, obtaining photorealistic rendering of novel views. However, NeRF has notable limitations. A significant drawback is that it does not capture surface geometry and only renders the object surface colors. Furthermore, the training of NeRF is exceedingly time-consuming. We propose Depth-NeRF as a solution to these issues. Specifically, our approach employs a fast depth completion algorithm to denoise and complete the depth maps generated by RGB-D cameras. These improved depth maps guide the sampling points of NeRF to be distributed closer to the scene’s surface, benefiting from dense depth information. Furthermore, we have optimized the network structure of NeRF and integrated depth information to constrain the optimization process, ensuring that the termination distribution of the ray is consistent with the scene’s geometry. Compared to NeRF, our method accelerates the training speed by 18%, and the rendered images achieve a higher PSNR than those obtained by mainstream methods. Additionally, there is a significant reduction in RMSE between the rendered scene depth and the ground truth depth, which indicates that our method can better capture the geometric information of the scene. With these improvements, we can train the NeRF model more efficiently and achieve more accurate rendering results.

Background Hepatocellular carcinoma (HCC) is characterized by high mortality, difficulty in early screening, relapse, and poor prognosis. This study aimed to explore the expression of ethanolamine-phosphate phospho-lyase (ETNPPL) and its clinical significance in HCC. Methods Differentially expressed mRNAs were screened using microarray analysis. Functional enrichment was performed using GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. We used qRT-PCR to measure the expression of ETNPPL in HCC tissues and paired paracarcinoma tissues. A receiver operating characteristic (ROC) curve and Kaplan-Meier curve were conducted to assess the diagnostic and prognostic values. Cell behaviors were evaluated using a scratch test and transwell assay. Results The results showed that numerous mRNAs are abnormally expressed in HCC. ETNPPL was decreased in HCC tissues and cells. The area under curve (AUC) of ETNPPL was 0.9089, demonstrating that ETNPPL had diagnostic value. Low expression of ETNPPL was related to poor prognosis for patients with HCC. Moreover, the over-expression of ETNPPL inhibited HCC cell migration and invasion. Conclusions In conclusion, downregulated ETNPPL was found in HCC and is related to poor patient prognosis and the promotion of cell metastasis. This suggests that ETNPPL serves both as a promising diagnosis and prognosis biomarker, and a therapy target of HCC.

Physical modeling, numerical simulation and field case analysis were carried out to find out the subsurface thermal oxidation state, thermal oxidation front characteristics and production dynamic characteristics of high pressure air injection thermal oxidation miscible flooding technology. The lighter the composition and the lower the viscosity of the crude oil, the lower the fuel consumption and the combustion temperature are. The thermal oxidation front of light oil and volatile oil can advance stably, and a medium-temperature thermal oxidation stable displacement state can be formed in the light oil reservoir under high pressure conditions. With strong thermal gasification and distillation, light oil and volatile oil are likely to form a single phase zone of gasification and distillation with thermal flue gas at the high-temperature and high-pressure heat front, finally, an air-injection thermal miscible front. In light oil reservoirs, the development process of high-pressure air-injection thermal miscible flooding can be divided into three stages: boosting pressure stage, low gas-oil ratio and high-efficiency stable production stage and high gas-oil ratio production stage. Approximately 70% of crude oil is produced during the boosting pressure stage and low gas-oil ratio high-efficiency and stable production stage.

The thickness of the indium tin oxide (ITO) layer is a critical parameter affecting the performance of solar cells. Traditional measurement methods require sample collection, leading to manufacturing interruptions and potential quality issues. In this paper, we propose a real-time, non-contact approach using deep learning and optical interference phenomena to estimate the thickness of ITO layers in solar cells. We develop a convolutional neural network (CNN) model that processes microscopic images of solar cells and predicts the ITO layer thickness. In addition, mean absolute error (MAE) and mean squared error (MSE) loss functions are combined to train the model. Experimental results demonstrate the effectiveness of our approach in accurately estimating the ITO layer thickness. The integration of computer vision and deep learning techniques provides a valuable tool for non-destructive testing and quality control in the manufacturing of solar cells. The loss of the model after training is reduced to 0.83, and the slope of the test value in the scatter plot with the true value of the ellipsometer is approximately equal to 1, indicating the high reliability of the model.

Abstract The liposoluble tanshinones are bioactive components in Salvia miltiorrhiza and are widely investigated as anti-cancer agents, while the molecular mechanism is to be clarified. In the present study, we identified that the human fragile histidine triad (FHIT) protein is a direct binding protein of sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of Tanshinone IIA (TSA), with a Kd value of 268.4 ± 42.59 nM. We also found that STS inhibited the diadenosine triphosphate (Ap3A) hydrolase activity of FHIT through competing for the substrate-binding site with an IC50 value of 2.2 ± 0.05 µM. Notably, near 100 times lower binding affinities were determined between STS and other HIT proteins, including GALT, DCPS, and phosphodiesterase ENPP1, while no direct binding was detected with HINT1. Moreover, TSA, Tanshinone I (TanI), and Cryptotanshinone (CST) exhibited similar inhibitory activity as STS. Finally, we demonstrated that depletion of FHIT significantly blocked TSA’s pro-apoptotic function in colorectal cancer HCT116 cells. Taken together, our study sheds new light on the molecular basis of the anti-cancer effects of the tanshinone compounds.

Viscosity-reducer flooding is an effective method to improve oil recovery after the water flooding of heavy oil, and water-in-oil emulsion (W/O emulsion) is easily formed during this process. W/O emulsion has a strong ability to improve mobility ratio and block off high permeability layers, which can effectively improve sweep coefficient and enhance oil recovery. The microscopic visual glass model is mainly used to study the microscopic oil displacement mechanism of dilute oil; however, there are few studies on the emulsification mechanism and influencing factors of heavy oil. The purpose of this paper is to study the mechanism of heavy oil emulsification caused by viscosity reducer at the microscopic level, and the effect of emulsification on heavy oil recovery. The visible physical experiments with the glass microscopic models with different permeability and pore sizes were carried out to study the mechanism and main controlling factors of emulsification and the oil displacement effect of viscosity reducer. On this basis, the software was used to calculate the oil recovery in different areas of the model in different flooding stages, which provides a more intuitive understanding of the oil displacement effect of viscosity reducer. The results showed that there are mainly three types of emulsifications between pores: pore throat-breaking emulsification, blind-end emulsification, and pore channel extrusion emulsification. Hence, the mechanism of the three types of emulsifications and the relationship between droplet size with shear stress have been explored. The shear stress increased with the increase of the shear rate, and the oil droplet size in the model decreased with the increase of the shear. The blocking mechanism of pore throat and the shearing action of viscosity-reducer solution are the main mechanisms of viscous oil emulsification between pores. Generally, the particle size of the emulsified oil droplets formed by the blocking action is large, and it is easy to form pore throat emulsion. The particle size of emulsified oil droplets formed by shearing of viscosity-reducer solution is small. When the pore diameter is smaller than the particle size of oil droplets, the mobility of oil droplets between pores is poor, which means the oil droplets easily accumulate at the blind end to form residual oil. From the results of viscosity-reducer flooding experiments, the heavy oil recovery in each area of the model has been significantly improved after viscosity-reducer flooding compared with water flooding, with the recovery factor in the edge area of the model improving by up to 24.22%. The viscosity-reducer solution has a significant displacement effect on the residual oil in the edge area of the model.

Summary: β-Catenin is a central component in the Wnt signaling pathway; its degradation has been tightly connected to ubiquitylation, but it is rarely examined by loss-of-function assays. Here we observe that endogenous β-catenin is not stabilized upon ubiquitylation depletion by a ubiquitylation inhibitor, TAK-243. We demonstrate that N-terminal phosphorylated β-catenin is quickly and strongly stabilized by a specific neddylation inhibitor, MLN4924, in all examined cell types, and that β-catenin and TCF4 interaction is strongly enhanced by inhibition of neddylation but not ubiquitylation. We also confirm that the E3 ligase β-TrCP2, but not β-TrCP1, is associated with neddylation and destruction of β-catenin. GSK3β and adenomatous polyposis coli (APC) are not required for β-catenin neddylation but essential for its subsequent degradation. Our findings not only clarify the process of β-catenin modification and degradation in the Wnt signaling pathway but also highlight the importance of reassessing previously identified ubiquitylation substrates.

The oil oxidation characteristics of the whole temperature regions from 30 °C to 600 °C during oil reservoir air injection were revealed by experiments. The whole oil oxidation temperature regions were divided into four different parts: dissolving and inflation region, low temperature oxidation region, medium temperature oxidation region and high temperature oxidation region. The reaction mechanisms of different regions were explained. Based on the oil oxidation characteristics and filed tests results, light oil reservoirs air injection development methods were divided into two types: oxygen-reducing air flooding and air flooding; heavy oil reservoirs air injection in-situ combustion development methods were divided into two types: medium temperature in-situ combustion and high temperature in-situ combustion. When the reservoir temperature is lower than 120 °C, oxygen-reducing air flooding should be used for light oil reservoir development. When the reservoir temperature is higher than 120 °C, air flooding method should be used for light oil reservoir development. For a normal heavy oil reservoir, when the combustion front temperature is lower than 400 °C, the development method is medium temperature in-situ combustion. For a heavy oil reservoir with high oil resin and asphalting contents, when the combustion front temperature is higher than 450 °C, the development method at this condition is high temperature in-situ combustion. Ten years field tests of air injection carried out by PetroChina proved that air has advantages in technical, economical and gas source aspects compared with other gas agents for oilfield gas injection development. Air injection development can be used in low/super-low permeability light oil reservoirs, medium and high permeability light oil reservoirs and heavy oil reservoirs. Air is a very promising gas flooding agent. Key words: air injection, full temperature regions, oil oxidation, reaction characteristics, coke formation, reservoir types, development methods

In the process of waterflooding development of heavy oil, W/O emulsion has a strong ability to improve the mobility ratio and block the high-permeability layer, which can effectively improve the sweep coefficient and enhance oil recovery. In this paper, the stability and droplet size distribution of emulsions under different conditions were studied by taking heavy oil and formation water from Jimusar Oilfield in Xinjiang as samples. On this basis, double-pipe core flooding experiments were carried out to study the shut-off ability and oil displacement efficiency of W/O emulsion, and then a numerical simulation was carried out. The results show that oil and water can be completely emulsified when the stirring speed is higher than 4000 r/min. A stable emulsion can be formed when the experimental temperature is lower than 60 °C. A lower water cut results in a more stable emulsion. The emulsion is difficult to stabilize after the salinity exceeds 10,000 mg/L. When the pH value is about 7, the stability of the emulsion is the worst. With the increase in stirring speed, the increase in temperature, and the decrease in water content and salinity, the emulsion droplet size range is relatively concentrated, and the average particle size is smaller. In heterogeneous reservoirs, the permeability of different percolation channels is quite different, such that the displacement fluid only percolates along the high-permeability channel and cannot drive oil effectively. The results of displacement experiments show that the emulsion with a water cut of 60% has high viscosity and obvious sweep ability, but its stability is very poor; the effect is opposite when the water cut is less than 40%. The shut-off ability of W/O emulsion disappears gradually when the permeability contrast is more than 5.92. The research results are of great significance for improving oil recovery in heterogeneous heavy oil reservoirs.

Polyacrylamide (HPAM) and other traditional polymers have poor temperature resistance and salinity tolerance and do not meet the needs of high-temperature and high-salinity reservoirs. In this study, a new temperature-resistant and salinity-tolerant polymer QJ75-39 was synthesized using acrylamide (AM) as a hydrophilic monomer, 1-acrylamide-2-methylpropanesulfonic acid (AMPS) and N-vinylpyrrolidone (NVP) as functional monomers and DS-16 as a hydrophobic monomer. Through laboratory experiments, the properties (temperature resistance, salinity tolerance and aging stability), polymer injection and core displacement effect of the polymer were studied. The experimental results showed that the new polymer could meet the needs of polymer flooding technology in high-temperature and high-salinity reservoirs. Experiments showed that the polymer had a temperature resistance of 95 °C and a salinity tolerance of 1.66 × 105 mg/L. When the temperature was 95 °C and the TDS was 55,376.8 mg/L, the viscosity of the polymer was 31.3 mPa s, and the viscosity remained above 30 mPa·s after aging for 60 days. The polymer had good injectivity between 300 and 600 mD, and the injection pressure could reach equilibrium quickly. The oil recovery effectively increased with the grsowth in the amount of injected polymer. When the injection amount was 0.5 PV, the enhanced oil recovery was 20.65%. This study is of great significance for the application and popularization of polymer flooding technology in high-temperature and high-salinity reservoirs.

The air oxidation of super-heavy oil at low temperature was studied in laboratory and its influences on oil viscosity, component and steam sweep efficiency before and after air-injection were analyzed. The feasibility, operation mode and air flooding effect at the late stage of steam assisted gravity drainage (SAGD) were investigated by numerical simulation. The experimental results show for vertical-horizontal well pair SAGD test area of Xing VI Formation in Block Du 84 of Liaohe Oilfield, the low temperature oxidation occurred between 150–250 °C (steam chamber temperature), the oil viscosity increased greatly after low temperature oxidation, consequently, the oil displacement efficiency dropped sharply. Three development methods in the late stage of SAGD were simulated, i.e., steam + air low temperature oxidation, only air low temperature oxidation and only air high temperature oxidation. By comparing production dynamic curves and residual oil distribution etc., high temperature oxidation reduced the heat loss in late stage of SAGD, recovered the residual oil effectively, and prolonged reservoir development time. Key words: super heavy oil, SAGD, air injection, low temperature oxidation, high temperature oxidation

The practice and theory of grouting engineering show that both injected medium porosity and grouting fluid weight play an important influence on the diffusion law and morphology of penetration grouting. However, the effects have not been well studied in the context of existing penetration grouting mechanisms. In this paper, the actual diffusion law and morphology of cement grout into the gravel soil are studied on the basis of indoor experiments, mathematical statistics, and theoretical analyses. Then, the three-dimensional space diffusion trajectory equation was quantitatively characterized. The influence of the coupling effect between gravel soil porosity and cement grout weight on diffusion morphologies of penetration grouting was discussed by the definition of the morphological deviation rate. Results show that actual penetration diffusion dimensions of cement grout into the gravel soil differ from that of theoretical values calculated by the penetration grouting mechanism, and its spatial diffusion morphology is approximated as ellipsoid. The coupling effect between gravel soil porosity and cement grout weight have a relatively significant effect on the diffusion morphologies of penetration grouting except for gravel soil with porosity 0.5. The research results can provide theoretical support and technical references for the practical grouting engineering of gravel soil.

Background Immune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.Methods The expression of programmed cell death-ligand 1 (PD-L1) and its regulation by miR-15b-5p were investigated in MSS CRC cell lines and tissues. The effects of miR-15b-5p on tumorigenesis and anti-PD-1 treatment sensitivity were verified both in vitro and in colitis-associated cancer (CAC) and APCmin/+ murine models. In vivo efficacy and mechanistic studies were conducted using antibodies targeting IL-17A and PD-1 in mice bearing subcutaneous CT26 and MC38 tumors.Results Evaluation of clinical pathological specimens confirmed that PD-L1 mRNA levels are associated with CD8+ T cell infiltration and better prognosis. miR-15b-5p was found to downregulate the expression of PD-L1 at the protein level, inhibit tumorigenesis and enhance anti-PD-1 sensitivity in CAC and APCmin/+ CRC models. IL-17A led to high PD-L1 expression in CRC cells through regulating the P65/NRF1/miR-15b-5p axis. Combined IL-17A and PD-1 blockade had efficacy in CT26 and MC38 tumors, with more cytotoxic T lymphocytes cells and fewer myeloid-derived suppressor cells in tumors.Conclusions IL-17A increases PD-L1 expression through the p65/NRF1/miR-15b-5p axis and promotes resistance to anti-PD-1 therapy. Blocking IL-17A improved the efficacy of anti-PD-1 therapy in MSS CRC murine models. IL-17A might serve as a therapeutic target to sensitize patients with MSS CRC to ICI therapy.

The mechanisms of oxygen-reduced air flooding (ORAF) and the explosion limit and the corrosion control approaches were studied based on the pilots of oxygen-reduced air flooding (ORAF) in the Dagang, Changqing and Daqing oil fields in China. On the foundation of indoor investigations and pilots, the explosion limits, oxygen reduction limits and corrosion control approaches were clarified. When the temperature of reservoir is equal to and higher than 120 °C, there is a violent reaction between oxygen and crude oil, that means the effect of low temperature oxidation would be fully taken use of to enhance oil recovery by air flooding directly; nitrogen dominated immiscible flooding with oxygen-reduced air should be applied in cases where reservoir temperature is below 120 °C with little oxygen consumption and little heat generated. The oxygen-reduced air flooding is suitable for 3 types of reservoirs: low permeability reservoir, water flooding development reservoir of high water-cut and high temperature and high salinity reservoir. In the process of development, in order to ensure safety, the oxygen reduction limits should be controlled fewer than 10%, while oxygen-reduced air can obviously reduce the corrosion rate of pipes; The surface pipelines and injection wells don't need to consider about oxygen corrosion with no water, special materials and structure of pipe or corrosion inhibitor can be applied to the surface pipelines and injection wellbores with water. Air/oxygen-reduced air is a low-cost displacement medium and it could be applied in many special conditions of low permeability reservoir for energy supplement, huff and puff and displacement, that means oxygen-reduced air flooding has become the most potential strategic technology in 20 years. Key words: oxygen-reduced air flooding, explosion limit, oxygen-reduction limit, low temperature oxidation, oxygen corrosion control

Campylobacter jejuni (C. jejuni) is considered as an opportunistic zoonotic pathogen that may cause gastroenteritis in humans and other animals. Wild birds may be as potential vectors of C. jejuni around urban and suburban areas. Here, 520 samples were collected from 33 wild bird species in urban and suburban areas, Beijing. In total 57 C. jejuni were isolated from seven species. It was found that Nineteen (33.33%, 19/57) isolates were resistant to at least one of 11 antibiotics, especially streptomycin (36.84%) and four isolates resistant to all. Nineteen (33.33%, 19/57) isolates were multi-drug resistance. Multilocus sequence typing (MLST) analysis of the isolates showed that 36 different sequence types (STs) belonged to four Clonal complexes and unassigned. Twenty STs (55.56%) and six alleles among them were first detected. Virulence genes including flaA, cadF, and the cytolethal distending toxin (CDT) gene cluster, were detected in all isolates, but truncated cdt gene clusters only detected in the isolates from the crow, daurian jackdaw and silver pheasant. In conclusion, it was the first detection of C. jejuni involved truncated cdt gene clusters from the silver pheasant. These wild birds around urban and suburban areas may pose potential public health problems as reservoir vectors of C. jejuni.

The propagating characteristics of combustion fronts and coke zones in the combustion assisted gravity drainage process were studied using 3D physical simulation experiments. The main mechanisms and factors affecting stable propagation of the combustion fronts were discussed. The experimental results show that the propagation of combustion front can be divided into startup stage, radial expands stage and moving forward stage. The top oil layer is ignited first at the startup stage. Ignition temperature, ignition time and air injection rate are the key parameters for successful ignition. At the radial expanding stage the combustion front grows in size and expands radically and downwards like a funnel, and the air injection rate should match the area of combustion front. After the combustion front propagates beyond the “toe” position, the burning zone would advance along the horizontal well at a certain angle. The controlled gas override and gas seal of the coke in the horizontal well contributes significantly to the overall stability of the process. In field pilot testing, well pattern, ignition parameters and regime of injection and production should be optimized to ensure the stable propagation of the combustion front. Key words: combustion assisted gravity drainage, horizontal well, combustion front, propagating characteristic, physical simulation

The silencing of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) by promoter methylation commonly occurs in human cancers. The relationship between MGMT promoter methylation and gastric cancer (GC) remains inconsistent. This study aimed to evaluate the potential value of MGMT promoter methylation in GC patients. Electronic databases were searched to identify eligible studies. The pooled odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were used to evaluate the effects of MGMT methylation on GC risk and clinicopathological characteristics. In total, 31 eligible studies including 2988 GC patients and 2189 nonmalignant controls were involved in meta-analysis. In the pooled analysis, MGMT promoter methylation was significantly associated with GC risk (OR = 3.34, P < 0.001) and substantial heterogeneity (P < 0.001). Meta-regression and subgroup analyses based on the testing method, sample material and ethnicity failed to explain the sources of heterogeneity. Interestingly, MGMT methylation showed a trend associated with gender, and methylation is lower in males compared with females (OR = 0.76, 95% CI = 0.56-1.03). We did not find a significant association in relation to tumor types, clinical stage, age status or H. pylori status in cancer (all P > 0.1). MGMT promoter methylation may be correlated with the prognosis of GCs in disease free survival (DFS) or overall survival (OS) for univariate analysis. MGMT promoter methylation may play a crucial role in the carcinogenesis and prognosis of GC. MGMT methylation was not correlated with tumor types, clinical stage, age status, H. pylori status. However, the result of the association of MGMT methylation and gender should be considered with caution.

This paper develops a novel model and protocol used in some specific scenarios, in which the participants of multiple groups with different permissions can finish the signature together. We apply the secret sharing scheme based on difference equation to the private key distribution phase and secret reconstruction phrase of our threshold signature scheme. In addition, our scheme can achieve the signature success because of the punishment strategy of the repeated rational secret sharing. Besides, the bit commitment and verification method used to detect players’ cheating behavior acts as a contributing factor to prevent the internal fraud. Using bit commitments, verifiable parameters, and time sequences, this paper constructs a dynamic game model, which has the features of threshold signature management with different permissions, cheat proof, and forward security.

Purpose: The objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer's disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients. Methods: In this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients. Results: The ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = -0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = -0.385, direct effects = -0.02, total indirect effects = -0.405). Conclusion: The ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms. [ABSTRACT FROM AUTHOR]

In order to improve the oil recovery of mid-deep heavy oil reservoirs, this study investigates the efficiency of enhanced oil recovery and the mechanisms of oil displacement in mid-deep heavy oil reservoirs using different injected gases (N2, CH4, CO2) and development approaches (gas flooding and gas huff-n-puff) through a series of experiments. These experiments include high-pressure physical properties tests of crude oil after gas injection, displacement efficiency tests of gas injection, and displacement efficiency tests of gas huff-n-puff. The results indicate that for mid-deep heavy oil reservoirs, the preferred optimal injection gas is CO2, with gas huff-n-puff being the most effective development method. Furthermore, a numerical simulation study was conducted to explore the adaptability parameters of CO2 huff-n-puff development in different well patterns, encompassing variables such as the amount of gas injected per cycle, crude oil viscosity, reservoir permeability, and oil layer thickness. [ABSTRACT FROM AUTHOR]