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Abstract Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

The majority of crack sensors do not offer simultaneously both a significant stretchability and an ultrahigh sensitivity. In this study, we present a straightforward and cost-effective approach to fabricate metal crack sensors that exhibit exceptional performance in terms of ultrahigh sensitivity and ultrahigh stretchability. This is achieved by incorporating a helical structure into the substrate through a modeling process and, subsequently, depositing a thin film of gold onto the polydimethylsiloxane substrate via sputter deposition. The metal thin film is then pre-stretched to generate microcracks. The sensor demonstrates a remarkable stretchability of 300%, an exceptional sensitivity with a maximum gauge factor reaching 107, a rapid response time of 158 ms, minimal hysteresis, and outstanding durability. These impressive attributes are attributed to the deliberate design of geometric structures and careful selection of connection types for the sensing materials, thereby presenting a novel approach to fabricating stretchable and highly sensitive crack-strain sensors. This work offers a universal platform for constructing strain sensors with both high sensitivity and stretchability, showing a far-reaching significance and influence for developing next-generation practically applicable soft electronics.

Abstract Background The advantages of anterior cervical decompression and fusion (ACDF) were well published, while research on postoperative results in different subtypes of cervical disk herniation (CDH) still remains blank. This study aimed to explore the surgical outcome between sequestration and other types in CDH. Methods This retrospective cohort study enrolled 108 patients treated with ACDF in our hospital. The participants were divided into two groups according to the existence of a sequestered disk. The Visual analog scale score, the Japanese Orthopedics Association (JOA) score and the Neck disability index score were used to evaluate postoperative outcome. Results Significant improvements were observed in both groups at every viewpoint (P

Abstract As one of the most intractable neurological diseases, spinal cord injury (SCI) often leads to permanent neurological impairment in patients. Unfortunately, due to the complex pathological mechanisms and unique postinjury microenvironment, there is currently no way to completely repair the injured spinal cord. In recent years, with the rapid development of tissue engineering technology, the combination of biomaterials and medicine has provided a new idea for treating SCI. Here, we systematically summarize representative biomaterials, including natural, synthetic, nano, and hybrid materials, and their applications in SCI treatment. In addition, we describe several state-of-the-art fabrication techniques for tissue engineering. Importantly, we provide novel insights for the use of biomaterial-based therapeutic strategies to reduce secondary damage and promote repair. Finally, we discuss several biomaterial clinical studies. This review aims to provide a reference and new insights for the future exploration of spinal cord regeneration strategies.

The purpose of this study was to explore the inherent links between elemental cycling in Rosa roxburghii Tratt litter and soil, as well as their coupled relationships, within barren soil environments typical of karst rocky desertification regions in Guizhou Province. Ecological stoichiometric methods were used to systematically analyze the nutrient concentrations of C, N, P, and K and their stoichiometry in the litter and soil of Rosa roxburghii, with a focus on the impacts of seasonal variations and rocky desertification regions. High C and K levels and low N and P levels are observed in the litter, whereas the soil has lower concentrations of C, N, P, and K, with nutrient replenishment priorities of N > P > K > C. Strong positive correlations are found among the C/N, C/P, and N/K stoichiometric ratios in both the litter and the soil. Furthermore, nutrient concentrations and stoichiometric ratios vary significantly by season. Seasonal variations influence nutrient concentrations, with notable increases in litter P and K levels and in soil N and P levels in September compared with March. Seasonal variations influence the stoichiometric ratios of C/N, C/P, and N/K in litter and soil, contributing to elemental balance and ecosystem stability. Moreover, significant variations in nutrient contents and stoichiometric ratios are observed across distinct rocky desertification grades. Nonrocky desertified areas present elevated P and K contents in litter, whereas light desertified areas present increased C and N concentrations. Moderately desertified areas presented increased soil P and K concentrations, whereas severely desertified areas presented the highest N levels. These discernible trends in nutrient profiles highlight the synergistic impacts of soil nutrient inadequacy and plant utilization strategies. These findings contribute to a better understanding of element cycling mechanisms in Rosa roxburghii woodland ecosystems, offering valuable information for sustainable forest management practices.

Abstract Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.

Abstract Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3−/− mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression.

Four-level cervical spondylotic myelopathy (CSM) is a common disease affecting a large number of people, with the optimal surgical strategy remaining controversial. This study compared the clinical outcomes, radiological parameters, and postoperative complications of primarily performed surgical procedures such as anterior cervical discectomy and fusion (ACDF), open-door laminoplasty (LAMP), and laminectomy with fusion (LF) in treating four-level CSM. A total of 116 patients who received ACDF (38 cases), LAMP (45 cases), and LF (33 cases) were followed up for a minimum of 24 months were enrolled in this study and retrospectively analyzed. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) scoring system, the Neck Disability Index (NDI), and the Visual Analogue Scale (VAS). Changes in the curvature of the cervical spine were determined using the cervical curvature index (CCI) and the C2–C7 Cobb angle. Cervical mobility was evaluated using the C2–C7 range of motion (ROM) and active cervical ROM (aROM). Complications were recorded and compared among the three groups. All patients achieved significant improvement in JOA, NDI, and VAS scores at the final follow-up (P 0.05). In addition, both C2–7 ROM and aROM were significantly reduced in the three groups and LAMP showed the least reduction relatively. As for complications, LAMP showed the lowest overall incidence of postoperative complications, and patients in the ACDF group were more susceptible to dysphagia, pseudoarthrosis than LAMP and LF. Considering improvements in clinical symptoms and neurological function, no remarkable difference was found among the groups. Nevertheless, LAMP had advantages over the other two surgical procedures in terms of preserving cervical mobility and reducing postoperative complications.

Abstract Objective To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. Methods Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. Results Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P

It is particularly important to improve the performance of mid-infrared (mid-IR) electro-optic (EO) modulator, which is one of the key devices that will expand the channels of optic communication, and will be utilized in optical free space communication, optical detection for gas molecules, etc. We present and theoretically design the performance of the high-speed mid-IR EO modulator based on lithium niobate on insulator (LNOI) at λ = 3 μm. We have designed, calculated, and optimized single-mode ridge waveguide, 1 × 2 multimode interference (MMI) couplers and coplanar waveguide (CPW) electrodes structures for x-cut lithium niobate. Our device with an extinction ratio greater than 40 dB, a half-wave voltage-length product is about 12 V·cm, and a EO bandwidth up to 12 GHz with interaction length of 15 mm. The performance of interaction length of 5 mm and 10 mm mid-IR EO modulator are also proposed and simulated for a compromise consideration between the EO bandwidth and driving voltage.

Abstract Background Although ACDF has been widely used in treating cervical spondylosis and related diseases, the complications along with this anterior surgical technique have hindered its application and affected the postoperative outcome of the patients. Here, we investigated the clinical and radiological outcomes of a new integrated low-profile anterior plate and cage system for anterior cervical discectomy and fusion (ACDF) in treating cervical spondylosis. Methods A total of 96 cervical spondylosis patients who underwent single-level ACDF between 2018 to 2020 in our institute were enrolled. There were 28 patients using the new implants and 68 patients using the zero-profile (Zero-P) implants. The Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) were used to evaluate the clinical outcomes. The cervical and segmental Cobb angle and range of motion (ROM) were used to assessed the radiological outcomes. Incidence of complications were also recorded. All data were recorded at pre-operation, 6-month and 12-month post-operation. Results All patients were followed-up for at least 1-year, the mean follow-up time was over one year. The fusion rate was similar in the two groups. There was no significant difference in the postoperative JOA score recovery rate, postoperative VAS score of neck and arm pain, postoperative ROM, and incidence of complications between two groups (P > 0.05). However, postoperative cervical and segmental Cobb angle were better maintained in the new low-profile implant group compared to Zero-P group. Conclusions The clinical outcomes of the new low-profile implant were satisfactory and comparable to that of zero-profile system. It may have advantages in improving and maintaining the cervical lordosis, and can be an alternative device for single-level cervical spondylosis treated with ACDF.

Recurrent low back pain after spinal surgeries, such as lumbar laminectomy, is a major complication of excessive epidural fibrosis. Although multiple preclinical and clinical methods have been aimed at ameliorating epidural fibrosis, their safety and efficacy remain largely unclear. Single implanted electrospun fibrous membranes provide physical barriers that can decrease tissue fibrosis after surgery; however, they also trigger local inflammation due to the implantation of a foreign body, thus subsequently attenuating their anti-fibrosis properties. Here, we designed a strategy that permits easy incorporation of mefloquine into polylactic acid membranes, and stable long-term mefloquine release, to potentially improve anti-fibrosis effects and relieve or prevent low back pain.The electrospun fibrous membranes grafted with mefloquine showed a well-controlled early temporary peak release, and secondary drug release occurred smoothly over several weeks. Histopathological and histomorphometric results indicated that the drug-loaded membranes had excellent anti-fibrosis effects after laminectomy in rats. Inflammation and neovascularization at the surgical site indicated that the mefloquine-grafted electrospun fibrous membranes provided sustained anti-inflammatory outcomes while effectively alleviating associated neuropathic pain hypersensitivity. In summary, our study indicated that polylactic acid-mefloquine grafted electrospun fibrous membranes may be a potential local agent to mitigate epidural fibrosis and support sensory neurological function after laminectomy, thereby potentially improving patients’ postoperative outcomes.

Abstract Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio‐synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene‐related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity‐modifying protein 1 (RAMP1) and cyclic AMP response element‐binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

With the advancement of modulation technology and the requirement for device miniaturization and integration, lithium niobate on insulator (LNOI) can be a versatile platform for this pursuit, as it can confine the transmitted light at the nanoscale, leading to a strong light–matter interaction, which can sensitively capture external variations, such as electric fields and temperature. This paper presents a compact microring modulator with versatile tuning based on X-cut LNOI. The LNOI modulator equipped with electrodes with a coverage angle of 120∘ achieved a maximum electro-optic (EO) tuning efficiency of 13 pm/V and a maximum extinction ratio of 11 dB. The asymmetry in the static or quasi-static electro-optic tuning of the microring modulator was also analyzed. Furthermore, we measured the thermal-optic effect of the device with a sensitivity of 26.33 pm/∘C, which can potentially monitor the environment temperature or compensate for devices’ functional behavior. The demonstrated efficient and versatile compact microring modulator will be an important platform for on-chip active or passive photonic components, microring-based sensor arrays and integrated optics.

Abstract Background Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. Methods In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. Results The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. Conclusions This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.

Abstract Background The incidence of degenerative disc disease caused by intervertebral disc injury is increasing annually, seriously affecting the quality of life of patients and increasing the disease burden on society. The mechanisms of intervertebral disc degeneration include changes in extracellular matrix (ECM) deposition and tissue fibrosis. sIL-13Rα2-Fc potently inhibits interleukin (IL)-13, as well as blocks related cell signaling pathways and inhibits fibrosis in certain tissues. However, it is unknown whether sIL-13Rα2-Fc inhibits fibrosis in injured intervertebral discs and slows the process of degeneration. We hypothesized that sIL-13Rα2-Fc delays the progression of intervertebral disc degeneration by inhibiting intervertebral disc fibrosis and improving ECM deposition. Methods A rat tail intervertebral disc degeneration model was established. Pathological changes in rat intervertebral disc tissue were observed by hematoxylin and eosin staining and Masson staining. Glycosaminoglycan (GAG), chondroitin sulfate (CS), keratan sulfate (KS), and hyaluronic acid (HA) contents were quantitatively analyzed by enzyme-linked immunosorbent assay. Type I and type II collagen expression levels were analyzed by reverse transcription-PCR and western blotting. Results Hematoxylin and eosin staining and Masson staining revealed annulus fibrosus rupture, disordered arrangement, decreased nucleus pulposus tissue, and decreased collagen fiber in the rat intervertebral disc tissue. Following treatment with sIL-13Rα2-Fc, pathological changes in the rat intervertebral disc were reduced. Rat intervertebral disc tissue showed decreased GAG, CS-KS, and (HA) contents, increased type I collagen levels, and decreased type II collagen levels in degenerated intervertebral discs. sIL-13Rα2-Fc intervention increased the contents of GAG, CS, KS, and HA; inhibited the expression of type I collagen; and promoted the expression of type II collagen. Conclusion These results demonstrate that intervertebral disc degeneration is associated with tissue fibrosis. sIL-13Rα2-Fc can regulate type I and type II collagen expression levels by increasing GAG, CS, KS, and HA contents, thereby slowing the progression of intervertebral disc degeneration.

Mechanical performance is crucial for lattice structures used in orthopedic applications because they should simultaneously possess high strength and high porosity. Although the additively manufactured Ti-6Al-4 V functionally graded porous structure (FGPS) has proven to be the most promising material owing to its good mechanical performance, the impact of porosity gradient pattern on their mechanical performance has scarcely been investigated. In this study, FGPSs with varied porosity gradient pattern and same overall porosity were designed by triply periodic minimal surface and fabricated by laser powder bed fusion (L-PBF), and their structural and mechanical properties were analyzed. A semi-empirical equation was derived to predict the mechanical properties of FGPSs. Hence, we discovered that the lattice with solid core exhibited the best mechanical performance among all FGPS designs. X-ray microscopy (XRM) analysis revealed a strong relationship between the internal micro-porosity of the L-PBF-fabricated samples and the dimensions of the manufactured components, further proving the rationale of the lattice with solid core design. In situ compression tests under XRM visualized the different failure mechanisms in the porous and dense portion of the lattice with solid core. The strengthening mechanism of the lattice with solid core was further revealed by finite element analysis.

Lumbar disc herniation (LDH) is a common cause for low back pain. In this study, we aimed to explore the effects of a specific Lactobacillus paracasei (L. paracasei), L. paracasei S16, on the symptoms of LDH using a mouse model of LDH. The results showed that L. paracasei S16 treatment improved the behavior, increased the cell proliferation, and decreased the apoptosis in LDH mice. Moreover, L. paracasei S16 treatment alleviated the aberrant inflammation response in the LDH mice, which is characterized by the decreased anti-inflammatory cytokines, increased pro-inflammatory cytokines, and decreased percentage of Th1 and Th2 cells and Th17/Treg ratio. 16S rRNA sequencing results showed that the LDH mice treated with L. paracasei S16 have higher relative abundance of Lachnospiraceae and Ruminococcaceae and lower abundance of Lactobacillaceae than mice in the LDH group. Additionally, the serum metabolites involved in the linoleic acid metabolism, alanine. aspartate, and glutamate, glycerophospholipid, and TCA cycle were significantly decreased and the metabolite involved in purine metabolism was significantly increased after the L. paracasei S16 treatment in the LDH mice. These results showed that administration of L. paracasei S16 can improve inflammation response, alter gut microbiota, and modulate serum metabolomics in a mouse model of LDH.

Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

To date, failed back surgery syndrome (FBSS) remains a therapy-refractory clinical condition after spinal surgery. The antiadhesion membrane is applied to prevent FBSS by isolating fibrosis; however, the inflammation stimulated by the foreign body and surgical trauma needs to be further resolved simultaneously. Therefore, we developed new electrospun polycaprolactone (PCL) fibrous membranes loaded with celecoxib (CEL) to prevent fibrosis and inflammation associated with FBSS. The CEL-loaded PCL fibers were randomly distributed, and the drug was released over two weeks. Fluorescence micrographs revealed that the fibroblasts proliferated less on the PCL-CEL fibrous membranes than in the PCL group and the blank control. In the rat laminectomy model after 4 weeks, magnetic resonance imaging of epidural fibrosis was least in the PCL-CEL group. Expression of COX-2 and PGE2 was lower in the PCL-CEL group. It concluded that the CEL-loaded PCL membrane could reduce fibrosis and inflammation in a rat model of FBSS via COX-2/PGE2 signaling pathways.

Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

Background/Aims: Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-β can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood. Methods: CHSY1 expression was examined in rat nucleus pulposus treated with TGF-β using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-β and to measure the effect of c-Jun and Sp1 on TGF-β mediated CHSY1 promoter activity and CHSY1 expression. Results: TGF-β increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-β. Furthermore, we found that TGF-β-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-β. Conclusion: Our results suggest that TGF-β induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling.

Second harmonic generation (SHG) is an important nonlinear process which is critical for applications, such as optical integrated circuit, nonlinear microscopy, laser, etc. Many challenges remain in the improvement of nonlinear conversion efficiency, since the typical value is of only 10−5 in nanostructures. Here, we theoretically demonstrate a periodic structure consisting of a lithium niobate (LN) bar and an LN disk, on a nanoscale (~300 nm) thin-film platform, which is proposed for a highly efficient SHG. By breaking the structure symmetry, a Fano resonance with a high Q, up to 2350 and a strong optical field enhancement reaching forty-two folds is achieved, which yields a high conversion efficiency, up to 3.165 × 10−4. In addition to its strong second harmonic (SH) signal, we also demonstrate that by applying only 0.444 V on the planar electrode configurations of the nanostructured LN, the wavelength of SH can be tuned within a 1 nm range, while keeping its relatively high conversion efficiency. The proposed structure with the high nonlinear conversion efficiency can be potentially applied for a single-molecule fluorescence imaging, high-resolution nonlinear microscopy and active compact optical device.

The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.

BACKGROUND: Results showed good clinical outcomes of anterior corpectomy and fusion (ACCF) for patients with cervical spondylotic myelopathy (CSM) during a short term follow-up; however, studies assessing long term results are relatively scarce. In this study we intended to assess the long term clinical and radiographic outcomes, find out the factors that may affect the long term clinical outcome and evaluate the incidence of adjacent segment disease (ASD). METHODS: This is a retrospective study of 145 consecutive CSM patients on ACCF treatment with a minimum follow-up of 5 years. Clinical data were collected from medical and operative records. Patients were evaluated by using the Japanese Orthopedic Association (JOA) scoring system preoperatively and during the follow-up. X-rays results of cervical spine were obtained from all patients. Correlations between the long term clinical outcome and various factors were also analyzed. FINDINGS: Ninety-three males and fifty-two females completed the follow-up. The mean age at operation was 51.0 years, and the mean follow-up period was 102.1 months. Both postoperative sagittal segmental alignment (SSA) and the sagittal alignment of the whole cervical spine (SACS) increased significantly in terms of cervical lordosis. The mean increase of JOA was 3.8 ± 1.3 postoperatively, and the overall recovery rate was 62.5%. Logistic regression analysis showed that preoperative duration of symptoms >12 months, high-intensity signal in spinal cord and preoperative JOA score ≤ 9 were important predictors of the fair recovery rate (≤ 50%). Repeated surgery due to ASD was performed in 7 (4.8%) cases. CONCLUSIONS: ACCF with anterior plate fixation is a reliable and effective method for treating CSM in terms of JOA score and the recovery rate. The correction of cervical alignment and the repeated surgery rate for ASD are also considered to be satisfactory.