Mechanistic Insights into a Novel Controllable Phase-Transition Polymer for Enhanced Oil Recovery in Mature Waterflooding Reservoirs.

Expanding swept volume technology via continuous-phase polymer solution and dispersed-phase particle gel is an important technique to increase oil production and control water production in mature waterflooding reservoirs. However, problems such as the low viscosity retention rate, deep migration, and weak mobility control of conventional polymers, and the contradiction between migration distance of particle gel and plugging strength, restrict the long-term effectiveness of oil displacement agents and the in-depth sweep efficiency expanding capability in reservoirs. Combined with the technical advantages of polymer and particle gel, a novel controllable phase-transition polymer was developed and systematically studied to gain mechanistic insights into enhanced oil recovery for mature waterflooding reservoirs. To reveal the phase-transition mechanism, the molecular structure, morphology, and rheological properties of the controllable phase-transition polymer were characterized before and after phase transition. The propagation behavior of the controllable phase-transition polymer in porous media was studied by conducting long core flow experiments. Two-dimensional micro visualization and parallel core flooding experiments were performed to investigate the EOR mechanism from porous media to pore level. Results show that the controllable phase-transition polymer could change phase from dispersed-phase particle gel to continuous-phase solution with the prolongation of ageing time. The controllable phase-transition polymer exhibited phase-transition behavior and good propagation capability in porous media. The results of micro visualization flooding experiments showed that the incremental oil recovery of the controllable phase-transition polymer was highest when a particle gel and polymer solution coexisted, followed by a pure continuous-phase polymer solution and pure dispersed-phase particle gel suspension. The recovery rate of the novel controllable phase-transition polymer was 27.2% after waterflooding, which was 8.9% higher than that of conventional polymer, providing a promising candidate for oilfield application.

Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway.

Sepsis can impair gastrointestinal (GI) barrier integrity. Oral probiotics (PT) can maintain the balance of GI microflora and improve GI function. 5-Hydroxytryptamine (5-HT) is a key promoter of GI injury caused by sepsis. However, the mechanism by which PT attenuates sepsis by regulating 5-HT is not fully understood. In this study, C57BL6 mice were intragastric administrated with normal saline (NC) or PT once a day for 4 weeks before cecal ligation and puncture (CLP). Compared with NC-CLP mice, PT-CLP mice had lower clinical score, higher body temperature. The survival rate of PT-CLP mice was significantly improved. The levels of inflammatory cytokines and 5-HT were obviously decreased in PT-CLP mice, and GI peristalsis and barrier function were enhanced. Moreover, sepsis downregulated the expression of tight junction proteins, while PT pretreatment could maintain them at the level of sham operation group. Furthermore, PT pretreatment increased the expression of serotonin transporter and monoamine oxidase A. PT administration could inhibit NF-κB activity, and activate ERK activity. In conclusion, long-term supplementation of PT before CLP can prevent sepsis-induced GI mucosal barrier dysfunction in mice, which may be partially mediated by upregulating the 5-HT degradation pathway via activating ERK signaling.

A reinforcement learning method for optimal control of oil well production using cropped well group samples.

The influence of geological development factors such as reservoir heterogeneity needs to be comprehensively considered in the determination of oil well production control strategy. In the past, many optimization algorithms are introduced and coupled with numerical simulation for well control problems. However, these methods require a large number of simulations, and the experience of these simulations is not preserved by the algorithm. For each new reservoir, the optimization algorithm needs to start over again. To address the above problems, two reinforcement learning methods are introduced in this research. A personalized Deep Q-Network (DQN) algorithm and a personalized Soft Actor-Critic (SAC)algorithm are designed for optimal control determination of oil wells. The inputs of the algorithms are matrix of reservoir properties, including reservoir saturation, permeability, etc., which can be treated as images. The output is the oil well production strategy. A series of samples are cut from two different reservoirs to form a dataset. Each sample is a square area that takes an oil well at the center, with different permeability and saturation distribution, and different oil-water well patterns. Moreover, all samples are expanded by using image enhancement technology to further increase the number of samples and improve the coverage of the samples to the reservoir conditions. During the training process, two training strategies are investigated for each personalized algorithm. The second strategy uses 4 times more samples than the first strategy. At last, a new set of samples is designed to verify the model's accuracy and generalization ability. Results show that both the trained DQN and SAC models can learn and store historical experience, and push appropriate control strategies based on reservoir characteristics of new oil wells. The agreement between the optimal control strategy obtained by both algorithms and the global optimal strategy obtained by the exhaustive method is more than 95%. The personalized SAC algorithm shows better performance compared to the personalized DQN algorithm. Compared to the traditional Particle Swarm Optimization (PSO), the personalized models were faster and better at capturing complex patterns and adapting to different geological conditions, making them effective for real-time decision-making and optimizing oil well production strategies. Since a large amount of historical experience has been learned and stored in the algorithm, the proposed method requires only 1 simulation for a new oil well control optimization problem, which showing the superiority in computational efficiency.

Prolyl 4-hydroxylase P4HA1 Mediates the Interplay Between Glucose Metabolism and Stemness in Pancreatic Cancer Cells.

INTRODUCTION: Cancer stem cells (CSCs) are profoundly implicated in tumor initiation and progression as well as drug resistance and tumor recurrence of many cancer types, especially pancreatic ductal adenocarcinoma (PDAC). Previously, we revealed that prolyl 4-hydroxylase subunit alpha 1 (P4HA1) enhances the Warburg effect and tumor growth in PDAC. However, the possible connection between P4HA1 and cancer stemness in PDAC remains obscure. In this study, P4HA1-dependent cancer stemness was studied by sphere-formation assay and detection of stemness markers. METHODS: Glycolytic capacity in cancer stem cells and their parental tumor cells was investigated by glucose uptake, lactate secretion, and expression of glycolytic genes. Glycolysis inhibitors were used to determine the link between cancer stemness and glycolysis. A subcutaneous xenograft model was generated to investigate P4HA1-induced stemness and glycolysis in vivo. RESULTS: We revealed that ectopic expression of P4HA1 increased the stemness of PDAC cells as evidenced by the increased proportion of CD133+ cells, elevated sphere-formation ability, and the upregulated levels of cancer stemness-related proteins (SOX2, OCT4, and NANOG). Blocking tumor glycolysis with 2-Deoxy-D-glucose (2-DG) or a selective inhibitor of glucose transporter 1 (STF-31) significantly reduced the stem properties of PDAC cells, suggesting that P4HA1-induced glycolysis was essential for the stem-like phenotype of PDAC cells. In addition, in vivo study reaffirmed a promotive effect of P4HA1 on tumor glycolysis and cancer stemness. CONCLUSION: Collectively, our findings suggest that P4HA1 not only affects tumor metabolic reprogramming but also facilitates cancer stemness, which might be exploited as a vulnerable target for PDAC treatment.

CD73 is a hypoxia-responsive gene and promotes the Warburg effect of human gastric cancer cells dependent on its enzyme activity.

Background: The Warburg effect is closely associated with malignant phenotypes and poor prognosis in gastric cancer. CD73 is a glycosylphosphatidylinositol (GPI) anchored cell surface protein that functions as an oncogene in a variety of human cancers. However, the relationship between CD73 and the Warburg effect has yet to be fully understood. Methods: Integrative analysis was performed to identify glycolysis-related genes in gastric cancer. Loss-of-function and gain-of-function are performed to demonstrate the roles of CD73 in gastric cancer cell proliferation and glycolysis. Cell biological, molecular, and biochemical approaches are used to uncover the underlying mechanism. Results: In this study, we find that CD73 is a glycolysis-associated gene and is induced by hypoxia in gastric cancer. Genetic silencing of CD73 reduces gastric cancer cell proliferation and glycolytic ability. Opposite effects were observed by CD73 overexpression. Importantly, pharmacological inhibition of CD73 activity by APCP inhibits tumor growth, which can be largely compromised by the addition of adenosine, suggesting an enzyme activity-dependent effect of CD73 in gastric cancer. Furthermore, hijacking tumor glycolysis by 2-DG or galactose largely abrogated the oncogenic roles of CD73, indicating that CD73 promotes tumor growth in a glycolysis-dependent manner in gastric cancer. By the subcutaneous xenograft model, we confirmed the promotive roles of CD73 in regulating cell proliferation and glycolysis in gastric cancer. Conclusions: This study provides strong evidence of the involvement of CD73 in the Warburg effect and indicates that it could be a novel antitumor strategy to target tumor metabolism in gastric cancer.

MTERFD1 promotes cell growth and irradiation resistance in colorectal cancer by upregulating interleukin-6 and interleukin-11.

The role of the novel oncogene, mitochondrial transcription termination factor (MTERFD1), in human colorectal cancer (CRC) is unclear. Here, we report the role MTERFD1 in CRC. We conducted plasmid construction and transfection analyses, cell proliferation assays, apoptosis detection assays, ELISA, western blotting, and qRT-PCR using cell culture applications. MTERFD1 was upregulated in human and chemically induced mouse CRC tissues. In vitro functional assays showed that MTERFD1 overexpression promoted human CRC cell proliferation, whereas knockdown of endogenous MTERFD1 significantly enhanced apoptosis in these cells. MTERFD1 expression was positively linked to irradiation resistance in CRC cells. Furthermore, interleukin (IL)-6 and IL-11 were identified as the effector molecules of MTERFD1 in its oncogenic role and irradiation resistance in CRC cells. Our results demonstrated that MTERFD1 played an oncogenic role in CRC development and enhanced irradiation resistance by regulating IL-6 and IL-11 in CRC cells. MTERFD1 may serve as a potential prognostic and therapeutic marker for radiotherapy in CRC.

Hedgehog Signaling Activation in Hepatic Stellate Cells Promotes Angiogenesis and Vascular Mimicry in Hepatocellular Carcinoma.

Previous studies have established that hedgehog (Hh) signaling mediates tumor-stroma interaction and promotes hepatocellular carcinoma progression. Here, we demonstrated that activation of Hh signaling in hepatic stellate cell (HSC) line LX-2 by Huh-7-derived sonic Hh led to increased secretion of angiogenic factors and promoted angiogenesis in vitro. The activated LX-2 also enhanced vascular mimicry of hepatoma cells. Furthermore, co-injection of Huh-7 and LX-2 significantly accelerated tumor growth with enhanced angiogenesis compared with Huh-7 alone, which could be partly abrogated by Hh signaling inhibitor. Collectively, our data showed that paracrine Hh signaling mediated pro-angiogenic function of HSC and enhanced hepatoma growth.

Software for the interactive visualisation of experimental data in the genomic context.

Time-lagging in expression occurs when a gene's expression triggers a delayed expression in its co-regulated or anti-co-regulated peers. Arbitrary time-lagging also might appear due to experiment or measurement error. Traditional methods will either under-estimate or completely miss such correlation, which is not unusual and plays important roles. Since the traditional similarity measurement cannot capture the true relationship, a simple time-lagging captured algorithm integrated with some existing time-lagging and similarity measurement techniques is proposed with parallel implementation. Improvements such as isolation of experimental conditions and weighted averages are used to achieve better accuracy and give user flexibility to differentiate different experiments.