Microstructure and mechanical properties of Al-Si alloy modified with Al-3P

Al-Si alloy was modified with Al-3P master alloy at 740℃.The effects of Si content(7,8,9,10 and 11 wt.%) and adding amount of alterant A1-3P(0,0.1,0.3,0.6,1.0 and 1.5 wt.%) on microstructures and tensile properties of the alloy were investigated with optical microscope(OP),Image Pro Plus 6.0,scanning electron microscope(SEM) and universal testing machine.When the content of Al-3P is 0.6 wt.%,the area fraction of primary a(Al) in the Al-Si alloy increases more compared to the unmodified alloy with an increase in Si content,which could be explained by the movement of non-equilibrium eutectic point.When the Si content is constant(Al-lOSi),with the increase of Al-3P content,the increased rate in area fraction of primary a(Al) phase in the Al-lOSi alloy increases first and then decreases.And when 0.6 wt.% Al-3P is added,the increase in area fraction of primary a(Al) phase is the largest.Compared to the unmodified Al-lOSi alloy,the tensile strength and elongation of Al-lOSi alloy increase by 2.3% and 47.0%,respectively,after being modified with 0.6 wt.% Al-3P alloy.The fracture mode of the modified Al-lOSi alloy is ductile fracture.

Therapeutic targets in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs) are the most common type of mesenchymal tumor of the gastrointestinal tract. The tumorigenesis of GISTs is driven by gain-of-function mutations in KIT or plateletderived growth factor receptor α(PDGFRA),resultingin constitutive activation of the tyrosine kinase and its downstream signaling pathways. Oncogenic KIT or PDGFRA mutations are compelling therapeutic targets for the treatment of GISTs,and the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GISTs. However,most GIST patients develop clinical resistance to imatinib and other tyrosine kinase inhibitors. Five mechanisms of resistance have been characterized:(1) acquisition of a secondary point mutation in KIT or PDGFRA;(2) genomic amplification of KIT;(3) activation of an alternative receptor tyrosine kinase;(4) loss of KIT oncoprotein expression; and(5) wild-type GIST. Currently,sunitinib is used as a secondline treatment for patients after imatinib failure,and regorafenib has been approved for patients whose disease is progressing on both imatinib and sunitinib. Phase Ⅱ/Ⅲ trials are currently in progress to evaluate novel inhibitors and immunotherapies targeting KIT,its downstream effectors such as phosphatidylinositol 3-kinase,protein kinase B and mammalian target of rapamycin,heat shock protein 90,and histone deacetylase inhibitor. Other candidate targets have been identified,including ETV1,AXL,insulin-like growth factor 1 receptor,KRAS,FAS receptor,protein kinase c theta,ANO1(DOG1),CDC37,and aurora kinase A. These candidates warrant clinical evaluation as novel therapeutic targets in GIST.

RNA-based nanomedicines and their clinical applications

RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases.These include antisense oligonucleotides(ASOs),small interfering RNAs(siRNAs),endogenous microRNAs(miRNAs),messenger RNAs(mRNAs),clustered regularly interspersed short palindromic repeats-associated protein 9(CRISPR/Cas9),single guide RNAs(sgRNAs),as well as RNA aptamers.These therapeutic agents exert their effects through various mechanisms such as gene inhibition,addition,replacement,and editing.The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare.One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273(Moderna)and BNT162b2(Pfizer/BioNTech)that have been successfully employed in response to the coronavirus disease 2019(COVID-19)pandemic.This review aims to highlight the advantages of RNA-based nanomedicines,provides an overview of significant developments in delivery systems,elucidates the molecular mechanisms of action underlying RNA-based nanomedicines,and discusses their clinical applications.Additionally,the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.