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The authors present an assessment of the utility of “third-generation” nanopore sequencing for the confirmation and characterization of mobile element insertions. and discuss how implementation of long-read nanopore sequencing can offer benefits over existing molecular approaches.
Epithelial-to-mesenchymal transition of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. In the present study, the miR-184/TP63 axis modulates the TGF-β1-induced fibrotic alterations in epithelial cell lines and bleomycin-induced pulmonary fibrosis in mice, confirming that miR-184/TP63 axis is involved in IPF progression.
Ascorbate can act as an oxidant to induce tumor cell death at a pharmacological dose. Here the authors show that this response is associated with increases in GPCR Gi/o activity. This effect promotes rises in intracellular Ca2+ influx through transient receptor potential channel activity in retinoblastoma cells.
Cardiovascular diseases are the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is a major risk for cardiovascular disease. Herein, the authors demonstrate that circPAN3 ameliorates myocardial I/R injury by absorbing miR-421 to regulate Pink1-mediated autophagy, which may provide potential therapeutic targets in I/R injury.
This study demonstrates that NFAT5 promotes oral squamous cell carcinoma progression in the hyperosmotic environment through increased expression of DPAGT1, an essential enzyme for protein glycosylation, and altered EGFR subcellular localization from the cytoplasm to the plasma membrane in tumor cells.
Photoactivatable-Cre (PA-Cre) knock-in mice was established and characterized for the spatial regulation of Cre recombinase activity with blue light exposure. Spot irradiation or long-term irradiation using a wireless LED could induce locus-specific recombination. The PA-Cre knock-in mice promise a useful resource to elucidate gene function in vivo spatiotemporally.
The authors describe a sarcoma with a novel fusion between NUTM1 and MXI1, a member of the MAD gene family. Transcriptome analysis and in vitro studies showed that MXI1-NUTM1 partially phenocopied MYC, providing evidence that MAD family members, normally repressors of MYC activity, can be converted into MYC-like mimics by fusion to NUTM1.
This study describes how miR-221-3p in endothelial cells reduces angiogenesis by inhibiting hypoxia-inducible factor-1α. Because antagonism of miR-221-3p significantly improves the cardiac function of mice with heart failure it may be a new and effective molecular target for progressing and treatment of heart failure.
In this paper, the authors describe the development and validation of a novel image signature-based radiomics model. A total of 655 glioma patients were enrolled to build this model which is shown to be an effective tool to achieve multilayer preoperative diagnosis and prognostic stratification of gliomas.
Both ASIC1a and VEGF are highly expressed in rheumatoid arthritis synovial tissue and are associated with vascular disease. Interfering with ASIC1a in vitro using silencing, blocking, and overexpression interferes with the release of VEGF under acid stimulation. Blocking ASIC1a in the articular cavity of rats with adjuvant arthritis not only reduces the expression of VEGF in the synovium, but also reduces the proliferation and lesions of blood vessels and interferes with the development of the disease.
SOX2 is expressed frequently in small cell lung cancer (SCLC). ASCL1 is a potent driver of SOX2 expression and regulates INSM1 expression in the major subtype, SCLC-A (ASCL1). However, SOX2 also regulates distinct genes in the hippo pathway in the minor subtype SCLC-Y (YAP1). These results show that ASCL1-SOX2 axis is a potential therapeutic target in SCLC.
Computational modeling has emerged as a promising and cost-effective alternative method for screening potentially endocrine active compounds. This study applies classic machine learning algorithms and deep learning approaches to a panel of over 7500 compounds tested against 18 Toxicity Forecaster assays related to nuclear estrogen receptor (ERα and ERβ) activity.
This study shows in vivo and in vitro evidence to support a novel tree shrew model of lung fibrosis. Tree shrews are genetically, anatomically, and metabolically closer to humans than rodents or dogs; therefore, the tree shrew model presents a unique opportunity for basic and translational research in lung fibrosis.
Polarization-second harmonic microscopy was utilized to investigate whether collagen ultrastructure in thyroid due to four carcinoma types and Graves’ disease could be differentiated in human histopathology samples. Three parameters were extracted, revealing that the degree of linear polarization and χ(2)zzz/χ(2)zxx were effective in differentiating some diseases, while the parameter χ(2)xyz/χ(2)zxx was less effective.
This study demonstrates that small clusters (sCLs) of tumor cells with high expression of LGR5 continuously form in the invasive front in a colorectal cancer xenograft model. This structure is characterized by stress response and partial/hybrid epithelial-mesenchymal transition. These sCLs are an important contributor to tumor growth and the expansion of cancer stem cells.
Overexpression of pigment epithelium-derived factor (PEDF) in placenta-derived mesenchymal stem cells (PD-MSCs) improved the mitochondrial activities, and induced regeneration of oxidative stress-damaged RPE through regulating oxidative status and mitochondrial biogenesis. Therefore, genetic modification of PD-MSCs with PEDF might be a new cell therapy for treatment of retinal degenerative diseases.
Combination of antihypertensive drugs with NSAID analgesics may cause a syndrome called triple whammy (TW) acute kidney injury (AKI), most often in the elderly. A rat model reveals that the TW-AKI is a prerenal form of AKI, only occurring in previously dehydrated rats, a condition particularly rife among the aged.
In this study, the authors assess the early pathogenesis of cystic fibrosis (CF) pig gallbladder disease. The CF pig gallbladder epithelium lacks cAMP-stimulated anion and fluid transport. CF pig gallbladders also demonstrate increased luminal mucins MUC5AC and MUC5B accumulation without significant changes in the epithelial expression of gel-forming mucins compared to non-CF pigs.
The authors investigated the role of extracellular cold-inducible RNA-binding protein (eCIRP) in acute pancreatitis (AP) and found that eCIRP acts as a potent regulator of neutrophil extracellular traps (NETs) formation in AP. They observed that eCIRP itself is one of the NETs associated proteins. Furthermore, they demonstrate that C23 (a potent eCIRP inhibitor) reduces NETs formation and inflammation in AP.