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Bone-tendon (B-T) healing is a clinical challenge due to its limited regeneration capability. Fibrocartilage regeneration and bone formation at the healing site are two critical factors for B-T healing. Promoting fibrocartilage regeneration and bone formation by tissue-engineering may be a promising treatment strategy. In this study, we innovatively fabricated two kinds of acellular scaffolds from bone or fibrocartilage tissues, namely the book-type the acellular bone scaffold (BABS) and the book-type acellular fibrocartilage scaffold (BAFS). Histologically, the two scaffolds well preserved the native extracellular matrix (ECM) structure without cellular components. In vitro studies showed BABS is superior in osteogenic inducibility, while BAFS has good chondrogenic inducibility. To comparatively investigate the efficacy on B-T healing, the BABS or BAFS were, respectively, implanted into a rabbit partial patellectomy model. Macroscopically, a regenerated bone-tendon insertion (BTI) was bridging the residual patella and patellar-tendon with no signs of infection and osteoarthritis. Radiologically, more new bone was formed at the healing interface in the BABS group as compared with the BAFS or control (CTL) groups (p < 0.05). Histologically, at postoperative week 16, histological scores were significantly better for regenerated fibrocartilage in the BAFS group or BABS group compared with the CTL group, but the BAFS group showed a significantly larger score than the BABS groups (p < 0.05). Biomechanical evaluation indicated a higher failure load and stiffness were shown in the BAFS group than those in the BABS or CTL groups at week 16 (p < 0.05). This study indicated that the BAFS is a more promising scaffold for B-T healing in comparison with the BABS. [ABSTRACT FROM AUTHOR]

Background: Tendon-bone interface (TBI) injuries are common in sports activities. Owing to the limited regenerative ability of the TBI, its functional healing remains a difficulty in clinical practice. Icariin (ICA) provides strong stimulation for osteogenesis. Platelet-rich plasma (PRP) can be used as a carrier for bioactive molecules, although its ability to provide sustained release for such molecules needs improvement. Hypothesis: Freeze-dried PRP (FD-PRP) as a carrier for ICA can provide sustained release of ICA into the tendon-bone (T-B) healing site, thus accelerating T-B healing. Study Design: Controlled laboratory study. Methods: A total of 84 New Zealand rabbits with partial patellectomy in the hindlimb were randomly allocated into 3 different treatments: ICA incorporated with FD-PRP (ICA/FD-PRP), FD-PRP alone (FD-PRP), or saline control (CTL). The rabbit patella–patellar tendon (PP) interfaces were postoperatively harvested at postoperative week 8 or 16 for gross, radiological, histological, and mechanical evaluations. Results: Our results showed that FD-PRP can act as a carrier for sustained release of ICA into the T-B healing site. Macroscopically, no signs of infection or osteoarthritis were shown in the regenerated PP interfaces, and the area of cartilaginous metaplasia in the FD-PRP and ICA/FD-PRP groups at postoperative week 16 was significantly larger than that of the CTL group (P < .05 for all). Radiologically, micro–computed tomography showed that new bone which formed at the healing site in the ICA/FD-PRP group was significantly increased, remodeled, and mineralized in comparison with the CTL group (P < .05 for all). Histologically, the ICA/FD-PRP group exhibited a significant native PP interface, as shown by the enlargement and remodeling of new bone, well-organized collagen fibers, and robust production of proteoglycans in the regenerated fibrocartilage. The mechanical strength of the regenerated PP interface was significantly improved in the ICA/FD-PRP group. Significantly higher failure load and stiffness were shown in the ICA/FD-PRP group compared with the CTL and FD-PRP groups, respectively (P < .05 for all). Conclusion: FD-PRP is a suitable sustained-release carrier for ICA, and ICA/FD-PRP can provide sustained release of ICA into the T-B healing site, thus effectively accelerating T-B healing. Clinical Relevance: Findings of this study demonstrate the feasibility of using FD-PRP as a carrier for ICA to improve T-B healing and provide a foundation for future clinical application. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate the dosage effect of low-intensity pulsed ultrasound stimulation on tendon-bone healing. Design: Standard partial patellectomies were performed on 120 mature New Zealand rabbits randomly assigned into the following three groups: a control group (daily mock sonication, 20 mins), a qd group (daily ultrasonication, 20 mins), and a bid group (ultrasonication twice a day, 20 mins each time). The rabbits were killed 8 or 16 wks postoperatively, and the microarchitectural, histological, and mechanical properties of the patella-patellar tendon interface were evaluated. Results: Microcomputed tomography analysis showed that the bid group exhibited more new bone formation and mineralization than the other groups in the tendon-bone healing position at both 8 and 16 wks postoperatively. Histological assessments confirmed that the bid group exhibited a significantly better patella-patellar tendon interface than the other groups, as shown by the increased formation and remodeling of newly formed bone and a fibrocartilage layer. The biomechanical properties of the regenerated patella-patellar tendon interface significantly improved in the bid group. Conclusions: Low-intensity pulsed ultrasound stimulation treatment twice a day wasmore effective than the once-a-day treatment on tendon-bone healing. [ABSTRACT FROM AUTHOR]

We investigated the hypothesis that if the area, length, and mineralization of newly formed bone could be used to predict the healing quality of patella-patellar tendon (PPT) junction after partial patellectomy. Twenty-four rabbits underwent partial patellectomy and their PPT complexes of the operated limbs were harvested at weeks 6, 12, and 18 postoperatively. The area, length, and mineralization of newly formed bone at PPT junction healing interface was evaluated radiographically and peripheral quantitative computational tomographically. The healing quality of PPT complexes in terms of its tensile property was determined by biomechanical testing. The results showed that the area, length, and mineral content of newly formed bone, and its tensile strength increased significantly with follow-up time. The area of newly formed bone was strongly correlated with the failure load, ultimate strength and energy at failure ( r = 0.75, 0.76, and 0.70, respectively, p < 0.01 for all). The length of newly formed bone was also found to be correlated with failure load, ultimate strength and energy at failure ( r = 0.61, 0.54, 0.67, respectively, p < 0.01 for all). In addition, the bone mineral content of newly formed bone but not its bone mineral density was moderately correlated with failure load, ultimate strength and energy at failure ( r = 0.44, 0.51, 0.42, respectively, p < 0.05 for all). In conclusion, the area, length, and mineralization of newly formed bone at the PPT junction after partial patellectomy may serve as useful noninvasive indices in assessing the quality of the bone-tendon junction repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:672-677, 2011 [ABSTRACT FROM AUTHOR]

The article focuses on the evaluation of the healing characteristics at the cartilage-to-tendon (C-T) and the bone-to-tendon (B-T) healing junction in rabbits undergoing partial inferior patellectomy. Rabbits were removed with patella-patellar tendon complex. Results show that C-T interface significantly greater with 69.5% and 85.9% than the 45.9% and 60.1% at the B-T interfcae. Findings also indicated tha the C-T junction have better healing process that with the B-T repair at certain week span.

Background: Low-intensity pulsed ultrasound has been demonstrated to be beneficial for accelerating fracture healing, delayed union, nonunion, and soft tissue repair. Hypothesis: Low-intensity pulsed ultrasound accelerates healing of bone-to-tendon junction repair by promoting osteogenesis and tissue remodeling at the healing junction. Study Design: Controlled laboratory study. Methods: Standard partial patellectomy was conducted in forty-eight 18-week-old rabbits divided into an ultrasound treatment and control group. Daily ultrasound was delivered 3 days after surgery onto the patellar tendon-patella healing junction and continuously up to weeks 2, 4, 8, and 16 postoperatively, when the patella-patellar tendon complexes were harvested for radiographic, histologic, and biomechanical evaluations. Results: Radiographic measurements showed significantly more newly formed bone at the patellar tendon-patella healing junction in the ultrasound group compared with the controls at week 8 (4.91 ± 2.74 mm² vs 2.50 ± 1.83 mm², P < .05) and week 16 (7.22 ± 2.34 mm² vs 4.61 ± 2.22 mm², P < .05) after partial patellectomy. Histologically, the ultrasound group at weeks 8 and 16 showed improved tissue integration, characterized by trabecular bone expansion from the remaining patella and regeneration of fibrocartilage layer at the patellar tendon-patella healing junction. Fluorescence microscopy revealed earlier bone formation in the ultrasound group when compared with the controls at week 8 (1.78 ± 0.32 vs 1.23 ± 0.43, P < .01) and week 16 (2.10 ± 0.67 vs 1.29 ± 0.35, P < .01). Mechanical testing showed significantly higher failure load and ultimate strength in the ultrasound group (300.2 ± 61.7 N and 7.10 ± 1.29 MPa, respectively) as compared with controls (222.3 ± 65.1 N and 5.26 ± 1.36 MPa, respectively) at week 16 (P < .05 for both). Conclusion: Low-intensity pulsed ultrasound was able to accelerate bone-to-tendon junction repair. Clinical Relevance: These results may help establish treatment efficacy for accelerating bone-to-tendon junction repair and facilitating earlier rehabilitation. [ABSTRACT FROM AUTHOR]

Clinochlore is a major hydrous mineral in subduction zones, and its thermophysical properties at high temperature and pressure are critical to the thermal structures of subduction zones. Here, we used the pulse heating method to measure thermal diffusivity and thermal conductivity of clinochlore at 0.5-4.0 GPa and 298-1373 K. Our results indicate that upon heating, thermal diffusivity and thermal conductivity decrease from ~9.6 x 10-7 m² s-1 to 4.3 x 10-7 m² s-1 and from ~3.5 W m-1 K-1 to 1.9 W m-1 K-1, respectively, before dehydration, but this trend is reversed after dehydration. In general, the pressure derivatives for the thermal transport properties also decrease with temperature before dehydration. Lattice heat transfer is the dominant mechanism before dehydration, but fluid is involved after dehydration. Using our experimental data, we simulated the temperature distribution of subducting slabs containing clinochlore at volume fractions of 0%, 10%, 20%, 50%, and 100%. Our simulations showed that the heat insulation effect caused by the presence of clinochlore could result in an increase in temperature by 30-60 K for the upper part of the subducting slab. [ABSTRACT FROM AUTHOR]

Hemorrhage and immune cell infiltration are the main pathological features of spinal cord injury (SCI). Excessive iron deposition is caused by leaking hemosiderin which may over-activate ferroptosis pathways, resulting in lipid peroxidation and mitochondrial dysfunction in cells. Inhibiting ferroptosis after SCI has been shown to aid functional recovery. However, the essential genes involved in cellular ferroptosis following SCI are still unknown. Here we show that Ctsb is a statistical significance gene by collecting multiple transcriptomic profiles and identifying differentially expressed ferroptosis-related genes, which are abundantly expressed in myeloid cells after SCI and widely distributed at the epicenter of the injury. The expression score of ferroptosis, calculated by ferroptosis driver/suppressor genes, was high in macrophages. Furthermore, we discovered that inhibiting cathepsin B (CTSB), specifically with a small-molecule drug, CA-074-methyl ester (CA-074-me), reduced lipid peroxidation and mitochondrial dysfunction in macrophages. We also found that alternatively activated M2-polarized macrophages are more susceptible to hemin-induced ferroptosis. Consequently, CA-074-me could reduce ferroptosis, induce M2 macrophage polarization, and promote the neurological function recovery of mice after SCI. Our study comprehensively analyzed the ferroptosis after SCI from the perspective of multiple transcriptomes and provided a novel molecular target for SCI treatment. [ABSTRACT FROM AUTHOR]

The attachment site of the rotator cuff (RC) is a classic fibrocartilaginous enthesis, which is the junction between bone and tendon with typical characteristics of a fibrocartilage transition zone. Enthesis development has historically been studied with lineage tracing of individual genes selected a priori, which does not allow for the determination of single-cell landscapes yielding mature cell types and tissues. Here, in together with open-source GSE182997 datasets (three samples) provided by Fang et al., we applied Single-cell RNA sequencing (scRNA-seq) to delineate the comprehensive postnatal RC enthesis growth and the temporal atlas from as early as postnatal day 1 up to postnatal week 8. And, we furtherly performed single-cell spatial transcriptomic sequencing on postnatal day 1 mouse enthesis, in order to deconvolute bone-tendon junction (BTJ) chondrocytes onto spatial spots. In summary, we deciphered the cellular heterogeneity and the molecular dynamics during fibrocartilage differentiation. Combined with current spatial transcriptomic data, our results provide a transcriptional resource that will support future investigations of enthesis development at the mechanistic level and may shed light on the strategies for enhanced RC healing outcomes. [ABSTRACT FROM AUTHOR]

Proper mechanical stimulation can improve rotator cuff enthesis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prrx1+ cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of Prrx1+ cells to enhance enthesis injury repair. Meantime, TGF-β signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-β1 to promote migration of Prrx1+ cells. Inhibition of TGF-β signaling eliminated the stimulatory effect of mechanical stimulation on Prrx1+ cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-βR2 translocation to the primary cilia or deletion of Ift88 in Prrx1+ cells also restrained the mechanics-induced Prrx1+ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-β1 and enhance the mobilization of Prrx1+ cells to promote enthesis injury repair via ciliary TGF-β signaling. [ABSTRACT FROM AUTHOR]

Water-soluble polyaniline-poly(acrylic acid) (PANI-PAA) composites with excellent processability and electroactivity were prepared by a one-step in situ polymerization. PAA as a matrix not only improves the solubility of PANI in water but also prevents the formation of macroscopic PANI clusters. The corrosion-inhibition performance of 316 stainless steel (316SS) was evaluated in 0.5 M HCl by electrochemical measurements in the presence of PANI-PAA composites. The results show that PANI-PAA acts as a mixed-type inhibitor, and its inhibition efficiency (IE(R)) increases with inhibitor concentration. The adsorption of the inhibitor on 316SS surface obeys a Langmuir adsorption isotherm. The PANI-PAA composite with an optimized concentration of 200 ppm shows marked increase in IE(R), i.e., 91.68%. The enhanced efficiency is attributed to an insulating interfacial layer formed by the adsorption of PANI-PAA, which obstructs the corrosion reaction at the interface. [ABSTRACT FROM AUTHOR]

Background Genetic factors plays an important role in early failure of total hip arthroplasty (THA) etiology and MMP-1 gene polymorphism rs5854 may be involved. The present study was conducted to reveal the possible association between MMP-1 rs5854 C/T polymorphism and the risk of early failure of THA (aseptic loosening). Methods The rs5854 single nucleotide polymorphism (SNP) in MMP-1 gene was genotyped in 63 subjects who were diagnosed as aseptic loosening after total hip arthroplasty within 10 years and in 81 age and gender matched controls. Results The genotype frequencies of the MMP-1 rs5854 C/T polymorphism were 57.1% (CC), 28.6% (CT), and 14.3% (TT) in patients with failure of THA, and 79.0% (CC), 17.3% (CT), and 3.7% (TT) in the controls (P = 0.0099). Rs5854 polymorphism was found to be significantly associated with increased risk of aseptic loosening. Conclusion The results showed the rs5854 SNP was associated with increased risk of the early aseptic loosening susceptibility. [ABSTRACT FROM AUTHOR]

During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these firstgeneration modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective. [ABSTRACT FROM AUTHOR]

The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal-spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression. [ABSTRACT FROM AUTHOR]

The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal -spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression. [ABSTRACT FROM AUTHOR]

Study Design: An advanced imaging of vasculature with synchrotron radiation X-ray in a rat model.Objective: To develop the potential for quantitative assessment of vessel network from two-dimensional (2D) to 3D visualization by synchrotron radiation X-ray phase contrast tomography (XPCT) in rat spinal cord model.Summary Of Background Data: Investigation of microvasculature contributes to the understanding of pathological development of spinal cord injury. A few of X-ray imaging is available to visualize vascular architecture without usage of angiography or invasive casting preparation.Methods: A rat spinal cord injury model was produced by modified Allen method. Histomorphometric detection was simultaneously analyzed by both histology and XPCT from 2D to 3D visualization. The parameters including tissue lesion area, microvessel density, vessel diameter, and frequency distribution of vessel diameter were evaluated.Results: XPCT rendered the microvessels as small as capillary scale with a pixel size of 3.7 μm. It presented a high linear concordance for characterizing the 2D vascular morphometry compared with the histological staining (r = 0.8438). In the presence of spinal cord injury model, 3D construction quantified the significant angioarchitectural deficiency in the injury epicenter of cord lesion (P<0.01).Conclusion: XPCT has a great potential to detect the smallest vascular network with pixel size up to micron dimension. It is inferred that the loss of abundant microvessels (≤40 μm) is responsible for local ischemia and neural dysfunction. XPCT holds a promise for morphometric analysis from 2D to 3D imaging in experimental model of neurovascular disorders.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

The large-scale preparation of ultralarge graphene oxide (ULGO) is urgently needed for developing advanced devices and high-performance nanocomposites. However, it is extremely difficult to produce ULGO in an industrially viable, high-efficiency manner because of the inevitable sheet fragmentation and significant gelation behavior occurred in existing methods. We propose a stationary oxidation-monolithic crystalline swelling strategy that can completely convert graphite to ULGO. This new stationary oxidation method minimizes the sheet fracture and prevents the exfoliation of oxidized layers without sacrificing the oxidation rate, resulting in oxidized flakes with high crystalline and lateral sizes the same as raw graphite. The oxidized graphite flakes undergo a monolithic crystalline swelling during the purification, leading to the formation of a three-dimensional ordered structure without peeling. This enables graphite oxide to be purified by spontaneous sedimentation within 1 h as gelation is avoided and to be exfoliated exhaustively into single-layered ULGO sheets through mild mechanical shaking, with an average size of 108 µm and the largest size of 256 µm. These ULGO sheets can form liquid crystals at a record dispersion concentration (as low as 0.2 mg/mL). The ULGO papers show outstanding mechanical properties and electrical conductivities (after HI reduction) that outperform the reported results. [ABSTRACT FROM AUTHOR]

Study Design: The synchrotron radiation-based micro-computed tomography (SRμCT) and micro-CT (μCT) were applied to comparatively assess the intervertebral disc (IVD) and endplate (EP).Objective: To explore a new approach to evaluate the detailed structure of the IVD and EP during maturation and aging in a murine model.Summary Of Background Data: Till date, methods to observe the morphological changes in the IVD and EP from rodents have been relatively limited. SRμCT has been recognized as a potential way to visualize the structures containing sclerous and soft tissue. Our study focused on comparing the capacity of SRμCT and μCT in evaluating the detailed structure of the IVD and EP.Methods: Both SRμCT and μCT were performed to depict the structure of spinal tissue from 4-month-old mice. Then, the imaging quality was evaluated in the three-dimensional (3D) reconstructed model. Further, the changes in the EP and IVD during the maturation and aging process were assessed morphologically and quantitatively using SRμCT.Results: The 3D reconstructed model of the EP from both μCT and SRμCT provided detailed information on its inner structure. However, the IVD was only depicted using SRμCT. Multi-angle observations of the 3D structure of EP and IVD from mice of different ages (15 days, 2 months, 4 months, and 18 months) were dynamically performed by SRμCT. Quantitative evaluations indicated that the total volume of EP and IVD, the average height of IVD and the canal-total volume ratio of EP increased from 15-day-old mice to 4-month-old mice and decreased in 18-month-old mice.Conclusion: The EP and IVD were clearly visualized using SRμCT. Compared with μCT, SRμCT provided a better ultrahigh resolution image of soft tissue and hard tissue simultaneously, which makes it a promising approach for the noninvasive study of disc degeneration.Level Of Evidence: N /A. [ABSTRACT FROM AUTHOR]

Background/Aims: Spinal tuberculosis (TB) is a common and dangerous form of extrapulmonary TB with unclear mechanisms in its occurrence and progression. This study investigated the clinical significances of bone morphogenetic protein-4 (BMP-4), osteopontin (OPN), and vitamin D receptor (VDR) gene polymorphism, mRNA and protein expression in spinal TB patients. Methods: BMP-4 and OPN gene polymorphisms were detected by direct DNA sequencing, while VDR-FokI polymorphisms were analyzed using PCR-RFLP. mRNA and protein expression was measured using real-time PCR and Western blot, respectively. Results: A significant lower frequency of TT genotype and T allele at 6007C>T polymorphism in BMP- 4 gene; higher frequency of GG genotype and G allele at -66T>G polymorphism in OPN gene, and higher frequency of the ff genotype and f allele at the VDR-FokI polymorphism were observed in patients with spinal TB compared to controls. TT genotype of 6007C>T polymorphism correlated with a lower BMP-4 mRNA and protein expression, -66GG genotype correlated with a high OPN mRNA and protein expression, and ff genotype correlated with the lower VDR mRNA and protein levels in the intervertebral disc tissues. The TT genotype and low BMP-4 gene expression; the -66GG genotype and high OPN gene expression; and the ff genotype and low VDR gene expression significantly correlated with the clinical severity of spinal TB. Conclusion: The 6007C>T polymorphism of BMP-4, -66T>G polymorphism of OPN, and VDR-FokI polymorphism are the susceptible factors of spinal TB and indicators of the clinical severity. These three genes may collaborate in the development of spinal TB. [ABSTRACT FROM AUTHOR]

Previous evidence has suggested that microRNAs (miRNAs or miRs), which belong to a class of non‑coding RNAs, shape cellular processes by regulating gene expression. Abnormal expression of miRNAs has been associated with tumorigenesis in multiple cancers. However, the function of miR‑336 in osteosarcoma (OS) remains unknown. The experimental procedures used in the present study included flow cytometry, reverse transcription‑quantitative polymerase chain reaction, luciferase reporter assay, invasion assay, western blot analysis and in vivo implantation. The results of the present study demonstrated that miR‑336 may serve as a tumor suppressor in OS. Downregulation of miR‑336 was observed in human OS specimens as well as OS cell lines. In addition, a significant negative correlation between sex determining region Y‑box 2 (Sox‑2) expression and miR‑336 was demonstrated. miR‑336 was confirmed to target the 3'‑untranslated region of Sox‑2 to inhibit proliferation, migration and invasion of OS cells. Consistently, restoration of Sox‑2 expression counteracted the effect of miR‑336, and recovered the tumorigenic potential of OS cells. The present study established a novel association between miR‑336 and Sox‑2 in OS. This relationship between miR‑336 and Sox‑2 may lead to improved knowledge concerning OS progression and sheds light on potential novel therapeutic interventions for OS treatment. [ABSTRACT FROM AUTHOR]

The large-scale application of graphene-polymer composites needs a simple, low-cost method that simplifies the preparation process of graphene and optimizes the structure and properties of composites. We propose the first interlayer polymerization in chemically expanded graphite (CEG) with large specific surface areas, which allows CEG to be spontaneously exfoliated into single- and few-layer graphene in poly(methyl methacrylate) (PMMA). Our results demonstrate that besides weakened interlayer interactions, the surface wettability of CEG to monomers is a critical prerequisite for the desired graphene exfoliation, dispersion, and performance optimization of composites. The slightly oxidized CEG (LCEG) improved to some extent the affinity for the monomer but is not sufficient to achieve complete exfoliation of LCEG, so that the resulting composites reveal the mechanical and electrical properties that are far poorer than those of the surface-modified LCEG-based composites. The latter not only exhibit a significantly enhanced elastic modulus, increased as much as 3-fold relative to that of the neat PMMA, but also show an extremely high electrical conductivity, of >1700 S/m. Such a novel interlayer polymerization approach is expected to accelerate the use of industrial applications of a wide range of graphene-based composites. [ABSTRACT FROM AUTHOR]

A full understanding of the mechanisms behind spinal cord injury (SCI) processes requires reliablethree-dimensional (3D) imaging tools for a thorough analysis of changes in angiospatial architecture. We aimed to use synchrotron radiation μCT (SRμCT) to characterize 3Dtemporal-spatialchanges in microvasculature post-SCI.Morphometricalmeasurements revealed a significant decrease invascular volume fraction, vascular bifurcation density, vascular segment density, and vascular connectivity density 1 day post-injury, followed by a gradual increase at 3, 7, and 14 days. At 1 daypost-injury, SRμCT revealed an increase in vascular tortuosity (VT), which reached a plateau after 7 days and decreased slightly during the healing process. In addition, SRμCT imagesshowed that vessels were largely concentrated in the gray matter 1 day post-injury. The maximalendothelial cell proliferation rate was detected at 7 days post-injury. The 3Dmorphology of the cavity appears in the spinal cord at 28 days post-injury. We describe a methodology for 3D analysis of vascular repair in SCI and reveal that endogenous revascularization occurs during the healingprocess. The spinal cord microvasculature configuration undergoes 3D remodeling andmodification duringthe post-injury repair process. Examination of these processesmight contribute to a full understandingof the compensatory vascular mechanisms after injury and aid in the development of novel and effective treatment for SCI. [ABSTRACT FROM AUTHOR]

The production of ultralarge graphene oxide (ULGO) is hindered by sluggish diffusion process of the oxidizing agents into graphite layers, as well as sheet fracture resulting from inhomogeneous oxidation. Previous methods rely on an excess amount of oxidants or multiple oxidation to overcome large diffusion resistance, but at the cost of ULGO yield and environmental risk. Here, we discover the chemical expansion of graphite (CEG) with high solvent-accessible surface areas can effectively boost mass diffusion and facilitate exhaustive oxidation at low oxidant dosage (2 wt equiv). The oxidizing reaction is therefore controlled by the chemical reactivity of graphite with oxidant rather than the diffusion of oxidant, which results in a ∼100% yield of ULGO nanosheets with an area-average size of 128 μm. The worm-like structure of CEG and its oxide provides a chance to recover excess sulfuric acid using a 100-mesh filter, where subsequent exfoliation to ULGO nanosheets is achieved by mild agitation or shaking in several minutes. The ULGO paper prepared by blade casting exhibits superior mechanical properties (Young's modulus of 11.9 GPa and tensile strength of 110.8 MPa) and electrical conductivity (∼613 S/cm after HI reduction). [ABSTRACT FROM AUTHOR]

Study Design: The micro-computed tomography (micro-CT) was applied to assess the effect of tetramethylpyrazine (TMP) on experimental spinal cord injury (SCI).Objective: The aim of the study was to explore the therapeutic effect of TMP on a rat SCI model using micro-CT.Summary Of Background Data: SCI is a devastating event and always accompanied by severe vascular injury. Promoting angiogenesis after SCI has recently been recognized as a potential way to enhance the neurological function recovery. How the TMP promotes angiogenesis and improved locomotor function recovery after SCI has, however, not been fully clarified. In this study, we used micro-CT to evaluate the effect on the microvasculature changes after TMP treatment.Methods: The contusion SCI model was induced in rats by a modified Allen's impact method. In the TMP treatment group, rats were injected intraperitoneally with TMP. The control group was treated with saline. Hindlimb motor function was evaluated using the Basso, Beattie, Bresnahan score. Histology was employed to examine the pathological changes and quantified at 28 days after injury. Spinal cord vessel network and angiogenesis were assessed using micro-CT.Results: Angiogenesis was increased in groups treated with TMP compared with rat in the control groups (P < 0.05). Micro-CT vividly depicted the three-dimensional morphology changes of the spinal cord microvasculature after injury and demonstrated more vessels number, vessel volume fraction, and vessel connectivity value in the groups treated with TMP than in the control groups (P < 0.05). In addition, the injury-induced lesion area in TMP group was attenuated in comparison with control groups. Similarly, neurological functions were greatly improved in groups treated with TMP compared with rats in the control groups.Conclusion: Micro-CT is useful for detecting angiogenesis after SCI. TMP therapy reduced the neuronal loss, promoted angiogenesis, and exerted a positive effect on neurological function recovery after SCI.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis. The neuroinflammation following SCI plays an important role during the secondary injury phase. C-C motif chemokine ligand 20 (CCL20) works like a magnet to attract inflammatory cells and subsequently regulate inflammation. However, the role and mechanisms of CCL20 in neuroinflammation following traumatic injury are poorly understood.Methods: A modified Allen's weight drop method was applied to induce a rat moderate contusion injury model. HE staining was used to assess spinal cord histopathology, and the water content test was used to estimate spinal cord edema. Motor function scores were quantified to evaluate locomotor ability, and leukocyte infiltration was observed by CD45 immunofluorescence and flow cytometry. Additionally, qRT-PCR and ELISA were used to determine inflammatory mediator gene expression. Th17 cell recruitment was identified by flow cytometry.Results: Compared with the injury control groups, histological analysis of the lesion area and tissue edema revealed reduced spinal cord edema and decreased lesion volume in the group administrated with CCL20 neutralizing antibody. Locomotor activity, as assessed by Basso, Beattie, and Bresnahan (BBB) score, showed that CCL20 blockade was beneficial for motor function recovery. Results also showed that leukocyte infiltration was reduced by neutralizing CCL20 at 7 days post-injury. More importantly, expression levels of IL-1β, IL-6, and TNF-α at 24 h after SCI demonstrated that a reduced inflammatory reaction in the CCL20 antibody group compared with the injury controls. Although CCL20 altered the expression of IL-1β, IL-6, and TNF-α, it had no effect on anti-inflammatory IL-10 expression at 24 h after damage. Notably, tissue flow cytometry confirmed that Th17 cell recruitment in the CCL20 antibody group was decreased compared with the control groups at 14 days post-injury. Additionally, IL-17A expression, which is mainly secreted by Th17 cell, suggested that CCL20 blockade also reduced IL-17A levels at 14 days after SCI.Conclusions: These results suggested that CCL20 aggravates neuroinflammation following SCI via regulation of Th17 cell recruitment and IL-17A level. Thus, CCL20-target therapy could be a promising clinical application for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Spontaneous exfoliation of MoS2 is achieved in H2O2-NMP mixed solvents with a yield of over 60 wt%, operated under mild conditions. H2O2-prompted sheet-tailoring effect induces a size evolution of MoS2 nanosheets from micro-scale to nano-scale. Furthermore, the concurrent dissolution also affords an approach to introduce structural defects in the nanosheets. [ABSTRACT FROM AUTHOR]

Background: Porous biphasic calcium phosphate (BCP) ceramics exhibit good biocompatibility and bone conduction but are not inherently osteoinductive. To overcome this disadvantage, we coated conventional porous BCP ceramics with nano-hydroxyapatite (nHA). nHA was chosen as a coating material due to its high osteoinductive potential. Methods: We used a hydrothermal deposition method to coat conventional porous BCP ceramics with nHA and assessed the effects of the coating on the physical and mechanical properties of the underlying BCP. Next, its effects on mesenchymal stem cell (MSC) attachment, proliferation, viability, and osteogenic differentiation were investigated. Results: nHA formed a deposited layer on the BCP surface, and synthesized nHA had a rod-like shape with lengths ranging from ~50–200 nm and diameters from ~15–30 mm. The nHA coating did not significantly affect the density, porosity, flexural strength, or compressive strength of the underlying BCP (P > 0.1). Scanning electron microscopy showed MSC attachment to the scaffolds, with a healthy morphology and anchorage to nHA crystals via cytoplasmic processes. The densities of MSCs attached on BCP and nHA-coated BCP scaffolds were 62 ± 26 cells/mm2 and 63 ± 27 cells/mm2 (P > 0.1), respectively, after 1 day and 415 ± 62 cells/mm2 and 541 ± 35 cells/mm2 (P < 0.05) respectively, after 14 days. According to an MTT assay, MSC viability was higher on nHA-coated BCP scaffolds than on BCP scaffolds (P < 0.05). In addition, MSCs on nHA-coated BCP scaffolds produced more alkaline phosphatase, collagen type I, and osteocalcin than MSCs on BCP scaffolds (P < 0.05). Conclusions: Our results demonstrate that BCP scaffolds coated with nHA were more conducive for MSC adhesion, proliferation, and osteogenic differentiation than conventional, uncoated BCP scaffolds, indicating that nHA coating can enhance the osteoinductive potential of BCP ceramics, making this material more suitable for applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

The high surface area of graphene nanosheets (GNs) enables them to load metal nanoparticles (NPs) for various applications such as catalysis, sensors and biomedicine. To optimize the performance, it is desired to establish an effective approach that can tune the morphology of metal nanoparticles (NPs) on GNs. We here demonstrate that GN-poly(acrylic acid) (GN/PAA) brushes can control the size and spatial distributions of iron and silver NPs. Results of Raman, Fourier transform infrared and x-ray photoelectron spectroscopy confirm the covalent bonding between PAA chains and GNs. Thermogravimetric analysis reveals a PAA grafting density of ∼0.055 chain nm-2. Transmission electron microscopy is used to study the effect of PAA chain length and precursor concentration on the morphology of the metal NPs deposited on PAA brushes and graphene oxide (GO). Short PAA brushes are found to be effective for controlling the spatial and size distributions of the NPs, resulting in small particle sizes and homogeneous distributions compared to those deposited on GO. The concentration of precursors has a limited effect on the dimension of the NPs in the brushes due to the key role that polyelectrolyte brushes play in controlling the growth of NPs. [ABSTRACT FROM AUTHOR]

Silicate nanorods (attapulgite, ATT) were organically modified and homogeneously dispersed in a cyanate ester (CE) resin. ATT dispersions and networks were characterized by rheological and microscopic measurements. Amine groups grafted onto the particle surface catalyzed the cyclotrimerization of the CE monomers and enabled the CE monomers to enter the inter-rod spacing of loose aggregates easily, resulting in homogenization of the particle size distribution in the nanocomposites. The addition of nanorods decreased the density of organic networks and increased intracyclizations. Covalent bonding at the interface was confirmed by Fourier transform infrared (FTIR) spectroscopy and dynamic mechanical analysis (DMA), which establishes a basis for enhancing/optimizing mechanical properties of CE resins. Nanocomposite modulus, strength, and toughness increased 40, 42, and 55%, respectively, relative to the neat resin, although high nanorod loadings (e.g., 8 wt %) showed negligible benefit. The interplay between nanorod and resin networks governed the mechanical properties of the nanocomposites. The curing reaction decreased the size of particle aggregates and thus reduced the percolation threshold of particle networks. Particle networks induced the formation of more linear or branching polymer molecular structures, resulting in weaker particle−matrix interactions. These factors reduced the stress transfer efficiency and crack propagation resistance, impairing the extent of reinforcing at high particle loadings. [ABSTRACT FROM AUTHOR]

Single-walled carbon nanotubes (SWNTs) with high covalent bonding density of polymer layers have been prepared by a “grafting to” approach, where the benzyl chloride groups of styrene copolymers (Mn47 600) reacted with the alkyne groups on SWNTs under relatively mild conditions, resulting in a higher grafting efficiency, as high as 81 wt % of (TGA). Microscopic observations clearly displayed the uniform, thick polymer layers formed on the SWNT surface. The high density of covalent bonding between polymer and nanotubes was confirmed by Raman, 1H NMR, and FTIR, which makes them well dissolved in organic solvents and homogeneously dispersed in polymer matrices. The in situ UV−vis observations during the dissolution indicated that for such a multifunctional system almost no cross-links occurred between SWNTs due to the physical absorption and steric hindrance of polymer chains during the functionalization of SWNTs. The functionalized SWNTs exhibited a pronounced effect on the mechanical properties of polystyrene composites. Only 0.06 wt % of SWNTs resulted in 82% and 78% of increases in tensile strength and elastic modulus of the composites, respectively, indicating an efficient interfacial stress transfer between SWNTs and polymer. [ABSTRACT FROM AUTHOR]

Purpose. To investigate cloning, expression, and mutation analysis of the putative candidate tumor suppressor gene related with nasopharyngeal carcinoma (NPC). Methods. We studied the expression profiles in the NPC cell line HNE1 with the normal nasopharyngeal epithelial cell as control by using cDNA array representing 11,000 cDNA clusters. EST W95442 was found down-regulated in HNE1. Subsequently, the corresponding gene sequence including this EST was established by cDNA cloning and the RACE (rapid amplification of cDNA end) procedure. The expression pattern of this gene was examined by using Northern blot analysis in various human tissues. Furthermore, we screened the mutations of the coding sequence of the gene using reverse transcription-polymerase chain reaction and single-strand conformation polymorphisms (RT-PCR-SSCP) as well as direct sequencing analysis. Results. A novel gene (GenBank accession No. AF462348) was cloned and named NOR1 standing for oxidored-nitro domain-containing protein 1 (Human Gene Nomenclature Committee-approved symbol). Northern blot analysis revealed that the NOR1 gene had two transcripts (1.2 kb, 1.6 kb), and expressed ubiquitously in human tissues. Moreover, a Glu58Gly mutation in the exon 1 of NOR1 was detected in two of 25 NPC biopsies. Conclusions. We cloned a novel gene NOR1, and the Glu58Gly polymorphism of NOR1 may be involved in the development and/or progression of NPC suggesting that NOR1 could be a candidate tumor repressor gene related with NPC. [ABSTRACT FROM AUTHOR]

Silver nanowire (Ag NW) based films are considered as a promising alternative for traditional indium tin oxide but still suffer from some limitations, including insufficient conductivity, transparency and environmental instability. We here report a novel etching synthesis strategy to improve the performance of Ag NW films. Different from the traditional methods to synthesize high aspect ratios of NWs or employ electrically conductive coatings, we find it effective to reduce the high-reactivity defects of NWs for optimizing the comprehensive performance of Ag NW films. In this strategy etching can suppress the generation of high-reactivity defects and meanwhile the etching growth of NWs can be accomplished in an uneven ligand distribution environment. The resulting Ag NWs are uniformly straight with a sharp-edged structure. The transparent conductive film obtained exhibits simultaneous improvements in electrical conductivity, transparency and air stability. Even after exposure in air for 200 days and no protective coatings, the film can still meet the highest requirement of practical applications, with a figure of merit 361 (i.e., FoM > 350). These results not only demonstrate the importance of defect control in the synthesis of Ag NWs, but also pave a way for further optimizing the performance of Ag NW-based films. [ABSTRACT FROM AUTHOR]