Ultrathin MgB2 films fabricated on Al2O3 substrate by hybrid physical-chemical vapor deposition with high Tc and Jc

Ultrathin MgB2 superconducting films with a thickness down to 7.5 nm are epitaxially grown on (0001) Al2O3 substrate by hybrid physical-chemical vapor deposition method. The films are phase-pure, oxidation-free and continuous. The 7.5 nm thin film shows a Tc(0) of 34 K, which is so far the highest Tc(0) reported in MgB2 with the same thickness. The critical current density of ultrathin MgB2 films below 10 nm is demonstrated for the first time as Jc ~ 10^6 A cm^{-2} for the above 7.5 nm sample at 16 K. Our results reveal the excellent superconducting properties of ultrathin MgB2 films with thicknesses between 7.5 and 40 nm on Al2O3 substrate.Comment: 7 pages, 4 figures, 2 table

Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes.

INTRODUCTION: Cartilage degeneration driven by catabolic stimuli is a critical pathophysiological process in osteoarthritis (OA). We have defined fibroblast growth factor 2 (FGF-2) as a degenerative mediator in adult human articular chondrocytes. Biological effects mediated by FGF-2 include inhibition of proteoglycan production, up-regulation of matrix metalloproteinase-13 (MMP-13), and stimulation of other catabolic factors. In this study, we identified the specific receptor responsible for the catabolic functions of FGF-2, and established a pathophysiological connection between the FGF-2 receptor and OA. METHODS: Primary human articular chondrocytes were cultured in monolayer (24 hours) or alginate beads (21 days), and stimulated with FGF-2 or FGF18, in the presence or absence of FGFR1 (FGF receptor 1) inhibitor. Proteoglycan accumulation and chondrocyte proliferation were assessed by dimethylmethylene blue (DMMB) assay and DNA assay, respectively. Expression of FGFRs (FGFR1 to FGFR4) was assessed by flow cytometry, immunoblotting, and quantitative real-time PCR (qPCR). The distinctive roles of FGFR1 and FGFR3 after stimulation with FGF-2 were evaluated using either pharmacological inhibitors or FGFR small interfering RNA (siRNA). Luciferase reporter gene assays were used to quantify the effects of FGF-2 and FGFR1 inhibitor on MMP-13 promoter activity. RESULTS: Chondrocyte proliferation was significantly enhanced in the presence of FGF-2 stimulation, which was inhibited by the pharmacological inhibitor of FGFR1. Proteoglycan accumulation was reduced by 50% in the presence of FGF-2, and this reduction was successfully rescued by FGFR1 inhibitor. FGFR1 inhibitors also fully reversed the up-regulation of MMP-13 expression and promoter activity stimulated by FGF-2. Blockade of FGFR1 signaling by either chemical inhibitors or siRNA targeting FGFR1 rather than FGFR3 abrogated the up-regulation of matrix metalloproteinases 13 (MMP-13) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 5 (ADAMTS5), as well as down-regulation of aggrecan after FGF-2 stimulation. Flow cytometry, qPCR and immunoblotting analyses suggested that FGFR1 and FGFR3 were the major FGFR isoforms expressed in human articular chondrocytes. FGFR1 was activated more potently than FGFR3 upon FGF-2 stimulation. In osteoarthritic chondrocytes, FGFR3 was significantly down regulated (P < 0.05) with a concomitant increase in the FGFR1 to FGFR3 expression ratio (P < 0.05), compared to normal chondrocytes. Our results also demonstrate that FGFR3 was negatively regulated by FGF-2 at the transcriptional level through the FGFR1-ERK (extracellular signal-regulated kinase) signaling pathway in human articular chondrocytes. CONCLUSIONS: FGFR1 is the major mediator with the degenerative potential in the presence of FGF-2 in human adult articular chondrocytes. FGFR1 activation by FGF-2 promotes catabolism and impedes anabolism. Disruption of the balance between FGFR1 and FGFR3 signaling ratio may contribute to the pathophysiology of OA.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain

INTRODUCTION: Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. METHODS: Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. RESULTS: After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. CONCLUSIONS: Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration

Emerging roles of SUMO modification in arthritis

Dynamic modification involving small ubiquitin-like modifier (SUMO) has emerged as a new mechanism of protein regulation in mammalian biology. Sumoylation is an ATP-dependent, reversible post-translational modification which occurs under both basal and stressful cellular conditions. Sumoylation profoundly influences protein functions and pertinent biological processes. For example, sumoylation modulates multiple components in the NFκB pathway and exerts an anti-inflammatory effect. Likewise, sumoylation of peroxisome proliferator-activated receptor γ (PPARγ) augments its anti-inflammatory activity. Current evidence suggests a role of sumoylation for resistance to apoptosis in synovial fibroblasts. Dynamic SUMO regulation controls the biological outcomes initiated by various growth factors involved in cartilage homeostasis, including basic fibroblast growth factors (bFGF or FGF-2), transforming growth factor-β (TGF-β) and insulin-like growth factor-1 (IGF-1). The impact of these growth factors on cartilage are through sumoylation-dependent control of the transcription factors (e.g., Smad, Elk-1, HIF-1) that are key regulators of matrix components (e.g., aggrecan, collagen) or cartilage-degrading enzymes (e.g., MMPs, aggrecanases). Thus, SUMO modification appears to profoundly affect chondrocyte and synovial fibroblast biology, including cell survival, inflammatory responses, matrix metabolism and hypoxic responses. More recently, evidence suggests that, in addition to their nuclear roles, the SUMO pathways play crucial roles in mitochondrial activity, cellular senescence, and autophagy. With an increasing number of reports linking SUMO to human diseases like arthritis, it is probable that novel and equally important functions of the sumoylation pathway will be elucidated in the near future

Salinity effects on soil P cycling

[Methods] The field experiments were conducted in the growing (July) and non-growing seasons (January) in both the freshwater and brackish C. malaccensis wetlands. Three 1 × 1 m quadrats (5 m apart) were randomly established at each site, and three soil cores (0–20 cm) were randomly collected in each quadrat and pooled into one sample. All samples were then stored in a portable refrigerator and immediately transported to the laboratory. The samples were homogenized and then split into two subsamples: one subsample was air-dried for the determination of P fractions and physicochemical parameters, and the other subsample was frozen at −80°C for DNA extraction. Plant biomasses were also collected during each season. We used the Hedley scheme of sequential extraction to estimate the fractions and availabilities of soil P (Hedley et al., 1982), which can effectively distinguish between Pi and Po. Briefly, soil samples were successively extracted using an anion-exchange resin (resin-P), 0.5 M NaHCO3 (NaHCO3-Pi and NaHCO3-Po), 0.1 M NaOH (NaOH-Pi and NaOH-Po), 0.1 M NaOH with sonication (NaOHs-Pi and NaOHs-Po), and 1 M HCl (HCl-Pi). The residual soils were then digested with 4 mL of H2SO4 and 1 mL of HClO4 (residual-P). The concentration of P was measured using a spectrophotometer. The P was further classified as labile P (resin-P, NaHCO3-Pi, and NaHCO3-Po), moderately labile P (NaOH-Pi and NaOH-Po), and stable P (NaOHs-Pi, NaOHs-Po, HCl-P, and residual-P) based on its availability to plants and microbes (Rodrigues et al., 2016). The salinity of the water was measured in situ using a salinometer (Oakton Instruments, Springfield, USA). Soil electric conductivity (EC) and pH were determined using a 2265FS EC meter (Spectrum Technologies Inc., Aurora, USA) and a pH meter (IQ Scientific Instruments, Carlsbad, USA), respectively. Soil moisture was evaluated by determining the amount of water lost at 105°C. Soil organic C (SOC) was analyzed using the dichromate oxidation method. Soil concentrations of total C (TC) and N (TN) were measured using an elemental analyzer (Elementar, Frankfurt, Germany). Soil concentrations of ammonium-N (NH4+-N) and nitrate-N (NO3−-N) were determined using flow-injection analysis (Skalar Analytical SAN++, Lachat, Netherland) and extraction with 2 M KCl. The soil texture was determined using a Mastersizer 2000 particle-size analyzer (Malvern Panalytical Ltd., Melvin, UK). Plant biomasses were measured by drying samples to constant weight at 70°C. Soil microbial DNA was extracted using an OMEGA DNA Kit following the manufacturer’s instructions. The quality and quantity of the extracted DNA were determined using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Waltham, USA) and agarose gel electrophoresis, respectively. The extracted microbial DNA was processed, and metagenomic shotgun sequencing libraries were constructed with insert sizes of 400 bp using an Illumina TruSeq Nano DNA LT Library Preparation Kit. Each library was sequenced on an Illumina HiSeq X-ten platform (Illumina, San Diego, USA) using the PE150 strategy at Personal Biotechnology Co., Ltd. (Shanghai, China). Please refer to the Supporting Information for more detailed descriptions (Appendix I). We obtained a total of 931 million qualified sequences from 12 metagenomes, ranging from 69 million to 88 million sequences per sample for downstream analyses (Table S1). [Usage Notes] The dataset can be opened using regular Office software.Accelerated sea-level rise is expected to cause the salinization of freshwater wetlands, but the responses to salinity of the availability of soil phosphorus (P) and of microbial genes involved in the cycling and transformation of P remain unexplored. Our results suggest that the P-cycling microbial community abundance and P availability respond positively to moderate increases in salinity by promoting the microbial solubilization and mineralization of soil P in brackish wetlands. Changes in microbial communities and microbially mediated P cycling may represent microbial strategies to adapt to moderate salinity levels, which in turn control soil function and nutrient balance.National Natural Science Foundation of China. Natural Science Foundation of Fujian Province. Fundación Ramón Areces Project. Spanish Government. Catalan Government.Peer reviewe

Target identification of baicalein derivative using DNA-programmed photoaffinity labeling

The natural product baicalein derivative baicalein-8-sulfonic acid (BaSO3H) showed significant inhibitory effects on hepatocarcinoma cells viabilities and colony formation, but its molecular target(s) and mechanism were still not clearly elucidated. Using a DNA-programmed photoaffinity labeling method, we identified 12 targets that specifically bound with BaSO3H. Among these, BaSO3H bound with c-Jun N-terminal kinase 2 (JNK2) at an affinity of 33.1 nM (Kd) to induce apoptosis and autophagy in hepatocarcinoma cells

A current review of molecular mechanisms regarding osteoarthritis and

Osteoarthritis afflicts millions of individuals across the world resulting in impaired quality of life and increased health costs. To understand this disease, physicians have been studying risk factors, such as genetic predisposition, aging, obesity, and joint malalignment; however have been unable to conclusively determine the direct etiology. Current treatment options are short-term or ineffective and fail to address pathophysiological and biochemical mechanisms involved with cartilage degeneration and the induction of pain in arthritic joints. OA pain involves a complex integration of sensory, affective, and cognitive processes that integrate a variety of abnormal cellular mechanisms at both peripheral and central (spinal and supraspinal) levels of the nervous system Through studies examined by investigators, the role of growth factors and cytokines has increasingly become more relevant in examining their effects on articular cartilage homeostasis and the development of osteoarthritis and osteoarthritis-associated pain. Catabolic factors involved in both cartilage degradation in vitro and nociceptive stimulation include IL-1, IL-6, TNF-α, PGE2, FGF-2 and PKCδ, and pharmacologic inhibitors to these mediators, as well as compounds such as RSV and LfcinB, may potentially be used as biological treatments in the future. This review explores several biochemical mediators involved in OA and pain, and provides a framework for the understanding of potential biologic therapies in the treatment of degenerative joint disease in the future

Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc

Lactoferricin (LfcinB) antagonizes biological effects mediated by angiogenic and catabolic growth factors, in addition to pro-inflammatory cytokines and chemokines in human endothelial cells and tumor cells. However, the effect of LfcinB on intervertebral disc (IVD) cell metabolism has not yet been investigated. Using bovine nucleus pulposus (NP) cells, we analyzed the effect of LfcinB on proteoglycan (PG) accumulation, PG synthesis, and anabolic gene expression. We assessed expression of genes for matrix-degrading enzymes such as matrix metalloproteases (MMPs) and a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS family), as well as their endogenous inhibitors, tissue inhibitor of metalloproteases (TIMPs). In order to understand the specific molecular mechanisms by which LfcinB exerts its biological effects, we investigated intracellular signaling pathways in NP cells. LfcinB increased PG accumulation mainly via PG synthesis in a dose-dependent manner. Simultaneously, LfcinB dose-dependently downregulated catabolic enzymes. LfcinB\u27s anti-catabolic effects were further demonstrated by a dose-dependent increase in multiple TIMP family members. Our results demonstrate that ERK and/or p38 mitogen-activated protein kinase pathways are the key signaling cascades that exert the biological effects of LfcinB in NP cells, regulating transcription of aggrecan, SOX-9, TIMP-1, TIMP-2, TIMP-3, and iNOS. Our results suggest that LfcinB has anabolic and potent anti-catabolic biological effects on bovine IVD cells that may have considerable promise in the treatment of disc degeneration in the future