Anatomy and Pathology/Oncology Retinal Thickness and Axial Length

PURPOSE. To examine the relationships between axial length and foveal and peripheral retinal thickness. METHODS. Using optical coherence tomography, foveal retinal thickness was measured in participants of the population-based Beijing Eye Study without optic nerve or macula diseases. Inner and outer nuclear layer thickness as surrogate for retinal thickness was assessed in the fundus periphery in human globes enucleated due to malignant uveal melanoma or painful glaucoma. RESULTS. The study included 1117 individuals with a mean age of 64.2 6 9.7 years (range: 50-93 years) and mean axial length of 23.4 6 1.04 mm (range: 20.29-28.68 mm). In multivariate analysis, thicker central foveal thickness was associated with male sex (P < 0.001; standardized regression coefficient beta: À0.13; nonstandardized regression coefficient B: À5.84; 95% confidence interval (CI): À8.56, À3.13); urban region of habitation (P ¼ 0.02; beta: 0.07; B: 3.56; 95% CI: 0.55, 6.57); thinner lens thickness (P ¼ 0.01; beta: À0.08; B: À5.11; 95% CI: À9.01, À1.21); thinner subfoveal choroidal thickness (P ¼ 0.04; beta: À0.07; B: À0.01; 95% CI: À0.03, À0.001); and longer axial length (P < 0.001; beta: 0.18; B: 3.79; 95% CI: 2.41, 5.17). In the same multivariate model, superior, inferior, and temporal foveal thickness was not significantly associated with axial length (P ¼ 0.26, P ¼ 0.19, P ¼ 0.08, respectively), while thicker nasal foveal thickness was associated with longer axial length (P ¼ 0.009; beta: 0.09; B: 1.50; 95% CI: 0.37, 2.62). In the histomorphometric part of the study including 32 eyes (sagittal diameter: 27.0 6 4.2 mm; range: 22-37 mm), mean thickness of the inner and outer nuclear layers at the equator and at the midpoint equator/posterior pole decreased with longer axial length (P ¼ 0.004; beta: À0.48; and P ¼ 0.02; beta: À0.44, respectively). CONCLUSIONS. Myopic axial globe elongation was associated with retinal thinning in the equatorial and pre-equatorial region, while foveal retinal thickness was mostly unaffected by axial length. It suggests that axial elongation takes place predominantly in the equatorial and pre-equatorial region of the eye

Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle

mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering etc. However, optimization of mRNA molecules and efficient in vivo delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for in vitro and in vivo expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by in vitro transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development

Upscaling Evapotranspiration from a Single-Site to Satellite Pixel Scale

It is of great significance for the validation of remotely sensed evapotranspiration (ET) products to solve the spatial-scale mismatch between site observations and remote sensing estimations. To overcome this challenge, this paper proposes a comprehensive framework for obtaining the ground truth ET at the satellite pixel scale (1 × 1 km resolution in MODIS satellite imagery). The main idea of this framework is to first quantitatively evaluate the spatial heterogeneity of the land surface, then combine the eddy covariance (EC)-observed ET (ET_EC) to be able to compare and optimize the upscaling methods (among five data-driven and three mechanism-driven methods) through direct validation and cross-validation, and finally use the optimal method to obtain the ground truth ET at the satellite pixel scale. The results showed that the ET_EC was superior over homogeneous underlying surfaces with a root mean square error (RMSE) of 0.34 mm/d. Over moderately and highly heterogeneous underlying surfaces, the Gaussian process regression (GPR) method performed better (the RMSEs were 0.51 mm/d and 0.60 mm/d, respectively). Finally, an integrated method (namely, using the ET_EC for homogeneous surfaces and the GPR method for moderately and highly heterogeneous underlying surfaces) was proposed to obtain the ground truth ET over fifteen typical underlying surfaces in the Heihe River Basin. Furthermore, the uncertainty of ground truth ET was quantitatively evaluated. The results showed that the ground truth ET at the satellite pixel scale is relatively reliable with an uncertainty of 0.02–0.41 mm/d. The upscaling framework proposed in this paper can be used to obtain the ground truth ET at the satellite pixel scale and its uncertainty, and it has great potential to be applied in more regions around the globe for remotely sensed ET products’ validation

Integrated Validation of Coarse Remotely Sensed Evapotranspiration Products over Heterogeneous Land Surfaces

Validation of remotely sensed evapotranspiration (RS_ET) products is important because their accuracy is critical for various scientific applications. In this study, an integrated validation framework was proposed for evaluating RS_ET products with coarse spatial resolution extending from homogenous to heterogeneous land surfaces. This framework was applied at the pixel and river basin scales, using direct and indirect validation methods with multisource validation datasets, which solved the spatial mismatch between ground measurements and remotely sensed products. The accuracy, rationality of spatiotemporal variations, and error sources of RS_ET products and uncertainties during the validation process were the focuses in the framework. The application of this framework is exemplified by validating five widely used RS_ET products (i.e., GLEAM, DTD, MOD16, ETMonitor, and GLASS) in the Heihe River Basin from 2012 to 2016. Combined with the results from direct (as the priority method) and indirect validation (as the auxiliary method), DTD showed the highest accuracy (1-MAPE) in the vegetation growing season (75%), followed by ETMonitor (71%), GLASS (68%), GLEAM (54%), and MOD16 (44%). Each product reasonably reflected the spatiotemporal variations in the validation dataset. ETMonitor exhibited the highest consistency with the ground truth ET at the basin scale (ETMap) (R = 0.69), followed by GLASS (0.65), DTD (0.63), MOD16 (0.62), and GLEAM (0.57). Error sources of these RS_ET products were mainly due to the limitations of the algorithms and the coarse spatial resolution of the input data, while the uncertainties in the validation process amounted to 15–28%. This work is proposed to effectively validate and improve the RS_ET products over heterogeneous land surfaces

Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia

International audienceSmall interfering RNA (siRNA) therapeutic is considered to be a promising modality for the treatment of hyperlipidemia. Establishment of a thermostable clinically applicable delivery system remains a most challenging issue for siRNA drug development. Here, a series of ionizable lipid-like materials were rationally designed; 4 panels of lipid formulations were fabricated and evaluated on the basis of four representative structures. The lead lipid (A1-D1-5) was stable at 40°C, and the optimized formulation (iLAND) showed dose and time dual-dependent gene silencing pattern with median effective dose of 0.18 mg/kg. In addition, potent and durable reduction of serum cholesterol and triglyceride were achieved by administering siRNAs targeting angiopoietin-like 3 or apolipoprotein C3 ( APOC3 ) in high-fat diet–fed mice, db/db mice, and human APOC3 transgenic mice, respectively, accompanied by displaying ideal safety profiles. Therefore, siRNA@iLAND prepared with thermostable A1-D1-5 demonstrates substantial value for siRNA delivery, hyperlipidemia therapy, and prevention of subsequent metabolic diseases

The Heihe Integrated Observatory Network: A Basin-Scale Land Surface Processes Observatory in China

Research on land surface processes at the catchment scale has drawn much attention over the past few decades, and a number of watershed observatories have been established worldwide. The Heihe River Basin (HRB), which contains the second largest inland river in China, is an ideal natural field experimental area for investigation of land surface processes involving diverse landscapes and the coexistence of cold and arid regions. The Heihe Integrated Observatory Network was established in 2007. For long-term observations, a hydrometeorological observatory, ecohydrological wireless sensor network, and satellite remote sensing are now in operation. In 2012, a multiscale observation experiment on evapotranspiration over heterogeneous land surfaces was conducted in the midstream region of the HRB, which included a flux observation matrix, wireless sensor network, airborne remote sensing, and synchronized ground measurements. Under an open data policy, the datasets have been publicly released following careful data processing and quality control. The outcomes highlight the integrated research on land surface processes in the HRB and include observed trends, scaling methods, high spatiotemporal resolution remote sensing products, and model–data integration in the HRB, all of which are helpful to other endorheic basins in the “Silk Road Economic Belt.” Henceforth, the goal of the Heihe Integrated Observatory Network is to develop an intelligent monitoring system that incorporates ground-based observatory networks, unmanned aerial vehicles, and multi-source satellites through the Internet of Things technology. Furthermore, biogeochemical processes observation will be improved, and the study of integrating ground observations, remote sensing, and large-scale models will be promoted further