In adult zebrafish, relatively quiescent progenitor cells show lesion-induced generation of motor neurons. Developmental motor neuron generation from the spinal motor neuron progenitor domain (pMN) sharply declines at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated from the same domain. We demonstrate here that within 48 h of a spinal lesion or specific genetic ablation of motor neurons at 72 hpf, the pMN domain reverts to motor neuron generation at the expense of oligodendrogenesis. By contrast, generation of dorsal Pax2-positive interneurons was not altered. Larval motor neuron regeneration can be boosted by dopaminergic drugs, similar to adult regeneration. We use larval lesions to show that pharmacological suppression of the cellular response of the innate immune system inhibits motor neuron regeneration. Hence, we have established a rapid larval regeneration paradigm. Either mechanical lesions or motor neuron ablation is sufficient to reveal a high degree of developmental flexibility of pMN progenitor cells. In addition, we show an important influence of the immune system on motor neuron regeneration from these progenitor cells.

In mammals, increased Notch signaling is held partly responsible for a lack of neurogenesis after a spinal injury. However, this is difficult to test in an essentially nonregenerating system. We show that in adult zebrafish, which exhibit lesion-induced neurogenesis, e.g., of motor neurons, the Notch pathway is also reactivated. Although apparently compatible with neuronal regeneration in zebrafish, forced activity of the pathway significantly decreased progenitor proliferation and motor neuron generation. Conversely, pharmacological inhibition of the pathway increased proliferation and motor neuron numbers. This demonstrates that Notch is a negative signal for regenerative neurogenesis, and, importantly, that spinal motor neuron regeneration can be augmented in an adult vertebrate by inhibiting Notch signaling.

SummaryIn contrast to mammals, zebrafish regenerate spinal motor neurons. During regeneration, developmental signals are re-deployed. Here, we show that, during development, diffuse serotonin promotes spinal motor neuron generation from pMN progenitor cells, leaving interneuron numbers unchanged. Pharmacological manipulations and receptor knockdown indicate that serotonin acts at least in part via 5-HT1A receptors. In adults, serotonin is supplied to the spinal cord mainly (90%) by descending axons from the brain. After a spinal lesion, serotonergic axons degenerate caudal to the lesion but sprout rostral to it. Toxin-mediated ablation of serotonergic axons also rostral to the lesion impaired regeneration of motor neurons only there. Conversely, intraperitoneal serotonin injections doubled numbers of new motor neurons and proliferating pMN-like progenitors caudal to the lesion. Regeneration of spinal-intrinsic serotonergic interneurons was unaltered by these manipulations. Hence, serotonin selectively promotes the development and adult regeneration of motor neurons in zebrafish.

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Rationale: Peripheral nerves are unique in their remarkable elasticity. Schwann cells (SCs), important components of the peripheral nervous system (PNS), are constantly subjected to physiological and mechanical stresses from dynamic stretching and compression forces during movement. So far, it is not clear if SCs sense and respond to mechanical signals. It is also unknown whether mechanical stimuli can interfere with the intercellular communications between neurons and SCs, and what role extracellular vesicles (EVs) play in this process. The present study aimed to examine the effect of mechanical stimuli on the EV-mediated intercellular communication between neurons and SCs, explore their effect on axonal regeneration, and investigate the underlying mechanism. Methods: Purified SCs were stimulated using a magnetic force-based mechanical stimulation (MS) system and EVs were purified from mechanically stimulated SCs (MS-SCs-EVs) and non-stimulated SCs (SCs-EVs). The effect of MS-SCs-EVs on axonal elongation was examined in vitro and in vivo . High throughput miRNA sequencing was performed to compare the differential miRNA profiles between MS-SCs-EVs and SCs-EVs. The functional role of differentially expressed miRNAs on neurite extension in MS-SCs-EVs was examined. Also, the putative target genes of differentially expressed miRNAs in MS-SCs-EVs were predicted by bioinformatics tools, and the regulatory effect of those miRNAs on putative target genes was validated both in vitro and in vivo . Results: The MS-SCs-EVs showed an average size of 137.52±1.77 nm, and could be internalized by dorsal root ganglion (DRG) neurons. Compared to SCs-EVs, MS-SCs-EVs showed a stronger ability to enhance neurite outgrowth in vitro and nerve regeneration in vivo . High throughput miRNA sequencing identified a number of differentially expressed miRNAs in MS-SCs-EVs. Further analysis of those EV-miRNAs demonstrated that miR-23b-3p played a predominant role in MS-SCs-EVs since its deprivation abolished their enhanced axonal elongation. Furthermore, we identified neuropilin 1 (Nrp1) in neurons as the target gene of miR-23b-3p in MS-SCs-EVs. This observation was supported by the evidence that miR-23b-3p could decrease Nrp1-3'-UTR-WT luciferase activity in vitro and down-regulate Nrp1 expression in neurons. Conclusion: Our findings suggested that mechanical stimuli are capable of modulating the intercellular communication between neurons and SCs by altering miRNA composition in MS-SCs-EVs. Transfer of miR-23b-3p by MS-SCs-EVs from mechanically stimulated SCs to neurons decreased neuronal Nrp1 expression, which was responsible, at least in part, for the beneficial effect of MS-SCs-EVs on axonal regeneration. Our results highlighted the potential therapeutic value of MS-SCs-EVs and miR-23b-3p-en...

Diagnosing the evolution trends of vegetation and its drivers is necessary for ecological conservation and restoration. However, it remains unclear what the underlying distribution pattern of these trends and its correlation with some drivers at large spatial-temporal scales. Here we use the normalized difference vegetation index (NDVI) to quantify the activity of vegetation by Theil–Sen median trend analysis and the Mann–Kendall test, Pearson correlation analysis and Boosted regression trees (BRT) model. Results show that about 34% of the global continent area has experienced greening in the grid annual NDVI from 1982 to 2015. The major greening areas were observed in the Sahel, European, India and south China. Only 10% of the global continent land areas were browning, and these were observed in Canada, South America, central Africa and Central Asia. BRT model shows that rainfall is the most important factor affecting vegetation evolution (63.1%), followed by temperature (15%), land cover change (8.6%), population (6.5%), elevation (6.4%) and nightlight (0.4%). It’s about 21% of the world’s continent were affected by rainfall, mainly in arid regions such as central Asia and Australia. The main temperature-affected areas accounted for 36%, located near the equator or in high latitudes.

GBR is currently accepted as one of the most effective approaches for bone defect regeneration relating to dental implant. Icariin is the main active ingredient in the extraction of total flavonoids from the Chinese traditional herb Epimediumbrevicornum Maxim. In this study, ICA was successfully incorporated into the nanofibers barrier membrane (ICA-SF/PLCL) as osteoinduction factor by coaxial electrospinning and was released in a sustained and controlled manner. The entire release period included two stages: an initial burst stage (47.54 ± 0.06% on 5 d) and a decreasing and constant stage (82.09 ± 1.86% on 30 d). The membrane has good biocompatibility with BMMSCs anchored and significantly promoted its osteogenic activity. Moreover, in vivo experiment, bone defect covered by ICA-SF/PLCL membrane in rat cranium were statistically repaired compare to other groups. 12 weeks after implantation, in the test group, the new bone formation spread to cover most of the defect region with volume and density of approximately 15.95 ± 3.58 mm3 and 14.02 ± 0.93%. These results demonstrated that ICA-SF/PLCL nanofibrous membrane could be a promising barrier applicated for GBR.

Silicate carbon sink (SCS) is the net carbon sink that affects the global carbon cycle over a period of millions of years or more (Tao et al., 2011). On the geological time scale, there is a negative feedback mechanism which includes rock weathering, increased CO 2 concentrations, and subsequent environmental changes (Maher & Chamberlain, 2014). Rising CO 2 concentrations leads to periods of global warming, which in turn promote rock weathering, absorbing more CO 2 (