Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma

Small extracellular vesicles(exosomes)are important components of the tumor microenvironment.They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication.Exosomes transmit biological molecules obtained from parent cells,such as proteins,lipids,and nucleic acids,and are involved in cancer development.MicroRNAs(miRNAs),the most abundant contents in exosomes,are selectively packaged into exosomes to carry out their biological functions.Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis,progression,and drug resistance of hepatocellular carcinoma(HCC).In addition,exosomes have great industrial prospects in the diagnosis,treatment,and prognosis of patients with HCC.This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC.Finally,we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.

Local inhomogeneity of mechanical properties in stir zone of friction stir welded AA1050 aluminum alloy

The local inhomogeneity of the stir zone in friction stir welded face-centered cubic metal was investigated,which has multiple activated slip systems during plastic deformation,by selecting commercial AA1050 aluminum alloy as an ideal experimental material.The local inhomogeneity was evaluated by uniaxial tensile tests using small samples with a 1 mm gauge length.The corresponding microstructural parameters such as grain size,misorientation angle distribution,and micro-texture,were quantified by the backscattered electron diffraction technique.A comprehensive model was used to reveal the microstructure−mechanical property relationship.The experimental results showed that the uniaxial tensile property changes significantly across the weld.The maximum ultimate tensile strength(UTS)occurred in the center of the stir zone,which was 99.0 MPa.The weakest regions were located at the two sides of the stir zone.The largest difference value in UTS reached 14.9 MPa,accounting for 15%of the maximum UTS.The analysis on the structure−mechanical property relationship suggests that the micro-texture change with the location formed during the rotational material flow is the main reason for the local inhomogeneity.

Liver injury changes the biological characters of serum small extracellular vesicles and reprograms hepatic macrophages in mice

BACKGROUND Serum small extracellular vesicles(sEVs)and their small RNA(sRNA)cargoes could be promising biomarkers for the diagnosis of liver injury.However,the dynamic changes in serum sEVs and their sRNA components during liver injury have not been well characterized.Given that hepatic macrophages can quickly clear intravenously injected sEVs,the effect of liver injury-related serum sEVs on hepatic macrophages deserves to be explored.AIM To identify the characteristics of serum sEVs and the sRNAs during liver injury and explore their effects on hepatic macrophages.METHODS To identify serum sEV biomarkers for liver injury,we established a CCL4-induced mouse liver injury model in C57BL/6 mice to simulate acute liver injury(ALI),chronic liver injury(CLI)and recovery.Serum sEVs were obtained and characterized by transmission electron microscopy and nanoparticle tracking analysis.Serum sEV sRNAs were profiled by sRNA sequencing.Differentially expressed microRNAs(miRNAs)were compared to mouse liver-enriched miRNAs and previously reported circulating miRNAs related to human liver diseases.The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs and conditioned cultures of ALI serum sEVs with primary hepatic macrophages.RESULTS We found that both ALI and CLI changed the concentration and morphology of serum sEVs.The proportion of serum sEV miRNAs increased upon liver injury,with the liver as the primary contributor.The altered serum sEV miRNAs based on mouse studies were consistent with human liver disease-related circulating miRNAs.We established serum sEV miRNA signatures for ALI and CLI and a panel of miRNAs(miR-122-5p,miR-192-5p,and miR-22-3p)as a common marker for liver injury.The differential serum sEV miRNAs in ALI contributed mainly to liver steatosis and inflammation,while those in CLI contributed primarily to hepatocellular carcinoma and hyperplasia.ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages but increased CD206 expression in resident macrophages in vitro.CONCLUSION Serum sEVs acquired different concentrations,sizes,morphologies and sRNA contents upon liver injury and could change the phenotype of liver macrophages.Serum sEVs therefore have good diagnostic and therapeutic potential for liver injury.

Clarifying effect of welding conditions on microstructure and mechanical properties of friction stir spot-welded DH590 automotive high-strength steel plates

Friction stir spot welding was successfully applied to the 1.2-mm-thick DH590 dual-phase steel plates by using a polycrystalline cubic boron nitride rotating tool.During welding,the rotation speed ranged from 600 to 1000 r/min and the penetration depth ranged from 0.1 to 0.3 mm.In the spot joints,the size of the stir zone increased with the increase in rotation speed as well as the penetration depth of the tool.Comparing with the banded ferrite and martensite structure of the base metal,a mixed microstructure of ferrite and tempered martensite,refined bainite structure and coarse martensite structure were found in the heat-affected zone,thermomechanically affected zone and stir zone of the joints,respectively.Two kinds of interfacial shapes were formed between the upper and lower steel plates,and the formation of the bonded interface was dominated mainly by the penetration depth of the rotating tool rather than the rotation speed.It was revealed that the joints with straight interfaces showed higher shear tensile loads comparing with those with hook-like interfaces.Shear tensile tests showed that the maximum shear tensile load reached about 15.56 kN when the rotation speed and penetration depth were set as 800 r/min and 0.3 mm,respectively.The specimen was fractured through plug failure mode with a total elongation of about 5.6 mm.