The
formation of a fluid-filled cystic cavity after spinal cord injury
(SCI) is a major obstacle for neural regeneration. In this study,
the post-SCI cavity was bridged by a functional self-assembling peptide
(F-SAP) nanofiber hydrogel coupled with growth factor “cocktail”.
A sustained release of growth factors was achieved by carefully tailoring
the physical hindrances and charge-induced interactions between the
growth factors and the peptide nanofibers. Such an engineering microenvironment
elicited axon regeneration, as determined by tracing of the descending
pathway in the dorsal columns and immunochemical detection of regenerating
axons beyond the lesion. Furthermore, the dynamic spatiotemporal activation
line of endogenous NSCs (eNSCs) after severe SCI was thoroughly investigated.
The results indicated that the growth factor-coupled F-SAP greatly
facilitated eNSC proliferation, neuronal differentiation, maturation,
myelination, and more importantly, the formation of interconnection
with severed descending corticospinal tracts. The robust endogenous
neurogenesis essentially led to the recovery of locomotion and electrophysiological
properties. In conclusion, the growth factor-coupled F-SAP nanofiber
hydrogel elucidated the therapeutic effect of eliciting endogenous
neurogenesis by locally reassembling an extracellular matrix.
Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future.
We herein report the preparation of solid and salt‐stabilized silylzinc pivalates from the corresponding silyllithium reagents via transmetalation with Zn(OPiv)2. These resulting organosilylzinc pivalates show enhanced air and moisture stability and unique reactivity in the silylative difunctionalization of alkenes. Thus, a practical chelation‐assisted nickel‐catalyzed regioselective alkyl and benzylsilylation of alkenes has been developed, which provides an easy method to access alkyl silanes with broad substrate scope and wide functional group compatibility. Kinetic experiments highlight that the OPiv‐coordination is crucial to improve the reactivity of silylzinc pivalates. Furthermore, late‐stage functionalizations of druglike molecules and versatile modifications of the products illustrate the synthetical utility of this protocol.
The manipulation of light in metal–organic frameworks (MOFs) to investigate the volatile organic compound vapor–MOF interactions by using optical fiber devices is demonstrated.
We propose an ultra-broadband mode converter based on the structure of a length-apodized long-period grating, where π-phase shifts are introduced at strategic locations of the grating profile. Using a 3-section length-apodized grating structure, we design and fabricate an LP-LP and an LP-LP mode converter with a sidewall grating and a surface grating formed along a polymer channel waveguide, respectively. The fabricated LP-LP and LP-LP mode converters provide a conversion efficiency higher than 99% over a bandwidth of ~120 nm and ~150 nm, respectively, or a conversion efficiency higher than 90% over a bandwidth of ~180 nm and ~300 nm, respectively. The transmission characteristics of these devices are weakly sensitive to polarization and temperature variations. These mode converters can find applications in ultra-broadband mode-division-multiplexing transmission systems based on few-mode fibers and the design principle can be applied to general grating-based mode-coupling devices for a wide range of applications.
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