Changes of peripapillary vascular density and its correlation with nerve fiber layer thickness in patients with unilateral retinal vein occlusion

Objective:To observe the changes of peripapillary vascular density(VD)and its correlation with retinal nerve fiber layer(RNFL)thickness in patients with unilateral retinal vein occlusion(RVO)by optical coherence tomography angiography(OCTA).Methods:Prospective case-control study.Thirty-two patients(32 eyes)with RVO diagnosed at the Eye Hospital of China Academy of Chinese Medical Sciences from September 2020 to June 2021 were selected.Another 32 outpatients(32 eyes)with normal ocular examination were selected as the normal control group.Optic disc blood flow imaging was performed in all subjects using the OCTA to measure peripapillary RNFL thickness,peripapillary vessel density,optic disc area,and disc rim area.The correlation between peripapillary vascular density and RNFL,optic disc area and disc rim area in eyes with unilateral RVO was analyzed.Results:Compared with the normal control group,the prevalence of hypertension was higher in the unilateral RVO group,and the difference was statistically significant(P<0.05).Compared with the normal control group,the overall,inferior and temporal RNFL thickness around the optic disc was thinner in patients with unilateral RVO,and the difference was statistically significant(P<005).Compared with the normal control group,the overall VD,internal ring,external ring and inferior VD around the optic disc were slightly decreased in patients with unilateral RVO,and the differences were statistically significant(P<0.05).The results of Pearson correlation analysis indicated that RNFL thickness was positively correlated with peripapillary global VD(r=0.648,P<0.001),RNFL thickness was positively correlated with intrapapillary ring VD(r=0.427,P=0.015),and RNFL thickness was positively correlated with peripapillary VD(r=0.666,P<0.001).Conclusion:The results showed that the RNFL thickness around the optic disc was thinner in patients with unilateral RVO,especially in the inferior and temporal area,and the full area VD around the optic disc was decreased,especially in the internal ring,external ring and inferior area.In patients with unilateral RVO,peripapillary RNFL was positively correlated with peripapillary global,internal ring and external ring VD.

Microneedle-array patch with pH-sensitive formulation for glucoseresponsive insulin delivery

Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes.Herein,a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles(NPs)(SNP(I))together with glucose oxidase(GOx)-and catalase(CAT)-loaded pH-insensitive NPs(iSNP(G+C))is constructed for transcutaneous glucose-responsive insulin delivery.SNP(I)are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer,and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C)under hyperglycemic conditions.CAT in iSNP(G+C)can further consume excess H_(2)O_(2) generated during GOx oxidation,and thus reduce the risk of inflammation toward the normal skin.The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.

An Intracellular pH-Actuated Polymer for Robust Cytosolic Protein Delivery

Robust cytosolic protein delivery requires both efficient protein binding with delivery vehicles and effective protein release after cell internalization.Although a variety of stimuli-responsive carriers have been designed,simultaneously integrating these two functions in one versatile carrier is challenging.Herein,we developed a polyamidoamine(PAMAM)-based polymer with an intracellular pHactuated hydrophobic-to-hydrophilic transition for this purpose.

Integrated analysis of plasma rotation effect on HL-3 hybrid scenario

The hybrid scenario,which has good confinement and moderate MHD instabilities,is a proposed operation scenario for international thermonuclear experimental reactor(ITER).In this work,the effect of plasma rotation on the HL-3 hybrid scenario is analyzed with the integrated modeling framework OMFIT.The results show that toroidal rotation has no obvious effect on confinement with a high line averaged density of n_(bar)~(7)×10^(19)m^(-3).In this case,the ion temperature only changes from 4.7 keV to 4.4 keV with the rotation decreasing from 10^(5) rad/s to 10^(3) rad/s,which means that the turbulent heat transport is not dominant.While in the scenarios characterized by lower densities,such as n_(bar)~4×10^(19)m^(-3),turbulent transport becomes dominant in determining heat transport.The ion temperature rises from 3.8 keV to 6.1 keV in the core as the rotation velocity increases from 10^(3) rad/s to 10^(5) rad/s.Despite the ion temperature rising,the rotation velocity does not obviously affect electron temperature or density.Additionally,it is noteworthy that the variation in rotation velocity does not significantly affect the global confinement of plasma in scenarios with low density or with high density.

A polyamidoamine(PAMAM)derivative dendrimer with high loading capacity of TLR7/8 agonist for improved cancer immunotherapy

Tumor associated macrophages(TAMs)tend to exhibit tumor-promoting M2 phenotype and contribute to the development of immunosuppressive microenvironment of solid tumors.Reprograming TAMs from M2 into tumoricidal M1 phenotype is robust for stimulating tumor immunosuppressive microenvironment(TIME).In this study,we developed a poly(amidoamine)(PAMAM)derivative dendrimer(denoted as fourth generation-N,N-diethylaminoethyl(G4-DEEA))for efficient loading of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)to remodel the TIME for potent cancer immunotherapy,G4-DEEA exhibited a high loading capacity of R848 up to 35.9 wt%by taking advantage of its dendritic structure.The resulting formulation(designated as G4-DEEA@R848)effectively polarized M2 macrophages into M1 phenotype in vitro,and improved the maturation and activation of antigen-presenting cells.In the 4T1 orthotopic breast cancer model,G4-DEEA@R848 showed a stronger tumor inhibitory effect than free drug.The mechanistic studies suggested that G4-DEEA@R848 could significantly stimulate the TIME by repolarizing TAMs into M1 phenotype,reducing the presence of immunosuppressive myeloid cells and increasing the infiltration of tumor cytotoxic T cells.This study provides a simple but effective dendrimer-based strategy to improve the formulation of R848 for improved cancer immunotherapy.