Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4+ T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy.
Titanium disulfide (TiS2) is investigated as an advanced conversion electrode for sodium (Na)‐ion batteries (NIB) in an ether‐based electrolyte (NaPF6/glyme (DME)). The as‐prepared TiS2 demonstrates a high reversible capacity of 1040 mA h g−1 at 0.2 A g−1 with the capacity contribution of 521 mA h g−1 in the voltage region below 1.0 V (vs Na/Na+), remarkable initial coulombic efficiency of 95.9% and superior rate capability of 621 mA h g−1 at 40 A g−1. The high conductivity of the Ti‐based compounds and nanosized particles generated by chemical conversion reactions could minimize the entropic barrier for the reversible conversion, resulting in high reversibility and ultrafast charge/discharge ability of the electrode. Moreover, with its strong ability to adsorb soluble polysulfide intermediates, the as‐prepared TiS2 electrode exhibits superior cycling stability over 9000 cycles, serving as a stable and ultra‐high capacity conversion electrode for NIBs.
Accumulating evidence indicates the occurrence and development of diabetic complications relates to not only constant high plasma glucose, but also glucose fluctuations which affect various kinds of molecular mechanisms in various target cells and tissues. In this review, we detail reactive oxygen species and their potentially damaging effects upon glucose fluctuations and resultant downstream regulation of protein signaling pathways, including protein kinase C, protein kinase B, nuclear factor-κB, and the mitogen-activated protein kinase signaling pathway. A deeper understanding of glucose-fluctuation-related molecular mechanisms in the development of diabetic complications may enable more potential target therapies in future.
development of anode materials because graphite as the most successful commercial anode for LIBs has a poor Nastorage performance due to the mismatch between the large ion radius of Na + and the relatively narrow interlayer distance (<0.37 nm). [7][8][9] Hard carbon, composed of rich graphitic microcrystallites, pores, and defects, has been considered as a potential anode candidate for commercialization because it can deliver a considerable capacity of ≈300 mAh g -1 with a low discharge voltage and has abundant resources and low cost. [10][11][12][13] However, hard carbon still suffers from challenges of poor rate capability and cyclability. Great efforts have been made to overcome these obstacles. One strategy is to optimize precursors and reaction conditions. Based on this, a series of hard carbons derived from cellulose, [14] sugar, [15] polymers, [16,17] and biomass-based materials [18][19][20] have been reported with long cycle performance but limited storage capacity (<350 mAh g −1 ). Another strategy is to tune intrinsic carbon structures by heteroatom doping, such as boron, nitrogen, phosphorus, and sulfur. [21] Among them, N doping and S doping are the most widely investigated, since they can promote the adsorption of Na + and introduce abundant active sites for sodium storage, leading to an enhanced capacity. But they also bring an issue of relative high discharge voltage related to the high average oxidation voltage of N-related functional groups or reactive S dopant. [22][23][24][25][26] Compared with N and S doping, P doping can exhibit a stronger adsorption ability and display a great superiority of low discharge voltage (<1.0 V). [27][28][29][30][31][32][33] Unfortunately, the doping content of P is relatively low (<10 wt%), resulting in insufficient active sites for limited Na-storage capacity of hard carbon (<400 mAh g −1 ). The low doping levels can be attributed to following aspects: 1) The high binding energy and long bond length of PC (compared with CC) lead to severe lattice distortion when P is incorporated into the carbon skeleton, thus requiring a higher reaction energy. 2) The doped phosphorus is mostly in the form of PO x rather than elemental phosphorus. The electron-donating properties of P make it oxygen-sensitive and easy to oxidize to PO x groups, which can only be suspended outside the carbon plane, further hindering more P doping. 3) Most of the synthesis systems reported currently are unable to construct an oxygen-free Phosphorus doped carbons are of particular interest as anode materials because of their large interlayer spacing and strong adsorption of Na + ions. However, it remains challenging to achieve high phosphorus doping due to the limited choices of phosphorus sources and the difficulty in constructing oxygen-free synthesis system. Herein, a new synthesis strategy is proposed to prepare ultrahigh phosphorus-doped carbon (UPC) anodes for high performance sodium ion batteries (SIBs). By using two commonly available, miscible, evaporable liquids in PCl 3 and C 6 H 12 , ...
BackgroundMesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified.MethodsWe inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs.ResultsHere we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway.ConclusionsOur findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy.
An additive-free and free-standing GPE with excellent Li+ mobility and polysulfide localization is prepared via a facile route.
Nanoengineering of metal electrodes are of great importance for improving the energy density of alkali-ion batteries, which have been deemed one of most effective tools for addressing the poor cycle stability of metallic anodes. However, the practical application of nanostructured electrodes in batteries is still challenged by a lack of efficient, low-cost, and scalable preparation methods. Herein, we propose a facile chemical dealloying approach to the tunable preparation of multidimensional Sb nanostructures. Depending on dealloying reaction kinetics regulated by different solvents, zero-dimensional Sb nanoparticles (Sb-NP), two-dimensional Sb nanosheets (Sb-NS), and three-dimensional nanoporous Sb are controllably prepared via etching Li−Sb alloys in H 2 O, H 2 O-EtOH, and EtOH, respectively. Morphological evolution mechanisms of the various Sb nanostructures are analyzed by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction measurements. When applied as anodes for sodium ion batteries (SIBs), the as-prepared Sb-NS electrodes without any chemical modifications exhibit high reversible capacity of 620 mAh g −1 and retain 90.2% of capacity after 100 cycles at 100 mA g −1 . The excellent Na + storage performance observed is attributable to the twodimensional nanostructure, which ensures high degrees of Na + accessibility, robust structural integrity, and rapid electrode transport. This facile and tunable approach can broaden ways of developing high performance metal electrodes with designed nanostructures for electrochemical energy storage and conversion applications.
A covalent sulfur−carbon (covalent-SC) composite is successfully prepared in situ by a wet-chemical solvothermal method based on the strong interaction between carbon disulfide (CS 2 ) and red phosphorus. It is demonstrated that sulfur uniformly distributes among the boundary and interior of the carbon skeleton with the formation of S−C bonds. Moreover, the interior sulfur can be electrochemically activated under 0.5 V and then functions as a capacity sponsor, because Na + can freely transfer into the carbon interlayer (with a stable enlarged distance of ∼0.4 nm after the first cycle) via adsorption-like behavior to be combined with the interior sulfur in the following cycles. Thus, the activated covalent-SC composite delivers ultrahigh reversible capacities of 888.9 and 811.4 mAh g −1 after 600 and 950 deep cycles at 0.8C and 1.6C, respectively. Furthermore, it exhibits outstanding rate performance with the capacity of 700 mAh g −1 at a high rate of 8.1C.
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