Cardiovascular Risk After SARS-CoV-2 Infection Is Mediated by IL18/IL18R1/HIF-1 Signaling Pathway Axis

ObjectivesCurrently, cardiovascular risk associated with COVID-19 has been brought to people’s attention, but the mechanism is not clear. The aim of this study is to elucidate the mechanisms based on multiple omics data.MethodologyWeighted gene co-expression network analysis (WGCNA) was used to identify key pathways. Combination analysis with aneurysm and atherosclerosis related pathways, hypoxia induced factor-1 (HIF-1) signaling were identified as key pathways of the increased cardiovascular risk associated with COVID-19. ScMLnet algorithm based on scRNA-seq was used to explore the regulation of HIF-1 pathway by intercellular communication. Proteomic analysis was used to detect the regulatory mechanisms between IL18 and HIF-1 signaling pathway. Pseudo time locus analysis was used to study the regulation of HIF1 signaling pathway in macrophages and vascular smooth muscle cells (VSMC) phenotypic transformation. The Virtual Inference of protein-activity by Enriched Regulon (VIPER) analysis was used to study the activity of regulatory proteins. Epigenetic analysis based on methylation revealed epigenetic changes in PBMC after SARS-CoV-2 infection. Potential therapeutic compounds were explored by using Cmap algorithm.ResultsHIF-1 signaling pathway is a common key pathway for aneurysms, atherosclerosis and SARS-CoV-2 infection. Intercellular communication analysis showed that macrophage-derived interleukin-18 (IL-18) activates the HIF-1 signaling pathway through IL18R1. Proteomic analysis showed that IL18/IL18R1 promote NF-κB entry into the nucleus, and activated the HIF-1 signaling pathway. Macrophage-derived IL18 promoted the M1 polarization of macrophages and the syntactic phenotype transformation of VSMCs. MAP2K1 mediates the functional regulation of HIF-1 signaling pathway in various cell types. Epigenetic changes in PBMC after COVID-19 infection are characterized by activation of the type I interferon pathway. MEK inhibitors are the promising compounds for the treatment of HIF-1 overactivation.ConclusionsThe IL18/IL18R1/HIF1A axis is expected to be an therapeutic target for cardiovascular protection after SARS-CoV-2 infection. MEK inhibitors may be an choice for cardiovascular protection after SARS-COV-2 infection

Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar

Hypertrophic scar (HS) is a common skin disorder characterized by excessive extracellular matrix (ECM) deposition. However, it is still unclear how the cellular composition, cell-cell communications, and crucial transcriptionally regulatory network were changed in HS. In the present study, we found that FB-1, which was identified a major type of fibroblast and had the characteristics of myofibroblast, was significantly expanded in HS by integrative analysis of the single-cell and bulk RNA sequencing (RNA-seq) data. Moreover, the proportion of KC-2, which might be a differentiated type of keratinocyte (KC), was reduced in HS. To decipher the intercellular signaling, we conducted the cell-cell communication analysis between the cell types, and found the autocrine signaling of HB-1 through COL1A1/2-CD44 and CD99-CD99 and the intercellular contacts between FB-1/FB-5 and KC-2 through COL1A1/COL1A2/COL6A1/COL6A2-SDC4. Almost all the ligands and receptors involved in the autocrine signaling of HB-1 were upregulated in HS by both scRNA-seq and bulk RNA-seq data. In contrast, the receptor of KC-2, SDC4, which could bind to multiple ligands, was downregulated in HS, suggesting that the reduced proportion of KC-2 and apoptotic phenotype of KC-2 might be associated with the downregulation of SDC4. Furthermore, we also investigated the transcriptionally regulatory network involved in HS formation. The integrative analysis of the scRNA-seq and bulk RNA-seq data identified CREB3L1 and TWIST2 as the critical TFs involved in the myofibroblast of HS. In summary, the integrative analysis of the single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data greatly improved our understanding of the biological characteristics during the HS formation.

New Media Advertising Communication Analysis Model Based on Extension Neural Network

In order to improve the effect of new media advertising communication analysis, this paper combines the scalable neural network to construct the new media advertising communication analysis model. Moreover, this paper analyzes in detail the basic theories of fuzzy neural network and extension evaluation, the structure design and learning algorithm, and classification of fuzzy neural network. In particular, this paper summarizes the optimization algorithms and methods of neural network structure. In addition, this paper improves the algorithm to meet the needs of new media advertising data analysis and builds an intelligent system framework. The experimental verification shows that the new media advertising communication analysis model based on the extension neural network proposed in this paper meets the new media advertising communication analysis effect.

Single-cell transcriptomic landscapes of a rare human laryngeal chondrosarcoma

Propose Laryngeal chondrosarcoma is a rare non-epithelial malignant tumor. At present, the cell type composition and molecular mechanism of laryngeal chondrosarcoma have not been systematically studied. Methods This study focused on the histopathological and imaging features of a rare primary laryngeal chondrosarcoma in a 74-year-old male. The tumor and its paracancerous cartilage tissue were single-cell sequenced and analyzed and a total of 5455 single cells were obtained. Immunohistochemical levels were also verified. Results In total five cell types were identified, including chondrocytes, myeloid cells, fibroblasts, lymphocytes, and endothelial cells. We carried out further subgroup analysis, focusing on the classification and differentiation of chondrocytes, functional enrichment analysis, and cellular communication analysis of all cell types, and explored the tumor microenvironment (TME) of laryngeal chondrosarcoma. Immunohistochemistry revealed the SLAMF9 gene was specifically expressed in non-immune cells of chondrosarcoma, but was barely expressed in the normal cartilage tissues adjacent to chondrosarcomas. Conclusion This single-cell sequencing approach provides clues for deciphering the potential mechanisms of tumor heterogeneity and TME composition in laryngeal chondrosarcoma, and represents an important step towards the treatment of laryngeal chondrosarcoma.

Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer

Colorectal cancer (CRC) manifests as gastrointestinal tumors with high intratumoral heterogeneity. Recent studies have demonstrated that CRC may consist of tumor cells with different consensus molecular subtypes (CMS). The advancements in single-cell RNA sequencing have facilitated the development of gene regulatory networks to decode key regulators for specific cell types. Herein, we comprehensively analyzed the CMS of CRC patients by using single-cell RNA-sequencing data. CMS for all malignant cells were assigned using CMScaller. Gene set variation analysis showed pathway activity differences consistent with those reported in previous studies. Cell–cell communication analysis confirmed that CMS1 was more closely related to immune cells, and that monocytes and macrophages play dominant roles in the CRC tumor microenvironment. On the basis of the constructed gene regulation networks (GRNs) for each subtype, we identified that the critical transcription factor ERG is universally activated and upregulated in all CMS in comparison with normal cells, and that it performed diverse roles by regulating the expression of different downstream genes. In summary, molecular subtyping of single-cell RNA-sequencing data for colorectal cancer could elucidate the heterogeneity in gene regulatory networks and identify critical regulators of CRC.

Chimpanzee vowel-like sounds and voice quality suggest formant space expansion through the hominoid lineage

The origins of human speech are obscure; it is still unclear what aspects are unique to our species or shared with our evolutionary cousins, in part due to a lack of a common framework for comparison. We asked what chimpanzee and human vocal production acoustics have in common. We examined visible supra-laryngeal articulators of four major chimpanzee vocalizations (hoos, grunts, barks, screams) and their associated acoustic structures, using techniques from human phonetic and animal communication analysis. Data were collected from wild adult chimpanzees, Taï National Park, Ivory Coast. Both discriminant and principal component classification procedures revealed classification of call types. Discriminating acoustic features include voice quality and formant structure, mirroring phonetic features in human speech. Chimpanzee lip and jaw articulation variables also offered similar discrimination of call types. Formant maps distinguished call types with different vowel-like sounds. Comparing our results with published primate data, humans show less F1–F2 correlation and further expansion of the vowel space, particularly for [i] sounds. Unlike recent studies suggesting monkeys achieve human vowel space, we conclude from our results that supra-laryngeal articulatory capacities show moderate evolutionary change, with vowel space expansion continuing through hominoid evolution. Studies on more primate species will be required to substantiate this. This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part II)’.

Quantifiers in Natural Language: Efficient Communication and Degrees of Semantic Universals

While the languages of the world vary greatly, they exhibit systematic patterns, as well. Semantic universals are restrictions on the variation in meaning exhibit cross-linguistically (e.g., that, in all languages, expressions of a certain type can only denote meanings with a certain special property). This paper pursues an efficient communication analysis to explain the presence of semantic universals in a domain of function words: quantifiers. Two experiments measure how well languages do in optimally trading off between competing pressures of simplicity and informativeness. First, we show that artificial languages which more closely resemble natural languages are more optimal. Then, we introduce information-theoretic measures of degrees of semantic universals and show that these are not correlated with optimality in a random sample of artificial languages. These results suggest both that efficient communication shapes semantic typology in both content and function word domains, as well as that semantic universals may not stand in need of independent explanation.

The influences of teachers’ communicational style upon the learning style of high school students

This study, conducted over 2 years (2019–2020), aimed to highlight how teachers’ communication style influences the learning style of high school students. We used research methods of the S.C. Questionnaire (communication analysis), a questionnaire to identify students’ learning styles, and guidance interview structured on 10 items. Both questionnaires were administered according to GDPR rules. We also used IBM Statistical Package for the Social Sciences 25 for statistical data processing. The outcomes of this research are as follows: (a) it allows a better understanding of the teaching–learning process in high school students; (b) it highlights how the teacher’s communication style influences the learning style of high school students, in both face-to-face teaching activities and online teaching–learning activities; and (c) it highlights the methods that facilitate the analysed phenomenon. Keywords: Teachers’ communication, style, student’s learning style, Influence, High school

Gift im Bier: A Context-sensitive Analysis of Culturally-rooted Messages and Humor in Risk Communication on Glyphosate in Germany

Glyphosate is the world’s most used and controversially debated herbicide. Its approval in the European Union (EU) is expiring in 2022. At the time of its last approval procedures in the EU in 2016/2017, there was a heated public debate in Germany about the carcinogenic risk of glyphosate. In this context, the Munich Environmental Institute published a study which concluded there were chemical residues of glyphosate in the 14 most-popular German beers. In this article, I analyze the “Gift im Bier” (poison in beer) case by examining central stakeholders’ reactions using a message-centered approach for risk communication and reflect on culturally-rooted messages, including the use of humor, within risk communication. Ultimately, I will argue for a contextsensitive and message-centered approach to risk communication analysis.