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Horizontal wells are the primary method for developing bottom-water reservoirs. Accurately understanding the production contribution of each segment of a horizontal well and the downhole production performance serves as the basis for water control completion design. This understanding holds significant importance for enhancing well productivity, reducing costs, and improving efficiency. To address the deficiencies in the research on fluid flow in horizontal wells, ANYSY FLUENT is employed to analyze and evaluate influence rules and degree of target parameters—such as permeability distribution, production pressure difference, crude oil viscosity, and density—on the fluid in both the reservoir and the wellbore. The analysis reveal that the main locations of the reservoir and annulus distribution surface are near the toe of the wellbore. The number of diversion surfaces is correlated with permeability distribution, production pressure difference, crude oil viscosity, and crude oil density. Permeability distribution and oil viscosity play a dominant role: the number of distribution surface in the high-permeability heel section is significantly higher than that in the toe, and the number of distribution surface for crude oil with a viscosity of 200 cP is notably greater than that for 50 cP crude oil. The impacts of pressure drop and oil density are relatively minor: the number of distribution surface is the same under pressure differences of 1.5 MPa and 2.5 MPa, and the same holds true for crude oils with densities of 850 kg/m³ and 950 kg/m³. The research findings fills the gap in the study of fluid flow directions in horizontal wells and possess substantial scientific and engineering value for the effective development of bottom water reservoirs, as well as the production and management of horizontal wells.

Background Paenibacillus polymyxa WLY78 is a Gram-positive, endospore-forming and N 2 -fixing bacterium. Our previous study has demonstrated that GlnR acts as both an activator and a repressor to regulate the transcription of the nif ( ni trogen f ixation) operon ( nifBHDKENXhesAnifV ) according to nitrogen availability, which is achieved by binding to the two GlnR-binding sites located in the nif promoter region. However, further study on the GlnR-mediated global regulation in this bacterium is still needed. Results In this study, global identification of the genes directly under GlnR control is determined by using chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assays (EMSA). Our results reveal that GlnR directly regulates the transcription of 17 genes/operons, including a nif operon, 14 nitrogen metabolism genes/operons ( glnRA , amtBglnK , glnA1 , glnK1 , glnQHMP , nasA , nasD1 , nasD2EF , gcvH , ansZ , pucR , oppABC , appABCDF and dppABC) and 2 carbon metabolism genes ( ldh3 and maeA1 ). Except for the glnRA and nif operon, the other 15 genes/operons are newly identified targets of GlnR. Furthermore, genome-wide transcription analyses reveal that GlnR not only directly regulates the expression of these 17 genes/operons, but also indirectly controls the expression of some other genes/operons involved in nitrogen fixation and the metabolisms of nitrogen and carbon. Conclusion This study provides a GlnR-mediated regulation network of nitrogen fixation and the metabolisms of nitrogen and carbon.

In order to analyse the effect of the injection point size of the CBM (Coalbed Methane) well level monitor on the amplitude and frequency of pressure pulsations in the wellhead manifold, numerical simulations and experiments were carried out to investigate the effect of different injection point sizes on the amplitude and frequency of pressure pulsations downstream of the sudden expansion structure. Using compressed air as the fluid and the size of the injection point as the variable, the amplitude and frequency of pressure pulsations at different locations downstream of the sudden expansion structure were tested. The results show that the pressure pulsation amplitude is affected by the size of the injection point, and the larger the injection point is, the larger the pressure pulsation amplitude is; the size of the injection point has less influence on the pressure pulsation frequency downstream of the protruding and expanding structure, and the pressure pulsation frequency at 0.5 m and 1 m downstream of the protruding and expanding structure is in the vicinity of 76 Hz. Therefore, the echo signal processing should be filtered around this frequency to obtain accurate liquid level echo signals, so as to improve the accuracy of liquid level monitoring and realise the efficient development of coalbed methane wells.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and is closely linked to oxidative stress. This study aimed to identify and validate key oxidative stress-related genes and pathways involved in COPD using integrated bioinformatics and experimental approaches. Public COPD datasets were obtained from the Gene Expression Omnibus (GEO) database, and oxidative stress-related genes were retrieved from the GeneCards database. Differentially expressed genes (DEGs) were screened and analyzed for functional enrichment. Machine-learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest, were used to identify hub genes and evaluate diagnostic value by calculating the area under the receiver operating characteristic (ROC) curve (AUC). Single-cell RNA sequencing (scRNA-seq) data were analyzed to determine the distribution of hub genes across different cell types. Finally, a COPD combined oxidative stress cell model was established using human bronchial epithelial cells (BEAS-2B), and key gene expression was experimentally validated. We identified 76 overlapping genes associated with both COPD and oxidative stress, mainly enriched in necroptosis, JAK-STAT, MAPK, and related pathways. 12 hub genes were screened using machine-learning methods. Single-cell analysis showed that TPPP3 and VEGFA were predominantly expressed in epithelial cells. Experimental validation confirmed the bioinformatics predictions at the gene level. This study identified and validated 12 oxidative stress-related hub genes in COPD, highlighting TPPP3 and VEGFA as key genes enriched in epithelial cells and potentially involved in tissue remodeling. These findings not only provide insights for exploring new therapeutic strategies but may also serve as potential diagnostic biomarkers or candidate therapeutic targets for COPD.

Objective Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4 + T cells in RA and the specific molecular mechanism. Methods Peripheral venous blood was collected from human subjects, and CD4 + T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4 + T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels. Results CD4 + T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4 + T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4 + T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4 + T cells. Conclusions Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4 + T cells from RA patients.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in people over the age of 55. AMD currently affects approximately 8% of the world’s population, and the number is growing as the global population ages. Growing evidence suggests that pathological choroidal neovascularization (CNV) is often related to more severe and rapid vision loss and blindness associated with AMD. The typical clinical treatment is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond well to this therapy, and the potential risks of long-term repeated injections cannot be ignored. Therefore, there is an urgent need to explore the specific mechanisms of CNV development and find new, safe, and effective treatments. In this study, our data indicate that ferroptotic damage of retinal pigment epithelium (RPE) and its induced VEGFA overexpression are critical promoting factors in the development of CNV. Vitamin K can mediate the protection of RPE cells from ferroptotic damage and regulate the expression of eIF2α-ATF4-VEGFA in a VKOR/FSP1-dependent manner, inhibiting new angiogenesis to alleviate CNV. On the contrary, vitamin K antagonists (VKA) represented by warfarin, can promote RPE ferroptotic damage and related vascular proliferation in mice and eventually aggravate CNV lesions. However, vitamin K still showed significant protective effects even in the presence of VKA. Due to its significant anti-ferroptosis and anti-neovascular effects, as well as its relative safety and convenience of use, vitamin K has excellent potential in the treatment of CNV and is expected to become a clinically effective and safe new CNV treatment strategy.

Tendon-bone insertion (TBI) injuries and diseases are one of the common musculoskeletal conditions that can severely impair an individual’s daily activities and quality of life. The healing process following an injury is intricate and depending on microenvironmental factors such as mechanical loading, inflammatory responses, and the extracellular matrix. Tendon stem/progenitor cells (TSPCs) primarily contribute to the replenishment of tendon cells via self-renewal and differentiation, which is essential for tendon-bone healing. Exosomes, small extracellular vesicles from various cell types, have attracted significant interest for their potential in regenerative medicine, particularly for treating tendon disorders. Recent studies indicate that exosomes from various cell sources, including mesenchymal stem cells (MSCs) and adipose-derived stem cells (ADSCs), can effectively modulating the activity of TSPCs and enhance their therapeutic potential. This review provides an overview of the mechanisms and functions of stem cell-derived exosomes in altering the properties of TSPCs and facilitating tendon-bone healing. In conclusion, exosomes offer a promising therapeutic approach for TBI injuries. However, further clinical validation is required. Utilizing the regenerative capabilities of exosomes could address promotion of tendon-bone healing and enhance the quality of life for affected patients.

Objective To evaluate the effect of myopia on retinal vascular bifurcation. Methods A cross-sectional study that retrospectively analyzed the fundus photographs and clinical data of 493 people who participated in routine physical examinations in Huadong Sanatorium. One eye of each subject was included in the analysis. Retinal vascular bifurcation measurements were extracted by using a validated computer program. One-way ANOVA and analysis of covariance were performed to compare the measurements across high myopia, low to moderate myopia, and non-myopia groups. Results The mean age was 41.83 ± 10.43 years and 63.49% were women. The mean spherical equivalent refraction (SER) was − 4.59 ± 3.07 D. Ninety-nine (20.08%) eyes met the definition of high myopia (SER ≤ -6.0 D), along with 234 (47.46%) low to moderate myopia (-6.0 D < SER <-0.5 D), and 160 (32.45%) non-myopia (SER ≥ -0.5 D). The differences in the arteriolar branching angle, venular branching coefficient, venular asymmetry ratio, venular angular asymmetry, and venular junctional exponent among the three groups remained significant ( p  < 0.05) after multivariate adjustment. Pairwise comparisons showed arteriolar branching angle and venular angular asymmetry in high myopia were significantly lower than low to moderate myopia ( p  < 0.001, p  = 0.014 respectively) and non-myopia ( p  = 0.007, p  = 0.048 respectively). Venular asymmetry ratio and venular branching coefficient in high myopia were significantly higher than low to moderate myopia ( p  = 0.029, p  = 0.001 respectively) and non-myopia ( p  = 0.041, p  = 0.043 respectively). There was a significant difference in venular junctional exponent between high myopia and low to moderate myopia ( p  = 0.031). Conclusion The vascular bifurcation differs in dependence on the myopic refractive error and a significant increase in the difference can be observed in high myopic eyes.

IntroductionThis study focused on a Chinese Antarctic krill vessel utilising continuous pumping fishing technology. The resistance characteristics of Antarctic krill ships trawling in floating ice areas is of great significance for the navigation and fishing of krill ships in ice areas.MethodsFirstly, MATLAB programming using discrete elements combined with genetic algorithms was used to construct a normal distribution ice flow model. Secondly, a fluid-structure coupling interface is created through the contact between the fluid and the trawl grid, and the displacement and resistance of the trawl grid are evaluated on the shared interface. Finally, the effects of ice density and ship sailing speed on ice resistance were studied.Results and discussionThe results of the calculations results show that ice resistance is positively related to the concentration and speed of floating ice, moreover, there is a special speed point where ice resistance increases rapidly. As the speed increases, the proportion of trawl resistance to the total resistance continues to increase, while the proportion of ice resistance continues to decrease. This paper provides a reference for the navigation and fishing resistance assessment of Antarctic krill ships in floating ice areas.

The strong perioperative stress response caused by surgical anesthesia can significantly suppress immune function, and the body is in a state of immunosuppression for 3 to 4 days after surgery, which leads to an increase in the probability of postoperative infection. Traditional Chinese medicine believes that acupuncture points can \"reconcile yin and yang\", promote the recovery of immune function, and help reduce the incidence of postoperative infection. Macrophages are an important type of immune cells that participate in the body's innate immunity. They have powerful phagocytosis and clearance functions. They can be polarized into M1 and M2 types under the regulation of the body, and play different roles in fighting microbial infections. Among them, the M1 type can participate in the elimination of pathogens. In this study, we will investigate the perioperative acupoint electrical stimulation to alleviate the immunosuppressive state of surgical stress mice, clarify the regulation of perioperative acupoint electrical stimulation on glucocorticoids and the relationship between NF-κB molecules and macrophage polarization.The key molecules of related pathways were verified by glucocorticoid receptor inhibitors, and it was found that electrical stimulation of acupoints during the perioperative period can affect the polarization of macrophages in surgically stressed mice to the M1 type by reducing the level of glucocorticoids and promoting the expression of NF κB molecules. Further reveal the partial mechanism of electroacupuncture regulating the anti-inflammatory and pro-inflammatory processes of macrophages in the immune response.