Construction of Z-scheme g-C3N4 / MnO2 /GO ternary photocatalyst with enhanced photodegradation ability of tetracycline hydrochloride under visible light radiation.

A facile wet-chemical method was adopted to synthesize g-C3N4/MnO2/GO heterojunction photocatalyst for visible-light photodegradation of tetracycline hydrochloride (TC). The addition of MnO2 and GO increased the absorption of visible light and the specific surface area of the photocatalyst. The results of photoluminescence, electrochemical impedance spectroscopy, and photocurrent response indicated that CMG-10 had the lowest electron-hole recombination probability, which was beneficial for the photocatalytic reaction. The ternary photocatalyst exhibited enhanced photoelectric performance and superior photocatalytic activity with 91.4% removal of TC (10 mg/L) under a mere 60 min visible light illumination, which showed enhanced photocatalytic degradation when compared with binary (CM, 77.95%; CG, 78.83%) and single (C3N4, 55.5%; MnO2, 36.41%) photocatalysts. A pH of 6 was optimal for the CMG-10 photocatalytic degradation of TC, and the optimal photocatalyst dosage was 0.5 g/L. Common coexisting ions influenced the removal of TC by influencing the production of active species. The catalyst is stable and reusable with only a 10% reduction in removal efficiency after four cycles. According to the active species analysis, the Z-scheme mechanism was a charge transfer behavior in the composite photocatalyst, which could prevent the recombination of photogenerated carriers. This study presents a photocatalytic approach to the effective removal of TC from water bodies, which provides practical implications to advance the use of photocatalytic technology in the restoration of aqueous environmental pollution.

Curve Similarity Model for Real-Time Gait Phase Detection Based on Ground Contact Forces.

This paper proposed a new novel method to adaptively detect gait patterns in real time through the ground contact forces (GCFs) measured by load cell. The curve similarity model (CSM) is used to identify the division of off-ground and on-ground statuses, and differentiate gait patterns based on the detection rules. Traditionally, published threshold-based methods detect gait patterns by means of setting a fixed threshold to divide the GCFs into on-ground and off-ground statuses. However, the threshold-based methods in the literature are neither an adaptive nor a real-time approach. In this paper, the curve is composed of a series of continuous or discrete ordered GCF data points, and the CSM is built offline to obtain a training template. Then, the testing curve is compared with the training template to figure out the degree of similarity. If the computed degree of similarity is less than a given threshold, they are considered to be similar, which would lead to the division of off-ground and on-ground statuses. Finally, gait patterns could be differentiated according to the status division based on the detection rules. In order to test the detection error rate of the proposed method, a method in the literature is introduced as the reference method to obtain comparative results. The experimental results indicated that the proposed method could be used for real-time gait pattern detection, detect the gait patterns adaptively, and obtain a low error rate compared with the reference method.

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption.

BACKGROUND: At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. METHODS: We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14. RESULTS: Among mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1ß. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-ß, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9. CONCLUSION: CORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.

Adjustable Method for Real-Time Gait Pattern Detection Based on Ground Reaction Forces Using Force Sensitive Resistors and Statistical Analysis of Constant False Alarm Rate.

A new approach is proposed to detect the real-time gait patterns adaptively through measuring the ground contact forces (GCFs) by force sensitive resistors (FSRs). Published threshold-based methods detect the gait patterns by means of setting a fixed threshold to divide the GCFs into on-ground and off-ground statuses. However, the threshold-based methods in the literature are neither an adaptive nor a real-time approach. To overcome these drawbacks, this study utilized the constant false alarm rate (CFAR) to analyze the characteristics of GCF signals. Specifically, a sliding window detector is built to record the lasting time of the curvature of the GCF signals and one complete gait cycle could be divided into three areas, such as continuous ascending area, continuous descending area and unstable area. Then, the GCF values in the unstable area are used to compute a threshold through the CFAR. Finally, the new gait pattern detection rules are proposed which include the results of the sliding window detector and the division results through the computed threshold. To verify this idea, a data acquisition board is designed to collect the GCF data from able-bodied subjects. Meanwhile, in order to test the reliability of the proposed method, five threshold-based methods in the literature are introduced as reference methods and the reliability is validated by comparing the detection results of the proposed method with those of the reference methods. Experimental results indicated that the proposed method could be used for real-time gait pattern detection, detect the gait patterns adaptively and obtain high reliabilities compared with the reference methods.

Self-Tuning Threshold Method for Real-Time Gait Phase Detection Based on Ground Contact Forces Using FSRs.

This paper presents a novel methodology for detecting the gait phase of human walking on level ground. The previous threshold method (TM) sets a threshold to divide the ground contact forces (GCFs) into on-ground and off-ground states. However, the previous methods for gait phase detection demonstrate no adaptability to different people and different walking speeds. Therefore, this paper presents a self-tuning triple threshold algorithm (STTTA) that calculates adjustable thresholds to adapt to human walking. Two force sensitive resistors (FSRs) were placed on the ball and heel to measure GCFs. Three thresholds (i.e., high-threshold, middle-threshold andlow-threshold) were used to search out the maximum and minimum GCFs for the self-adjustments of thresholds. The high-threshold was the main threshold used to divide the GCFs into on-ground and off-ground statuses. Then, the gait phases were obtained through the gait phase detection algorithm (GPDA), which provides the rules that determine calculations for STTTA. Finally, the STTTA reliability is determined by comparing the results between STTTA and Mariani method referenced as the timing analysis module (TAM) and Lopez-Meyer methods. Experimental results show that the proposed method can be used to detect gait phases in real time and obtain high reliability when compared with the previous methods in the literature. In addition, the proposed method exhibits strong adaptability to different wearers walking at different walking speeds.

Transplantation of Autologous Bone Marrow Mononuclear Cells Regulates Inflammation in a Rabbit Model of Carotid Artery Atherosclerosis.

OBJECTIVE: It is well known that inflammation plays key roles in the development of atherosclerosis and that the transplantation of bone marrow mononuclear cells (BMMNCs) can suppress inflammation in rodent models of ischemic diseases. Here, we explored whether transplantation of autologous BMMNCs could prevent the progression of atherosclerosis by the alleviation of inflammatory responses in a rabbit model of carotid artery atherosclerosis. METHODS AND RESULTS: The atherosclerotic rabbit model was established by air desiccation followed by a high-cholesterol diet for 8 weeks. Then, 1 × 107 BMMNCs labeled with BrdU or an equal volume of vehicle were injected into the rabbits via the ear vein. Using an ultrasonographic imaging method, we found that autologous BMMNC treatment significantly decreased the area of atherosclerotic plaques compared to the vehicle-treated group (p < 0.05). The results were further confirmed by hematoxylin-eosin staining. RT-PCR results demonstrated that BMMNC treatment significantly reduced the expression of interleukin (IL)-6 and CD147 but increased the expression of IL-10 and transforming growth factor-ß compared with vehicle treatment (p < 0.05), which was consistent with Western blot results. CONCLUSIONS: Transplantation of autologous BMMNCs delays the development of atherosclerosis, most probably via the attenuation of inflammatory responses, which could be a new approach for treating carotid atherosclerosis.

CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs for protection after ischemic stroke in mice.

Cell-based therapy is considered to be a promising therapeutic strategy for stroke treatment. Although unfractionated bone marrow mononuclear cells (BMMNCs) have been tried in both preclinical and clinical trials, the effective subpopulations need to be identified. In this study, we used fluorescence-activated cell sorting to harvest the CXCR4(+)CD45(+) and CXCR4(+)CD45(-) BMMNC subpopulations from transgenic mice that express enhanced green fluorescent protein. We then allogeneically grafted unfractionated BMMNCs or a subpopulation into mice subjected to transient middle cerebral artery occlusion (tMCAO) and compared the effects on stroke outcomes. We found that CXCR4(+)CD45(-) BMMNCs, but not CXCR4(+)CD45(+) BMMNCs, more effectively reduced infarction volume and neurologic deficits than did unfractionated BMMNCs. Brain tissue from the ischemic hemisphere of mice treated with CXCR4(+)CD45(-) BMMNCs had higher levels of vascular endothelial growth factor and lower levels of TNF-α than did tissue from mice treated with unfractionated BMMNCs. In contrast, CXCR4(+)CD45(+) BMMNCs showed an increase in TNF-α. Additionally, CXCR4(+)CD45(+) and CXCR4(+)CD45(-) populations exhibited more robust migration into the lesion areas and were better able to express cell-specific markers of different linages than were the unfractionated BMMNCs. Endothelial and astrocyte cell markers did not colocalize with eGFP(+) cells in the brains of tMCAO mice that received CXCR4(+)CD45(+) BMMNCs. In vitro, the CXCR4(+)CD45(-) BMMNCs expressed significantly more Oct-4 and Nanog mRNA than did the unfractionated BMMNCs. However, we did not detect gene expression of these two pluripotent markers in CXCR4(+)CD45(+) BMMNCs. Taken together, our study shows for the first time that the CXCR4(+)CD45(-) BMMNC subpopulation is superior to unfractionated BMMNCs in ameliorating cerebral damage in a mouse model of tMCAO and could represent a new therapeutic approach for stroke treatment.

Cerebral ischemia increases bone marrow CD4+CD25+FoxP3+ regulatory T cells in mice via signals from sympathetic nervous system.

Recent evidence has shown that an increase in CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells may contribute to stroke-induced immunosuppression. However, the molecular mechanisms that underlie this increase in Treg cells remain unclear. Here, we used a transient middle cerebral artery occlusion model in mice and specific pathway inhibitors to demonstrate that stroke activates the sympathetic nervous system, which was abolished by 6-OHDA. The consequent activation of ß2-adrenergic receptor (AR) signaling increased prostaglandin E2 (PGE2) level in bone marrow. ß2-AR antagonist prevented the upregulation of PGE2. PGE2, which acts on prostaglandin E receptor subtype 4 (EP4), upregulated the expression of receptor activator for NF-κB ligand (RANKL) in CD4(+) T cells and mediated the increase in Treg cells in bone marrow. Treatment of MCAO mice with RANKL antagonist OPG inhibited the increase in percent of bone marrow Treg cells. PGE2 also elevated the expression of indoleamine 2,3 dioxygenase in CD11C(+) dendritic cells and promoted the development of functional Treg cells. The effect was neutralized by treatment with indomethacin. Concurrently, stroke reduced production of stromal cell-derived factor-1 (SDF-1) via ß3-AR signals in bone marrow but increased the expression of C-X-C chemokine receptor (CXCR) 4 in Treg and other bone marrow cells. Treatment of MCAO mice with ß3-AR antagonist SR-59230A reduced the percent of Treg cells in peripheral blood after stroke. The disruption of the CXCR4-SDF-1 axis may facilitate mobilization of Treg cells and other CXCR4(+) cells into peripheral blood. This mechanism could account for the increase in Treg cells, hematopoietic stem cells, and progenitor cells in peripheral blood after stroke. We conclude that cerebral ischemia can increase bone marrow CD4(+)CD25(+)FoxP3(+) regulatory T cells via signals from the sympathetic nervous system.

Bone marrow mononuclear cells exert long-term neuroprotection in a rat model of ischemic stroke by promoting arteriogenesis and angiogenesis.

Transplanted bone marrow-derived mononuclear cells (BMMNCs) can promote arteriogenesis and angiogenesis by incorporating into vascular walls and differentiating into smooth muscle cells (SMCs) and endothelial cells (ECs). Here, we explored whether BMMNCs can enhance arteriogenesis and angiogenesis and promote long-term functional recovery in a rat model of permanent middle cerebral artery occlusion (pMCAO). Sprague-Dawley rats were injected with vehicle or 1×10(7) BMMNCs labeled with BrdU via femoral vein 24 h after induction of pMCAO. Functional deficits were assessed weekly through day 42 after pMCAO, and infarct volume was assessed on day 7. We visualized the angioarchitecture by latex perfusion on days 14 and 42. BMMNC transplantation significantly reduced infarct volume and neurologic functional deficits compared with untreated or vehicle-treated ischemic groups. In BMMNC-treated rats, BrdU-positive cells were widely distributed in the infarct boundary zone, were incorporated into vessel walls, and enhanced the growth of leptomeningeal anastomoses, the circle of Willis, and basilar arteries. BMMNCs were shown to differentiate into SMCs and ECs from day 14 after stroke and preserved vascular repair function for at least 6 weeks. Our data indicate that BMMNCs can significantly enhance arteriogenesis and angiogenesis, reduce infarct volume, and promote long-term functional recovery after pMCAO in rats.

Emergy-based ecological efficiency evaluation and optimization method for logistics park.

With the rapid development of logistics park, how to evaluate and optimize the ecological efficiency of logistics park to achieve its sustainable development has become a concern of academia. In order to achieve this goal, this paper puts forward a method based on emergy, which processes the data in a unified dimension. By constructing the ecological efficiency evaluation model of logistics park, it quantitatively evaluates the ecological efficiency of logistics park, and analyzes the correlation between various factors and ecological efficiency. The application results of H logistics park show that fuel oil, information technology, net profit, and waste gas are closely related to the ecological efficiency of logistics park, and the correlation coefficients are 0.8248, -0.6949, 0.8544, and 0.7661, respectively. On this basis, the paper puts forward some suggestions to improve the ecological efficiency of the logistics park. This paper provides theoretical and methodological support for the evaluation and optimization of the ecological efficiency of the logistics park.

DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. METHODS: Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. RESULTS: A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups (P < 0.05). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups (P < 0.05). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups (P < 0.05). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups (P < 0.05). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group (P < 0.05). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group (P < 0.05). CONCLUSION: The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion.

Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis.

Correction to: Preconditioning with VEGF Enhances Angiogenic and Neuroprotective Effects of Bone Marrow Mononuclear Cell Transplantation in a Rat Model of Chronic Cerebral Hypoperfusion.

The original version of this article unfortunately contained a careless error in Fig. 2b-c, where the pictures of group Vehicle were the same with group VEGF.

Danhong Injection Protects Hemorrhagic Brain by Increasing Peroxiredoxin 1 in Aged Rats.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high incidence, mortality and disability rate. Danhong injection (DHI) is beneficial for ischemic stroke, but is prohibited for ICH due to risk of bleeding. The present study aims to explore the potential therapeutic time window and molecular mechanism of DHI in a collagenase-induced ICH model in aged rats. DHI administration after ICH could significantly improve body weight and neurological deficits, and reduce the hematoma volume and brain water content when compared to the vehicle control. Furthermore, the protective effect of DHI administration on days 1-3 after ICH was superior to those on days 3-5 or 7-9 after ICH. DHI remarkably increased the Peroxiredoxin 1 (Prx1) expression in astrocytes and reduced the expression of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-ß (IL-1ß) after ICH. The immediate treatment of Prx1 inhibiter chelerythrine (Che) after ICH abolished the protective effect of DHI. Furthermore, the Che treatment reduced the expression of Prx1 in astrocytes, but increased the expression of TNF-α and IL-1ß after ICH. DHI treatment could not reverse these changes. Therefore, the earlier DHI is administered, the better the neuroprotective effect. DHI exerts antioxidative and anti-inflammatory function by increasing Prx1 in astrocytes. These present results may change the established understanding of DHI, and reveal a novel treatment approach for ICH.

Neuroprotective Action of Teriflunomide in a Mouse Model of Transient Middle Cerebral Artery Occlusion.

Teriflunomide has been reported to inhibit microglial activation in experimental models of traumatic brain injury. However, its roles in ischemic stroke and underlying mechanisms of action are still undiscovered. In this study, we investigated the effects of teriflunomide on brain edema, neurologic deficits, infarct volume, neuroinflammation, blood-brain barrier (BBB) permeability, and neurogenesis in a mouse model of transient middle cerebral artery occlusion (tMCAO). tMCAO mice treated with teriflunomide showed lower brain water content on day 3, milder neurologic deficits and smaller infarct volume on day 7 than those treated with vehicle. Additionally, mice received teriflunomide had fewer activated Iba-1-positive microglia and lower protein levels of interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and 3-Nitrotyrosine (3-NT) compared with those received vehicle on day 3. Further, teriflunomide alleviated Evans blue dye leakage, increased pericyte coverage and protein levels of platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor ß (PDGFRß) and Bcl2, and decreased the number of PDGFRß/matrix metalloproteinase 9 (MMP9)-positive cells. Moreover, teriflunomide reduced the loss of zonula occludens-1 (ZO-1) and occludin. Finally, teriflunomide significantly upregulated the number of 5-bromo-20-deoxyuridine (BrdU)/doublecortin (DCX)-positive cells and expression of mammalian achaete-scute homolog 1 (Mash1), DCX and Pbx1 in subventricular zone (SVZ) on day 7 after stroke. Our results indicate that teriflunomide exhibits protective roles in ischemic stroke by inhibiting neuroinflammation, alleviating BBB disruption and enhancing neurogenesis.

Wnt-3a alleviates neuroinflammation after ischemic stroke by modulating the responses of microglia/macrophages and astrocytes.

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/ß-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.

EPO promotes axonal sprouting via upregulating GDF10.

Erythropoietin (EPO) has an exact neuroprotective effect on stroke. However, it remains unknown whether it participates in axonal sprouting after neuron damage. Growth and differentiation factor 10 (GDF10) has been shown to be a trigger of axonal sprouting after stroke. Hence, it was hypothesized that EPO promotes axonal sprouting mainly through GDF10. In the present in vitro experiment, it was found that EPO could promote axonal sprouting and GDF10 expression in a dose-dependent manner. The knockdown of GDF10 using siRNA abolished the effect of EPO-mediated axonal sprouting, indicating that GDF10 is the executor of EPO-mediated axonal sprouting. The treatment of neurons with nuclear factor-kappaB (NF-κB) inhibitor JSH-23 could inhibit the accumulation of NF-κB phospho-p65 (p-p65) in the nucleus, the upregualtion of GDF10 and extending of axonal length. Furthermore, the addition of Janus kinase 2 (JAK2) inhibitor CEP-33779 or phosphoinositide 3-kinase (PI3K) inhibitor LY294002 to the culture medium also blocked the nuclear translocation of p-p65, the expression of GDF10, and axonal sprouting, suggesting that EPO induces axonal sprouting via activating cellular JAK2 and PI3K signaling. Impeding JAK2 signaling with CEP-33779 can suppress the phosphorylation of PI3K, and this confirms that the upstream of PI3K signaling is JAK2. These present results provide a novel insight into the role of EPO and the molecular mechanism of axonal sprouting, which is beneficial for the development of novel approaches for neurological recovery after brain injury, including stroke.