RESUMO
The effects of adding nickel on the phase transition temperature, microstructure, and mechanical properties of medium-carbon spring steel have been investigated. The results show that adding nickel reduces the martensite start (Ms) temperature, improves hardenability, and refines the sub-microstructure of the martensite, thereby improving yield stress. The yield strength of martensitic steel increases by approximately 100 MPa due to a synergistic combination of grain refinement strengthening and dislocation strengthening, with an increase in the nickel content from 0 wt.% to 1 wt.%. The cryogenic impact toughness of martensitic steel also improved with a higher nickel content due to packet and block refinement and an increase in the proportion of high-angle grain boundaries (HAGBs).
RESUMO
Lung cancer is one of the most common malignancies worldwide. Since the global outbreak of the coronavirus disease 2019 (COVID-19) pandemic in 2020, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on lung cancer has been extensively studied. Despite reports about SARS-CoV-2 infection inducing a significant increase in the number of medical visits for patients with cancer, the virus has also been reported to produce some unknown benefits. The present study reports the case of a patient with lung cancer whose tumor lesion was reduced in size after SARS-CoV-2 infection even though the therapeutic regimen remained unchanged. Although the mechanism involved is not yet understood, this case supports the novel idea of applying SARS-CoV-2 in oncolytic virotherapy.
RESUMO
The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.
Assuntos
Dependovirus , Endonucleases , Miniaturização , RNA , Edição de RNARESUMO
Clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) and base editors (BEs) are revolutionary gene-editing technology that has been widely utilized in biology, biotechnology and medicine. However, recent reports show that CRISPR-Cas9-mediated genome editing can induce a p53-mediated stress response and cell cycle arrest in human cells, while not illustrated in gene-editing animals. In the study, to verify whether there is a phenomenon of p53 activation, by analysing nine gene-edited rabbits using CRISPR-Cas9 and BEs, we provide the first evidence that no apparent p53 expression changes in those rabbits generated by Cas9 or BE-edited, suggesting that p53 may not need to consider for application in gene-edited animals.