Rab11 promotes single Mauthner cell axon regeneration in vivo through axon guidance molecule Ntng2b.

Effective axon regeneration within the central nervous system (CNS) is pivotal for achieving functional recovery following spinal cord injury (SCI). Numerous extrinsic and intrinsic factors exert influences on the axon regeneration. While prior studies have demonstrated crucial involvement of specific members the Rab protein family in axon regeneration in the peripheral nervous system (PNS), the precise function of Rab11 in CNS axon regeneration in vivo remains elusive. Thus, our study aimed to elucidate the impact of Rab11 on the axon regeneration of Mauthner cells (M-cells) in zebrafish larvae. Our findings demonstrated that overexpression of Rab11bb via single-cell electroporation significantly promoted axon regeneration in individual M-cells. Conversely, knockdown of Rab11bb inhibited the axon regeneration of M-cells. RNA-seq analysis revealed an upregulation of ntng2b following Rab11bb overexpression. As we hypothesized, overexpression of Ntng2b markedly enhanced axon regeneration, while Ntng2b knockdown in the context of Rab11bb pro-regeneration substantially hindered axon regrowth. In conclusion, our study demonstrated that Rab11 promotes axon regeneration of single M-cell in the CNS through the Rab11/axon guidance/Ntng2b pathway.

MicroRNA-9 promotes axon regeneration of mauthner-cell in zebrafish via her6/ calcium activity pathway.

MicroRNA (miRNA), functioning as a post-transcriptional regulatory element, plays a significant role in numerous regulatory mechanisms and serves as a crucial intrinsic factor influencing axon regeneration. Prior investigations have elucidated the involvement of miRNA-9 in various processes, however, its specific contribution to axon regeneration in the central nervous system (CNS) remains uncertain. Hence, the zebrafish Mauthner axon regeneration model was employed to manipulate the expression of miRNA-9 in single cells, revealing that upregulation of miRNA-9 facilitated axon regeneration. Additionally, her6, a downstream target gene of miRNA-9, was identified as a novel gene associated with axon regeneration. Suppression of her6 resulted in enhanced Mauthner axon regeneration, as evidenced by the significantly improved regenerative capacity observed in her6 knockout zebrafish. In addition, modulation of her6 expression affects intracellular calcium levels in neurons and promoting her6 expression leads to a decrease in calcium levels in vivo using the new NEMOf calcium indicator. Moreover, the administration of the neural activity activator, pentylenetetrazol (PTZ) partially compensated for the inhibitory effect of her6 overexpression on the calcium level and promoted axon regeneration. Taken together, our study revealed a role for miRNA-9 in the process of axon regeneration in the CNS, which improved intracellular calcium activity and promoted axon regeneration by inhibiting the expression of downstream target gene her6. In our study, miRNA-9 emerged as a novel and intriguing target in the intricate regulation of axon regeneration and offered compelling evidence for the intricate relationship between calcium activity and the facilitation of axon regeneration.

Engineering Atomically Dispersed Cu-N1S2 Sites via Chemical Vapor Deposition to Boost Enzyme-Like Activity for Efficient Tumor Therapy.

Single-atom nanozymes (SAzymes), with well-defined and uniform atomic structures, are an emerging type of natural enzyme mimics. Currently, it is important but challenging to rationally design high-performance SAzymes and deeply reveal the interaction mechanism between SAzymes and substrate molecules. Herein, this work reports the controllable fabrication of a unique Cu-N1S2-centred SAzyme (Cu-N/S-C) via a chemical vapor deposition-based sulfur-engineering strategy. Benefiting from the optimized geometric and electronic structures of single-atom sites, Cu-N/S-C SAzyme shows boosted enzyme-like activity, especially in catalase-like activity, with a 13.8-fold increase in the affinity to hydrogen peroxide (H2O2) substrate and a 65.2-fold increase in the catalytic efficiency when compared to Cu-N-C SAzyme with Cu-N3 sites. Further theoretical studies reveal that the increased electron density around single-atom Cu is achieved through electron redistribution, and the efficient charge transfer between Cu-N/S-C and H2O2 is demonstrated to be more beneficial for the adsorption and activation of H2O2. The as-designed Cu-N/S-C SAzyme possesses an excellent antitumor effect through the synergy of catalytic therapy and oxygen-dependent phototherapy. This study provides a strategy for the rational design of SAzymes, and the proposed electron redistribution and charge transfer mechanism will help to understand the coordination environment effect of single-atom metal sites on H2O2-mediated enzyme-like catalytic processes.

A Bioinspired Five-Coordinated Single-Atom Iron Nanozyme for Tumor Catalytic Therapy.

Single-atom nanozymes (SAzymes) represent a new research frontier in the biomedical fields. The rational design and controllable synthesis of SAzymes with well-defined electronic and geometric structures are essential for maximizing their enzyme-like catalytic activity and therapeutic efficacy but remain challenging. Here, a melamine-mediated pyrolysis activation strategy is reported for the controllable fabrication of iron-based SAzyme containing five-coordinated structure (FeN5 ), identified by transmission electron microscopy imaging and X-ray absorption fine structure analyses. The FeN5 SAzyme exhibits superior peroxidase-like activity owing to the optimized coordination structure, and the corresponding catalytic efficiency of Fe-species in the FeN5 SAzyme is 7.64 and 3.45 × 105 times higher than those in traditional FeN4 SAzyme and Fe3 O4 nanozyme, respectively, demonstrated by steady-state kinetic assay. In addition, the catalytic mechanism is jointly disclosed by experimental results and density functional theory studies. The as-synthesized FeN5 SAzyme demonstrates significantly enhanced antitumor effect in vitro and in vivo due to the excellent peroxidase-like activity under tumor microenvironment.

A Photoresponsive Nanozyme for Synergistic Catalytic Therapy and Dual Phototherapy.

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (•OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.