Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic ...effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 μL exosomes via the tail vein (200 μg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1β release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.
A general and efficient organocatalytic asymmetric polymerization approach for the synthesis of chiral covalent organic frameworks (CCOFs) has been developed. With a chiral 2‐methylpyrrolidine ...catalyst, a series of tris(N‐salicylideneamine)‐derived β‐ketoenamine‐CCOFs are directly constructed from prochiral aldehyde‐ and primary amine‐monomers. The adopted aminocatalytic asymmetric Schiff‐base condensation herein is performed under ambient conditions with clear green synthetic advantages over the conventional acid‐catalysed solvothermal methods. The obtained β‐ketoenamine‐CCOFs can be further metalated by a solid‐state coordination approach, and the resulting CuII@CCOFs can highly promote an asymmetric A3‐coupling reaction. Specifically, a CuII@CCOF@chitosan aerogel was fabricated as a highly efficient fixed‐bed model reactor for scaled‐up catalysis. The concept of aminocatalytic asymmetric polymerization might open a new way for constructing the CCOFs via asymmetric organocatalysis.
A new and general organocatalytic asymmetric polymerization approach for the chiral covalent organic framework (CCOF) synthesis under ambient conditions is presented. The metalated CCOF can be further shaped into a fixed‐bed reactor by incorporation with ecofriendly and low‐cost chitosan to realize the scaled‐up catalytic asymmetric A3‐coupling reaction in a green and facile way.
MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b ...(miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg miR-29b antagomir was injected via the tail vein. MiR-29b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of miR-29b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of miR-29b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the miR-29 antagomir for 48 hours. The results revealed that miR-29b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of miR-29b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (approval No. 201709276S) on September 27, 2017.
The development of new catalytic systems for the conversion of biomass‐derived molecules into liquid fuels has attracted much attention. We propose a non‐noble bimetallic catalyst based on ...nickel–tungsten carbide for the conversion of the platform molecules 5‐(hydroxymethyl)furfural into the liquid‐fuel molecule 2,5‐dimethylfuran (DMF). Different catalysts, metal ratios and reaction conditions have been tested and give rise to a 96% yield of DMF. The catalysts have been characterized and are discussed. The reaction mechanism is also explored through capture of reaction intermediates. The analysis of the reaction mixture over different catalysts is presented and helps to understand the role of nickel and tungsten carbide during the reaction.
W ai Ni: A nickel–tungsten carbide on active carbon (Ni‐W2C/AC) catalyst converts the biomass platform molecule 5‐(hydroxymethyl)furfural (HMF) into the liquid fuel molecule 2,5‐dimethylfuran (DMF) via the intermediate 5‐methylfurfural. Synergy between the Ni and W2C components combines their hydrogenating and deoxygenating abilities and allows to achieve high yields of DMF.
The catalytic transfer hydrogenation of furfural to the fuel additives 2‐methylfuran (2‐MF) and 2‐methyltetrahydrofuran (2‐MTHF) was investigated over various bimetallic catalysts in the presence of ...the hydrogen donor 2‐propanol. Of all the as‐prepared catalysts, bimetallic Cu‐Pd catalysts showed the highest catalytic activities towards the formation of 2‐MF and 2‐MTHF with a total yield of up to 83.9 % yield at 220 °C in 4 h. By modifying the Pd ratios in the Cu‐Pd catalyst, 2‐MF or 2‐MTHF could be obtained selectively as the prevailing product. The other reaction conditions also had a great influence on the product distribution. Mechanistic studies by reaction monitoring and intermediate conversion revealed that the reaction proceeded mainly through the hydrogenation of furfural to furfuryl alcohol, which was followed by deoxygenation to 2‐MF in parallel to deoxygenation/ring hydrogenation to 2‐MTHF. Finally, the catalyst showed a high reactivity and stability in five catalyst recycling runs, which represents a significant step forward toward the catalytic transfer hydrogenation of furfural.
Identifying the intermediates: The catalytic transfer hydrogenation of biomass‐derived furfural to fuel additives 2‐methylfuran and 2‐methyltetrahydrofuran is performed over a bimetallic Cu‐Pd catalyst in the presence of 2‐propanol. The reaction proceeds via the intermediate furfuryl alcohol, which is then deoxygenated/hydrogenated to the desired products.
Peroxymonosulfate (PMS) is extensively used as an oxidant to develop the sulfate radical-based advanced oxidation processes in the decontamination of organic pollutants and various PMS activation ...methods have been explored. Visible-light-assisted PMS activation to construct a Fenton-like process has shown a great potential for pollution control. In our work, BiVO4 nanosheets were prepared using a hydrothermal process and used to activate PMS under visible light. A rapid degradation of ciprofloxacin (CIP) was achieved by dosing PMS (0.96 g/L), BiVO4 (0.32 g/L) under visible light with a reaction rate constant of 77.72-fold higher than that in the BiVO4/visible light process. The electron spin resonance and free radical quenching experiments indicate that reactive species of •O2−, h+, •OH and SO4•− all worked, where h+, •OH and SO4•− were found as the dominant contributors to the CIP degradation. The spectroscopic analyses further demonstrate that the photoinduced electrons were directly involved in the PMS activation process. The generated •O2− was partially utilized to activate PMS and more •OH was produced because of the chain reactions between SO4•− and H2O/OH−. In this process, PMS acted as an electron acceptor to transfer the photo-induced charges from the conduction band of BiVO4 and PMS was successfully activated to yield the high-powered oxidative species. From the degradation intermediates of CIP detected by a liquid-chromatography-mass spectrometer, the possible degradation pathways were proposed. The substantially decreased toxicity of CIP after the reaction was also observed. This work might provide new insights into the visible-light-assisted PMS activation mechanisms and is useful to construct environmentally-friendly catalytic processes for the efficient degradation of organic pollutants.
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•PMS was effectively activated by BiVO4 nanosheets for water purification under visible light.•Separation of electron/hole pairs and generation of oxidative species were enhanced.•Visible-light-assisted PMS activation Fenton-like mechanism was elucidated.•High mineralization and low biotoxicity validated the application potential of the system.
The continued threat of emerging, highly lethal infectious pathogens such as Middle East respiratory syndrome coronavirus (MERS‐CoV) calls for the development of novel vaccine technology that offers ...safe and effective prophylactic measures. Here, a novel nanoparticle vaccine is developed to deliver subunit viral antigens and STING agonists in a virus‐like fashion. STING agonists are first encapsulated into capsid‐like hollow polymeric nanoparticles, which show multiple favorable attributes, including a pH‐responsive release profile, prominent local immune activation, and reduced systemic reactogenicity. Upon subsequent antigen conjugation, the nanoparticles carry morphological semblance to native virions and facilitate codelivery of antigens and STING agonists to draining lymph nodes and immune cells for immune potentiation. Nanoparticle vaccine effectiveness is supported by the elicitation of potent neutralization antibody and antigen‐specific T cell responses in mice immunized with a MERS‐CoV nanoparticle vaccine candidate. Using a MERS‐CoV‐permissive transgenic mouse model, it is shown that mice immunized with this nanoparticle‐based MERS‐CoV vaccine are protected against a lethal challenge of MERS‐CoV without triggering undesirable eosinophilic immunopathology. Together, the biocompatible hollow nanoparticle described herein provides an excellent strategy for delivering both subunit vaccine candidates and novel adjuvants, enabling accelerated development of effective and safe vaccines against emerging viral pathogens.
To improve vaccination efforts against Middle East respiratory syndrome coronavirus (MERS‐CoV), a virus‐mimicking vaccine is herein prepared with a capsid‐like hollow polymeric nanoparticle loaded with STING agonists and coated in MERS‐CoV antigens. The viromimetic nanoparticle facilitates safe and effective vaccination against the lethal virus and offers a versatile platform for combatting emerging infectious threats.
Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large‐area, homogeneous, and self‐standing porphyrin‐covalent ...organic framework (COF)‐based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph‐membrane exhibits highly effective antibacterial and anti‐inflammatory effects via synergistic light‐induced singlet oxygen (1O2) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph‐membrane‐based biocompatible “band‐aid” type dressing is fabricated, and its excellent anti‐infection and tissue remodeling activities are fully evidenced by in vivo chronic wound‐healing experiments. This study may inspire and promote the fabrication of many more new types of COF‐based multifunctional biomaterials for various skin injuries in clinical medicine.
An ibuprofen‐loaded porphyrin‐COF‐based biocompatible and non‐toxic “band‐aid” type dressing is fabricated, and its excellent synergistic photodynamic antibacterial and controllable drug anti‐inflammatory effects are fully evidenced by in vitro and in vivo bacteria‐infected chronic wound‐healing experiments.
A catalytic transfer hydrogenation process was developed for the production of γ-valerolactone (GVL) from ethyl levulinate (EL) and a H-donor at room temperature. Ethyl levulinate was almost ...quantitatively converted to γ-valerolactone. Further, a two step process for producing GVL from biomass derived platform molecules was also reported.
During embryonic and adult neurogenesis, neuronal stem cells follow a highly conserved path of differentiation to give rise to functional neurons at various developmental stages. Epigenetic ...regulation--including DNA modifications, histone modifications, and noncoding regulatory RNAs, such as microRNA (miRNA) and long noncoding RNA (lncRNA)--plays a pivotal role in embryonic and adult neurogenesis. Here we review the latest in our understanding of the epigenetic regulation in neurogenesis, with a particular focus on newly identified cytosine modifications and their dynamics, along with our perspective for future studies.
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