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OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab&reg, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab&reg, was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab&reg, IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 &plusmn, 2.8. The average TBR over the 10-day period was 5.8 &plusmn, 0.6 in mice injected with Miltuximab&reg, IR800 versus 2.4 &plusmn, 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab&reg, IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab&reg, IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

Links prediction based on supervised learning is a main research topic in the field of complex network analysis. The core process of these methods is that the network is divided into training and target sets, then a classification model is used to learn the training set and forecast the missing links in target set. Such methods have two major challenges: first, we need to dig deep network information to define a set of features; Second, how to incorporate feature selection model to mine discriminative features. To solve the above problem, a model which integrates community features and mRMR feature selection was proposed. Such model first discovered global features associated with the link through the community, then used classical mRMR algorith-m metrics to measure the correlation between features, and filter out the best representative candidates by clearing noisy information. Experimental results show our proposed model can effectively improve the performance of link classification.

Object Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration. Methods A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically. Results No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs. Conclusions These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.

Tantalum oxide films were synthesized by pulsed laser deposition (PLD). The influences of annealing temperatures and oxygen pressures on the crystalline, morphological and optical properties were investigated. Experimental results indicate that annealed film became crystallized in orthorhombic structure at 700 °C. The root-mean-square (RMS) roughness of the film became higher with the increase of annealing temperature. The transmittance and the optical band gap of the film increased with the increase of annealing temperature and the increase of annealing oxygen pressure. In addition and interestingly, crystallinity led to a decrease of transparency due to the increase of scattering losses, which resulted from the polycrystalline structure and the increase of RMS roughness. At the optimized ambience of 600 °C and 20 Pa, the transmittance of the annealed film achieved about 93% (the transmittance of bare substrate) at its peak values. And its optical band gap was 4.18 eV, which was close to the theoretical value of 4.2 eV.

Circumferential tears of the Annulus Fibrosus (AF) are frequently observed pathological features of degenerate lumbar discs and have been associated with vascular propagation and the generation of low back pain. In order to evaluate the potential of novel biological agents to repair annular defects and arrest disc degeneration we required an animal model that would permit injection of cells or their cryoprotectant into adjacent lumbar discs of the same animal. Three lumbar discs (L2/3, L3/4 and L4/5) of 6 sheep were subjected to a peripheral lateral annular surgical incision. The adjacent uninjured lumbar L1/2 and L5/6 discs served as uninjured controls. After three months the spines were radiographed and disc height indices (DHI) calculated and Pfirrmann disc degeneration scores determined from MRI spinal images. Isolated lumbar discs were analysed morphologically, histologically and biochemically using published procedures. Disc height index measurements of injured discs revealed an average decrease of 23.67% relative to baseline values (p

Silicon dioxide (SiO 2 ) film is an important material for semiconductor industry as the gate dielectric material, and optical industry as antireflective coatings, and so on. The sol-gel method has been widely used for the deposition of oxide thin films due to several advantages such as simple and low-cost equipment, normal atmospheric conditions, and ease control of the precursor composition doping. In this work, SiO 2 thin film was deposited on BK7 glass substrate by spin-coating and dip-coating techniques, respectively. Three precursor concentrations were investigated, i.e., tetraethylorthosilicate (TEOS): ethanol: water= 1:7:7, 1:10:10 and 1:15:15 (molar ratio). X-Ray Diffraction spectrometry (XRD), scanning electron microscopy (SEM), and UV-VIS-NIR scanning spectrophotometry were used to characterize the crystallinity, morphological and optical properties of deposited SiO 2 thin films. Results show that all the SiO 2 thin films deposited by the spin-coating and dip-coating are amorphous. SEM analysis confirms that the deposited SiO 2 thin films have high surface quality and tight adherence with the substrate. The transmittance measurements indicate that dip-coated SiO 2 thin film from gel of low precursor concentration represents better transmittance than that from high concentrations at the range of 600-1200nm. SiO 2 thin film spin-coated from gel of high precursor concentration has better transmittance than that by dip-coating, but of opposite results for the films deposited from gels of low precursor concentrations.