Exosomes are lipid-bilayer enclosed nano-sized vesicles that transfer functional cellular proteins, mRNA and miRNAs. Mesenchymal stem cells (MSCs) derived exosomes have been demonstrated to prevent ...memory deficits in the animal model of Alzheimer's disease (AD). However, the intravenously injected exosomes could be abundantly tracked in other organs except for the targeted regions in the brain. Here, we proposed the use of central nervous system-specific rabies viral glycoprotein (RVG) peptide to target intravenously-infused exosomes derived from MSCs (MSC-Exo) to the brain of transgenic APP/PS1 mice. MSC-Exo were conjugated with RVG through a DOPE-NHS linker.
RVG-tagged MSC-Exo exhibited improved targeting to the cortex and hippocampus after being administered intravenously. Compared with the group administered MSC-Exo, in the group administered RVG-conjugated MSC-Exo (MSC-RVG-Exo) plaque deposition and Aβ levels were sharply decreased and activation of astrocytes was obviously reduced. The brain targeted exosomes derived from MSCs was better than unmodified exosomes to improve cognitive function in APP/PS1 mice according to Morris water maze test. Additionally, although MSC-Exo injected intravenously reduced the expression of pro-inflammatory mediators TNF-α, IL-β, and IL-6, but the changes of anti-inflammatory factors IL-10 and IL-13 were not obvious. However, administration of MSC-RVG-Exo significantly reduced the levels of TNF-α, IL-β, and IL-6 while significantly raised the levels of IL-10, IL-4 and IL-13.
Taken together, our results demonstrated a novel method for increasing delivery of exosomes for treatment of AD. By targeting exosomes to the cortex and hippocampus of AD mouse, there was a significant improvement in learning and memory capabilities with reduced plaque deposition and Aβ levels, and normalized levels of inflammatory cytokines.
Endoplasmic reticulum (ER) stress occurs in plants during certain developmental stages or under adverse environmental conditions, as a result of the accumulation of unfolded or misfolded proteins in ...the ER. To minimize the accumulation of misfolded proteins in the ER, a protein quality control (PQC) system monitors protein folding and eliminates misfolded proteins through either ER-associated protein degradation (ERAD) or autophagy. ER stress elicits the unfolded protein response (UPR), which enhances the operation in plant cells of the ER protein folding machinery and the PQC system. The UPR also reduces protein folding demands in the ER by degrading mRNAs encoding secretory proteins. In plants subjected to severe or chronic stress, UPR promotes programmed cell death (PCD). Progress in the field in recent years has provided insights into the regulatory networks and signaling mechanisms of the ER stress responses in plants. In addition, novel physiological functions of the ER stress responses in plants for coordinating plant growth and development with changing environment have been recently revealed.
We develop Random Batch Methods for interacting particle systems with large number of particles. These methods use small but random batches for particle interactions, thus the computational cost is ...reduced from O(N2) per time step to O(N), for a system with N particles with binary interactions. On one hand, these methods are efficient Asymptotic-Preserving schemes for the underlying particle systems, allowing N-independent time steps and also capture, in the N→∞ limit, the solution of the mean field limit which are nonlinear Fokker-Planck equations; on the other hand, the stochastic processes generated by the algorithms can also be regarded as new models for the underlying problems. For one of the methods, we give a particle number independent error estimate under some special interactions. Then, we apply these methods to some representative problems in mathematics, physics, social and data sciences, including the Dyson Brownian motion from random matrix theory, Thomson's problem, distribution of wealth, opinion dynamics and clustering. Numerical results show that the methods can capture both the transient solutions and the global equilibrium in these problems.
The hierarchical aggregation of molecular nanostructures from multiple components is a grand synthetic challenge, which requires highly selective linkage control. We demonstrate how two orthogonal ...linkage groups, that is, organotin and lanthanide cations, can be used to drive the aggregation of a giant molecular metal oxide superstructure. The title compound {(Sn(CH3)2)2O4{CeW5O18 TeW4O16CeSn(CH3)24TeW8O314}2}46− (1 a) features dimensions of ca. 2.2×2.3×3.4 nm3 and a molecular weight of ca. 25 kDa. Structural analysis shows the hierarchical aggregation from several independent subunits. Initial biomedical tests show that 1 features an inhibitory effect on the proliferation of HeLa cells based on an apoptosis pathway. In vivo experiments in mice reveal the antiproliferative activity of 1 and open new paths for further development of this new compound class.
Hierarchical assembly of a giant heterometallic polyoxotungstate supercluster with a molecular weight of ca. 25 kDa is reported. Geometrically unrestricted cerium(III) and geometrically restricted dimethyl tin cation linkers are used to gain access to a giant molecular species featuring three different polyoxometalate building units. The compound demonstrates in vitro and in vivo antiproliferative activity against HeLa cervical cancer cell lines.
This paper estimates the charging demand of an early electric vehicle (EV) market in Beijing and proposes an assignment model to distribute charging infrastructure. It finds that each type of ...charging infrastructure has its limitation, and integration is needed to offer a reliable charging service. It also reveals that the service radius of fast charging stations directly influences the final distribution pattern and an infrastructure deployment strategy with short service radius for fast charging stations has relatively fewer disturbances on the power grid. Additionally, although the adoption of electric vehicles will cause an additional electrical load on the Beijing's power grid, this additional load can be accommodated by the current grid's capacity via the charging time management and the battery swap strategy.
► Charging posts, fast charging stations, and battery swap stations should be integrated. ► Charging posts at home parking places will take a major role in a charging network. ► A service radius of 2km is proposed for fast charging stations deployment. ► The additional charging load from EVs can be accommodated by charging time management.
This paper studies fixed-time leader-following lag consensus problem of second-order multiagent systems with input delay. Using fixed-time distributed observer, we obtain the leader's states for each ...followers. An extension of the Artstein's reducing transformation is employed to transform the delayed error system into a second-order system without time delay and a novel nonsingular terminal sliding mode protocol is proposed to achieve fixed-time consensus. The presented sliding mode controller can avoid singularity, eliminate chattering, and achieve exact convergence. It is mathematically proved that the presented protocol can achieve exact fixed-time leader-following lag consensus. Moreover, the upper bound of convergence time only depends on observer parameters, controller parameters, network parameters, and delay time, which makes it possible to determine the convergence time offline regardless of initial condition. The presented protocol is applied to coordinated lag tracking control of single-link robotic manipulators and the results validate the effectiveness of the proposed fixed-time protocol.
A photochemical C–N coupling of aryl halides with nitroarenes is demonstrated for the first time. Catalyzed by a NiII complex in the absence of any external photosensitizer, readily available ...nitroarenes undergo coupling with a variety of aryl halides, providing a step‐economic extension to the widely used Buchwald–Hartwig C–N coupling reaction. The method tolerates coupling partners with steric‐congestion and functional groups sensitive to bases and nucleophiles. Mechanistic studies suggest that the reaction proceeds via the addition of an aryl radical, generated from a NiI/NiIII cycle, to a nitrosoarene intermediate.
C–N coupling of aryl halides with nitroarenes is achieved by nickel catalysis under light irradiation and mild basic conditions, with no need for any external photosensitizers, offering a nitro version for the Buchwald–Hartwig C–N coupling reaction.
The fabrication of nanowire (NW)‐based flexible electronics including wearable energy storage devices, flexible displays, electrical sensors, and health monitors has received great attention both in ...fundamental research and market requirements in our daily lives. Other than a disordered state after synthesis, NWs with designed and hierarchical structures would not only optimize the intrinsic performance, but also create new physical and chemical properties, and integration of individual NWs into well‐defined structures over large areas is one of the most promising strategies to optimize the performance of NW‐based flexible electronics. Here, the recent developments and achievements made in the field of flexible electronics composed of integrated NW structures are presented. The different assembly strategies for the construction of 1D, 2D, and 3D NW assemblies, especially the NW coassembly process for 2D NW assemblies, are comprehensively discussed. The improvements of different NW assemblies on flexible electronics structure and performance are described in detail to elucidate the advantages of well‐defined NW assemblies. Finally, a short summary and outlook for future challenges and perspectives in this field are presented.
Directional assembly of nanowires into 1D, 2D, and 3D assemblies toward flexible electronic devices benefits many potential applications. 1D assemblies with fiber structures can be used as flexible electronics for textiles, 2D assemblies can be used as transparent electrodes or units for logic circuits, and 3D assemblies can be used in the fabrication of pressure sensors or high‐performance energy‐storage devices.
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