Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors.Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein‐protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375.Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation.Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Enhance the prevention and treatment of vascular cognitive impairment

DOI：10.3969/j.issn.1672-6731.2011.02.00

Metagenomic next-generation sequencing for pulmonary infections diagnosis in patients with diabetes

Abstract Background Diabetes mellitus is a major cause of high mortality and poor prognosis in patients with pulmonary infections. However, limited data on the application of metagenomic next-generation sequencing (mNGS) are available for diabetic patients. This study aimed to evaluate the diagnostic performance of mNGS in diabetic patients with pulmonary infections. Methods We retrospectively reviewed 184 hospitalized patients with pulmonary infections at Guizhou Provincial People’s Hospital between January 2020 to October 2021. All patients were subjected to both mNGS analysis of bronchoalveolar lavage fluid (BALF) and conventional testing. Positive rate by mNGS and the consistency between mNGS and conventional testing results were evaluated for diabetic and non-diabetic patients. Results A total of 184 patients with pulmonary infections were enrolled, including 43 diabetic patients and 141 non-diabetic patients. For diabetic patients, the microbial positive rate by mNGS was significantly higher than that detected by conventional testing methods, primarily driven by bacterial detection (microbes: 95.3% vs. 67.4%, P = 0.001; bacteria: 72.1% vs. 37.2%, P = 0.001). mNGS and traditional tests had similar positive rates with regard to fungal and viral detection in diabetic patients. Klebsiella pneumoniae was the most common pathogen identified by mNGS in patients with diabetes. Moreover, mNGS identified pathogens in 92.9% (13/14) of diabetic patients who were reported negative by conventional testing. No significant difference was found in the consistency of the two tests between diabetic and non-diabetic groups. Conclusions mNGS is superior to conventional microbiological tests for bacterial detection in diabetic patients with pulmonary infections. mNGS is a valuable tool for etiological diagnosis of pulmonary infections in diabetic patients

The positive rate of IgM and IgG antibodies against SARS-CoV-2 is similar in severe and non-severe COVID-19 patients

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly in China and globally. In order to control the spread of the epidemic, it is important to find an efficient diagnostic method

Double hairpin-assembled probe-mediating catalytic hairpin assembly and primer exchange reaction for sensitive and label-free miRNA analysis in gastric carcinoma

Abstract The aberrant expression of microRNA (miRNA) is closely associated with various pathological processes, such as the development of gastric cancer. High-efficiency quantification of miRNAs is significant for the diagnosis, prognosis, and treatment of cancers. However, the sensitive and reliable detection of miRNA remains a huge challenge. We depict here a novel fluorescent approach for sensitive and label-free miRNA detection by exploiting a designed detection scaffold to integrate the catalytic hairpin assembly and primer exchange reaction (PER). In this method, the detection scaffold that is constructed based on the hybridization between two hairpin structure probes (H1 probe and H2 probe), is capable of specifically recognizing target miRNA and activating signal amplification, and the PER process transcribes numerous G-rich sequences to induce ThT-based label-free signal generation. Based on the efficient signal amplification strategy and label-free signal generation mode, the method exhibits a wide detection range of 7 orders of magnitude and a high repeatability (coefficient of variation, 2.76%), implying that the proposed approach will be a robust tool in quantification of miRNA and early diagnosis of disease. Graphical abstrac

Wilms’ tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90

Abstract Background Wilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear. Methods Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation. Results WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro. Conclusion WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL