Transcriptional Profiling and Machine Learning Unveil a Concordant Biosignature of Type I Interferon-Inducible Host Response Across Nasal Swab and Pulmonary Tissue for COVID-19 Diagnosis.

Background: COVID-19, caused by SARS-CoV-2 virus, is a global pandemic with high mortality and morbidity. Limited diagnostic methods hampered the infection control. Since the direct detection of virus mainly by RT-PCR may cause false-negative outcome, host response-dependent testing may serve as a complementary approach for improving COVID-19 diagnosis. Objective: Our study discovered a highly-preserved transcriptional profile of Type I interferon (IFN-I)-dependent genes for COVID-19 complementary diagnosis. Methods: Computational language R-dependent machine learning was adopted for mining highly-conserved transcriptional profile (RNA-sequencing) across heterogeneous samples infected by SARS-CoV-2 and other respiratory infections. The transcriptomics/high-throughput sequencing data were retrieved from NCBI-GEO datasets (GSE32155, GSE147507, GSE150316, GSE162835, GSE163151, GSE171668, GSE182569). Mathematical approaches for homological analysis were as follows: adjusted rand index-related similarity analysis, geometric and multi-dimensional data interpretation, UpsetR, t-distributed Stochastic Neighbor Embedding (t-SNE), and Weighted Gene Co-expression Network Analysis (WGCNA). Besides, Interferome Database was used for predicting the transcriptional factors possessing IFN-I promoter-binding sites to the key IFN-I genes for COVID-19 diagnosis. Results: In this study, we identified a highly-preserved gene module between SARS-CoV-2 infected nasal swab and postmortem lung tissue regulating IFN-I signaling for COVID-19 complementary diagnosis, in which the following 14 IFN-I-stimulated genes are highly-conserved, including BST2, IFIT1, IFIT2, IFIT3, IFITM1, ISG15, MX1, MX2, OAS1, OAS2, OAS3, OASL, RSAD2, and STAT1. The stratified severity of COVID-19 may also be identified by the transcriptional level of these 14 IFN-I genes. Conclusion: Using transcriptional and computational analysis on RNA-seq data retrieved from NCBI-GEO, we identified a highly-preserved 14-gene transcriptional profile regulating IFN-I signaling in nasal swab and postmortem lung tissue infected by SARS-CoV-2. Such a conserved biosignature involved in IFN-I-related host response may be leveraged for COVID-19 diagnosis.

microRNA-23a in Human Cancer: Its Roles, Mechanisms and Therapeutic Relevance.

microRNA-23a (miR-23a) is one of the most extensively studied miRNAs in different types of human cancer, and plays various roles in the initiation, progression, and treatment of tumors. Here, we comprehensively summarize and discuss the recent findings about the role of miR-23a in cancer. The differential expression of tissue miR-23a was reported, potentially indicating cancer stages, angiogenesis, and metastasis. miR-23a in human biofluid, such as plasma and salivary fluid, may be a sensitive and specific marker for early diagnosis of cancer. Tissue and circulating miR-23a serves as a prognostic factor for cancer patient survival, as well as a predictive factor for response to anti-tumor treatment. The direct and indirect regulation of miR-23a on multiple gene expression and signaling transduction mediates carcinogenesis, tumor proliferation, survival, cell migration and invasion, as well as the response to anti-tumor treatment. Tumor cell-derived miR-23a regulates the microenvironment of human cancer through manipulating both immune function and tumor vascular development. Several transcriptional and epigenetic factors may contribute to the dysregulation of miR-23a in cancer. This evidence highlights the essential role of miR-23a in the application of cancer diagnosis, prognosis, and treatment.

[The application of magnetoencephalography versus scalp electroencephalography in intractable temporal lobe epilepsy].

OBJECTIVE: To explore the clinical application value and feasibility of magnetoencephalography (MEG) in the localization of epileptogenic zone, as compared with scalp electroencephalography. METHODS: 69 patients were enrolled in this study, all the patients were examined with MEG and scalp EEG and received operative treatment. During the operation the patients underwent ECoG and deep EEG monitoring and after the operation the follow-up continued 2 - 3 years. Results were evaluated with Engel curative effect grading. RESULTS: Among the 69 patients there was 62 patients whose localization were limited to one lobe with MEG; while only 30 with EEG. We used Engels, grading to define the effectiveness of the operation. 57 among the 69 patients had effective results with an effective rate of 82.61%. When the lateralization of epileptogenic zone in these 57 patients was counted, the concordance rate of preoperative MEG and EEG with intraoperative EEG was 92.98% (53/57) and 33.33% (19/57) respectively with significant difference between MEG and EEG statistically (chi(2) = 30.250, P = 0.000). The scalp EEG of 34 patients with temporal lobe epilepsy showed bilateral temporal lobe epileptiform discharges or generalized spikes, while the epileptogenic foci were shown with MEG only unilaterally and confirmed by operation finally. CONCLUSIONS: MEG shows significant value in the lateralization of epileptogenic zone of temporal lobe epilepsy. MEG, with a higher time resolution and space resolution, can help to identify epileptogenic zone and mirror foci. MEG can clarify the spatial relationship between the irritative zone and structural lesions or functional areas.

Histamine stimulates production of osteoclast differentiation factor/receptor activator of nuclear factor-kappaB ligand by osteoblasts.

Histamine H(1),H(2), and H(3) receptors are expressed by osteoblastic MC3T3-E1 (E1) cells derived from mouse calvaria. Expression of the osteoclast differentiation factor (ODF)/receptor activator of nuclear factor-kappaB ligand (RANKL) transcript was induced in E1 cells and bone marrow stromal cells (ST2). Histamine markedly increased the steady-state level of ODF/RANKL mRNA in a dose-dependent manner. The effect of histamine on expression of ODF/RANKL mRNA by E1 cells was transient, with a peak at 6h. Western blot analysis revealed that histamine increased production of ODF/RANKL protein by E1 cells at 12h. In cocultures of E1 cells and mouse bone marrow cells, histamine stimulated osteoclastogenesis in the presence of 1,25-dihydroxyvitamin D(3) and this effect was blocked by preincubation with neutralizing antibody against ODF/RANKL. These results suggest that histamine regulates osteoclastogenesis, at least in part, through induction of ODF/RANKL expression by osteoblasts and bone marrow stromal cells.