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Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI. miRNAs promote neuronal survival and axon growth after SCI. The expression of dre-miR-21 was increased after SCI. Dre-miR-21 targets nop56 mRNA, which causes the Nop56 expression level to reduce, thus reducing the nuclei of ribosomal RNA methylation level, increasing the resistance of neurons, and promoting neuronal cell survival. The level of dre-miR-125c is increased after SCI, and dre-miR-125c targets kpnb1 mRNA and reduces the concentration of Kpnb1 at the axon site, thereby promoting axon outgrowth. At the same time, Kpnb1 is a retrograde signal protein of nerve injury, and reducing the expression level of Kpnb1 can inhibit cell death caused by excessive stress response. [ABSTRACT FROM AUTHOR]

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases. [ABSTRACT FROM AUTHOR]

A 2D ultrasonic burnishing technology was employed to strengthen 7075 aluminum alloy. The running-in experiments for original and burnished samples were implemented, and the running-in performance was explored qualitatively and quantitatively. The results show that the worn surface of an original sample exhibited the peelings, scratches, and abrasive particles, yet the wear form of a burnished sample was relatively single, mainly with scratches. The quantitative parameter "maximum distance between phase points dmax" was calculated. During the friction and wear process, the dmax of friction coefficient signal displayed the variation of first decreasing and then stabilizing, which was consistent with the running-in and steady-state stages of the friction system. Compared with the original sample, the burnished sample had a less dmax, which indicated that the phase trajectory had a more convergence, and the friction system had a better stability. This study can guide surface strengthening and running-in performance analysis. [ABSTRACT FROM AUTHOR]

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices. Zwitterionic hydrogels are nonfouling and hemocompatibility but several key challenges such as weak mechanical strength and low adhesion hamper their application as coating materials for devices. Here, the authors report a microgel reinforced zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. [ABSTRACT FROM AUTHOR]

Red mudstone has low compressive strength and weak water resistance. Assessing its mesostructure has attracted numerous investigations to explain the macroscopic behaviors. However, less attention is dedicated to mesoscopic image segmentation and structural heterogeneity. This study aims to simplify and quantify the mesostructure of the red mudstone. A segmentation strategy based on U-Net deep learning framework is proposed to simplify the backscattered electron image. To quantify the mesostructural heterogeneity, the randomly grown seed method and the mean structural similarity (MSSIM) index are used to assess and predict the representative elementary area (LREA). Results show that the complex mesostructure can be simplified into brittle mineral aggregation, matrix, and pore based on the U-Net segmentation. The LREAs assessed by the two methods are consistent (100 ~ 280 μm), in which the MSSIM can prevent cumbersome parametric calculations. In addition, the LREA can be predicted by the limited image area. Our findings demonstrate that the quantifiability of red mudstone mesostructure is governed by the geometric features of components and their dispersion and distribution at multiple scales, which dictate the severity of original defects of the mesostructure and shape the diversity of red mudstones. This study could be used as a starting point in the improvement of our understanding of the mesostructural evolution of the red beds under different conditions. [ABSTRACT FROM AUTHOR]

Summary: This study provides a national estimate of the incidence of hospitalizations and assesses the clinical features and outcomes during inpatient admission due to osteoporotic fractures diagnosed by ICD-10-CM/PCS among the elderly in the USA, using the US Nationwide Inpatient Sample, 2016–2018. Purpose: To provide a national estimate of the incidence of hospitalizations and assess the clinical features and outcomes during inpatient admission due to osteoporotic fractures (OFs) among the elderly in the USA. Methods: The study included all inpatients aged 65 years and older who participated in the US Nationwide Inpatient Sample (NIS). We conducted a retrospective analysis of hospitalizations with OFs diagnosed by the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS), using the US NIS, 2016–2018. Trends in epidemiological characteristics and outcomes were calculated by annual percentage change (APC). Results: From 2016 to 2018, there were an estimated 0.16 million hospitalizations for OFs, and the estimated annual incidence rate changed from 995 cases per 1 million persons in 2016 to 1114 cases per 1 million persons in 2018 (APC, 5.8% [95% CI, 0.0 to 12.0]; P > 0.05). Over two-thirds of the patients (68.2%) were age-related osteoporosis with current pathological fracture, and OFs were more likely to occur in vertebra (51.7%) and femur (34.7%). During the hospitalization, the average length of stay (LOS) was 5.83 days, the average cost reached $60,901.04, and the overall mortality was 2.3%. All outcomes including LOS, average cost and mortality did not change significantly in 2016–2018 (all P values for trend were over 0.05). Conclusion: Between 2016 and 2018, the incidence rate of OFs remained relatively stable, but the total number of cases was huge. OFs was predominantly age-related, mostly in vertebrae and femurs, with relatively stable cost and mortality during hospitalization. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years. Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5 nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In the original version of this article, unfortunately, the images in Fig. 4 and 7 are mixed. The correct version of the Fig.4 and 7 is given below [ABSTRACT FROM AUTHOR]

Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, can induce neuronal differentiation, promote neurite extension and exert a neuroprotective effect in central nervous system (CNS) injuries; however, comparatively little is known regarding its action on mouse embryonic neural stem cells (NSCs) and the underlying molecular mechanism. Recent studies suggested that c-Jun N-terminal kinase (JNK) is required for neurite outgrowth and neuronal differentiation during neuronal development. In the present study, we cultured mouse embryonic NSCs and treated the cells with 1 mM VPA for up to 7 days. The results indicate that VPA promotes the neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons; moreover, VPA induces the phosphorylation of c-Jun by JNK. In contrast, the specific JNK inhibitor SP600125 decreased the VPA-stimulated increase in neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Taken together, these results suggest that VPA promotes neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Moreover, JNK activation is involved in the effects of VPA stimulation. [ABSTRACT FROM AUTHOR]

The Ras/Raf/ERK1/2 signaling pathway plays an important role in central and peripheral neurons in functions such as dendritic arborization, neuronal polarity, and axon assembly. However, emerging evidence also shows that up-regulation of this signaling pathway may lead to the development of spinal cord injury. The present study aimed to determine the effects of Ras/Raf/ERK1/2 signaling pathway inhibition on properties of spinal cord-injured neurons. First, neurons from spinal cord-injured C57BL/6 J mouse pups and sham-operated C57BL/6 J mouse pups were harvested. Then, immunofluorescence, western blotting, cell adhesion and cell migration assays, and DiI labeling were employed to investigate the effect of Ras/Raf/ERK1/2 signaling pathway inhibition on spinal cord-injured neurons. Immunofluorescence results of synapse formation indicated that the experimental spinal cord injury model was successfully established. Western blot results identified upregulated Erk phosphorylation in the spinal cord-injured neurons, and also showed that U0126 inhibited phosphorylation of Erk, which is a downstream kinase in the Ras/Raf signaling pathway. Additionally, cell migration and adhesion was significantly increased in the spinal cord-injured neurons. DiI labeling results also showed an increased formation of mature spines after inhibition of Ras/Raf/ERK1/2 signaling. Taken together, these results suggested that the Ras/Raf/ERK1/2 signaling pathway could serve as an effective treatment target for spinal cord injury. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 ( SNHG12) has a role in cell proliferation and migration. Angiomotin, encoded by the AMOT gene, is a protein that regulates the migration and organization of endothelial cells. SNHG12 and AMOT have been shown to play a role in a variety of human cancers but have yet to be studied in detail in human osteosarcoma. Tissue samples from primary osteosarcoma ( n = 20) and adjacent normal tissues ( n = 20), the osteosarcoma cell lines, SAOS-2, MG-63, U-2 OS, and the human osteoblast cell line hFOB (OB3) were studied using Western blot for angiomotin, and quantitative real-time polymerase chain reaction for the expression of SNHG12 and AMOT. The expression of SNHG12 was knocked down using RNA interference. Cell migration assays were performed. Cell apoptosis was studied using flow cytometry. SNHG12 and AMOT messenger RNA (mRNA) expression was upregulated in osteosarcoma tissues and cell lines when compared with normal tissues and cells. Upregulation of AMOT mRNA was associated with upregulation of SNHG12. Knockdown of SNHG12 reduced the expression of angiomotin in osteosarcoma cells and suppressed cell proliferation and migration but did not affect cell apoptosis. This preliminary study has shown that the lncRNA SNHG12 promotes cell proliferation and migration by upregulating AMOT gene expression in osteosarcoma cells in vivo and in vitro. Further studies are recommended to investigate the role of SNHG12 and AMOT expression in tumor cell proliferation and migration and angiogenesis in osteosarcoma and a range of malignant mesenchymal tumors. [ABSTRACT FROM AUTHOR]

Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3′ untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to review our experiences with tibial lengthening over an intramedullary nail in comparison to the conventional Ilizarov method. Methods: We performed a retrospective comparison of tibial lengthening using the conventional Ilizarov method (group A: 23 limbs in 13 patients) versus over a nail (group B: 51 limbs in 26 patients). The percentage increase in tibial length, lengthening index, external fixation index, consolidation index and complications were assessed. Results: The mean gain in tibial length was 7.4 cm, which represents a mean increase of 26.0%. There was no difference in lengthening index or consolidation index; however, the patients in group A wore the external fixator longer than those in group B (281.5 versus 129.0 days), which represents a larger external fixation index (40.0 versus 17.4 day/cm). Group A had a higher complication rate (1.0 versus 0.47 per tibia) than group B. Conclusions: Tibial lengthening over an intramedullary nail confers advantages over the conventional Ilizarov method, including shorter time needed for external fixation and lower complication rates. [ABSTRACT FROM AUTHOR]

A correction to the article "Epidemiological characteristics of adult SCIWORA in Tianjin, China: a preliminary study" that was published in the December 20, 2011 issue is presented.

Activation of endogenous neural stem cells (NSC) is one of the most potential measures for neural repair after spinal cord injury. However, methods for regulating neural stem cell behavior are still limited. Here, we investigated the effects of nicotinamide riboside promoting the proliferation of endogenous neural stem cells to repair spinal cord injury. Nicotinamide riboside promotes the proliferation of endogenous neural stem cells and regulates their differentiation into neurons. In addition, nicotinamide riboside significantly restored lower limb motor dysfunction caused by spinal cord injury. Nicotinamide riboside plays its role in promoting the proliferation of neural stem cells by activating the Wnt signaling pathway through the LGR5 gene. Knockdown of the LGR5 gene by lentivirus eliminates the effect of nicotinamide riboside on the proliferation of endogenous neural stem cells. In addition, administration of Wnt pathway inhibitors also eliminated the proliferative effect of nicotinamide riboside. Collectively, these findings demonstrate that nicotinamide promotes the proliferation of neural stem cells by targeting the LGR5 gene to activate the Wnt pathway, which provides a new way to repair spinal cord injury.Graphical Abstract: Activation of endogenous neural stem cells (NSC) is one of the most potential measures for neural repair after spinal cord injury. However, methods for regulating neural stem cell behavior are still limited. Here, we investigated the effects of nicotinamide riboside promoting the proliferation of endogenous neural stem cells to repair spinal cord injury. Nicotinamide riboside promotes the proliferation of endogenous neural stem cells and regulates their differentiation into neurons. In addition, nicotinamide riboside significantly restored lower limb motor dysfunction caused by spinal cord injury. Nicotinamide riboside plays its role in promoting the proliferation of neural stem cells by activating the Wnt signaling pathway through the LGR5 gene. Knockdown of the LGR5 gene by lentivirus eliminates the effect of nicotinamide riboside on the proliferation of endogenous neural stem cells. In addition, administration of Wnt pathway inhibitors also eliminated the proliferative effect of nicotinamide riboside. Collectively, these findings demonstrate that nicotinamide promotes the proliferation of neural stem cells by targeting the LGR5 gene to activate the Wnt pathway, which provides a new way to repair spinal cord injury. [ABSTRACT FROM AUTHOR]