Non-invasively differentiate non-alcoholic steatohepatitis by visualizing hepatic integrin αvβ3 expression with a targeted molecular imaging modality

BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrin αvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrin αvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrin αvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrin αvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrin αvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrin αvβ3 expression with MRI.

High mobility ultrathin ZnO p–n homojunction modulated by Zn_(0.85)Mg_(0.15)O quantum barriers

The adding of ZnMgO asymmetric double barriers(ADB)in p-ZnO2(Li,N)/n-ZnO homojunction affects the p-n junction device performance prominently.Two different homojunctions are fabricated on Si(100)substrates by pulsed laser deposition;one is the traditional p-ZnO2(Li,N)/n-ZnO homojunction with different thicknesses named as S_(1)(250 nm)and S2(500 nm),the other is the one with ADB embedded in the n-layer named as Q(265 nm).From the photoluminescence spectra,defect luminescence present in the S-series devices is effectively limited in the Q device.The current-voltage curve of the Q device shows Zener-diode rectification property because the two-dimensional electron gas tunnels through the narrow ZnMgO barrier under a reverse bias,thus decreasing the working p-n homojunction thickness from 500 nm to 265 nm.The ADB-modified homojunction shows higher carrier mobility in the Q device.The electroluminescence of the ZnO homojunction is improved in Q compared to S_(2),because the holes in p-type ZnO(Li,N)can cross the wide ZnMgO barrier under a forward bias voltage into the ZnO quantum well.Therefore,electron-hole recombination occurs in the narrow bandgap of n-type ZnO,creating an ultraviolet light-emitting diode using the ZnO homojunction.

Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells

γδT cells have been reported to exert immunosuppressive functions in multiple solid malignant diseases,but their immunosuppressive functional subpopulation in breast cancer(BC)is still undetermined.Here,we collected 40 paired BC and normal tissue samples from Chinese patients for analysis.First,we showed thatγδT1 cells comprise the majority of CD3+T cells in BC;next,we found that CD73+γδT1 cells were the predominant regulatory T-cell(Treg)population in BC,and that their prevalence in peripheral blood was also related to tumour burden.In addition,CD73+γδT1 cells exert an immunosuppressive effect via adenosine generation.We also found that BC could modulate CD73 expression onγδT cells in a non-contact manner.The microarray analysis and functional experiments indicated that breast tumour cell-derived exosomes(TDEs)could transmit lncRNA SNHG16,which upregulates CD73 expression,to Vδ1 T cells.Regarding the mechanism,SNHG16 served as a ceRNA by sponging miR-16–5p,which led to the derepression of its target gene SMAD5 and resulted in potentiation of the TGF-β1/SMAD5 pathway to upregulate CD73 expression in Vδ1 T cells.Our results showed that the BC-derived exosomal SNHG16/miR-16–5p/SMAD5-regulatory axis potentiates TGF-β1/SMAD5 pathway activation,thus inducing CD73 expression in Vδ1 T cells.Our results first identify the significance of CD73+Vδ1 Tregs in BC,and therapy targeting this subpopulation or blocking TDEs might have potential for BC treatment in the future.

Flexible electrical stimulation device with Chitosan-Vaseline®dressing accelerates wound healing in diabetes

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization.Disruptions of the endogenous electric fields(EFs)may lead to disordered cell migration.Electrical stimulation(ES)that mimics endogenous EFs is a promising method in treating diabetic wounds;however,a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required.Chitosan-Vaseline■gauze(CVG)has been identified to facilitate wound healing;it also promotes moisture retention and immune regulation and has antibacterial activity.For this study,we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds.We found that high voltage monophasic pulsed current(HVMPC)promoted healing of diabetic wounds in vivo.In studies carried out in vitro,we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells(HUVECs)by activating PI3K/Akt and ERK1/2 signaling.Overall,we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis,enhancing epithelialization,and inhibiting scar formation.These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.