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Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE‐secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV‐secreting cell and understanding the biological cargo of EVs to develop EV‐based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); early‐stage hESC‐RPE (20–21 days in culture), mid‐stage hESC‐RPE (30–31 days in culture) and late‐stage hESC‐RPE (60–61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV‐based intraocular therapeutics utilizing RPE‐secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases. [ABSTRACT FROM AUTHOR]

ObjectiveRecent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.MethodsWe measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.ResultsCLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).ConclusionsCLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.

This paper presents an analysis of 3D amplitude and functional parameters for worn surfaces of composites with polyamide 6 as matrix and different glass bead concentrations (0%, 2.5%, 5%, 10%, 20%, 30% and 50%wt). The worn surfaces after dry sliding of a steel pin on a disk, for 10 km, at constant velocity (0.5 m/s, 1 m/s and 1.5 m/s) and under an average pressure of 1 MPa. There were done two tests under the same conditions. On each worn track, there were investigated three surfaces of 500 μm x 500 μm with a contact profilometer. The number of points on the scan line was 200 points and the step between lines was 5μm. The following amplitude parameters were measured and calculated for assessed surfaces: the arithmetic mean deviation, Sa, the root mean square deviation, Sq, the maximum height of surface prominence, Sp, the maximum surface depth, Sv, the maximum height, St, the skewness factor, Ssk and the kurtosis, Sku. The discussed functional parameters are the reduced peak height, Spk, the height of the core of the surface, Sk and the depth of the valley zone, Svk. The comparison of their values makes posible to evaluate if the worn surface could function in a new running or the replacement of the component is recommended. Considering that machine components have intermittent operation, these worn surfaces becoming initial surfaces for the following cycle of contact operation. Based on the average values of amplitude and functional parameters, it was found that a relatively good surface quality is preserved for concentrations of 10...30%wt glass beads, for v=0.5...1 m/s (Sa and Sq having similar trend); for lower concentrations and for 50% glass beads, the parameter values increase but without identifying a distinct relationship with the working regime, especially for 2.5 and 5% glass beads. [ABSTRACT FROM AUTHOR]

This paper presents an analysis based on experimental data for pointing out the behavior of rapeseed oil when it is additivated with a modifier of friction and wear, the nano hexagonal Boron nitride. All tests are done on a four-ball machine, in mild regime. Test parameters were sliding velocity (0.38 m/s, 0.53 m/s, 0.69 m/s, corresponding to the spindle rotational speed of the four-ball machine of 1000 rpm, 1400 rpm, 1800 rpm (±10 rpm),), force (100 N – 300 N), test duration 1 h. There were calculated the average friction coefficient during the test and the average wear scar diameter (WSD) for each test. The same test parameters were done twice and the values in this paper are the average of these two tests. Wear was discussed for the same velocity range, in terms of WSD, but for comparing tests with different sliding velocity (implicitly, different sliding distances), there was used the wear rate of the wear scar diameter. The results on wear parameters, using additivated rapeseed oil, do not show spectacular results for the parameters tested in this study, but underline the “insensitivity” of the lubricants to the variation of the test regime (especially with respect to sliding speed), which is desirable for certain applications. [ABSTRACT FROM AUTHOR]