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Cemented natural fractures (CNFs) are commonly found in unconventional shale and tight sandstone reservoirs. During the process of hydraulic fracturing, CNFs can affect the propagation of hydraulic fractures and thus impact oil and gas production. However, the interaction behavior between CNFs and hydraulic fractures is still unclear. In this study, a fully fluid-solid coupling numerical model simulating hydraulic fracture propagation was developed to simulate the interaction propagation of hydraulic fractures and CNFs based on the particle flow method. The numerical model results are in good agreement with published experimental results, indicating the reliability of the model. The model was used to analyze the effects of natural fracture cementation strength, inclination angle, and fracturing fluid viscosity on the interaction propagation morphology of fractures. The influence of induced stress fields on the interaction propagation of fractures was also studied. The simulation results indicate that the CNF with different inclination angles may have different critical cementation strength ratios. When the cementation strength ratio is relatively small, the hydraulic fracture is arrested by the CNF, the CNF is opened, generating significant shear fractures. A new fracture propagation pattern was discovered in this study, where the hydraulic fracture is arrested by the weakly CNF and generates bifurcation fractures that communicate with the tips of the natural fracture. Additionally, low viscosity fracturing fluid facilitates the generation of complex fracture networks during the interaction propagation of the hydraulic fracture and the weakly CNF.

Hydraulic fracturing is a key technology for enhancing coalbed methane recovery. Preconditioning the reservoir with acidizing or oxidative fluids can significantly improve stimulation outcomes; however, comparative studies evaluating these fluids in coal seams are still limited. In this work, deep coal samples (depth > 2500 m) were treated with five different pre-fracturing fluids—slick water (PAM), hydrochloric acid (HCl), hydrochloric and hydrofluoric (HCl + HF) acid, sodium hypochlorite (NaClO), and hydrogen peroxide (H 2 O 2 )—and their effects on porosity, permeability, and mechanical properties were systematically compared using low-field NMR, SEM, and mechanical testing. The potential relationships between changes in mechanical parameters and pore-fracture structure were also examined. Results show that all five fluids increased total porosity by 33.98 ~ 45.04%. The HCl + HF produced the most dramatic permeability enhancement (13,561.54%), whereas HCl alone reduced permeability by 78.01%. Moreover, HCl + HF led to the most pronounced reduction in both compressive and tensile strength. Kendall correlation analysis revealed several significant relationships: Young’s modulus ( E ) correlated negatively with total porosity ( φ t ) and average roughness ( R a ); Poisson’s ratio ( ν ) showed a positive correlation with φ t ; and tensile strength ( R t ) was negatively correlated with R a . These findings provide practical insights for selecting pre-fracturing fluids based on desired reservoir weakening or permeability enhancement objectives.

Efficient proteostasis and immune evasion are both critical for tumor progression. The chaperonin TRiC/CCT complex, which mediates the folding of cytoskeletal and signaling proteins, has been associated with oncogenesis; however, the specific role of its subunit CCT4 in tumor-immune interactions remain unclear. To address this gap, we integrated transcriptomics, proteomics, genomics, epigenetics and immunogenomics data. A comprehensive pan-cancer analysis was conducted (including the expression patterns, clinical relevance, prognosis value, immune infiltration of pan-cancer). Then an in-depth analysis of lung adenocarcinoma (LUAD) was carried out through enrichment analysis and single-cell RNA sequencing, and verified through cell experiments. CCT4 was found to be aberrantly upregulated across a majority of tumor types, particularly in LUAD, where elevated expression was associated with advanced stage and inferior survival outcomes. High CCT4 levels were linked to reduced immune cell infiltration and diminished anti-tumor immune signaling, specifically manifested as increased Th2 cell infiltration and decreased Th1 and CD8 T-cell signatures. Single-cell analyses revealed coordinated overexpression of all CCT subunits in tumor epithelial cells, supporting a global TRiC activation. However, CCT4 was preferentially enriched within highly proliferative subclusters, suggesting partial subunit-specific regulation. CCT4 knockdown suppressed LUAD cell proliferation, migration, and invasion . CCT4 links enhanced proteostasis with immune evasion in LUAD, acting partly through TRiC complex activity and possibly through independent nuclear functions. These findings refine the understanding of how proteostatic machinery contributes to immune modulation in cancer and highlight CCT4 as a potential molecular node bridging tumor growth and immune suppression.

The flow of fluid through the porous matrix of a reservoir rock applies a seepage force to the solid rock matrix. Although the seepage force exerted by fluid flow through the porous matrix of a reservoir rock has a notable influence on rock deformation and failure, its effect on hydraulic fracture (HF) propagation remains ambiguous. Therefore, in this study, we improved a traditional fluid–solid coupling method by incorporating the role of seepage force during the fracturing fluid seepage, using the discrete element method. First, we validated the simulation results of the improved method by comparing them with an analytical solution of the seepage force and published experimental results. Next, we conducted numerical simulations in both homogeneous and heterogeneous sandstone formations to investigate the influence of seepage force on HF propagation. Our results indicate that fluid viscosity has a greater impact on the magnitude and extent of seepage force compared to injection rate, and that lower viscosity and injection rate correspond to shorter hydraulic fracture lengths. Furthermore, seepage force influences the direction of HF propagation, causing HFs to deflect towards the side of the reservoir with weaker cementation and higher permeability.

Lung cancer ranks as the primary contributor to cancer-related fatalities on a global scale, hallmarked by a poor prognosis. Programmed cell death (PCD) is critically involved in regulating the onset, progression, and treatment of lung adenocarcinoma (LUAD). Existing prognostic models concerning PCD focus solely on individual mechanisms and fail to account for the intricate interaction among multiple regulatory mechanisms. In this study, the LUAD samples were sorted into low immune cell invasion subtype (C1) and high immune cell invasion subtype (C2) by clustering analysis. A PCD prognostic signature model was developed by LASSO Cox regression analysis. Tumors in the high-risk group were categorized as “cold” and characterized by immunosuppression, which was linked to an unfavorable prognosis and sensitivity to drug therapy. However, the opposite was true for the low-risk group, which was associated with a favorable prognosis and sensitivity to immunotherapy. Single-cell analysis found that the PCD signature model could activate several immune cells, thereby affecting the tumor microenvironment (TME) of LUAD. Furthermore, ENO1, could be used as a target for LUAD prognosis and immunotherapy. This study aims to comprehensively explore the functional mechanisms of various PCD regulatory patterns in LUAD to provide accurate prognosis and personalized treatment plans.

Breast cancer (BC) represents a highly heterogeneous malignancy and continues to be a leading source of death among women worldwide. Enhancing diagnostic and therapeutic approaches necessitates a thorough grasp of the underlying molecular pathways and the identification of dependable biomarkers. Although palmitoyl transferases, particularly ZDHHC9, have been associated with the progression of various cancers, their specific role in BC remains incompletely understood. In this investigation, TCGA and GTEx databases were utilized to analyze the expression patterns of ZDHHC9 and to evaluate its prognostic significance. Moreover, the regulatory pathways involving ZDHHC9 were explored via co-expression analysis and differential gene enrichment studies. Insights into ZDHHC9 expression across different cell types and its potential oncogenic pathways were derived from scRNA sequencing analysis. Additionally, immunophenoscore (IPS), EaSIeR and immunotherapy cohorts were utilized to predict immunotherapy responses. The biological significance of ZDHHC9 was verified through and experiments. Our findings revealed that ZDHHC9 is markedly overexpressed in BC, with elevated levels of ZDHHC9 being correlated with poor survival outcomes, suggesting its role as an independent risk factor in BC. Furthermore, high ZDHHC9 expression was found to be associated with multiple immune cell types within BC. Notably, patients exhibiting lower ZDHHC9 expression demonstrated a higher likelihood of benefitting from immunotherapy. Lastly, the vivo and vitro experiments consistently demonstrated that suppression of ZDHHC9 expression could reduce BC cell proliferation. This study highlights ZDHHC9 as a potential prognostic marker, a regulator of tumor immunity, and a biomarker of therapeutic response in BC, offering a promising avenue for improving BC diagnosis and treatment.

The circadian rhythm is an endogenous clock system that coordinates and optimizes various physiological and pathophysiological processes, which accord with the master and the peripheral clock. Increasing evidence indicates that endogenous circadian rhythm disruption is involved in the lesion volume and recovery of ischemic stroke. As a critical recovery mechanism in post-stroke, angiogenesis reestablishes the regional blood supply and enhances cognitive and behavioral abilities, which is mainly composed of the following processes: endothelial cell proliferation, migration, and pericyte recruitment. The available evidence revealed that the circadian governs many aspects of angiogenesis. This study reviews the mechanism by which circadian rhythms regulate the process of angiogenesis and its contribution to functional recovery in post-stroke at the aspects of the molecular level. A comprehensive understanding of the circadian clock regulating angiogenesis in post-stroke is expected to develop new strategies for the treatment of cerebral infarction.

Background Stroke is a leading cause of death and disability worldwide, yet its treatment still faces significant challenges. Mendelian randomization (MR) has been widely used to discover new biomarkers and therapeutic targets. This study aimed to identify therapeutic targets for stroke within the plasma proteome range using MR. Methods We conducted a two-sample MR study, evaluating the causal relationships between 2,940 plasma proteins from the UK Biobank-Proteome-wide Association Study (UKB-PPP) and stroke, with further validation in 4,907 plasma proteins from Iceland. Subsequently, drug target proteins were determined using Bayesian colocalization, Summary data-based Mendelian randomization (SMR), and protein-protein interaction (PPI) network construction to validate the role of selected disease-associated proteins. Results Preliminary MR analysis identified 11 proteins (LPA, FURIN, MST1, FKBPL, SH2B3, MMP12, F11, ITGAV, DDHD2, VSIR and GAS6) significantly associated with stroke or stroke subtypes. Through SMR and colocalization analysis, 4 potential drug target proteins were identified: FURIN as a potential drug target for stroke and any ischemic stroke, F11 as a potential drug target for cardioembolic stroke, DDHD2 and VSIR as potential drug targets for small vessel stroke. It is worth noting that F11 is currently being used in the development of multiple drugs, FURIN is not only associated with stroke but also appears to have abnormal expression in several cardiovascular diseases. Although research on DDHD2 and VSIR in the context of stroke is relatively limited, current findings indicate that DDHD2 is related to synaptic plasticity, while VSIR is associated with microglia and immune responses. Conclusion This study found that the plasma proteins FURIN, F11, DDHD2, and VSIR show promise as potential therapeutic targets for stroke and its subtypes, providing genetic evidence to support precision drug development and insights into the underlying pathological mechanisms of stroke. Clinical trial number Not applicable.

C-type lectin domain family 12 member A (CLEC12A) is a type II transmembrane glycoprotein widely expressed in innate immune cells, where it plays a crucial role in immune modulation and has been implicated in cancer progression. However, its precise function in oncogenesis and immune infiltration remains incompletely understood. To investigate this, we utilized multiple databases to assess the mRNA and protein expression levels of CLEC12A across normal tissues and a broad spectrum of cancers. We also evaluated its prognostic and diagnostic significance in pan-cancer contexts. Furthermore, the relationship between CLEC12A expression and immune cell infiltration, immune checkpoints, and immune predictors was explored. In addition, Weighted Gene Co-Expression Network Analysis (WGCNA) and differential expression analysis were performed to examine the biological relevance of CLEC12A in lung adenocarcinoma (LUAD). We also leveraged various databases to predict CLEC12A’s response to immunotherapy and drug sensitivity. Finally, in vitro experiments validated the functional role of CLEC12A in LUAD. Our comprehensive pan-cancer analysis revealed that CLEC12A exhibited distinct expression patterns across different cancer types, suggesting its potential as both a diagnostic and prognostic biomarker. Notably, CLEC12A expression was strongly correlated with immune cell infiltration, immune checkpoints, and immune predictors. Functional enrichment analysis highlighted that increased CLEC12A expression in LUAD was associated with a variety of immune-related biological processes and pathways. Moreover, CLEC12A showed significant predictive value for immunotherapy outcomes, and several drugs targeting CLEC12A were identified. In vitro experiments further demonstrated that CLEC12A overexpression inhibited the proliferation, migration, and invasion of LUAD cells. Taken together, our findings position CLEC12A as a promising candidate for cancer detection, prognosis, and as a therapeutic target, particularly in LUAD, where it may serve as a potential target for both immunotherapy and targeted therapy.

Gastrodiae rhizoma (GR) formula granules and preparations have been used as a popular traditional Chinese medicine for clinical treatment since they have good pharmacological activity to treat nervous system diseases. Gastrodin and parishins have been the main active components in aqueous extracts for GR formula granules, but their pharmacological activities and metabolism are different. For quality control of the extracts, the extraction conditions should be investigated to accurately control the contents of two kinds of components. In this paper, the transfer rate of six index components (including gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, and parishin E) obtained by HPLC were used as indicators to investigate the effect of pH on the GR extraction process. The results demonstrated that pH is a key factor for preventing transforming parishins into gastrodin and maintaining high content of parishins in the extracts. It can be concluded that the weak acid environment could improve the transfer rate of parishins, thus ensuring the gastrodin and parishins consistency between GR raw materials and its aqueous extracts. Therefore, pH is an essential condition for accurate quality control of the extracts.