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The paper by Mohapatra et al. (p 298, this issue) describes how fluvastatin sensitizes pancreatic cancer cells toward radiation therapy and suppresses radiation- and/or TGF-β-induced tumor-associated fibrosis. The cover shows images of developing zebrafish embryos as a model for this study.
The authors developed a deep convolutional neural network-based algorithm to support pathological muscle diagnosis. The algorithm differentiated idiopathic inflammatory myopathies and outperformed nine human physicians under limited diseases and conditions. These results suggest that the algorithm has the potential to be used directly in clinical settings.
Active learning (AL) model is a framework designed for single-cell RNA sequence (scRNA-seq) clustering. This model requires that the researchers label a small number of cells selected by a sample selection algorithm. The labeled cells are then used for the supervision of the clustering, to significantly boost the clustering performance of scRNA-seq.
It is unclear how to best classify cancer outcomes using ‘omic data. We developed a multimetric feature-selection based multinomial logistic regression model that outperformed random forest models in classifying 4-category outcome of colorectal cancer. Adding microsatellite instability and oncogenic-driver data to clinical and transcriptomic data improves models’ performances, with pathologic staging, HBS1L, TSPYL4, and TP53TG3B as important features. Interestingly, precision and recall of tuned algorithms change as the feature number changes, but accuracy does not.
An artificial intelligence (AI) model was developed to discriminate between fibroadenomas and phyllodes tumors on core biopsy images. It employed a two-stage architecture comprising a convolutional neural network (CNN) component for feature extraction, and a recurrent neural network (RNN) component for whole-slide classification, with an overall slide-level accuracy of 87.5%.
Cardiac hypertrophy is a common cardiovascular disease worldwide, and this study may provide novel potential therapeutic targets. The authors demonstrate that TINCR improves cardiac hypertrophy by acting as a competitive endogenous RNA for miR-211-3p and thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis.
This study investigates the role of c-Abelson (c-Abl) kinase in neutrophil extracellular trap (NET) formation and inflammation during sepsis. The authors demonstrate that c-Abl kinase plays a pivotal role in NET formation, pulmonary formation of CXC chemokines and lung injury in sepsis. Authors conclude that targeting c-Abl kinase might be a useful strategy to ameliorate local and systemic inflammation in sepsis.
This paper provides new insights into the potential therapeutic effects of vitamin E on COPD. The authors show that vitamin E relieves chronic obstructive pulmonary disease (COPD) by negatively regulating the EGFR/MAPK pathway and inhibiting COX2-mediated translocation of phosphorylated STAT3 to the nucleus. Moreover, overexpression of COX2 reverses the protective effect of vitamin E in a rat model of COPD.
Sustained high circulating levels of fibroblast growth factor (FGF) 21 improve obesity/systemic insulin resistance and promote ketone body production as a second hepatic disposal system for excess free fatty acids. Liver-derived ketone bodies may be utilized for energy in skeletal muscle. The potential FGF21-related crosstalk between the liver and extrahepatic organs is a promising strategy against nonalcoholic fatty liver disease.
Fluvastatin, a cholesterol-lowering drug, radiosensitizes pancreatic cancer (PC) cells partly by inhibiting DNA damage response and/or autophagic flux. Fluvastatin also significantly suppresses intra-tumor radiation-induced fibrosis, as it inhibits radiation/TGF-β-induced activation of pancreatic stellate cells. Together, fluvastatin and radiation co-treatment may be a potential therapeutic approach against PC and warrants further clinical evaluation.
The authors examined the indirect effects of mesenchymal stem cells (MSCs) on spinal infusion through macrophages. They found that posterior spinal fusion is improved by placental growth factor (PlGF)-expressing MSCs, likely through attraction of macrophages and indution their M2 polarization, which in turn promotes the bone formation.
miR-21-5p directly decreases levels of Jag1, which inhibits the Notch pathway and subsequently promotes the differentiation of adipose-derived stem cells into myelin-forming Schwann cells. Exploiting this signalling pathway may be an effective new method for the treatment of nerve injury.