Intercellular Signal Transduction Research Articles

Multi-omics Analysis Revealed that the CCN Family Regulates Cell Crosstalk, Extracellular Matrix, and Immune Escape, Leading to a Poor Prognosis of Glioma.

The CCN family is a group of matricellular proteins associated with the extracellular matrix. This study aims to explore the role of the CCN family in glioma development and its implications in the tumor microenvironment. Through analysis of bulk RNA-seq cohorts, correlations between CCN family expression and glioma subtypes, patient survival, and bioactive pathway enrichment were investigated. Additionally, single-cell datasets were employed to identify novel cell subgroups, followed by analyses of cell communication and transcription factors. Spatial transcriptomic analysis was utilized to validate the CCN family's involvement in glioma. Results indicate overexpression of CYR61,CTGF, and WISP1 in glioma, associated with unfavorable subtypes and reduced survival. Enrichment analyses revealed associations with oncogenic pathways, while CTGF and WISP1 expression correlated with increased infiltration of regulatory T cells and M2 macrophages. Single-cell analysis identified MES-like cells as the highest CCN expression. Moreover, intercellular signal transduction analysis demonstrated active pathways, including SPP1-CD44, in cell subgroups with elevated CYR61 and CTGF expression. Spatial transcriptomic analysis confirmed co-localization of CYR61,CTGF and SPP1-CD44 with high oncogenic pathway activity. These findings suggest that CCN family members may serve as potential prognostic biomarkers and therapeutic targets for glioma.

DNA-Binding Proteins and Passenger Proteins in Plasma DNA-Protein Complexes: Imprint of Parental Cells or Key Mediators of Carcinogenesis Processes?

Knowledge of the composition of proteins that interact with plasma DNA will provide a better understanding of the homeostasis of circulating nucleic acids and the various modes of interaction with target cells, which may be useful in the development of gene targeted therapy approaches. The goal of the present study is to shed light on the composition and architecture of histone-containing nucleoprotein complexes (NPCs) from the blood plasma of healthy females (HFs) and breast cancer patients (BCPs) and to explore the relationship of proteins with crucial steps of tumor progression: epithelial-mesenchymal transition (EMT), cell proliferation, invasion, cell migration, stimulation of angiogenesis, and immune response. MALDI-TOF mass spectrometric analysis of NPCs isolated from blood samples using affine chromatography was performed. Bioinformatics analysis showed that the shares of DNA-binding proteins in the compositions of NPCs in normal and cancer patients are comparable and amount to 40% and 33%, respectively; in total, we identified 38 types of DNA-binding motifs. Functional enrichment analysis using FunRich 3.13 showed that, in BCP blood, the share of DNA-binding proteins involved in nucleic acid metabolism increased, while the proportion of proteins involved in intercellular communication and signal transduction decreased. The representation of NPC passenger proteins in breast cancer also changes: the proportion of proteins involved in transport increases and the share of proteins involved in energy biological pathways decreases. Moreover, in the HF blood, proteins involved in the processes of apoptosis were more represented in the composition of NPCs and in the BCP blood-in the processes of active secretion. For the first time, bioinformatics approaches were used to visualize the architecture of circulating NPCs in the blood and to show that breast cancer has an increased representation of passenger proteins involved in EMT, cell proliferation, invasion, cell migration, and immune response. Using breast cancer protein data from the Human Protein Atlas (HPA) and DEPC, we found that 86% of NPC proteins in the blood of BCPs were not previously annotated in these databases. The obtained data may indirectly indicate directed protein sorting in NPCs, which, along with extracellular vesicles, can not only be diagnostically significant molecules for liquid biopsy, but can also carry out the directed transfer of genetic material from donor cells to recipient cells.

Eliminating extracellular autoinducing peptide signals inhibits the Staphylococcus aureus quorum sensing agr system

An accessory gene regulator (agr) in the quorum sensing (QS) system in Staphylococcus aureus contributes to host infection, virulence factor production, and resistance to oxidative damage. Artificially maintaining the inactive state of agr QS impedes the host infection strategy of S. aureus and inhibits toxin production. The QS system performs intercellular signal transduction, which is activated by the mature autoinducer peptide (AIP). It is released from cells after AgrD peptide processing as an intercellular signal associated with increased bacterial cell density. This study evaluated the effectiveness of inhibiting agr QS wherein AIP trap carriers were made to coexist when culturing Staphylococcus aureus. Immersing a nitrocellulose (NC) membrane in Staphylococcus aureus ATCC 12600 culture inhibited QS-dependent α-hemolysin production, which significantly reduced the hemolysis ratio of sheep red blood cells by the culture supernatant. A quartz crystal microbalance analysis supported AIP adsorption onto the NC membrane. Adding the NC membrane during culture was found to maintain the expression levels of the agr QS gene agrA and α-hemolysin gene hla lower than that when it was not added. Eliminating extracellular AIP signals allowed agr QS to remain inactive and prevented QS-dependent α-hemolysin expression. Isolating intercellular signals secreted outside the cell is an effective strategy to suppress gene expression in bacterial cells that collaborate via intercellular signaling.

CellDialog: A Computational Framework for Ligand-receptor-mediated Cell-cell Communication Analysis III.

Intercellular communication significantly influences tumor progression, metastasis, and therapy resistance. An intercellular communication inference method includes two main procedures: ligand-receptor interaction (LRI) curation and LRI-mediated intercellular communication strength measurement. The construction of a comprehensive, high-confident and well-organized LRI database contributes to intercellular communication inference. Here, we developed a computational framework named CellDialog to reconstruct an intercellular connectivity network based on the combined expression of ligands and receptors involved in sender and receiver cells. CellDialog first captures high-confident LRIs through LRI feature extraction, feature selection, and classification. Furthermore, CellDialog uses a three-point estimation approach to measure the LRI-mediated intercellular communication strength by combining LRI filtering and single-cell RNA sequencing data. A comparison analysis of CellDialog and the other tools was conducted, and it was found that CellDialog can efficiently decode intercellular communications. Additionally, CellDialog offers a heatmap view and network view for intercellular communication visualization. In summary, CellDialog provides a tool that allows researchers to analyze intercellular signal transduction. It is freely available at https://github.com/plhhnu/CellDialog.

Developmental expression patterns of genes mutated in patients with neurodevelopmental disorders

Neurodevelopmental disorders (NDDs) comprise a heterogeneous spectrum of disorders with diverse manifestations, such as microcephaly, structural brain abnormalities, epilepsy, developmental delay, intellectual disability, and autism spectrum disorders [1]. Although relatively rare, each type of NDDs represents a significant population of neurological patients. The global prevalence of NDDs exceeds 15% [2]. NDDs typically arise from molecular cascades that are highly regulated and disrupted by either gene mutations or environmental factors. The genetic basis of a substantial proportion of such disorders is hard to discern given that not all are inherited according to Mendelian principles and involve allelic variations from multiple genes. However, roughly 40% of NDDs are believed to be caused by the disruption of a single gene, indicating monogenic conditions. [3] Understanding and predicting the physiological function of a protein encoded by a specific gene, determining its interactions with other proteins, and investigating the role of the gene in organ and tissue development requires a close examination of its expression. Thus, a crucial initial step in researching genes associated with neurodevelopmental disorders is to investigate the expression patterns of these genes in the mouse brain at various embryonic developmental stages. In situ RNA hybridization was used to analyze gene expression patterns in slices of mouse brain tissue. Fixed in 4% paraformaldehyde/phosphate-buffered saline/diethylpyrocarbonate mouse brain samples at embryonic (E12.5, E15.5, E18.5) and postnatal (P1, P21) developmental stages were sectioned using a Leica CM1520 cryostat with 15 µm slice thickness. Next, we conducted in situ hybridization of cellular mRNA using DIG-dUTP-labeled RNA probes that were previously synthesized by PCR with cDNA and gene-specific primers. 5-bromo-4-chloro-3-indolyl phosphate/nitroblue tetrazolium (BCIP/NBT) was used, which produces an insoluble dark blue or purple sediment visible under a light microscope by reaction with alkaline phosphatase, to visualize the localization of mRNA expression in tissues. The study examined the expression of a member of the CCDC gene family which encodes proteins involved in intercellular transmembrane signal transduction. In situ hybridization was performed on mouse brain slices, revealing significant mRNA expression of the gene in the cerebral cortex. Additionally, mouse knockout experiments are planned to investigate the gene’s role in brain development.

Integrin β5 is an independent prognostic marker for intrahepatic cholangiocarcinoma in a Chinese population.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and a major cause of cancer mortality worldwide. Integrin β5 (ITGB5) is considered to be involved in the intercellular signal transduction and regulation of tumorigenesis and development. The present study investigated the association between ITGB5 expression levels and the prognosis of ICC, as well as the effects of ITGB5 on the proliferation and invasion of ICC cells. RNA-sequencing transcriptomic profiling data of ICC samples were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Tissue specimens from patients with ICC treated at Taizhou People's Hospital were collected and the ITGB5 expression levels were evaluated using immunohistochemical staining. The biological function of ITGB5 in ICC was investigated using Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and in vitro experiments using HuCCT1 cells. After knocking down ITGB5 expression, cell proliferation was detected using Cell Counting Kit-8 assay, while cell invasion was assessed using Transwell assays. According to TCGA dataset, ITGB5 was highly expressed in ICC; however, there was no significant difference in prognosis between patients with high and low ITGB5 expression levels. High expression of ITGB5 was present in the tissues of patients with ICC from the GEO database, which was associated with poor prognosis. Survival analyses of the clinical data obtained in the present study revealed that high expression levels of ITGB5 in patients with ICC were associated with a reduced overall survival. GO and GSEA indicated that genes associated with ITGB5 were enriched in the extracellular matrix-receptor interaction and focal adhesion signaling pathways. Silencing ITGB5 inhibited the proliferation and invasion of ICC cells. In conclusion, ITGB5 may act as an essential regulator of ICC development and progression by influencing the proliferation and invasion of ICC cells. However, future studies with larger sample sizes are required to validate the role of ITGB5 in the prognosis of patients with ICC.

Inflammation-related signaling pathways in tendinopathy.

Tendon is a connective tissue that produces movement by transmitting the force produced by muscle contraction to the bones. Most tendinopathy is caused by prolonged overloading of the tendon, leading to degenerative disease of the tendon. When overloaded, the oxygen demand of tenocytes increases, and the tendon structure is special and lacks blood supply, which makes it easier to form an oxygen-deficient environment in tenocytes. The production of reactive oxygen species due to hypoxia causes elevation of inflammatory markers in the tendon, including PGE2, IL-1β, and TNF-α. In the process of tendon healing, inflammation is also a necessary stage. The inflammatory environment formed by cytokines and various immune cells play an important role in the clearance of necrotic material, the proliferation of tenocytes, and the production of collagen fibers. However, excessive inflammation can lead to tendon adhesions and hinder tendon healing. Some important and diverse biological functions of the body originate from intercellular signal transduction, among which cytokine mediation is an important way of signal transduction. In particular, NF-κB, NLRP3, p38/MAPK, and signal transducer and activator of transcription 3, four common signaling pathways in tendinopathy inflammatory response, play a crucial role in the regulation and transcription of inflammatory factors. Therefore, summarizing the specific mechanisms of inflammatory signaling pathways in tendinopathy is of great significance for an in-depth understanding of the inflammatory response process and exploring how to inhibit the harmful part of the inflammatory response and promote the beneficial part to improve the healing effect of the tendon.

Biogenesis and function of exosome lncRNAs and their role in female pathological pregnancy.

Preeclampsia, gestational diabetes mellitus, and recurrent spontaneous abortion are common maternal pregnancy complications that seriously endanger women's lives and health, and their occurrence is increasing year after year with a rejuvenation trend. In contrast to biomarkers found freely in tissues or body fluids, exosomes exist in a relatively independent environment and provide a higher level of stability. As backbone molecules, guidance molecules, and signaling molecules in the nucleus, lncRNAs can regulate gene expression. In the cytoplasm, lncRNAs can influence gene expression levels by modifying mRNA stability, acting as competitive endogenous RNAs to bind miRNAs, and so on. Exosomal lncRNAs can exist indefinitely and are important in intercellular communication and signal transduction. Changes in maternal serum exosome lncRNA expression can accurately and timely reflect the progression and regression of pregnancy-related diseases. The purpose of this paper is to provide a reference for clinical research on the pathogenesis, diagnosis, and treatment methods of pregnancy-related diseases by reviewing the role of exosome lncRNAs in female pathological pregnancy and related molecular mechanisms.

In-situ monitoring of signal transduction between skin cells induced by UVB irradiation using scanning electrochemical microscopy

Skin is the first barrier of the immune system, protecting the body from various damages of the external environment, the signal transduction between skin cells plays an important role in skin healing and injury. Scanning electrochemical microscopy (SECM) combined with a Transwell co-culture device has been proposed to in-situ investigate the signal transduction between skin cells with UVB irradiation, in which, keratinocyte HaCaT cells and fibroblast HFF cells were used as signaling cells and signal-receiving cells, respectively. Extracellular ROS and pH, cell membrane permeability and cell height were in-situ monitored by multi-potential step waveform in SECM (SECM-MPSW), potentiometric mode, shear force mode and the probe approach curve (PAC) combined with COMSOL simulation, respectively. The results revealed that UVB irradiation stimulated HaCaT cells to release excess H+, which diffused to HFF cells and increased the ROS release and membrane permeability with unchanged cell height. Therefore, this work provides an effective way to in-situ investigate intercellular signal transduction.

The therapeutic potential of exosomes in lung cancer.

Lung cancer (LC) is one of the most common malignancies globally. Besides early detection and surgical resection, there is currently no effective curative treatment for metastatic advanced LC. Exosomes are endogenous nano-extracellular vesicles produced by somatic cells that play an important role in the development and maintenance of normal physiology. Exosomes can carry proteins, peptides, lipids, nucleic acids, and various small molecules for intra- and intercellular material transport or signal transduction. LC cells can maintain their survival, proliferation, migration, invasion, and metastasis, by producing or interacting with exosomes. Basic and clinical data also show that exosomes can be used to suppress LC cell proliferation and viability, induce apoptosis, and enhance treatment sensitivity. Due to the high stability and target specificity, good biocompatibility, and low immunogenicity of exosomes, they show promise as vehicles of LC therapy. We have written this comprehensive review to communicate the LC treatment potential of exosomes and their underlying molecular mechanisms. We found that overall, LC cells can exchange substances or crosstalk with themselves or various other cells in the surrounding TME or distant organs through exosomes. Through this, they can modulate their survival, proliferation, stemness, migration, and invasion, EMT, metastasis, and apoptotic resistance.

In Situ Investigation of Intercellular Signal Transduction Based on Detection of Extracellular pH and ROS by Scanning Electrochemical Microscopy.

Intercellular signal transduction plays an important role in the regulation of biological activities. Herein, a Transwell chamber-based two-layer device combined with scanning electrochemical microscopy (SECM) technology has been proposed for in situ investigation of intercellular signal transduction. The cells in the device were cultured on two layers: the lower layer was for signaling cells, and the upper layer was for signal-receiving cells. The extracellular pH (pHe) and ROS (reactive oxygen species, ROSe) were in situ monitored by SECM potentiometric mode and SECM-MPSW (multipotential step waveform), respectively. When the signaling cells, including MCF-7, HeLa, and HFF cells, were electrically stimulated, the ROS release of the signal-receiving cells was promoted. By detecting the pH at the cell surface, it was found that more H+ generated by the signaling cells and two cell layers at a shorter distance could both cause the signal-receiving cells to release more ROS, revealing that H+ is one of the signaling molecules of intercellular communication. This SECM-based in situ monitoring strategy provides an effective way to investigate intercellular signal transduction and explore the corresponding mechanism.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022.

Lipids are biological molecules that play vital roles in all living organisms. They perform many cellular functions, such as 1) forming cellular and subcellular membranes, 2) storing and using energy, and 3) serving as chemical messengers during intra- and inter-cellular signal transduction. The large-scale study of the pathways and networks of cellular lipids in biological systems is called "lipidomics" and is one of the fastest-growing omics technologies of the last two decades. With state-of-the-art mass spectrometry instrumentation and sophisticated data handling, clinical studies show how human lipid composition changes in health and disease, thereby making it a valuable medium to collect for clinical applications, such as disease diagnostics, therapeutic decision-making, and drug development. This review gives a comprehensive overview of current workflows used in clinical research, from sample collection and preparation to data and clinical interpretations. This is followed by an appraisal of applications in 2022 and a perspective on the exciting future of clinical lipidomics.

Modeling mitochondrial DNA diseases: from base editing to pluripotent stem-cell-derived organoids.

Mitochondrial DNA (mtDNA) diseases are multi-systemic disorders caused by mutations affecting a fraction or the entirety of mtDNA copies. Currently, there are no approved therapies for the majority of mtDNA diseases. Challenges associated with engineering mtDNA have in fact hindered the study of mtDNA defects. Despite these difficulties, it has been possible to develop valuable cellular and animal models of mtDNA diseases. Here, we describe recent advances in base editing of mtDNA and the generation of three-dimensional organoids from patient-derived human-induced pluripotent stem cells (iPSCs). Together with already available modeling tools, the combination of these novel technologies could allow determining the impact of specific mtDNA mutations in distinct human cell types and might help uncover how mtDNA mutation load segregates during tissue organization. iPSC-derived organoids could also represent a platform for the identification of treatment strategies and for probing the in vitro effectiveness of mtDNA gene therapies. These studies have the potential to increase our mechanistic understanding of mtDNA diseases and may open the way to highly needed and personalized therapeutic interventions.

Inflammation-the role of TRPA1 channel.

Recently, increasing numbers of studies have demonstrated that transient receptor potential ankyrin 1 (TRPA1) can be used as a potential target for the treatment of inflammatory diseases. TRPA1 is expressed in both neuronal and non-neuronal cells and is involved in diverse physiological activities, such as stabilizing of cell membrane potential, maintaining cellular humoral balance, and regulating intercellular signal transduction. TRPA1 is a multi-modal cell membrane receptor that can sense different stimuli, and generate action potential signals after activation via osmotic pressure, temperature, and inflammatory factors. In this study, we introduced the latest research progress on TRPA1 in inflammatory diseases from three different aspects. First, the inflammatory factors released after inflammation interacts with TRPA1 to promote inflammatory response; second, TRPA1 regulates the function of immune cells such as macrophages and T cells, In addition, it has anti-inflammatory and antioxidant effects in some inflammatory diseases. Third, we have summarized the application of antagonists and agonists targeting TRPA1 in the treatment of some inflammatory diseases.

COVID-19 Plasma Extracellular Vesicles Increase the Density of Lipid Rafts in Human Small Airway Epithelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the causative agent of the COVID-19 disease. COVID-19 viral infection can affect many cell types, including epithelial cells of the lungs and airways. Extracellular vesicles (EVs) are released by virtually all cell types, and their packaged cargo allows for intercellular communication, cell differentiation, and signal transduction. Cargo from virus-infected cells may include virally derived metabolites, miRNAs, nucleic acids, and proteins. We hypothesized that COVID-19 plasma EVs can induce the formation of signaling platforms known as lipid rafts after uptake by normal human small airway epithelial cells (SAECs). Circulating EVs from patients with or without COVID-19 were characterized by nanoparticle tracking analysis, Western blotting using specific antibodies, and transmission electron microscopy. Primary cultures of normal human small airway epithelial cells were challenged with EVs from the two patient groups, and lipid raft formation was measured by fluorescence microscopy and assessed by sucrose density gradient analysis. Collectively, our data suggest that circulating EVs from COVID-19-infected patients can induce the formation of lipid rafts in normal human small airway epithelial cells. These results suggest the need for future studies aimed at investigating whether the increased density of lipid rafts in these cells promotes viral entry and alteration of specific signaling pathways in the recipient cells.

Genetic difference between two Schistosoma japonicum isolates with contrasting cercarial shedding patterns revealed by whole genome sequencing

Schistosoma japonicum is one of the major infectious agents of human schistosomiasis, mainly endemic in China and the Philippines. We have previously reported the finding of two schistosome isolates, each with a different cercarial emergence pattern adapted to their different hosts. However, there are currently no whole-genome sequencing studies to investigate the underlining genetics of the adaptive traits. We sampled schistosomes in 2013 and 2020 from a hilly area Shitai (ST) and a marshland area Hexian (HX) of Anhui, China. Ten to 15 male or female adult worms from each site/year were sent for whole genome sequencing. Genetics were analyzed, and selection signals along genomes were detected. Gene enrichment analysis was performed for the genome regions under selection. The results revealed considerable genetic differentiation between the two isolates. The genome “windows” affected by natural selection were fewer in ST (64 windows containing 78 genes) than in HX (318 windows containing 276 genes). Twelve significantly enriched genes were identified in ST, but none in HX. These genes were mainly related to specific DNA binding and intercellular signaling transduction. Some functional region changes identified along the genome of the hilly schistosome may be related to its unique late afternoon cercarial emergence.

Bioinformatic analysis and preliminary validation of potential therapeutic targets for COVID-19 infection in asthma patients

BackgroundSevere acute respiratory syndrome coronavirus 2 causes coronavirus disease 19 (COVID-19). The number of confirmed cases of COVID-19 is also rapidly increasing worldwide, posing a significant challenge to human safety. Asthma is a risk factor for COVID-19, but the underlying molecular mechanisms of the asthma–COVID-19 interaction remain unclear.MethodsWe used transcriptome analysis to discover molecular biomarkers common to asthma and COVID-19. Gene Expression Omnibus database RNA-seq datasets (GSE195599 and GSE196822) were used to identify differentially expressed genes (DEGs) in asthma and COVID-19 patients. After intersecting the differentially expressed mRNAs, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify the common pathogenic molecular mechanism. Bioinformatic methods were used to construct protein–protein interaction (PPI) networks and identify key genes from the networks. An online database was used to predict interactions between transcription factors and key genes. The differentially expressed long noncoding RNAs (lncRNAs) in the GSE195599 and GSE196822 datasets were intersected to construct a competing endogenous RNA (ceRNA) regulatory network. Interaction networks were constructed for key genes with RNA-binding proteins (RBPs) and oxidative stress-related proteins. The diagnostic efficacy of key genes in COVID-19 was verified with the GSE171110 dataset. The differential expression of key genes in asthma was verified with the GSE69683 dataset. An asthma cell model was established with interleukins (IL-4, IL-13 and IL-17A) and transfected with siRNA-CXCR1. The role of CXCR1 in asthma development was preliminarily confirmed.ResultsBy intersecting the differentially expressed genes for COVID-19 and asthma, 393 common DEGs were obtained. GO and KEGG enrichment analyses of the DEGs showed that they mainly affected inflammation-, cytokine- and immune-related functions and inflammation-related signaling pathways. By analyzing the PPI network, we obtained 10 key genes: TLR4, TLR2, MMP9, EGF, HCK, FCGR2A, SELP, NFKBIA, CXCR1, and SELL. By intersecting the differentially expressed lncRNAs for COVID-19 and asthma, 13 common differentially expressed lncRNAs were obtained. LncRNAs that regulated microRNAs (miRNAs) were mainly concentrated in intercellular signal transduction, apoptosis, immunity and other related functional pathways. The ceRNA network suggested that there were a variety of regulatory miRNAs and lncRNAs upstream of the key genes. The key genes could also bind a variety of RBPs and oxidative stress-related genes. The key genes also had good diagnostic value in the verification set. In the validation set, the expression of key genes was statistically significant in both the COVID-19 group and the asthma group compared with the healthy control group. CXCR1 expression was upregulated in asthma cell models, and interference with CXCR1 expression significantly reduced cell viability.ConclusionsKey genes may become diagnostic and predictive biomarkers of outcomes in COVID-19 and asthma.BK47TRhWupise1JuLzTucxVideo

A lightweight classification of adaptor proteins using transformer networks

BackgroundAdaptor proteins play a key role in intercellular signal transduction, and dysfunctional adaptor proteins result in diseases. Understanding its structure is the first step to tackling the associated conditions, spurring ongoing interest in research into adaptor proteins with bioinformatics and computational biology. Our study aims to introduce a small, new, and superior model for protein classification, pushing the boundaries with new machine learning algorithms.ResultsWe propose a novel transformer based model which includes convolutional block and fully connected layer. We input protein sequences from a database, extract PSSM features, then process it via our deep learning model. The proposed model is efficient and highly compact, achieving state-of-the-art performance in terms of area under the receiver operating characteristic curve, Matthew’s Correlation Coefficient and Receiver Operating Characteristics curve. Despite merely 20 hidden nodes translating to approximately 1% of the complexity of previous best known methods, the proposed model is still superior in results and computational efficiency.ConclusionsThe proposed model is the first transformer model used for recognizing adaptor protein, and outperforms all existing methods, having PSSM profiles as inputs that comprises convolutional blocks, transformer and fully connected layers for the use of classifying adaptor proteins.

Stress conditions induced circRNAs profile of extracellular vesicles in brain microvascular endothelial cells.

Cerebral ischemia causes hypoxic injury and inflammation, and brain microvascular endothelial cells (BMVECs) dysfunction is an initial stage of blood-brain barrier disruption. Endothelial cells secrete extracellular vesicles (EVs) that are involved in intercellular signal transduction. EVs contain a variety of RNAs, proteins, and metabolites. Circular RNA (circRNA) is a member of the non-coding RNA. The expression profile and potential function of circRNAs in BMVECs are unknown. Here, human BMVECs have undergone hypoxia or TNF-α induction, and the changes in circRNAs were measured by RNA sequencing. A total of 70 circRNAs showed differential expression, including 43 previously unrecorded circRNAs and 27 recorded circRNAs. Since astrocyte end-feet encircle endothelial cells, they are considered the main targets of the EVs from BMVEC. The miRNA sequence data and bioinformatics were used to predict the circRNA-miRNA-mRNA networks in astrocytes. The gene ontology (GO) analysis showed the main downstream targets of circRNAs are DNA transcription regulation and protein kinase-related signaling pathways. These results suggest that altering circRNAs may be a potential therapeutic target for cerebral ischemia induced hypoxic injury and inflammation.

Immune cell metabolism and metabolic reprogramming.

Energy metabolism maintains the activation of intracellular and intercellular signal transduction, and plays a crucial role in immune response. Under environmental stimulation, immune cells change from resting to activation and trigger metabolic reprogramming. The immune system cells exhibit different metabolic characteristics when performing functions. The study of immune metabolism provides new insights into the function of immune cells, including how they differentiate, migrate and exert immune responses. Studies of immune cell energy metabolism are beginning to shed light on the metabolic mechanism of disease progression and reveal new ways to target inflammatory diseases such as autoimmune diseases, chronic viral infections, and cancer. Here, we discussed the relationship between immune cells and metabolism, and proposed the possibility of targeted metabolic process for disease treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11033-022-07474-2.