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The combination of higher-order topological insulators and valley photonic crystals has recently aroused extensive attentions due to the great potential in flexible and efficient optical field manipulations. Here, we computationally propose a photonic device for the 1550 nm communication band, in which the topologically protected electromagnetic modes with high quality can be selectively triggered and modulated on demand. Through introducing two valley photonic crystal units without any structural alteration, we successfully achieve multi-dimensional coupled topological states thanks to the diverse electromagnetic characteristics of two valley edge states. According to the simulations, the constructed topological photonic devices can realize Fano lines on the spectrum and show high-quality localized modes by tuning the coupling strength between the zero-dimensional valley corner states and the one-dimensional valley edge states. Furthermore, we extend the valley-locked properties of edge states to higher-order valley topological insulators, where the selected corner states can be directionally excited by chiral source. More interestingly, we find that the modulation of multi-dimensional coupled photonic topological states with pseudospin dependence become more efficient compared with those uncoupled modes. This work presents a valuable approach for multi-dimensional optical field manipulation, which may support potential applications in on-chip integrated nanophotonic devices.

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In the quest to connect bulk topological quantum numbers to measurable parameters in real materials, current established approaches often necessitate specific conditions, limiting their applicability. Here we propose and demonstrate an approach to link the non-trivial hierarchical bulk topology to the multidimensional partition of local density of states (LDOS), denoted as the bulk-LDOS correspondence. In finite-size topologically nontrivial photonic crystals, we observe the LDOS partitioned into three distinct regions: a two-dimensional interior bulk area, a one-dimensional edge region, and zero-dimensional corner sites. Contrarily, topologically trivial cases exhibit uniform LDOS distribution across the entire two-dimensional bulk area. Our findings provide a general framework for distinguishing topological insulators and uncovering novel aspects of topological directional band-gap materials, even in the absence of in-gap states.

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Circular RNA (circRNA) dysregulation has been linked to osteoarthritis (OA). The present study investigated the involvement of hsa_circ_0072568 (circ0072568) in OA. The expression of circ0072568 was detected in OA tissues and interleukin (IL)-1ß-stimulated human chondrocytes. After performing dual-luciferase reporter and RNA immunoprecipitation assays, MTT, enzyme-linked immunosorbent assay and western blot analysis were used to assess the functions of circ0072568 in IL-1ß-induced inflammation in chondrocytes in vitro. Circ0072568 was inhibited in OA tissues and the cell model in vitro. Circ0072568 overexpression protected the chondrocytes against IL-1ß-induced inflammation and extracellular matrix (ECM) breakdown. Circ0072568 directly attached to microRNA (miR)-382-5p and enhanced the production of topoisomerase 1 (TOP1). Furthermore, miR-382-5p overexpression or TOP1 knockdown attenuated the effects of circ0072568 in IL-1ß-stimulated human chondrocytes. On the whole, the present study demonstrates that the Circ0072568/miR-382-5p/TOP1 axis is involved in inflammation and ECM degradation in OA. These findings may contribute to the development of potential therapeutic strategies for OA.

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Backgrounds: Rheumatoid arthritis synovial fibroblasts (RASFs) are the primary cells responsible for destruction of marginal cartilage in rheumatoid arthritis (RA). G1dP3, a bioactive peptide derived from galectin-1 domain, possesses potent anti-inflammatory and anti-proliferation properties in RASFs. This study aimed to determine the effects of G1dP3 ferroptosis induction in RASFs and to further clarify the possible mechanisms. Methods: TNF-α was used to establish a RA model in MH7A cells. Cell Counting Kit-8 assays were employed to detect MH7A cell viability with different treatments. The occurrence of ferroptosis was examined by Lipid ROS assay, cellular labile iron pool measurement, reduced glutathione/oxidized glutathione activity, Gpx4 expression and transmission electron microscopy (TEM) morphology observation. Lentiviral-mediated siRNA interference was used to determine the downstream pathway. Results: G1dP3 markedly suppressed MH7A cell viability induced by TNF-α. G1dP3-treated MH7A cells presented the morphological features of ferroptosis. Moreover, G1dP3 triggered ferroptosis in MH7A cells by promoting the accumulation of lipid peroxides as well as iron deposition. Inhibition of ferroptosis alleviated G1dP3-mediated suppression of MH7A cell viability. Furthermore, G1dP3 increased p53 expression, which in turn transcriptionally suppressed SLC7A11, a key component of system Xc - essential for ferroptosis. Knockdown of p53 abrogated the ferroptotic effects of G1dP3 on MH7A cells. Conclusion: Our findings reveal that the bioactive peptide G1dP3 promotes RASFs ferroptosis cell death via a p53/SLC7A11 axis-dependent mechanism, suggesting its potential role in the treatment of RA.

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Aluminum (Al) can actively support plasmonic response in the ultraviolet (UV) range compared to noble metals (e.g., Au, Ag) and thus has broad applications including UV sensing, displays, and photovoltaics. High-quality Al films with no oxidation are essential and critical in these applications. However, Al is very prone to fast oxidation in air, which critically depends on the fabrication process. Here, we report that by leveraging the in situ sputter etching and sputter deposition of a 1 nm tetrahedral amorphous carbon (ta-C) film on the Al nanostructures, Al plasmonic activity can be improved. The prior sputter etching process greatly reduces the oxidized layer of the Al films, and the subsequent sputter deposition of ta-C keeps Al oxidation-free. The ta-C film outperforms the naturally passivated Al2O3 layer on the Al film because the ta-C film has a denser structure, higher permittivity, and better biocompatibility. Therefore, it can effectively improve the plasmonic response of Al and be beneficial to molecule sensing, which is proved in our experiments and is also verified in simulations. Our results can enable the various applications based on plasmon resonance in the UV range.

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BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that leads to small joints irreversible destruction. Despite intense efforts, the pathophysiology of RA currently remains unclear. We aimed to gain insight into the pathophysiology process in peptidomic perspective and to identify bioactive peptides for RA treatment. METHODS: The endogenous peptides in synovial tissue between control and rheumatoid arthritis group were identified by liquid chromatography-mass spectrometry (LC-MS/MS). Since the biological function of peptides were always associated with precursor proteins, the potential function of the differentially peptides were predicted by GO and pathway analysis of their precursors. Besides, peptides located in the domains of their precursors were identified. Finally, we determined the impact of galectin-1 derived peptide by administration on the damage to MH7A cells caused by TNF-α. RESULTS: Totally, 141 down-regulated peptides and 10 up-regulated peptides were identified (Fold change > 1.5 and P < 0.05). It indicated that these differentially peptides were tightly involved in the pathophysiology process of RA preliminarily. Finally, we identified a peptide derived from the domain of galectin-1 could inhibit the abnormal proliferation induced by TNF-α and promoted apoptosis of MH7A. CONCLUSION: In summary, our study provided a better understanding of endogenous peptides in RA. We found a peptide that might be used in anti-RA treatment.

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Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA), and adipose-derived mesenchymal stromal cells (ADSCs) can inhibit experimental collagen-induced arthritis model. This study aims to determine whether ADSCs also suppresses osteoclastogenesis and bone erosion in collagen-induced arthritis (CIA). Osteoclasts were induced from bone marrow-derived CD11b+ cells with receptor activator of nuclear factor-κ B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) stimulation and assessed with tartrate-resistant acid phosphatase (TRAP) staining. For human cells, osteoclasts were produced from human CD14+ cells. ADSCs were generated and added to cultures with different ratios with CD11b+ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF-κB and RANKL expression were determined by Western blotting and RT-qPCR. About 2 × 106 ADSCs or fibroblast cells were adoptively transferred to DBA1/J mice on day 14 after immunization with type II collagen/complete Freund's adjuvant (CII/CFA) while the onset and severity of the CIA were monitored. Adipose-derived mesenchymal stromal cells but not fibroblast cells completely suppressed osteoclastogenesis in vitro for human and mice. ADSCs injected after immunization and before of onset of CIA significantly suppressed disease development. Treatment with ADSCs dramatically decreased the levels of NF-κB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. We have demonstrated that ADSCs can inhibit RANKL-induced osteoclasts genesis via CD39 signals. Our findings also suggest that ADSCs can inhibit osteoclasts genesis without the involvement of regulatory T cells. ADSCs might represent a promising strategy for stem cell-based therapies for RA. Thus, manipulation of ADSCs may have therapeutic effects on RA and other bone erosion-related diseases.

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Repair of articular cartilage defects using bilayered scaffolds is problematic because tissue-engineered cartilage is prone to overgrowth toward subchondral bone, resulting in structural abnormalities of cartilage and subchondral bone. A "twice freeze-drying" technique was used to construct a dense isolation layer between the cartilage and subchondral bone layers in an integrated bilayered scaffold to prevent cartilage from excessive downgrowth. Briefly, beta-tricalcium phosphate was used for the subchondral bone layer of the scaffold, high-concentration chitosan/gelatin solution for the dense isolation layer, and low-concentration chitosan/gelatin solution for the cartilage layer. As controls, cell-free trilayered scaffolds, autologous osteochondral transplantation, and the bilayered scaffolds were used for repair of osteochondral defects. After 6 months, two of the eight goats in the bilayered scaffold group showed conspicuous cartilage downgrowth, whereas no excessive downgrowth of cartilage was observed in the trilayered scaffold group. Moreover, there was no difference in the repair efficacy between the trilayered scaffold and mosaicplasty group. The results confirmed that the trilayered scaffold effectively prevented cartilage downgrowth with better cartilage repair.

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To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-ß1 by 7.7-fold, and IGF-1 by 3.6-fold (p < 0.05), and platelets were increased in PRP by 2.9-fold, and TGF-ß1 by 3.3-fold (p < 0.05). From the sixth week post-operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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BACKGROUND/AIMS: Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. Global adiponectin (gAPN), secreted from adipose tissue, possesses potent anti-inflammatory and antiapoptotic properties in various cell types. This study aimed to investigate the role of autophagy induced by gAPN in the suppression of H2O2-induced apoptosis and the potential mechanism of gAPN-induced autophagy in chondrocytes. METHODS: H2O2 was used to induce apoptotic injury in rat chondrocytes. CCK-8 assay was performed to determine the viability of cells treated with different concentrations of gAPN with or without H2O2. Cell apoptosis was detected by flow cytometry and TUNEL staining. Mitochondrial membrane potential was examined using JC-1 fluorescence staining assay. The autophagy inhibitors 3-MA and Bafilomycin A1 were used to treat cells and then evaluate the effect of gAPN-induced autophagy. To determine the downstream pathway, chondrocytes were preincubated with the AMPK inhibitor Compound C. Beclin-1, LC3B, P62 and apoptosis-related proteins were identified by Western blot analysis. RESULTS: H2O2 (400 µM)-induced chondrocytes apoptosis and caspase-3 activation were attenuated by gAPN (0.5 µg/mL). gAPN increased Bcl-2 expression and decreased Bax expression. The loss of mitochondrial membrane potential induced by H2O2 was also abolished by gAPN. Furthermore, the antiapoptotic effect of gAPN was related to gAPN-induced autophagy by increased formation of Beclin-1 and LC3B and P62 degradation. In particular, the inhibition of gAPN-induced autophagy by 3-MA prevented the protective effect of gAPN on apoptosis induced by H2O2. Moreover, gAPN increased p-AMPK expression and decreased p-mTOR expression. Compound C partly suppressed the expression of autophagy-related proteins and restored the expression of p-mTOR suppressed by gAPN. Thus, the AMPK/mTOR pathway played an important role in the induction of autophagy and protection of H2O2-induced chondrocytes apoptosis by gAPN. CONCLUSIONS: gAPN protected chondrocytes from H2O2-induced apoptosis by inducing autophagy possibly associated with AMPK/mTOR signal-pathway activation.

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The inflammatory cytokine interleukin 17 (IL-17) is an important contributor of rheumatoid arthritis (RA) chronicity. Although several microRNAs (miRNAs) have been shown to regulate RA pathogenesis, the function of miRNAs in articular chondrocytes during rheumatoid arthritis pathogenesis is unclear. Here we showed that miR-23a was downregulated in articular cartilage tissues from rheumatoid arthritis patients. MiR-23a suppressed IL-17 inflammatory cytokine-induced NF-κB activation and several proinflammatory mediators expression, such as cytokine IL-6, chemokine MCP-1, and matrix metalloproteinase MMP-3 in articular chondrocytes. Furthermore, we found that the miR-23a expression was inversely correlated with IKKα expression in articular cartilage tissues from rheumatoid arthritis patients. We identified that IKKα was the direct target of miR-23a and miR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting the IKKα in primary articular chondrocytes. Together, our study provides the first evidence of a role for miR-23a regulated IL-17-mediated proinflammatory mediators expression in rheumatoid arthritis by directly targeting IKKα. Our findings provide novel evidence that may be useful for future studies exploring therapeutic approaches for rheumatoid arthritis by targeting miR-23a. Thus, miR-23a may be a common therapeutic target for rheumatoid arthritis.

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The aim of the present study was to investigate the protective mechanism of ginsenoside Rg1 against the apoptosis of rat bone marrow stem cells (rBMSCs) under oxidative stress, and to determine the association with the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. H2O2 was used to induce oxidative injury in rBMSCs. The cells in the H2O2 model group were treated with 800 µM H2O2 for 6 h to induce oxidative injury. The cells in the ginsenoside Rg1 group were treated with 10 µM ginsenoside Rg1 for 24 h, followed by H2O2 treatment. The cells in the Akt pathway blockage group were treated with 25 µM LY294002 for 1 h, followed by ginsenoside Rg1 + H2O2 treatment. The cell counting kit-8 assay was performed to determine cell viability. Cell apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results of flow cytometry and TUNEL staining indicated that the apoptotic rate of the H2O2 model group was significantly higher compared with that of the control group. Following the ginsenoside Rg1 pretreatment, the apoptotic rate was significantly reduced. In the Akt pathway blockage group, no significant alterations in the levels of cell apoptosis were observed compared with the H2O2 model group. Western blot analysis demonstrated that the ginsenoside Rg1 group had a significant downregulation of Bax and cleaved caspase­3 and an upregulation of Bcl­2 and phosphorylated Akt protein expression levels compared with the H2O2 model group and the Akt pathway blockage group. In conclusion, ginsenoside Rg1 had a protective effect against the H2O2­induced oxidative stress of rBMSCs, and the specific mechanism may be associated with the activation of the PI3K/Akt pathway by ginsenoside Rg1.

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Cytotoxic T lymphocyte antigen-4 (CTLA-4), a key gene that contributes to the susceptibility and clinical course of cancer, is an important down-regulator of T cell activation and proliferation. The +49A/G polymorphism is commonly studied because of its association with cancer risks. However, other polymorphisms, such as -1722T/C and -1661A/G, have not been studied in detail. We performed a meta-analysis using 43 eligible case-control studies with a total of 19,089 patients and 21,388 controls to examine the association between CTLA-4 +49A/G, -1722T/C, and -1661A/G polymorphisms and cancer risk. We searched the PubMed and EMBASE databases for all articles published up to July 17, 2013. Individuals with the +49 A allele (AA/AG vs. GG, odds ratio (OR) = 1.21, 95% confidence interval (95% CI) = 1.16-1.27) and -1661 G allele (AG/GG vs. AA, OR = 1.52, 95% CI = 1.34-1.73) had increased cancer risk. However, no significant association between cancer risk and the -1722T/C polymorphism was found (CC/CT vs. TT, OR = 1.04, 95% CI = 0.92-1.16). In subgroup analysis for the +49A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.25, 95 % CI = 1.18-1.31), patients with breast cancer (OR = 1.28, 95% CI = 1.15-1.42), and patients with lung cancer (OR = 1.20, 95 % CI = 1.07-1.35). For the -1661A/G polymorphism, increased cancer risk remained in the subgroups of Asians (OR = 1.52, 95% CI = 1.34-1.73), patients with breast cancer (OR = 1.48, 95% CI = 1.07-2.03), and patients with oral cancer (OR = 3.16, 95% CI = 1.84-5.45). However, no significant increase in cancer risk was found in the subgroups for the -1722T/C polymorphism. In conclusion, the results suggest that +49A/G and -1661A/G polymorphisms in CTLA-4 are risk factors for cancers, whereas the -1722T/C polymorphism is not associated with an increased risk of cancer.

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