Laser welding process and strength enhancement of carbon fiber reinforced thermoplastic composites and metals dissimilar joint:A review

Carbon fiber reinforced thermoplastic composites(CFRTP)and metals hybrid structures have been widely used in aircraft lightweight manufacturing.However,due to the significant difference in physical and chemical properties between CFRTP and metals,there are lots of challenges to connect them with high quality.Laser welding has a good application prospect in CFRTP and metals connection,and a significant research progress has been made in the exploration of CFRTP-metal laser joining mechanism,joining process optimization,joining strength improvement and joining defects controlling.However,there are still some problems need to be solved for this technology application.In this paper,the research progress of CFRTP-metal laser joining was summarized in three major aspects:theoretical modeling and simulation analysis,process exploration and parameter optimization,joint performance improvement and process innovation.And,problems and challenges of this technology were discussed,and the outlook of this research was provided.

Targeting the insulin-like growth factor-1 receptor in MTAP-deficient renal cell carcinoma

Renal cell carcinoma(RCC)has emerged as a metabolic disease characterized by dysregulated expression of metabolic enzymes.Patients with metastatic RCC have an unusually poor prognosis and near-universal resistance to all current therapies.To improve RCC treatment and the survival rate of patients with RCC,there is an urgent need to reveal the mechanisms by which metabolic reprogramming regulates aberrant signaling and oncogenic progression.Through an integrated analysis of RCC metabolic pathways,we showed that methylthioadenosine phosphorylase(MTAP)and its substrate methylthioadenosine(MTA)are dysregulated in aggressive RCC.A decrease in MTAP expression was observed in RCC tissues and correlated with higher tumor grade and shorter overall survival.Genetic manipulation of MTAP demonstrated that MTAP expression inhibits the epithelial-mesenchymal transition,invasion and migration of RCC cells.Interestingly,we found a decrease in the protein methylation level with a concomitant increase in tyrosine phosphorylation after MTAP knockout.A phospho-kinase array screen identified the type 1 insulin-like growth factor-1 receptor(IGF1R)as the candidate with the highest upregulation in tyrosine phosphorylation in response to MTAP loss.We further demonstrated that IGF1R phosphorylation acts upstream of Src and STAT3 signaling in MTAP-knockout RCC cells.IGF1R suppression by a selective inhibitor of IGF1R,linsitinib,impaired the cell migration and invasion capability of MTAP-deleted cells.Surprisingly,an increase in linsitinib-mediated cytotoxicity occurred in RCC cells with MTAP deficiency.Our data suggest that IGF1R signaling is a driver pathway that contributes to the aggressive nature of MTAP-deleted RCC.