The genomic and coding sequences of four members of grass carp interleukin (IL)-17 cytokine family, IL-17A/F2, IL-17A/F3, IL-17C and IL-17N, were isolated using rapid amplification of cDNA ends and ...conventional PCR techniques. A phylogenetic analysis showed that grass carp IL-17 family genes, including previously identified IL-17A/F1 and IL-17D, clustered with their counterparts from other fish species. IL-17D had two exons and one intron, while all the other members were composed of three exons and two introns. A multiple sequence alignment revealed that grass carp IL-17 family cytokines shared a cystine-knot motif that was highly conserved in mammals. A quantitative real-time PCR analysis revealed that these genes were expressed in the different examined tissues at varying levels. Moreover, they displayed different tissue expression patterns in fish at 24 h after intraperitoneal injection (IP) or anal intubation (AI) of Aeromonas hydrophila, implying roles in inflammatory responses. Next, we compared disease activity status and histopathological changes in intestinal tissues over a 7 day period after IP or AI, and then examine the potential differential effects of different infection routes on the expression profiles of IL-17 family genes in inflamed intestinal tissues. The intraperitoneal route resulted in more pronounced pathological symptoms than the anal route in terms of the disease activity index (DAI). Changes in the DAI highly coincided with the severity of intestinal inflammation. The two infection routes resulted in differential IL-17 family gene expression patterns over time in grass carp intestine, which suggests that IL-17 family members may play differential roles in mucosal and systemic immune responses and that IL-17N and IL-17A/F1 might possibly function as pro-inflammatory cytokines that provide defense against bacterial infection in grass carp intestine.
•Grass carp IL-17A/F2, IL-17A/F3, IL-17C and IL-17 N sequences were isolated.•Most grass carp IL-17 family genes exhibited an identical exon-intron structure.•Grass carp IL-17 family cytokines contained a cystine-knot motif found in mammals.•Tissue expression patterns of IL-17 family genes differed after bacterial infection.•IL-17 family members had unique roles in mucosal and systemic immune responses.
This study aimed to determine early diagnosis genes of acute myocardial infarction (AMI) and then validate their association with ferroptosis, immune checkpoints, and N6-methyladenosine (m6A), which ...may provide a potential method for the early diagnosis of AMI. Firstly, we downloaded microarray data from NCBI (GSE61144, GSE60993, and GSE42148) and identified differentially expressed genes (DEGs) in samples from healthy subjects and patients with AMI. Also, we performed systematic gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and used STRING to predict protein interactions. Moreover, MCC and MCODE algorithms in the cytoHubba plug-in were used to screen nine key genes in the network. We then determined the diagnostic significance of the nine obtained DEGs by plotting receiver operating characteristic curves using a multiscale curvature classification algorithm. Meanwhile, we investigated the relationship between AMI and immune checkpoints, ferroptosis, and m6A. In addition, we further validated the key genes through the GSE66360 dataset and consequently obtained nine specific genes that can be used as early diagnosis biomarkers for AMI. Through screening, we identified 210 DEGs, including 53 downregulated and 157 upregulated genes. According to GO, KEGG, and key gene screening results,
and
could be used for early prediction of AMI. Finally, we found that AMI was associated with ferroptosis, immune checkpoints, and m6A and
and
are effective markers for the diagnosis of AMI, which can provide new prospects for future studies on the pathogenesis of AMI.
This study aimed to identify the potential diagnostic biomarkers of coronary heart disease (CHD) from exosome-derived circRNA.
The microarray data of circRNA derived from the exosomes of patients ...with CHD and mRNA in acute myocardial infarction was retrieved from exoRBase website and GEO database (GSE61144), respectively, to identify the differentially expressed genes (DEGs). Our findings detected the differentially expressed circRNAs and mRNAs and predicted their correlation with microRNAs using the microRNA target prediction website, thus ascertaining the corresponding circ-microRNA and micro-mRNAs. Then, we performed systematic Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the differentially expressed mRNA. Protein-Protein Interactions (PPI) of these DEGs were examined using STRING. The receiver operator characteristic (ROC) curve was used to validate the diagnostic efficacy of circRNA in patients with CHD. Finally, the RNAs identified in this study were verified by quantitative real-time polymerase chain reaction (qRT-PCR).
A total of 85 differentially expressed circRNAs (4 up-regulated and 81 down-regulated) were identified by screening the circRNAs in exosome of CHD patients. Based on the prediction data of circRNA, mRNA, and the corresponding microRNA, a ceRNA network was constructed, including 7 circRNA nodes, 5 microRNA nodes, and 2 mRNA nodes. Finally, validated by qRT-PCR testing, we found circRNA0001785, circRNA0000973, circRNA0001741, and circRNA0003922 to be the promising candidate for the effective prediction of CHD. These potential diagnostic markers can provide insight for further research on the occurrence of CHD or even acute coronary syndrome (ACS).
Highlights
The first assembled flexible phase change nonwoven is reported by wet-spinning.
The unprecedented thermal properties of such flexible phase change nonwoven are achieved.
Such phase change ...nonwoven is highly applicable for mask and cloth intelligent temperature control.
Phase change materials have a key role for wearable thermal management, but suffer from poor water vapor permeability, low enthalpy value and weak shape stability caused by liquid phase leakage and intrinsic rigidity of solid–liquid phase change materials. Herein, we report for the first time a versatile strategy for designed assembly of high-enthalpy flexible phase change nonwovens (GB-PCN) by wet-spinning hybrid graphene-boron nitride (GB) fiber and subsequent impregnating paraffins (e.g., eicosane, octadecane). As a result, our GB-PCN exhibited an unprecedented enthalpy value of 206.0 J g
−1
, excellent thermal reliability and anti-leakage capacity, superb thermal cycling ability of 97.6% after 1000 cycles, and ultrahigh water vapor permeability (close to the cotton), outperforming the reported PCM films and fibers to date. Notably, the wearable thermal management systems based on GB-PCN for both clothing and face mask were demonstrated, which can maintain the human body at a comfortable temperature range for a significantly long time. Therefore, our results demonstrate huge potential of GB-PCN for human-wearable passive thermal management in real scenarios.
Copy number variation (CNV) is an important determinant of human diversity and plays important roles in susceptibility to disease. Most studies of CNV carried out to date have made use of chromosome ...microarray and have had a lower size limit for detection of about 30 kilobases (kb). With the emergence of whole-exome sequencing studies, we asked whether such data could be used to reliably call rare exonic CNV in the size range of 1–30 kilobases (kb), making use of the eXome Hidden Markov Model (XHMM) program. By using both transmission information and validation by molecular methods, we confirmed that small CNV encompassing as few as three exons can be reliably called from whole-exome data. We applied this approach to an autism case-control sample (n = 811, mean per-target read depth = 161) and observed a significant increase in the burden of rare (MAF ≤1%) 1–30 kb CNV, 1–30 kb deletions, and 1–10 kb deletions in ASD. CNV in the 1–30 kb range frequently hit just a single gene, and we were therefore able to carry out enrichment and pathway analyses, where we observed enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. In summary, our results showed that XHMM provided an effective means to assess small exonic CNV from whole-exome data, indicated that rare 1–30 kb exonic deletions could contribute to risk in up to 7% of individuals with ASD, and implicated a candidate pathway in developmental delay syndromes.
Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of ...circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.
Neuronal ELAV-like (nELAVL) RNA binding proteins have been linked to numerous neurological disorders. We performed crosslinking-immunoprecipitation and RNAseq on human brain, and identified nELAVL ...binding sites on 8681 transcripts. Using knockout mice and RNAi in human neuroblastoma cells, we showed that nELAVL intronic and 3' UTR binding regulates human RNA splicing and abundance. We validated hundreds of nELAVL targets among which were important neuronal and disease-associated transcripts, including Alzheimer's disease (AD) transcripts. We therefore investigated RNA regulation in AD brain, and observed differential splicing of 150 transcripts, which in some cases correlated with differential nELAVL binding. Unexpectedly, the most significant change of nELAVL binding was evident on non-coding Y RNAs. nELAVL/Y RNA complexes were specifically remodeled in AD and after acute UV stress in neuroblastoma cells. We propose that the increased nELAVL/Y RNA association during stress may lead to nELAVL sequestration, redistribution of nELAVL target binding, and altered neuronal RNA splicing.
In the framework of Industry 4.0, collaborative manufacturing across different supply chains is one of the most important business models. In order to avoid the uneven distribution of service ...requirements among service providers (i.e., non-equalization phenomenon), a lot of service strategies with different characteristics can be taken as candidate solutions to adjust the matching between service providers and service consumers. Based on the background, how to identify the application conditions of various service strategies in complex environment has become a serious challenge in the field. To solve this problem, the computational experiment-based evaluation method is proposed in this paper, including customization of service strategy, construction of experiment system, and experiment analysis of service strategy. In this paper, three possible service strategies are built to deal with the non-equalization phenomenon, i.e., non-equalization strategy, equalization strategy, collaborative equalization strategy. Experiment results show that: collaborative equalization strategy can effectively enhance the service utilization rate and reduce the completion time in short supply environment; equalization strategy is the optimal one in oversupply market environment. This case study can show that the proposed method is feasible and the result is satisfactory.
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) accounts for 85% of pancreatic carcinoma cases. Patients with PDAC have a poor prognosis. The lack of reliable prognostic biomarkers makes treatment ...challenging for patients with PDAC. Using a bioinformatics database, we sought to identify prognostic biomarkers for PDAC. MATERIAL AND METHODS Using proteomic analysis of the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database, we were able to identify core differential proteins between early and advanced pancreatic ductal adenocarcinoma tissue, and then we used survival analysis, Cox regression analysis, and area under the ROC curves to screen for more significant differential proteins. Additionally, the Kaplan-Meier plotter database was utilized to determine the relationship between prognosis and immune infiltration in PDAC. RESULTS We identified 378 differential proteins in early (n=78) and advanced stages (n=47) of PDAC (P<0.05). PLG, COPS5, FYN, ITGB3, IRF3, and SPTA1 served as independent prognostic factors of patients with PDAC. Patients with higher COPS5 expression had shorter overall survival (OS) and recurrence-free survival, and those with higher PLG, ITGB3, and SPTA1, and lower FYN and IRF3 expression had shorter OS. More importantly, COPS5, IRF3 were negatively associated with macrophages and NK cells, but PLG, FYN, ITGB3, and SPTA1 were positively related to the expression of CD8+ T cells and B cells. COPS5 affected the prognosis of PDAC patients by acting on B cells, CD8+ T cells, macrophages, and NK cells immune infiltration, while PLG, FYN, ITGB3, IRF3, and SPTA1 affected PDAC patient prognosis through some immune cells. CONCLUSIONS PLG, COPS5, FYN, IRF3, ITGB3 and SPTA1 could be potential immunotherapeutic targets and valuable prognostic biomarkers of PDAC.
The wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a ...series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.
In this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.
In summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.
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