Prediction of Potential miRNA-Disease Associations Based on a Masked Graph Autoencoder.

Biomedical evidence has demonstrated the relevance of microRNA (miRNA) dysregulation in complex human diseases, and determining the relationship between miRNAs and diseases can aid in the early detection and prevention of diseases. Traditional biological experimental methods have the disadvantages of high cost and low efficiency, which are well compensated by computational methods. However, many computational methods have the challenge of excessively focusing on the neighbor relationship, ignoring the structural information of the graph, and belittling the redundant information of the graph structure. This study proposed a computational model based on a graph-masking autoencoder named MGAEMDA. MGAEMDA is an asymmetric framework in which the encoder maps partially observed graphs into latent representations. The decoder reconstructs the masked structural information based on the edge and node levels and combines it with linear matrices to obtain the result. The empirical results on the two datasets reveal that the MGAEMDA model performs better than its counterparts. We also demonstrated the predictive performance of MGAEMDA using a case study of four diseases, and all the top 30 predicted miRNAs were validated in the database, providing further evidence of the excellent performance of the model.

Stomatin promotes neutrophil degranulation and vascular leakage in the early stage after severe burn via enhancement of the intracellular binding of neutrophil primary granules to F-actin.

BACKGROUND: The pathophysiology of severe burn injuries in the early stages involves complex emergency responses, inflammatory reactions, immune system activation, and a significant increase in vascular permeability. Neutrophils, crucial innate immune cells, undergo rapid mobilization and intricate pathophysiological changes during this period. However, the dynamic alterations and detailed mechanisms governing their biological behavior remain unclear. Stomatin protein, an essential component of the cell membrane, stabilizes and regulates the membrane and participates in cell signal transduction. Additionally, it exhibits elevated expression in various inflammatory diseases. While Stomatin expression has been observed in the cell and granule membranes of neutrophils, its potential involvement in post-activation functional regulation requires further investigation. METHODS: Neutrophils were isolated from human peripheral blood, mouse peripheral blood, and mouse bone marrow using the magnetic bead separation method. Flow cytometry was used to assess neutrophil membrane surface markers, ROS levels, and phagocytic activity. The expression of the Stomatin gene and protein was examined using quantitative real-time polymerase chain reaction and western blotting methods, respectively. Furthermore, the enzyme-linked immunosorbent assay was used to evaluate the expression of neutrophil-derived inflammatory mediators (myeloperoxidase (MPO), neutrophil elastase (NE), and matrix metalloproteinase 9 (MMP9)) in the plasma. Images and videos of vascular leakage in mice were captured using in vivo laser confocal imaging technology, whereas in vitro confocal microscopy was used to study the localization and levels of the cytoskeleton, CD63, and Stomatin protein in neutrophils. RESULTS: This study made the following key findings: (1) Early after severe burn, neutrophil dysfunction is present in the peripheral blood characterized by significant bone marrow mobilization, excessive degranulation, and impaired release and chemotaxis of inflammatory mediators (MPO, NE, and MMP9). (2) After burn injury, expression of both the stomatin gene and protein in neutrophils was upregulated. (3) Knockout (KO) of the stomatin gene in mice partially inhibited neutrophil excessive degranulation, potentially achieved via reduced production of primary granules and weakened binding of primary granules to the cell skeleton protein F-actin. (4) In severely burned mice, injury led to notable early-stage vascular leakage and lung damage, whereas Stomatin gene KO significantly ameliorated lung injury and vascular leakage. CONCLUSIONS: Stomatin promotes neutrophil degranulation in the early stage of severe burn injury via increasing the production of primary granules and enhancing their binding to the cell skeleton protein F-actin in neutrophils. Consequently, this excessive degranulation results in aggravated vascular leakage and lung injury.

Significance of liquid-liquid phase separation (LLPS)-related genes in breast cancer: a multi-omics analysis.

Currently, the role of liquid-liquid phase separation (LLPS) in cancer has been preliminarily explained. However, the significance of LLPS in breast cancer is unclear. In this study, single cell sequencing datasets GSE188600 and GSE198745 for breast cancer were downloaded from the GEO database. Transcriptome sequencing data for breast cancer were downloaded from UCSC database. We divided breast cancer cells into high-LLPS group and low-LLPS group by down dimension clustering analysis of single-cell sequencing data set, and obtained differentially expressed genes between the two groups. Subsequently, weighted co-expression network analysis (WGCNA) was performed on transcriptome sequencing data, and the module genes most associated with LLPS were obtained. COX regression and Lasso regression were performed and the prognostic model was constructed. Subsequently, survival analysis, principal component analysis, clinical correlation analysis, and nomogram construction were used to evaluate the significance of the prognostic model. Finally, cell experiments were used to verify the function of the model's key gene, PGAM1. We constructed a LLPS-related prognosis model consisting of nine genes: POLR3GL, PLAT, NDRG1, HMGB3, HSPH1, PSMD7, PDCD2, NONO and PGAM1. By calculating LLPS-related risk scores, breast cancer patients could be divided into high-risk and low-risk groups, with the high-risk group having a significantly worse prognosis. Cell experiments showed that the activity, proliferation, invasion and healing ability of breast cancer cell lines were significantly decreased after knockdown of the key gene PGAM1 in the model. Our study provides a new idea for prognostic stratification of breast cancer and provides a novel marker: PGAM1.

Parasitic capacitance modeling and measurements of conductive yarns for e-textile devices.

Conductive yarns have emerged as a viable alternative to metallic wires in e-Textile devices, such as antennas, inductors, interconnects, and more, which are integral components of smart clothing applications. But the parasitic capacitance induced by their micro-structure has not been fully understood. This capacitance greatly affects device performance in high-frequency applications. We propose a lump-sum and turn-to-turn model of an air-core helical inductor constructed from conductive yarns, and systematically analyze and quantify the parasitic elements of conductive yarns. Using three commercial conductive yarns as examples, we compare the frequency response of copper-based and yarn-based inductors with identical structures to extract the parasitic capacitance. Our measurements show that the unit-length parasitic capacitance of commercial conductive yarns ranges from 1 fF/cm to 3 fF/cm, depending on the yarn's microstructure. These measurements offer significant quantitative estimation of conductive yarn parasitic elements and provide valuable design and characterization guidelines for e-Textile devices.

Advances in Prepectoral Breast Reconstruction.

Breast reconstruction can be divided into prepectoral breast reconstruction (PPBR) and subpectoral breast reconstruction (SPBR) according to the implant plane. The original prepectoral breast reconstruction was abandoned for a long time due to the frequent and severe complications. Now, advances in materials technology and improved methods of mastectomy have made safe prepectoral breast reconstruction possible. Moreover, a number of studies have gradually demonstrated the advantages of prepectoral breast reconstruction. As prepectoral breast reconstruction becomes more and more attractive, it is time to review the current advances in prepectoral breast reconstruction.

ADM-assisted prepectoral breast reconstruction is not associated with high complication rate as before: a Meta-analysis.

Implant-related breast reconstruction can be divided into subpectoral breast reconstruction (SPBR) and prepectoral breast reconstruction (PPBR) according to the different anatomical planes. The previous stereotype was that PPBR had a high complication rate and was not suitable for clinical use. However, with the emergence of acellular dermal matrix (ADM), the clinical effect of PPBR has been improved. To compare the outcomes difference between SPBR and PPBR, We conducted this meta-analysis. Articles on SPBR versus PPBR were searched in PubMed, Web of Sciences, Embase, and Cochrane databases, strictly following the PRISMA guidelines. According to the set criteria, we included the literature that met the requirements. Extracted data were the incidence of adverse events and the duration of drainage. Results show that SPBR has a higher incidence rate in capsular contracture, animation deformity, infection, hematoma and delayed healing wound than PPBR. There are no significant differences in skin flap necrosis, seroma, implant loss, reoperation and duration of drainage between the two groups. Hence, PPBR is no longer a high complication surgical method and can be used in the clinical practice. However, there are few large sample studies at present, so it is necessary to carry out further studies on PPBR.

Primitive genotypic characteristics in umbilical cord neutrophils identified by single-cell transcriptome profiling and functional prediction.

The function and heterogeneity of neutrophils in neonatal umbilical cord blood (UCB) have not been characterized. In this study, we analyzed the neutrophils in UCB and healthy adults using single-cell RNA sequencing analysis for the first time. We found that neutrophils divided into six subpopulations (G2, G3, G4, G5a, G5b, and G5c) with different marker genes and different functions under homeostasis. Compared with healthy adults, neutrophils of UCB were more naïve and have more obvious degranulation and activation functions. Moreover, we found significant differences in the amount and function of G5b cells between healthy adults and UCB. The amount of G5b group in UCB was lower, but it has more degranulation, secretion and activation functions. In addition, we noted a new subset of G5c labeled by CD52, which almost did not exist in UCB. Besides, its differential genes were enriched in terms such as protein synthesis and mRNA transcription. Furthermore, uncharacteristic transcription factors ZNF-276, ZNF-319 and ZNF-354A were identified in our study. In summary, we first examined the heterogeneity and functional diversity of neutrophils in UCB, and these data provided new insights into the mechanism of neutrophil-mediated diseases of neonates and the wider use of neutrophils in UCB.

RecQ mediated genome instability 2 (RMI2): a potential prognostic and immunological biomarker for pan-cancers.

BACKGROUND: RecQ mediated genome instability 2 (RMI2) is an essential component of the BLM-TopoIIIa-RMI1-RMI2 (BTR) complex. However, the mysterious veil of the potential immunological relationship of RMI2 in tumorigenesis and development has not been revealed. METHODS: We conducted the differential expression (DE) analysis of the RMI2 in pan-cancer using data onto Oncomine, TIMER, and GEPIA databases. Afterward, survival analysis and clinical-stage correlation analysis were performed via the TCGA database. Subsequently, we used R software to further explore the relationship between the expression level of RMI2 and tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), tumor immune-infiltrated cells (TILs), immune checkpoints (ICP), mismatch repairs (MMRs) -related genes, m6A-related genes, DNA methylation-related genes. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional networks were also performed for annotation via gene set enrichment analysis (GSEA). RESULTS: The RMI2 expressed remarkably high in most cancer types compared to cancer adjacent normal tissues (P < 0.05). High expression of RMI2 was linked to unfavorable prognosis and advanced stage of disease, especially in LIHC and PAAD. RMI2 expression was related to TMB in 16 cancer types and MSI in 8 cancer types. Furthermore, it is significant positive correlations between RMI2 and stromal and immune cells, ICP-related genes, MMRs-related genes, m6A-related genes, and DNA methylation-related genes. Finally, GSEA analysis revealed that RMI2 was engaged in a variety of signaling pathways in pan-cancers. CONCLUSIONS: RMI2 may serve as a potential biological target and probably assume a crucial part in tumorigenesis and progression.

An immune subtype-related prognostic signature of hepatocellular carcinoma based on single-cell sequencing analysis.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is often associated with a poor prognosis. The main reason for this poor prognosis is that inconspicuous early symptoms lead to delayed diagnosis. Treatment options for advanced HCC remain limited and ineffective. In this context, the exploration of the immune microenvironment in HCC becomes attractive. In this study, we divided HCC into immune cell and non-immune cell subtypes, by single-cell sequencing analysis of GEO dataset GSE146115. We found differentially expressed genes in the two subtypes, which we used to construct a prognostic model for HCC through Cox and Lasso regressions. Our prognostic model can accurately evaluate the prognosis of HCC patients, and provide a reference for the design of immunotherapy for HCC.

Immune Landscape and an RBM38-Associated Immune Prognostic Model with Laboratory Verification in Malignant Melanoma.

BACKGROUND: Current studies have revealed that RNA-binding protein RBM38 is closely related to tumor development, while its role in malignant melanoma remains unclear. Therefore, this research aimed to investigate the function of RBM38 in melanoma and the prognosis of the disease. METHODS: Functional experiments (CCK-8 assay, cell colony formation, transwell cell migration/invasion experiment, wound healing assay, nude mouse tumor formation, and immunohistochemical analysis) were applied to evaluate the role of RBM38 in malignant melanoma. Immune-associated differentially expressed genes (DEGs) on RBM38 related immune pathways were comprehensively analyzed based on RNA sequencing results. RESULTS: We found that high expression of RBM38 promoted melanoma cell proliferation, invasion, and migration, and RBM38 was associated with immune infiltration. Then, a five-gene (A2M, NAMPT, LIF, EBI3, and ERAP1) model of RBM38-associated immune DEGs was constructed and validated. Our signature showed superior prognosis capacity compared with other melanoma prognostic signatures. Moreover, the risk score of our signature was connected with the infiltration of immune cells, immune-regulatory proteins, and immunophenoscore in melanoma. CONCLUSIONS: We constructed an immune prognosis model using RBM38-related immune DEGs that may help evaluate melanoma patient prognosis and immunotherapy modalities.

CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis.

Neutrophils release neutrophil extracellular traps (NETs) to capture and kill pathogens, but excessive NET release can damage the surrounding tissues. Myeloperoxidase (MPO) and neutrophil elastase (NE) are thought to be important in promoting histone depolymerization and DNA breakage in the nucleus. However, the detailed path by which MPO and NE enter the nucleus is unknown. In the present study, we observed that delayed fusion of azurophilic granules with the nuclear membrane 15-20 min after extracellular degranulation in activated neutrophils. In a subsequent experiment, we further demonstrated that this fusion leads to MPO entry into the nucleus and promotes nuclear histone depolymerization and DNA breakage, a process called 'targeted nuclear degranulation'. This process can be effectively inhibited by dexamethasone and accompanied by the continuous low levels of MPO in the nucleus after PMA stimulation. Meanwhile, we found that 'targeted nuclear degranulation' is dependent on the CD44 translocation and subsequent redistribution of CD44 / ERM (Ezrin/Radixin/Moesin) / F-actin complexes, which guides the movement of azurophilic granules towards the nucleus. Application of ERM phosphorylation inhibitors and importin activity inhibitors significantly reduced the complexes formation and redistribution. Taken together, these findings indicate for the first time that delayed 'targeted nuclear degranulation' after neutrophil activation is a key mechanism of NET formation. CD44/ERM/F-actin complex mediates this process, which providing targets with promising prospects for the precise regulation of NET formation.

Analysis of Multiple Human Tumor Cases Reveals the Carcinogenic Effects of PKP3.

Plakophilins (PKPs) act as a key regulator of different signaling programs and control a variety of cellular processes ranging from transcription, protein synthesis, growth, proliferation, and tumor development. The function and possible mechanism of PKP3 in ovarian cancer (OC) remain unknown. It is extremely important to investigate the expression and prognostic values of PKP3, as well as their possible mechanisms, and immune infiltration in OC. Therefore, in this paper we explored the potential oncogenic role of PKP3 in 33 tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The result outcomes showed that PKP3 is highly expressed in most cancers, and the expression level and prognosis of PKP3 showed little significance in cancer patients. Moreover, oncologists have found that members of the plakophilin family have different degrees of abnormality in ovarian cancer. PKP3 played a key part in carcinogenesis and aggressiveness of OC as well as malignant biological activity and can be used as a biomarker for early diagnosis and prognosis evaluation in OC.

A Novel Pyroptosis-Related lncRNA Signature for Predicting the Prognosis of Skin Cutaneous Melanoma.

PURPOSE: To construct a prognosis model of melanoma based on pyroptosis related genes. METHODS: Melanoma RNA-sequencing data was downloaded from TCGA. First, the lnRNAs related to pyroptosis were obtained through Pearson correlation analysis. Then, the prognosis model of pyroptosis related genes was constructed by Cox regression and Lasso regression. Melanoma patients were divided into high-risk and low-risk groups by risk score, and the differences in prognosis and immune microenvironment between the two groups were explored. RESULTS: We found that the high-risk group had a significantly poorer prognosis, and different groups differed in immune infiltration, m6A methylation, and immune checkpoint. CONCLUSION: Our prognostic model can provide a reference for the study of pyroptosis in melanoma cells and provide a new idea for melanoma treatment.

Database mining analysis revealed the role of the putative H+/sugar transporter solute carrier family 45 in skin cutaneous melanoma.

Metabolic reprogramming is common in various cancers. Targeting metabolism to treat tumors is a hot research topic at present. Among them, changes in glucose metabolism in cancer have been widely studied. The Warburg effect maintains a high metabolic level in the tumor, accompanied by changes in glucose transporters. The transmembrane transport of sugar was previously thought to be mediated by SGLT and GLUT. Recently, the Solute Carrier Family(SLC) 45 family may be the third sugar transporter. But the role and value of the SLC45 family in melanoma, a highly malignant skin tumor, is unclear. Our study found that the four members of the SLC45 family, SLC45A1-SLC45A4, were differentially expressed in melanoma, but only SLC45A2 and SLC45A3 had prognostic guiding values. Further analysis revealed that the co-expression patterns of SLC45A2 and SLC45A3 were enriched in multiple metabolic pathways, suggesting their potential role in melanoma. In addition, SLC45A2 and SLC45A3 are also associated with immune cell infiltration. In conclusion, SLC45A2 and SLC45A3 are good prognostic indicators for melanoma and have guiding value for the treatment of melanoma in the future.

Solute carrier transporter superfamily member SLC16A1 is a potential prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma.

Melanoma is a type of cancer with a relatively poor prognosis. The development of immunotherapy for the treatment of patients with melanoma has drawn considerable attention in recent years. It is of great clinical significance to identify novel promising prognostic biomarkers and to explore their roles in the immune microenvironment. The solute carrier (SLC) superfamily is a group of transporters predominantly expressed on the cell membrane and are involved in substance transport. SLC16A1 is a member of the SLC family, participating in the transport of lactate, pyruvate, amino acids, ketone bodies, etc. The role of SLC16A1 in tumor immunity has been recently elucidated, while its role in melanoma remains unclear. In this study, bioinformatics analysis was performed to explore the role of SLC16A1 in melanoma. The results showed that high SLC16A1 expression was correlated with decreased overall survival in patients with melanoma. The genes co-expressed with SLC16A1 were significantly enriched in metabolic regulation, protein ubiquitination, and substance localization. Moreover, SLC16A1 was correlated with the infiltration of immune cells. In conclusion, SLC16A1 is a robust prognostic biomarker for melanoma and may be used as a novel target in immunotherapy.

Single-Cell Transcriptome Profiling Reveals Neutrophil Heterogeneity and Functional Multiplicity in the Early Stage of Severe Burn Patients.

The pathophysiological mechanisms, especially the roles of immune cells, underlying early stages of severe burn injury have not yet been fully clarified. Here, we analyzed circulating neutrophils (PMNs) in healthy donors and early burned patients by single-cell RNA sequencing to provide a comprehensive transcriptional landscape of PMNs in heterogeneity and functional multiplicity. Circulating PMNs in the healthy donors and burned groups were divided into five subgroups (G3, G4, G5a, G5b, G5c) with different functions. The dominant subsets of PMNs in homeostasis and burn injury significantly differed between groups. In addition, cells in the same subpopulation had the same core identity markers but performed different functions in healthy and burned states. Under burned conditions, PMN activation was very evident and accompanied by clear degranulation and metabolic abnormalities. Interestingly, was found that PMN activation, degranulation, chemotaxis, phagocytosis and reactive oxygen species (ROS) production in burned patients significantly differed between day 1 and days 2 or 3, thus providing a theoretical basis for PMN interventions in early burn stages. Significantly, previously undescribed transcription factors were also identified, including ZNF-787, ZNF-467, ZNF-189, ZNF-770, ZNF-262. In conclusion, this study conducted for the first time a detailed analysis of the heterogeneity and functional multiplicity of PMNs in early stages of severe burn injuries. Our findings attempted to clarify the influence of PMN heterogeneity on the pathophysiology and related mechanisms of burn injuries, which can provide new ideas for further research in burn intervention.

Association between the ABCC11 gene polymorphism and the expression of apolipoprotein D by the apocrine glands in axillary osmidrosis.

It has been suggested that the adenosine triphosphate­binding cassette sub­family C member 11 (ABCC11) gene polymorphism and apolipoprotein D (ApoD), an odor precursor carrier, may be important in the formation of axillary odor. To date, few studies have examined the potential correlation between these two factors. The present study aimed to investigate the association between a 538 G>A single­nucleotide polymorphism (SNP) of the ABCC11 gene and the mRNA expression levels of ApoD in the apocrine gland of patients with osmidrosis. The 538 G>A polymorphism genotypes of 33 patients with a clinical diagnosis of osmidrosis were analyzed by polymerase chain reaction (PCR) and a base­quenched probe method, and they were divided into two groups according to the results. The G allele functions as a dominant gene; therefore, patients with the GG or GA genotype were allocated to Group I (n=28) and patients with the AA genotype to Group II (n=5). The mRNA expression levels of ApoD in the apocrine glands were determined by reverse transcription­PCR. The results indicated that the mRNA expression levels of ApoD were significantly higher in the apocrine glands of patients in Group I compared with those in Group II (P<0.01). In conclusion, the results indicated that the ABCC11 gene SNP of the 538 G>A allele was associated with a downregulation of the mRNA expression of ApoD in the apocrine glands, which may indicate a role for the ABCC11 gene in the mediation of osmidrosis by enhancing the transition of odor precursors via the ApoD pathway.