Treatment of diabetic peripheral neuropathy with engineered mesenchymal stromal cell-derived exosomes enriched with microRNA-146a provide amplified therapeutic efficacy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes mellitus with no effective treatment. We recently demonstrated that mesenchymal stromal cell (MSC)-derived exosomes (exo-naïve) alleviate neurovascular dysfunction and improve functional recovery. MicroRNA (miRNA), one of the exosomal cargos, downregulates inflammation-related genes, resulting in suppression of pro-inflammatory gene activation. In the present study, we developed engineered MSC-exosomes loaded with miR-146a (exo-146a) and compared the therapeutic effects of exo-146a with exo-naïve in diabetic (db/db) mice with DPN. Exo-146a possesses a high loading capacity, robust ability to accumulate in peripheral nerve tissues upon systemic administration, and evokes substantially enhanced therapeutic efficacy on neurological recovery compared with exo-naïve. Treatment of DPN in diabetic mice with exo-146a for two weeks significantly increased and decreased nerve conduction velocity, and thermal and mechanical stimuli threshold, respectively, whereas it took four weeks of exo-naive treatment to achieve these improvements. Compared with exo-naïve, exo-146a significantly suppressed the peripheral blood inflammatory monocytes and the activation of endothelial cells via inhibiting Toll-like receptor (TLR)-4/NF-κB signaling pathway. These data provide a proof-of-concept about both the feasibility and efficacy of the exosome-based gene therapy for DPN. The translation of this approach to the clinic has the potential to improve the prospects for people who suffer from DPN

Preparation and Enhancement of Thermal Conductivity of Heat Transfer Oil-Based MoS 2

The lipophilic MoS2 nanoparticles are synthesized by surface modification with stearic acid (SA). The heat transfer oil-based nanofluids, with the mass fraction of lipophilic nanoparticles varying from 0.25% up to 1.0%, are prepared and their thermal conductivity is determined at temperatures ranging from 40 to 200°C using an apparatus based on the laser flash method. It has been found that the nanofluids have higher thermal conductivity and the thermal conductivity enhancement increased not only with increasing mass fraction of nanoparticles, but also with increasing temperature in the range 40–180°C The results show a 38.7% enhancement of the thermal conductivity of MoS2 nanofluid with only 1.0% mass fraction at 180°C

Influence of Sex on Cognition and Peripheral Neurovascular Function in Diabetic Mice

Cognition impairment and peripheral neuropathy (DPN) are two major complications of diabetes. The aim of the present study is to investigate the effect of sex differences on cognition and DPN in diabetic mice. Male and female BKS.Cg

Comparative proteomic analysis of exosomes derived from endothelial cells and Schwann cells

Exosomes derived from endothelial cells and Schwann cells have been employed as novel treatments of neurological diseases, including peripheral neuropathy. Exosomal cargo plays a critical role in mediating recipient cell function. In this study, we thus performed a comprehensive proteomic analysis of exosomes derived from healthy mouse dermal microvascular endothelial cells (EC-Exo) and healthy mouse Schwann cells (SC-Exo). We detected 1,817and 1,579 proteins in EC-Exo and SC-Exo, respectively. Among them, 1506 proteins were present in both EC-Exo and SC-Exo, while 311 and 73 proteins were detected only in EC-Exo and SC-Exo, respectively. Bioinformatic analysis revealed that EC-Exo enriched proteins were involved in neurovascular function, while SC-Exo enriched proteins were related to lipid metabolism. Western blot analysis of 14 enriched proteins revealed that EC-Exo contained proteins involved in mediating endothelial function such as delta-like 4 (DLL4) and endothelial NOS (NOS3), whereas SC-Exo had proteins involved in mediating glial function such as apolipoprotein A-I (APOA1) and phospholipid transfer protein (PLTP). Collectively, the present study identifies differences in the cargo protein profiles of EC-Exo and SC-Exo, thus providing new molecular insights into their biological functions for the treatment of peripheral neuropathy

Genomic Inference of the Metabolism and Evolution of the Archaeal Phylum Aigarchaeota

Microbes of the phylum Aigarchaeota are widely distributed in geothermal environments, but their physiological and ecological roles are poorly understood. Here we analyze six Aigarchaeota metagenomic bins from two circumneutral hot springs in Tengchong, China, to reveal that they are either strict or facultative anaerobes, and most are chemolithotrophs that can perform sulfide oxidation. Applying comparative genomics to the Thaumarchaeota and Aigarchaeota, we find that they both originated from thermal habitats, sharing 1154 genes with their common ancestor. Horizontal gene transfer played a crucial role in shaping genetic diversity of Aigarchaeota and led to functional partitioning and ecological divergence among sympatric microbes, as several key functional innovations were endowed by Bacteria, including dissimilatory sulfite reduction and possibly carbon monoxide oxidation. Our study expands our knowledge of the possible ecological roles of the Aigarchaeota and clarifies their evolutionary relationship to their sister lineage Thaumarchaeota

The Dust Attenuation Scaling Relation of Star-Forming Galaxies in the EAGLE Simulations

Dust attenuation in star-forming galaxies (SFGs), as parameterized by the infrared excess (IRX $\equiv L_{\rm IR}/L_{\rm UV}$), is found to be tightly correlated with star formation rate (SFR), metallicity and galaxy size, following a universal IRX relation up to $z=3$. This scaling relation can provide a fundamental constraint for theoretical models to reconcile galaxy star formation, chemical enrichment, and structural evolution across cosmic time. We attempt to reproduce the universal IRX relation over $0.1\leq z\leq 2.5$ using the EAGLE hydrodynamical simulations and examine sensitive parameters in determining galaxy dust attenuation. Our findings show that while the predicted universal IRX relation from EAGLE approximately aligns with observations at $z\leq 0.5$, noticeable disparities arise at different stellar masses and higher redshifts. Specifically, we investigate how modifying various galaxy parameters can affect the predicted universal IRX relation in comparison to the observed data. We demonstrate that the simulated gas-phase metallicity is the critical quantity for the shape of the predicted universal IRX relation. We find that the influence of the infrared luminosity and infrared excess is less important while galaxy size has virtually no significant effect. Overall, the EAGLE simulations are not able to replicate some of the observed characteristics between IRX and galaxy parameters of SFGs, emphasizing the need for further investigation and testing for our current state-of-the-art theoretical models.Comment: 19 pages, 15 figures, accepted for publication in MNRA

A Simple Scoring Model for Prediction of Rupture Risk of Anterior Communicating Artery Aneurysms

Background: The rupture risk of anterior communicating artery aneurysms (ACoAAs) has been known to be higher than that of aneurysms at other locations. Thus, the aim of this study is to investigate the clinical and morphological characteristics associated with risk factors for the rupture of ACoAAs.Methods: In total, 361 consecutive patients with 361 ACoAAs between August 2011 and December 2017 were retrospectively reviewed. Patients and ACoAAs were divided into ruptured and unruptured groups. In addition to clinical characteristics, ACoAA characteristics were evaluated by CT angiography (CTA). A multiple logistic regression analysis was used to identify the independent risk factors associated with ACoAA rupture. The assignment score of these variables depends on the β coefficient. A receiver operating characteristic (ROC) curve analysis was used to calculate the optimal thresholds.Results: The multiple logistic regression model revealed that A1 dominance [odds ratio (OR) 3.034], an irregular shape (OR 3.358), and an aspect ratio ≥1.19 (AR; OR 3.163) increased the risk of rupture, while cerebral atherosclerosis (OR 0.080), and mean diameters ≥2.48 mm (OR 0.474) were negatively correlated with ACoAA rupture. Incorporating these five factors, the ROC analysis revealed that the threshold value of the multifactors was one, the sensitivity was 88.3%, and the specificity was 66.0%.Conclusions: The scoring model is a simple method that is based on A1 dominance, irregular shape, aspect ratio, cerebral atherosclerosis, and mean diameters from CTA and is of great value in the prediction of the rupture risk of ACoAAs