Screening and identification of the core immune-related genes and immune cell infiltration in severe burns and sepsis.

Severe burns often have a high mortality rate due to sepsis, but the genetic and immune crosstalk between them remains unclear. In the present study, the GSE77791 and GSE95233 datasets were analysed to identify immune-related differentially expressed genes (DEGs) involved in disease progression in both burns and sepsis. Subsequently, weighted gene coexpression network analysis (WGCNA), gene enrichment analysis, protein-protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, coexpression network analysis and clinical correlation analysis were performed. A total of 282 common DEGs associated with burns and sepsis were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the following enriched pathways in burns and sepsis: metabolic pathways; complement and coagulation cascades; legionellosis; starch and sucrose metabolism; and ferroptosis. Finally, six core DEGs were identified, namely, IL10, RETN, THBS1, FGF13, LCN2 and MMP9. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. Of these, RETN upregulation was associated with a worse prognosis. The immune-related genes and dysregulated immune cells in severe burns and sepsis provide potential research directions for diagnosis and treatment.

Effectiveness of Laparoscopic Pectopexy for Pelvic Organ Prolapse Compared with Laparoscopic Sacrocolpopexy.

STUDY OBJECTIVE: To evaluate the clinical benefits of laparoscopic pectopexy vs laparoscopic sacrocolpopexy in women with pelvic organ prolapse (POP). DESIGN: Prospective cohort study. SETTING: A tertiary hospital. PATIENTS: We included 203 patients with POP. INTERVENTIONS: Laparoscopic pectopexy or laparoscopic sacrocolpopexy. MEASUREMENTS AND MAIN RESULTS: Anatomic effectiveness was measured using the POP Quantification system, both before and after operation. Functional recovery effectiveness was evaluated using complications and recurrence rates within 1 year. Quality of life was assessed by the Pelvic Floor Distress Inventory-20 and Incontinence Quality of Life questionnaires at enrollment and postoperative months 3, 6, and 12. Comparisons between groups were performed using t test, chi-square test, and mixed-effects model with repeated measures. The analysis included 203 eligible patients (sacrocolpopexy, 101; pectopexy, 102). The proportion of robotic-assisted surgeries was lower in the pectopexy group than in the sacrocolpopexy group (15.7% vs 41.6%, p <.001). The average operation time of pectopexy was shorter than that of sacrocolpopexy (174.2 vs 187.7 minutes) with a mean difference of 13.5 minutes (95% confidence interval, 3.9-23.0; p = .006). Differences of intraoperative blood loss, length of hospital stay, and postoperative 7-day complications between groups were not significant. Anatomic successes were obtained in both groups with similar improvement in POP Quantification scores. The rate of urinary symptoms recurrence was higher in the pectopexy group (13.7%) than in the sacrocolpopexy group (5.0%) at the 1-year follow-up (odds ratio, 3.1; 95% confidence interval, 1.1-8.8, p = .032). The Pelvic Floor Distress Inventory-20 and Incontinence Quality of Life scores were better improved at postoperative months 3, 6, and 12 for laparoscopic pectopexy than for sacrocolpopexy. CONCLUSION: Laparoscopic pectopexy revealed comparable anatomic success, shorter operation time, and better improvement in quality of life scores of prolapse, colorectal-anal, and urinary symptoms at 1-year follow-up, possibly being an alternative when sacrocolpopexy is not practicable. However, clinicians should pay more attention to the recurrence of urinary symptoms after pectopexy.

Research on the evolutionary history of the morphological structure of cotton seeds: a new perspective based on high-resolution micro-CT technology.

Cotton (Gossypium hirsutum L.) seed morphological structure has a significant impact on the germination, growth and quality formation. However, the wide variation of cotton seed morphology makes it difficult to achieve quantitative analysis using traditional phenotype acquisition methods. In recent years, the application of micro-CT technology has made it possible to analyze the three-dimensional morphological structure of seeds, and has shown technical advantages in accurate identification of seed phenotypes. In this study, we reconstructed the seed morphological structure based on micro-CT technology, deep neural network Unet-3D model, and threshold segmentation methods, extracted 11 basics phenotypes traits, and constructed three new phenotype traits of seed coat specific surface area, seed coat thickness ratio and seed density ratio, using 102 cotton germplasm resources with clear year characteristics. Our results show that there is a significant positive correlation (P< 0.001) between the cotton seed size and that of the seed kernel and seed coat volume, with correlation coefficients ranging from 0.51 to 0.92, while the cavity volume has a lower correlation with other phenotype indicators (r<0.37, P< 0.001). Comparison of changes in Chinese self-bred varieties showed that seed volume, seed surface area, seed coat volume, cavity volume and seed coat thickness increased by 11.39%, 10.10%, 18.67%, 115.76% and 7.95%, respectively, while seed kernel volume, seed kernel surface area and seed fullness decreased by 7.01%, 0.72% and 16.25%. Combining with the results of cluster analysis, during the hundred-year cultivation history of cotton in China, it showed that the specific surface area of seed structure decreased by 1.27%, the relative thickness of seed coat increased by 8.70%, and the compactness of seed structure increased by 50.17%. Furthermore, the new indicators developed based on micro-CT technology can fully consider the three-dimensional morphological structure and cross-sectional characteristics among the indicators and reflect technical advantages. In this study, we constructed a microscopic phenotype research system for cotton seeds, revealing the morphological changes of cotton seeds with the year in China and providing a theoretical basis for the quantitative analysis and evaluation of seed morphology.

Therapeutic targets and signaling mechanisms of dasatinib activity against radiation skin ulcer.

Objective: To reveal the potential targets and signaling pathways of dasatinib in the treatment of radiation ulcers through network pharmacology and molecular docking technology. Methods: Pathological targets of radiation ulcers were screened using GeneCards database. At the same time, the pharmacological targets of dasatinib were obtained through SwissTargetPrediction (STP), Binding DB and Drugbank databases. Subsequently, the potential targets of dasatinib for anti-radiation ulcers were obtained after intersection by Venn diagram. Next, a protein-protein interaction (PPI) network was constructed through the STRING database and core targets were screened. Finally, the identified core targets were subjected to GO and KEGG enrichment analysis, co-expression network analysis, and molecular docking technology to verify the reliability of the core targets. Results: A total of 76 potential targets for anti-radiation ulcer with dasatinib were obtained, and 6 core targets were screened, including EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These genes were mainly enriched in Adherens junction, EGFR tyrosine kinase inhibitor resistance, Focal adhesion, Bladder cancer and PI3K-Akt signaling pathway. Molecular docking results showed that dasatinib binds well to the core target. Conclusion: Dasatinib may play a role in the treatment of radiation ulcers by regulating EGFR, ERBB2, FYN, JAK2, KIT, and SRC. These core targets may provide new insights for follow-up studies of radiation ulcers.

Genetic and immune crosstalk between severe burns and blunt trauma: A study of transcriptomic data.

Background: Severe burns and blunt trauma can lead to multiple organ dysfunction syndrome, the leading cause of death in intensive care units. In addition to infection, the degree of immune inflammatory response also affects prognosis. However, the characteristics and clinical relevance of the common mechanisms of these major diseases are still underexplored. Methods: In the present study, we performed microarray data analysis to identify immune-related differentially expressed genes (DEGs) involved in both disease progression in burns and blunt trauma. Six analyses were subsequently performed, including gene enrichment analysis, protein-protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, co-expression network analysis, and clinical correlation analysis. Results: A total of 117 common immune-related DEGs was selected for subsequent analyses. Functional analysis emphasizes the important role of Th17 cell differentiation, Th1 and Th2 cell differentiation, Cytokine-cytokine receptor interaction and T cell receptor signaling pathway in these two diseases. Finally, eight core DEGs were identified using cytoHubba, including CD8A, IL10, CCL5, CD28, LCK, CCL4, IL2RB, and STAT1. The correlation analysis showed that the identified core DEGs were more or less significantly associated with simultaneous dysregulation of immune cells in blunt trauma and sepsis patients. Of these, the downregulation of CD8A and CD28 had a worse prognosis. Conclusion: Our analysis lays the groundwork for future studies to elucidate molecular mechanisms shared in burns and blunt trauma. The functional roles of identified core immune-related DEGs and dysregulated immune cell subsets warrant further in-depth study.

Exploration of comorbidity mechanisms and potential therapeutic targets of rheumatoid arthritis and pigmented villonodular synovitis using machine learning and bioinformatics analysis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Pigmented villonodular synovitis (PVNS) is a tenosynovial giant cell tumor that can involve joints. The mechanisms of co-morbidity between the two diseases have not been thoroughly explored. Therefore, this study focused on investigating the functions, immunological differences, and potential therapeutic targets of common genes between RA and PVNS. Methods: Through the dataset GSE3698 obtained from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) were screened by R software, and weighted gene coexpression network analysis (WGCNA) was performed to discover the modules most relevant to the clinical features. The common genes between the two diseases were identified. The molecular functions and biological processes of the common genes were analyzed. The protein-protein interaction (PPI) network was constructed using the STRING database, and the results were visualized in Cytoscape software. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) logistic regression and random forest (RF) were utilized to identify hub genes and predict the diagnostic efficiency of hub genes as well as the correlation between immune infiltrating cells. Results: We obtained a total of 107 DEGs, a module (containing 250 genes) with the highest correlation with clinical characteristics, and 36 common genes after taking the intersection. Moreover, using two machine learning algorithms, we identified three hub genes (PLIN, PPAP2A, and TYROBP) between RA and PVNS and demonstrated good diagnostic performance using ROC curve and nomogram plots. Single sample Gene Set Enrichment Analysis (ssGSEA) was used to analyze the biological functions in which three genes were mostly engaged. Finally, three hub genes showed a substantial association with 28 immune infiltrating cells. Conclusion: PLIN, PPAP2A, and TYROBP may influence RA and PVNS by modulating immunity and contribute to the diagnosis and therapy of the two diseases.

WDR43 is a potential diagnostic biomarker and therapeutic target for osteoarthritis complicated with Parkinson's disease.

Osteoarthritis (OA) and Parkinson's disease (PD) are on the rise and greatly impact the quality of individuals' lives. Although accumulating evidence indicates a relationship between OA and PD, the particular interactions connecting the two diseases have not been thoroughly examined. Therefore, this study explored the association through genetic characterization and functional enrichment. Four datasets (GSE55235, GSE12021, GSE7621, and GSE42966) were chosen for assessment and validation from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was implemented to determine the most relevant genes for clinical features. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to explore the biological processes of common genes, and to display the interrelationships between common genes, the STRING database and the application Molecular Complex Detection Algorithm (MCODE) of Cytoscape software were leveraged to get hub genes. By intersecting the common genes with the differentially expressed genes (DEGs) acquired from GSE12021 and GSE42966, the hub genes were identified. Finally, we validated the diagnostic efficacy of hub genes and explored their correlation with 22 immune infiltrating cells. As a consequence, we discovered 71 common genes, most of which were functionally enriched in antigen processing and presentation, mitochondrial translation, the mRNA surveillance pathway, and nucleocytoplasmic transport. Furthermore, WDR43 was found by intersecting eight hub genes with 28 DEGs from the two validation datasets. Receiver Operating Characteristic (ROC) implied the diagnostic role of WDR43 in OA and PD. Immune infiltration research revealed that T-cell regulatory (Tregs), monocytes, and mast cells resting were associated with the pathogenesis of OA and PD. WDR43 may provide key insights into the relationship between OA and PD.

Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation.

Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. In SH-SY5Y cells and primary murine neurons, we report that OGD/R induces the accumulation of the microRNA miR-422a, leading to downregulation of miR-422a targets myocyte enhancer factor-2D (MEF2D) and mitogen-activated protein kinase kinase 6 (MAPKK6). Ectopic miR-422a inhibition attenuated OGD/R-induced cell death and apoptosis, whereas overexpression of miR-422a induced significant neuronal cell apoptosis. In addition, OGD/R decreased the expression of the long non-coding RNA D63785 (Lnc-D63785) to regulate miR-422a accumulation. Lnc-D63785 directly associated with miR-422a and overexpression of Lnc-D63785 reversed OGD/R-induced miR-422a accumulation and neuronal cell death. OGD/R downregulated Lnc-D63785 expression through increased methyltransferase-like protein 3 (METTL3)-dependent Lnc-D63785 m6A methylation. Conversely METTL3 shRNA reversed OGD/R-induced Lnc-D63785 m6A methylation to decrease miR-422a accumulation. Together, Lnc-D63785 m6A methylation by OGD/R causes miR-422a accumulation and neuronal cell apoptosis.

p38γ overexpression promotes osteosarcoma cell progression.

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. Recent studies demonstrate that p38 gamma (p38γ) phosphorylates retinoblastoma (Rb) to promote cyclin expression, cell-cycle entry and tumorigenesis. Studying the potential function of p38γ in human OS, we show that p38γ mRNA and protein expression are significantly elevated in OS tissues and OS cells, whereas its expression is relatively low in normal bone tissue and in human osteoblasts/osteoblastic cells. Knockdown of p38γ in established (U2OS) and primary human OS cells potently inhibited cell growth, proliferation, migration and invasion, while promoting cell apoptosis. Furthermore, CRISPR/Cas9-induced p38γ knockout inhibited human OS cell progression in vitro. Conversely, ectopic overexpression of p38γ in primary human OS cells augmented cell growth, proliferation and migration. Signaling studies show that retinoblastoma (Rb) phosphorylation and cyclin E1/cyclin A expression were decreased following p38γ shRNA knockdown and knockout, but increased after ectopic p38γ overexpression. Collectively, these results show that p38γ overexpression promotes human OS cell progression.

Reactive Oxygen Species-Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration.

The chronic inflammatory microenvironment is characterized by the elevated level of reactive oxygen species (ROS). Here, it is hypothesized that developing an ROS-scavenging scaffold loaded with rapamycin (Rapa@Gel) may offer a new strategy for modulating the local inflammatory microenvironment to improve intervertebral disk tissue regeneration. The therapeutic scaffold consisting of ROS-degradable hydrogel can be injected into the injured degeneration site of intervertebral disk (IVD) and can release therapeutics in a programmed manner. The ROS scavenged by scaffold reduces the inflammatory responses. It is found that when rats are treated with Rapa@Gel, this results in an increase in the percentage of M2-like macrophages and a decrease in M1-like macrophages in the inflammatory environment, respectively. Regeneration of IVD is achieved by Rapa@Gel local treatment, due to the increased M2 macrophages and reduced inflammation. This strategy may be extended to the treatment of many other inflammatory diseases.

LncRNA NEAT1/miR-29b-3p/BMP1 axis promotes osteogenic differentiation in human bone marrow-derived mesenchymal stem cells.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is quite important for the bone formation. Bone morphogenetic proteins (BMPs) are important to the skeleton formation. As a member of BMPs, BMP1 can induce bone and cartilage development. This study revealed the biological effect of BMP1 on the osteogenic differentiation. Firstly, the relative lower expression of BMP1 was detected in hBMSCs obtained from osteoporosis patients. The expression levels of osteoporosis-related genes (ALP, OCN, and OPN) were found to be decreased in hBMSCs treated with sh-BMP1. Mechanically, BMP1 was demonstrated to be the target mRNA of miR-29b-3p. Moreover, increasing studies indicate that long non-coding RNAs (lncRNAs) are crucial regulators in hBMSCs osteogenic differentiation by exerting ceRNA function. Further mechanism investigation revealed that lncRNA NEAT1 could regulate miR-29b-3p-BMP1 axis in hBMSCs. Finally, rescue assays were performed to validate the specific function of NEAT1-miR-29b-3p-BMP1 axis in the osteogenic differentiation of hBMSCs. In conclusion, NEAT1 promotes osteogenic differentiation in hBMSCs by regulating miR-29b-3p/BMP1 axis.