Tool String Research Articles

Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the mechanism. PubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was performed. 167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine closely. This study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.

Combining mendelian randomization analysis and network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate

BackgroundAn increasing number of environmental pollutants are associated with human diseases. We explored the mechanisms by which an aromatic small molecule -- Methyl-4-hydroxybenzoate (MEP) contribute to the development of glioblastoma (GBM). MethodsThe causality of MEP and GBM were identified via the Mendelian Randomization (MR) analysis. We identified the key targets by integrating the targets of GBM, differential expressed genes (DEGs) from GEO and target genes of MEP. The network of hub genes was obtained from STRING and Cytoscape tools and GO, KEGG enrichment analysis were conducted by clusterProfiler R package. These hub targets were executed molecular docking via Autodock software. ResultsMEP had a causal association with GBM as risk factors (P < 0.05, OR > 1). 46 key targets were derived, in which CASP3, MMP2 and CDK4 were screened as the hub targets. MEP might play a role in the GBM by affecting the pathways of neuroactive ligand-receptor interaction, Molecular docking analysis showed a good binding ability of between MEP and CASP3, MMP2, CDK4, CASP8 and MCL1. ConclusionsA causal relationship between MEP and GBM exists. CASP3, MMP2, CDK4, CASP8 and MCL1 have been identified as the crucial targets correlating with GBM. This discovery may provide an important insight into how environmental pollutants contribute to the development of GBM.

Design and Test of Hydraulic Bottom Seal Fracturing Tool for Coiled Tubing

Abstract As the main tool for reservoir reconstruction of Longdong shale reservoir in Changqing Oilfield, the coiled tubing bottom seal drag-segment fracturing tool is currently in the stage of scale promotion, providing tool support for the efficient development of Longdong shale oil. However, in the process of horizontal construction with large water vertical ratio and super long horizontal section, there are construction problems such as natural depth limitation of the tool and difficulty in setting the bottom packer, which seriously affect the construction efficiency and quality. In view of the above problems, this paper carried out the development of pumped coiled tubing hydraulic bottom seal drag-segment fracturing tool. With the technical ideas of pumping cup deepening and hydraulic setting bottom packer, the hydraulic setting type bottom packer, soluble cup pumping sub and supporting tools were designed and developed. By using the method of annular pumping and tubing accompanying injection, the tail cup pumping sub was used to generate throttle and larger cup outer diameter, forming a large hydraulic traction force to carry the tool string to break the depth limit. Without applying drilling pressure, the bottom packer was set by oil injection and displacement, and the setting state was lifted and lifted after the fracturing construction, providing a reliable tool scheme for solving the above engineering problems. The indoor evaluation results show that the traction effect of the bowl pumping short joint with small displacement of water is good, the bottom packer is smooth in the setting and unpacking action at 120°C, and the sealing is reliable under 70MPa pressure. The overall test of the tool string can realize the setting and unpacking action without the intervention of drill pressure. Six well tests were carried out in the field. The pumping depth was 430m under the condition of 740L/min water pumping displacement, and the oil injection displacement was increased to 550L/min. The hydraulic setting was fast and reliable, which effectively improved the construction capacity of the coiled tubing fracturing tool in the ultra-long horizontal well, greatly shortened the time consumption of interlayer conversion, and improved the speed and efficiency significantly.

Exploring multitarget potential of Piper nigrum fruit constituents for Alzheimer's disease: An AI-driven strategy

BackgroundAlzheimer's disease (AD) is a neurodegenerative disease that leads to development of cognition and memory dysfunctions. Currently, there is no known cure for AD, although limited medications are approved for the management of disease condition. Various plant-based leads give new hope for considering phytoconstituents as anti-AD drugs. The Piper nigrum L. fruit extract was reported to have anti-Alzheimer's activity. It creates an interest in the finding of active moieties that may be accountable for anti-AD activity. Hypothesis/PurposeIdentification of multitarget directed ligands isolated from Piper nigrum fruits through AI based studies. Study designThe phytochemical analysis of alkaloid fraction was carried out by LCMS, followed by the evaluation of constituents through in silico studies. MethodsThe fruits methanolic extract was prepared by cold maceration technique. The chemical profiling of the alkaloidal fraction was carried out using LCMS/MS analysis. The obtained compound's target hit genes were identified through network pharmacology studies using String, Metascape, and Cytoscape tools. Further, docking studies and MD simulations were carried out using AutoDock4 and Desmond-Maestro software. Then, electrochemical properties of hit compound P4 were determined using Gaussview6 software. ResultsFrom LCMS/MS analysis data, 29 compounds were considered based on compound intensity and accuracy (>95 %). Then, 41 common gene targets were identified from AD genes and compound-targeted genes. The 41 common genes in the PPI network suggested that AChE and BACE1 were the most abundant proteins. Further, docking studies revealed the hit compound P4 binding interaction and energies when compared to other 28 ligands. The molecular dynamics studies showed that P4-AChE and P4-BACE1 complexes were stable, and there were no RMSD and RMSF fluctuations were observed up to 100 ns. Further, PCA and MM-GBSA analysis data supported that complexes (P4-AChE and P4-BACE1) were stable. The DFT and surface properties indicated that compound P4 was ideal candidate for AD treatment and must be considered for further biological activity studies. ConclusionThe study identified compound P4 (dehydropipernonaline) from alkaloidal fraction of Piper nigrum fruits, suggesting it may be hit candidate for AD treatment.

Research on the Pass Capacity Model of Logging Tools for Complex Horizontal Wells

Shale gas, which exists in organic-rich shale or mud shale formations primarily in adsorbed or free states, poses significant development challenges due to the low permeability of shale formations. Traditional vertical wells are ineffective for shale gas extraction, making horizontal wells and large-scale hydraulic fracturing essential for efficient development. However, the complexity of the formation can lead to casing deformation, severely impacting the pass capacity of plug and perforation gun strings in the wellbore. This study analyzes the causes of casing deformation and discusses the rapid development of the cluster perforating technology in perforation operations, and discusses the challenges that might encountered during the process of wireline conveying or pumping. The irregular trajectory of horizontal wells and the high dogleg deflecting severity in the deviated sections can cause cluster perforating strings to suddenly get stuck during the downhole process, leading to a sudden increase in pumping pressure, which may result in premature seating of the fracturing bridge plug, or pull-off accidents at the weak point of the wireline. This research aims to improve engineering efficiency and prevent engineering accidents by conducting a pass capacity analysis of the perforating tool string, which is of significant engineering importance for shale gas development.

Pan-cancer analysis of the prognostic and immunological role of hippo-YAP signaling pathway

The Hippo-Yes-associated protein (Hippo-YAP) signaling pathway, a conserved pathway that regulates organ size, participates in tumor progression. However, there are few comprehensive analyses of tumor prognosis and immunity. In the present study, TCGA, GTEx, GEO, TIMER2, STRING, GSCA, ImmuCellAI, and other bioinformatics tools were used to reveal the involvement of the Hippo-YAP signaling pathway in the prognosis and immunity of pan-cancers. The obtained results showed that mRNA expression differences of Hippo-YAP pathway genes between normal samples and tumor samples in pan-cancers and some genes (such as TEAD4, MAP4K4, and STK3) might affect the prognosis of patients with skin cutaneous melanoma (SKCM) and pancreatic adenocarcinoma (PAAD). Furthermore, mutation and methylation of the Hippo-YAP signaling pathway genes in normal and primary tumor tissues differ in various cancers (KIRP, BRCA). Additionally, the relationship between the tumor microenvironment, molecular pathways, and the Hippo-YAP pathway indicated that it might lead to a suppressive immune microenvironment that affects the efficacy of immunotherapy. This is a pan-cancer overview of the Hippo-YAP signaling pathway genes, which explores the aberrant expression or mutation of this pathway that regulates the tumor microenvironment and immunotherapy.

ATM is a Prognostic Biomarker of Survival in Head and Neck Squamous Cell Carcinoma Patients

This review examines the role of ATM expression in head and neck squamous cell carcinoma (HNSCC). Analysis revealed significant overexpression of ATM in HNSCC cells compared to normal control samples, suggesting its involvement in cancer proliferation. ATM expression was notably upregulated across various clinical parameters, including different stages of cancer, racial groups, genders, and age groups, highlighting its role in cancer progression. Validation using the GEPIA2 tool confirmed strong ATM expression throughout all four stages of HNSCC, with the highest levels in stage II and the lowest in stage I. Promoter methylation analysis of ATM showed distinct patterns across different demographics and cancer stages, reinforcing its significance. The study also explored the relationship between ATM expression and patient outcomes using the KM plotter tool, finding that high ATM expression was associated with better overall survival (OS), while low ATM expression correlated with better disease-free survival (DFS). Genetic mutation analysis via cBioPortal identified minimal ATM mutations in HNSCC, including in-frame, splice, truncating, and missense mutations, suggesting their role in ATM dysregulation. The STRING tool was used to construct a protein-protein interaction (PPI) network, revealing that the ATM gene interacts with ten key genes (NBN, ATR, CHEK2, MDC1, MSH2, MSH6, MRE11, TP53, TP53BP1, BRCA1), indicating its involvement in various biological functions. Functional annotation of differentially expressed genes (DEGs) through the DAVID web server revealed their participation in critical biological processes, including double-strand break repair, cellular response to DNA damage, and DNA damage checkpoints. KEGG pathway analysis further linked DEGs to cellular senescence, platinum drug resistance, homologous recombination, p53 signaling, and the cell cycle, underscoring ATM’s multifaceted role in HNSCC.

Expression and Prognostic Potential of ESR1 in Breast Cancer

This study aims to explore the potential of ESR1 as a biomarker in breast cancer (BRCA) using bioinformatics analysis tools. The up-regulation of ESR1 expression in BRCA was investigated using UALCAN and GEPIA2, illustrating its role in BRCA progression. Furthermore, analyses based on various variables such as gender, age, race, and pathological stages of BRCA patients revealed a consistent up-regulation of ESR1, emphasizing its role in the development and progression of BRCA. Additionally, an analysis of ESR1 promoter methylation levels across various parameters revealed hypomethylation, affirming the inverse correlation between methylation and ESR1 expression. Prognostic analysis further indicated that overexpression of ESR1 is associated with poor overall survival, highlighting its potential as a prognostic biomarker in BRCA. Moreover, genetic mutation analysis using cBioPortal disclosed a minor role of ESR1 genetic mutations in BRCA, with only 2.5% of genetic alterations observed. The STRING and DAVID tools were utilized to conduct pathway enrichment analysis, revealing diverse biological functions of ESR1 and its 10 interconnected genes. Altogether, these results underscore the significance of understanding ESR1 up-regulation in BRCA and demonstrate its potential as a therapeutic, diagnostic, and prognostic biomarker.

Bioinformatics Analysis Screening and Identification of Key Biomarkers and Drug Targets in Human Glioblastoma.

Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive. The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development. The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma. This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape. The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma. The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.

To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry. Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation. Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA. Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

Role of 14-3-3 protein family in the pathobiology of EBV in immortalized B cells and Alzheimer's disease.

Several studies have revealed that Epstein-Barr virus (EBV) infection raised the likelihood of developing Alzheimer's disease (AD) via infecting B lymphocytes. The purpose of the current investigation was to assess the possible association between EBV infection and AD. The microarray datasets GSE49628, GSE126379, GSE122063, and GSE132903 were utilized to extract DEGs by using the GEO2R tool of the GEO platform. The STRING tool was used to determine the interaction between the DEGs, and Cytoscape was used to visualize the results. The DEGs that were found underwent function analysis, including pathway and GO, using the DAVID 2021 and ClueGo/CluePedia. By using MNC, MCC, Degree, and Radiality of cytoHubba, we identified seven common key genes. Gene co-expression analysis was performed through the GeneMANIA web tool. Furthermore, expression analysis of key genes was performed through GTEx software, which have been identified in various human brain regions. The miRNA-gene interaction was performed through the miRNet v 2.0 tool. DsigDB on the Enrichr platform was utilized to extract therapeutic drugs connected to key genes. In GEO2R analysis of datasets with |log2FC|≥ 0.5 and p-value <0.05, 8386, 10,434, 7408, and 759 genes were identified. A total of 141 common DEGs were identified by combining the extracted genes of different datasets. A total of 141 nodes and 207 edges were found during the PPI analysis. The DEG GO analysis with substantial alterations disclosed that they are associated to molecular functions and biological processes, such as positive regulation of neuron death, autophagy regulation of mitochondrion, response of cell to insulin stimulus, calcium signaling regulation, organelle transport along microtubules, protein kinase activity, and phosphoserine binding. Kyoto Encyclopedia of Genes and Genomes analysis discovered the correlation between the DEGs in pathways of neurodegeneration: multiple disease, cell cycle, and cGMP-PKG signaling pathway. Finally, YWHAH, YWHAG, YWHAB, YWHAZ, MAP2K1, PPP2CA, and TUBB genes were identified that are strongly linked to EBV and AD. Three miRNAs, i.e., hsa-mir-15a-5p, hsa-let-7a-5p, and hsa-mir-7-5p, were identified to regulate most of hub genes that are associated with EBV and AD. Further top 10 significant therapeutic drugs were predicted. We have discovered new biomarkers and therapeutic targets for AD, as well as the possible biological mechanisms whereby infection with EBV may be involved in AD susceptibility for the first time.

Transcriptome profiling reveals dysregulation of inflammatory and protein synthesis genes in PCOS

To analyze the differential expression genes of polycystic ovary syndrome (PCOS), clarify their functions and pathways, as well as the protein–protein interaction network, identify HUB genes, and explore the pathological mechanism. PCOS microarray datasets were screened from the GEO database. Common differentially expressed genes (co-DEGs) were obtained using GEO2R and Venn analysis. Enrichment and pathway analyses were conducted using the DAVID online tool, with results presented in bubble charts. Protein–protein interaction analysis was performed using the STRING tool. HUB genes were identified using Cytoscape software and further interpreted with the assistance of the GeneCards database. A total of two sets of co-DEGs (108 and 102), key proteins (15 and 55), and hub genes (10 and 10) were obtained. The co-DEGs: (1) regulated inflammatory responses and extracellular matrix, TNF, and IL-17 signaling pathways; (2) regulated ribosomes and protein translation, ribosome and immune pathways. The key proteins: (1) regulated inflammation, immunity, transcription, matrix metabolism, proliferation/differentiation, energy, and repair; (2) regulated ubiquitination, enzymes, companion proteins, respiratory chain components, and fusion proteins. The Hub genes: (1) encoded transcription factors and cytokines, playing vital roles in development and proliferation; (2) encoded ribosomes and protein synthesis, influencing hormone and protein synthesis, associated with development and infertility. The dysregulated expression of inflammation and protein synthesis genes in PCOS may be the key mechanism underlying its onset and progression.

Parameter optimization based on deepwater drilling system simulation: A pre-salt exploration well in Brazil

The vibration of downhole drilling tools is the primary factor that limits the ROP of deep-water salt drilling. Pre-drilling modeling is an essential method for analyzing the dynamic characteristics of the drilling system. Currently, there is limited research on coupling models between the single riser model and drill string model in deepwater drilling dynamics, which hampers offshore drilling dynamics development. In this study, we integrated the dynamic riser model with the flexible drillstring dynamic model, optimized the system's boundary conditions through experiments, and established an advanced full-scale deepwater drilling system. Through virtual drilling simulation analysis and energy flow calculations of the drilling process, we investigated the movement trajectory of the drillstring system at different positions and its correlation with downhole vibration in deepwater drilling. Finally, we performed parameter optimization on Brazil exploration well salt formation. The results indicate that the rotational speed significantly influences the vibration intensity and motion state of both the drill string and downhole drilling tool. Moreover, the kinetic energy and strain energy of BHA effectively reflect the motion state of the downhole drilling tool. When drilling salt and salt intercalation in the Brazil exploration well, the WOB was controlled within 200 kN and 180 kN, and the rotational speed was controlled within 180 rpm and 140 rpm, respectively. This ensured optimal stability and minimized vibrations within the drill string system. The virtual simulation work based on deepwater drilling systems can provide guidance for designing and planning actual drilling operations, as well as proposing reasonable drilling parameters to enhance stability and ROP in the drilling process.

Effect of SIRT7 on inhibiting the epithelial-mesenchymal transformation in pancreatic cancer cells and related mechanism

Objective: To investigate the effect and mechanism of SIRT7 in epithelial mesenchymal transformation (EMT) of pancreatic cancer cells. Methods: The pancreatic cancer cells were divided into siControl, siSIRT7, over-expression SIRT7, siSIRT7+siCOL4A1, and siSIRT7+siSLUG groups using siRNA or plasmid transfection. The proliferation, migration and invasion of pancreatic cancer cells were detected by EdU, wound healing assay and Transwell experiments, respectively. The expression of EMT and cancer stem cell (CSC) markers were detected by quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR) and western blot. RNA sequencing (RNA-seq) in SIRT7 knockdown PANC-1 cells was performed to explore the signaling pathways and target genes regulated by SIRT7. Then the target genes directly regulated by SIRT7 were identified with quantitative chromatin immunoprecipitation experiment (q-ChIP) and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR). The expressions of SIRT7 and target genes were detected by immunohistochemical (IHC) in pancreatic cancer tissues, and the correlation between SIRT7 and target gene expression was analyzed using TCGA dataset. The correlation between expression of SIRT7 or target genes and survival was analyzed on KM-plotter website. Finally, GeneMANIA, STRING and ENCORI were used to predict SIRT7-related proteins and miRNAs. Results: EdU assay showed that the cell proliferation rates in SIRT7-overexpressed PANC-1 [(19.33±0.35)%] and BxPC-3 cells [(17.00±1.89)%] were lower than those in the control group [(31.60±1.37)% and (24.33±0.78)%, respectively, P＜0.05]. The proliferation rates of SIRT7-knockdown PANC-1 [(23.94±1.00)% and (27.08±0.97)%] and BxPC-3 cells [(22.00±1.86)% and (25.96±1.61)%] were higher than those of the siControl group [(11.80±1.86)% and (13.42±1.39)%, respectively, P＜0.05]. In PANC-1 cells, the wound healing assay showed that the relative migration rate of SIRT7-overexpression cells [(76.67±2.74)%] was lower than that of control cells [(100.00±2.13)%, P＜0.05]; the relative migration rate of cells with SIRT7 knockdown [(134.22±4.08)% and (199.82±9.20)%, respectively] was higher than that of siControl group [(102.24±3.13)%, P＜0.05]. Compared with the control group, SIRT7 overexpression decreased the number of migrated BxPC-3 cells (45.66±1.69 vs 28.33±2.62, P＜0.05); while SIRT7 knockdown increased these numbers (65.66±2.86 and 82.00±2.94 versus 33.00±0.81, P＜0.01). Transwell experiment revealed that the number of invaded cells in SIRT7 overexpression groups (16.33±2.05 and 34.66±1.69) was lower than that control groups (54.33±4.64 and 58.66±5.90, P＜0.05); with SIRT7 knockdown, the numbers of invaded PANC-1 (63.66±2.49 and 69.33±3.29) and BxPC-3 cells (134.33±3.09 and 181.66±4.02) were higher than those in control groups (35.33±2.49 and 42.00±0.81, P˂0.05). Also, SIRT7 knockdown decreased the expressions of epithelial markers and increased the expressions of mesenchymal and CSC markers. RNA-seq analysis showed that SIRT7 was involved in regulating a variety of cancer-related signaling pathways, including the pancreatic cancer pathway and the EMT pathway. Furthermore, SIRT7 could directly bind to the promoter regions of target genes, such as COL4A1 and SLUG. SIRT7 was negatively correlated with the expression and function of COL4A1 and SLUG in pancreatic cancer cells. The expressions of SIRT7, COL4A1, SLUG and SOX2 were verified in pancreatic cancer tissues by IHC. Finally, SIRT7 was predicted to be associated with many proteins and miRNAs based on GeneMANIA, STRING, and ENCORI online tools. Conclusions: SIRT7 can inhibit the EMT of pancreatic cancer cells through transcriptionally inhibiting the expression of target genes, such as COL4A1 and SLUG. Thus, SIRT7 may serve as a potential tumor suppressor gene in pancreatic cancer.

Biological network comparison identifies a novel synergistic mechanism of Ginseng Radix-Astragali Radix herb pair in cancer-related fatigue

Ethnopharmacological relevanceGinseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. Aim of the studyThis study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). MethodsThe compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. ResultsIn the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. ConclusionThe herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.

Analysis of environmental pollutant Bisphenol F elicited prostate injury targets and underlying mechanisms through network toxicology, molecular docking, and multi-level bioinformatics data integration

Bisphenol F (BPF) has gained prominence as an alternative to bisphenol A (BPA) in various manufacturing applications, yet being detected in diverse environments and posed potential public health risk. This research aims to elucidate the putative toxic targets and underlying molecular mechanisms of prostate injury induced by exposure to BPF through multi-level bioinformatics data, integrating network toxicology and molecular docking. Systematically leveraging multilevel databases, we determined 276 targets related to BPF and prostate injury. Subsequent screenings through STRING and Cytoscape tool highlighted 27 key targets, including BCL2, HSP90AA1, MAPK3, ESR1, and CASP3. GO and KEGG enrichment analyses demonstrated enrichment of targets involved in apoptosis, abnormal hormonal activities, as well as cancer-related signal transduction cascades, ligand-receptor interaction networks, and endocrine system signaling pathways. Molecular docking simulations conducted via Autodock corroborated high-affinity binding interaction between BPF and key targets. The results indicate that BPF exposure can contribute to the initiation and progression of prostate cancer and prostatic hyperplastic by modulating apoptosis and proliferation, altering nerve function in blood vessel endothelial cells, and disrupting androgen metabolism. This study offers theoretical underpinnings for comprehending the molecular mechanisms implicated in BPF-elicited prostatic toxicity, while concomitantly establishing foundational framework for the development of prophylactic and therapeutic strategies for prostatic injuries related to polycarbonate and epoxy resin plastics incorporated with BPF, as well as environments afflicted by elevated levels of these compounds.

Research of active compounds from Allii Macrostemonis Bulbus and potential targets against Non-Hodgkin's Lymphoma based on Network pharmacology.

Non-Hodgkin's Lymphoma (NHL) is a series of lymphoid malignancies in some aggressive subtypes with unsatisfactory treatment effects. Allii Macrostemonis Bulbus (Xie Bai) is a traditional Chinese medicine with anti-cancer activities, which may potentially suppress aggressive NHL. This study tries to discover active components and targets of Xie Bai in treating NHL by network pharmacology-based approaches. Compounds and related targets of Xie Bai were collected from the Traditional Chinese Medicine Database and Analysis Platform. Target genes associated with NHL were searched by GeneCards and DisGeNET, then the overlapped targets were further analyzed by STRING tool, GO, and KEGG pathway enrichment analysis. Molecular docking was employed to verify the interaction between compounds and targets. 11 bioactive compounds were successfully identified, with 30 targets that were screened out for the treatment of NHL. Functional enrichment analysis suggested that Xie Bai exerted its potential effects against NHL via pathways in cancer, such as PI3K/ AKT, p53, and MAPK signaling pathways. Molecular docking results showed that 3 active compounds (quercetin, beta-sitosterol, and naringenin) had good affinity with selected 6 targets（TP53, AKT1, CASP3, CCND1, HPK1, and NLRP3). Identifying six potential genes could accurately be docked with Xie Bai and had close interactions with NHL, which may provide insight into further research and new treatment strategy.

Sand fill cleanout on wireline enables access to additional perforation zones in gas well producer

An Australian operator wanted to explore options for wireline conveyed sand bailing in one of their offshore deviated ‘S’ shape gas producing wells. The objective was to remove approximately 24 m of sand fill inside 9.625″ production casing, with an internal diameter (ID) of 8.681″. To limit the number of cleanout runs, the latest technology in wireline deployed suction tools with a 4.25″ overall diameter (OD) was chosen, which provided increased recovery volume, plus real-time surface control and monitoring. Because of the tool’s overall diameter, the landing nipple also required milling to allow access. Therefore, a specially designed 4.412″ mill bit was manufactured and run on a milling tool. The electric line deployed milling technology successfully milled through the landing nipple and a ball catcher in four runs, thus increasing the ID sufficiently to allow access for the cleanout tool string. A well fluid column of about seven bars is required to enable operation of the suction tool. The cleanout tool was configured with three bailer sections (seven max) for the first run, to determine sand recovery optimisation. Three different sizes of bailer filters are provided; prior knowledge of debris particle size is therefore advantageous. In this case, a slickline bailing sand sample had been recovered, which immediately aided filter choice. Seventeen bailing runs were conducted over 5 days, successfully recovering a total of 918 L of sand, equating to about 2.4 tons. Ultimately, the process enabled perforation of two additional gas zones to increase production.

Identification of novel genes associated with atherosclerosis in Bama miniature pig.

Atherosclerosis is a chronic cardiovascular disease of great concern. However, it is difficult to establish a direct connection between conventional small animal models and clinical practice. The pig's genome, physiology, and anatomy reflect human biology better than other laboratory animals, which is crucial for studying the pathogenesis of atherosclerosis. We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis, and further used bioinformatic tools to filter and identify underlying candidate genes. Candidate gene function prediction was performed using the online prediction tool STRING 12.0. Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes. We mapped differential single nucleotide polymorphisms (SNPs) to genes and obtained a total of 102 differential genes, then we used GO and KEGG pathway enrichment analysis to identify four candidate genes, including SLA-1, SLA-2, SLA-3, and TAP2. nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins, the primary structures of these two proteins have undergone amino acid changes, and the tertiary structures also show slight changes. In addition, immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer. We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis, highlighting the importance of antigen processing and immune response in atherogenesis.

Functional Investigation and Two-sample Mendelian Randomization Study of Inguinal Hernia Hub Genes Obtained by Bioinformatics Analysis.

Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. This study aims to identify potential gene markers for inguinal hernia and available drugs. Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.