Exosomes in stroke pathogenesis and therapy

Stroke is one of the leading causes of death and disability worldwide. Stroke recovery is orchestrated by a set of highly interactive processes that involve the neurovascular unit and neural stem cells. Emerging data suggest that exosomes play an important role in intercellular communication by transferring exosomal protein and RNA cargo between source and target cells in the brain. Here, we review these advances and their impact on promoting coupled brain remodeling processes after stroke. The use of exosomes for therapeutic applications in stroke is also highlighted

Automated Exploration of Reaction Network and Mechanism via Meta-dynamics Nanoreactor

We developed an automated approach to construct the complex reaction network and explore the reaction mechanism for several reactant molecules. The nanoreactor type molecular dynamics was employed to generate possible chemical reactions, in which the meta-dynamics was taken to overcome reaction barriers and the semi-empirical GFN2-xTB method was used to reduce computational cost. The identification of reaction events from trajectories was conducted by using the hidden Markov model based on the evolution of the molecular connectivity. This provided the starting points for the further transition state searches at the more accurate electronic structure levels to obtain the reaction mechanism. Then the whole reaction network with multiply pathways was obtained. The feasibility and efficiency of this automated construction of the reaction network was examined by two examples. The first reaction under study was the HCHO + NH3 biomolecular reaction. The second example focused on the reaction network for a multi-species system composed of dozens of HCN and H2O compounds. The result indicated that the proposed approach was a valuable and effective tool for the automated exploration of reaction networks

Epigenetics in Stroke Recovery

While the death rate from stroke has continually decreased due to interventions in the hyperacute stage of the disease, long-term disability and institutionalization have become common sequelae in the aftermath of stroke. Therefore, identification of new molecular pathways that could be targeted to improve neurological recovery among survivors of stroke is crucial. Epigenetic mechanisms such as post-translational modifications of histone proteins and microRNAs have recently emerged as key regulators of the enhanced plasticity observed during repair processes after stroke. In this review, we highlight the recent advancements in the evolving field of epigenetics in stroke recovery

Smart Emulsions Stabilized by a Multi-headgroup Surfactant Tolerant to High Concentrations of Acids and Salts

Retaining emulsions stable at high acidity and salinity is still a great challenge. Here, we report a novel multi-headgroup surfactant (C3H7−NH+(C10COOH)2, di-UAPAc) which can be reversibly transformed among cationic, anionic and zwitterionic forms upon pH variation. Stable oil-in-dispersion (OID) emulsions in strong acidity (pH=2) can be co-stabilized by low concentrations of di-UAPAc and silica nanoparticles. High salinity at pH=2 improves the adsorption of di-UAPAc on silica particles through hydrogen bonding, resulting in the transformation of OID emulsions into Pickering emulsions. Moreover, emulsification/demulsification and interconversion between OID and Pickering emulsions together with control of the viscosity and droplet size can be triggered by pH. The present work provides a new protocol for designing surfactants for various applications in harsh aqueous media, such as strong acidity and high salinity, involved in oil recovery and sewerage treatments

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

Coal Rock Breaking Simulation and Cutting Performance Analysis of Disc Cutters

The coal rock breaking ability of disc cutters directly affects the construction efficiency and safety of rescue tunnels in collapsed coal rock formations. This paper establishes the plastic constitutive relationship under the Drucker-Prager (D-P) plasticity criterion, builds up a finite-element analysis (FEA) model for the coal rock breaking with a single cutter on Abaqus FEA, and explores the influence laws of different penetrations and cutting velocities on the rock breaking performance of the cutter. The results show that: as the penetration increased from 3.0 mm to 7.0 mm, the mean vertical force of the cutter grew from 16.97 kN to 23.36 kN, and the mean rolling force rose from 1.79 kN to 3.95 kN. The increase of the cutter\u27s vertical force improves the cutting efficiency, but intensifies the vertical impact, which undermines construction safety. As the cutting velocity increased from 0.6 rad/s to 1.5 rad/s, the mean vertical force grew from 15.64 kN to 22.94 kN, and the mean rolling force rose from 1.46 kN to 4.23 kN. With the increase of cutting velocity, the cutting force grew at an increasing speed. The increase of cutting velocity can improve cutting efficiency, but an excessively fast cutting velocity will weaken the stability of the cutting operation, and add to the wear of the tool. The research method provides theoretical supports to the cutterhead design of tunnel boring machine (TBM) and tunnelling control in broken coal rock formation

CO₂/N₂ triggered switchable Pickering emulsions stabilized by alumina nanoparticles in combination with a conventional anionic surfactant

Stable n-decane-in-water Pickering emulsions were prepared using positively charged alumina nanoparticles in combination with a trace amount of the anionic surfactant sodium dodecyl sulfate (SDS) as stabilizer. Particles were hydrophobized in situ by adsorption of surfactant enhancing their surface activity. Emulsions can be readily demulsified by addition of an equal amount of a switchable surfactant, N'-dodecyl-N,N-dimethylacetamidine (DDAA), which can be transformed between a surface-active amidinium/cationic form and a surface-inactive amidine/neutral form by bubbling CO₂ or N₂, respectively. Following addition of cationic DDAA which prefers to form ion pairs with SDS, desorption of SDS from particles surfaces occurs and alumina particles are rendered hydrophilic resulting in demulsification of the emulsion. However, by bubbling N₂ into the demulsified mixture, DDAA molecules are converted to the amidine/neutral form leading to collapse of the ion pairs and re-establishment of the in situ hydrophobization of particles. Stable Pickering emulsions can be prepared again following homogenization. This simple demulsification/re-stabilization cycle can be repeated several times. Experimental evidence including measurement of the adsorption isotherm, zeta potentials, extent of particle adsorption at droplets interfaces in emulsions and microscopy is given to support the postulated mechanisms