Soluble Organic Cathodes Enable Long Cycle Life, High Rate, and Wide-Temperature Lithium-Ion Batteries.

Organic electrode materials free of rare transition metal elements are promising for sustainable, cost-effective, and environmentally benign battery chemistries. However, severe shuttling effect caused by the dissolution of active materials in liquid electrolytes results in fast capacity decay, limiting their practical applications. Here, using a gel polymer electrolyte (GPE) that is in situ formed on Nafion-coated separators, the shuttle reaction of organic electrodes is eliminated while maintaining the electrochemical performance. The synergy of physical confinement by GPE with tunable polymer structure and charge repulsion of the Nafion-coated separator substantially prevents the soluble organic electrode materials with different molecular sizes from shuttling. A soluble small-molecule organic electrode material of 1,3,5-tri(9,10-anthraquinonyl)benzene demonstrates exceptional electrochemical performance with an ultra-long cycle life of 10 000 cycles, excellent rate capability of 203 mAh g-1 at 100 C, and a wide working temperature range from -70 to 100 °C based on the solid-liquid conversion chemistry, which outperforms all previously reported organic cathode materials. The shielding capability of GPE can be designed and tailored toward organic electrodes with different molecular sizes, thus providing a universal resolution to the shuttling effect that all soluble electrode materials suffer.

Interleukin-37 contributes to the pathogenesis of gout by affecting PDZ domain-containing 1 protein through the nuclear factor-kappa B pathway.

OBJECTIVE: Our objective was to explore the molecular pathogenesis of the onset of gout and the mechanism underlying the effect of interleukin (IL)-37 on PDZ domain-containing 1 (PDZK1) protein through the nuclear factor-κB signaling pathway. METHODS: Real-time PCR and western blotting were used to detect expression of PDZK1 mRNA and protein, respectively, in the HK-2 cell line. The inhibitors pyrrolidine dithiocarbamate (PDTC) and wortmannin were added to HK-2 cells stimulated by IL-37, and changes in PDZK1 protein were detected by western blotting. RESULTS: Based on our previous research, we used 10 µmol/L PDTC. We detected no significant change in PDZK1 at the mRNA level among the IL-37, PDTC+IL-37, and wortmannin+IL-37 groups. With increasing IL-37 concentration, the protein level of PDZK1 increased. After adding wortmannin, the protein level of PDZK1 increased with increasing concentration of IL-37, albeit not significantly, and the level of PDZK1 remained lower than that with IL-37 alone. After adding PDTC, the protein level of PDZK1 showed a trend to decrease with increasing concentrations of IL-37 up to 40 ng/mL. The immunofluorescence results supported the western blot results. CONCLUSIONS: IL-37 can affect protein expression of PDZK1, but not at the translational level, in the pathogenesis of gout.

Performance Enhancement of Polymer Electrode Materials for Lithium-Ion Batteries: From a Rigid Homopolymer to Soft Copolymers.

Synthesizing redox-active units containing polymers is a promising route for improving the cycling stability of organic electrode materials. However, constructing uniform electrode architectures with good polymer dispersion is a big challenge in the case of polymer electrode materials. In this work, we design and synthesize two anthraquinone-containing copolymers and compare their electrochemical performance with that of the corresponding homopolymer. It is uncovered that the copolymers with soft units in the main chain display increased chain flexibility, thus leading to a slightly increased solubility. Because of this, the soft copolymers are less likely to precipitate during solvent volatilization of electrode preparation and thus can form more uniform electrode architectures. The cyclic voltammogram and electrochemical impedance spectroscopy measurements indicate that copolymer electrodes display decreased polarization and improved kinetics compared with the homopolymer electrode. The copolymers exhibit significantly enhanced cycling stability and improved rate performance. After 100 cycles, both copolymers reveal very high capacity retention of above 98%, while the homopolymer retains only 71% of its highest capacity. Moreover, the copolymer can discharge/charge at 1C for over 2000 cycles with almost no capacity fading, indicating excellent long-term cycling performance. This work further demonstrates the importance of molecular structure and electrode architecture in determining the electrochemical performance of polymer electrode materials.

Poorly Soluble 2,6-Dimethoxy-9,10-anthraquinone Cathode for Lithium-Ion Batteries: The Role of Electrolyte Concentration.

In this work, a 9,10-anthraquinone (AQ) derivative functionalized by two methoxy groups, 2,6-dimethoxy-9,10-anthraquinone (DMAQ), was synthesized and its electrochemical performance was comprehensively studied with different electrolyte concentrations. Density functional theory (DFT) calculations demonstrate that there exists a conjugation effect between oxygen atoms of methoxy groups and the AQ skeleton, which could extend the conjugate plane and increase intermolecular interaction. As a result, DMAQ shows considerably reduced solubility in ether solvent/electrolyte and greatly enhanced cycling performance compared with those of AQ. Interestingly, it is found that the electrolyte concentration plays an important role in determining the electrochemical performance. Cycling under a relatively low (2 M) or high (6 M) concentration electrolyte of lithium bis(trifluoromethanesulfonyl)imide in a mixture solvent of 1,3-dioxolane and 1,2-dimethoxyethane (1/1, v/v) displays unsatisfied cell performance. While a moderate electrolyte concentration of 4 M delivers the highest initial capacity and the best cycling stability. The work would shed light on the rational molecular structure design and electrolyte concentration optimization for achieving the high electrochemical performance of organic electrode materials.

Benzoquinone- and Naphthoquinone-Bearing Polymers Synthesized by Ring-Opening Metathesis Polymerization as Cathode Materials for Lithium-Ion Batteries.

Organic electrode materials have attracted great interest for next-generation lithium-ion batteries owing to their merits of low cost, resource sustainability, and environmental friendliness. Dissolution in organic electrolyte is one of critical factors that limit their development, and constructing corresponding polymers is an effective way to prevent it. Herein, the synthesis of benzoquinone- and naphthoquinone-bearing polymers by ring-opening metathesis polymerization of monomers with an exo-type four-membered ring between polymerizable norbornene and redox-active quinone units is reported. They exhibit significantly reduced solubility and clearly enhanced electrochemical performance. In particular, a high capacity (189.7 mAh g-1 at 0.1 C, 1 C=216.1 mA g-1 ), stable cycling (75.6 % capacity retention after 500 cycles at 2 C), and good rate capability (retaining 80.4 % from 0.1 to 2 C) were obtained for the naphthoquinone-bearing polymer, which stand out among naphthoquinone-bearing polymer electrode materials. This work offers rational molecular design and a new polymerization strategy to construct high-performance polymer electrode materials.

Optimization of Molecular Structure and Electrode Architecture of Anthraquinone-Containing Polymer Cathode for High-Performance Lithium-Ion Batteries.

Molecular structure and electrode architecture play very important roles in electrochemical performance of polymer electrode materials for lithium-ion batteries. Here, a series of anthraquinone-containing polymers with linear (with different molecular weights (MWs)) or cross-linked polymer structures were synthesized by (living) ring-opening metatheses (co)polymerization method. The influences of the molecular structures and electrode preparation process on the architectures and electrochemical performance of polymer electrodes were systematically investigated. It was found that the low MW linear polymers suffer from severe dissolution and thus result in low initial capacity and poor cycling stability. Under optimized electrode preparation process, high MW linear polymers can be uniformly composited with conductive additives and binders and deliver stable cycling performance. Cross-linked polymer shows significantly reduced solubility but a severe aggregation problem, leading to very poor electrochemical performance. Our findings shed light on the molecular structure design and electrode preparation process of polymer electrode materials for high-performance rechargeable batteries.

Efficacy and Safety of Loxoprofen Hydrogel Transdermal Patch Versus Loxoprofen Tablet in Chinese Patients with Myalgia: A Double-Blind, Double-Dummy, Parallel-Group, Randomized, Controlled, Non-Inferiority Trial.

BACKGROUND AND OBJECTIVE: Loxoprofen (LOX) is a nonsteroidal anti-inflammatory drug (NSAID). Although oral administration of LOX has been widely prescribed, clinical guidelines for osteoarthritis generally recommend topical rather than oral NSAIDs in specific patients. However, there is limited information on the effects of loxoprofen sodium oral (LOX-O) versus loxoprofen sodium hydrogel transdermal patch (LOX-T) in myalgia patients. Hence, this non-inferiority study was designed to compare the efficacy and safety of LOX-O versus LOX-T in Chinese patients with myalgia. METHODS: In this double-blind, double-dummy, parallel-group, randomized controlled trial, 182 Chinese patients were enrolled and randomized equally to either LOX-T or LOX-O treatment for 2 weeks. Patients in the LOX-T group applied one sheet of the active LOX-T once a day on the affected site and took one placebo tablet three times a day immediately after meals, whereas patients in the LOX-O group applied one sheet of the placebo patch once a day and took one active LOX-O three times a day. Primary endpoint was the proportion of patients with 50% overall improvement or higher at the final visit. The cutoff value of a non-inferiority difference was set as - 10%. RESULTS: In the full analysis set, the primary endpoint of final efficacy rate was 81.3% (n = 91) in the LOX-T group and 72.2% (n = 88) in the LOX-O group. The difference between the two groups was 9.1% [95% confidence interval (CI) - 3.1 to 21.3%], which showed that LOX-T was non-inferior compared with LOX-O. No serious adverse events occurred in either group. CONCLUSIONS: This trial showed the non-inferiority of LOX-T compared with LOX-O in efficacy and safety in Chinese patients with myalgia. Also, the characteristic features of topical LOX-T, such as better compliance and lower risk-benefit ratio, make it more favorable for clinical practice. TRIAL REGISTRATION: The study was registered in the isrctn.com registry (ISRCTN trial ID: ISRCTN16227145).

Ultrasound7 versus ultrasound12 in monitoring the response to infliximab in patients with rheumatoid arthritis.

This study aimed to assess the responsiveness of ultrasonography (US)-7 in patients with rheumatoid arthritis (RA). Eighty-two RA patients were recruited and followed up for 22 weeks. The clinical, laboratory, and X-ray assessments, along with grayscale US (GSUS) and power Doppler US (PDUS) examinations were performed at baseline, 6, 14, and 22 weeks after infliximab treatment. GSUS for synovitis and PDUS for synovitis and paratendinitis/tenosynovitis were assessed by a semi-quantitative (0 to 3) score, while GSUS for paratendinitis/tenosynovitis and bone erosion was qualitatively assessed as absent or present (0 or 1). US scores in both 7-joint (US7) and 12-joint (US12) systems were evaluated. After 6, 14, and 22 weeks of treatment with infliximab, indices such as US scores, 28-joint disease activity (DAS28) score, and tender and swelling joint count were all significantly improved compared to baseline. US7 scores were significantly correlated with that of US12. Strong correlations were identified between most US7 scores with DAS28, health assessment questionnaire (HAQ), and C-reactive protein (CRP) levels. When DAS28 was used as a reference, the US7 cutoff for disease remission was less than 35 for GS + PD and also less than 29 for GS and 1 for PD, respectively. Additionally, the positive percent agreement, negative percent agreement, and overall percent agreement for GS + PD were 77.78, 76.19, and 76.67 %, respectively, which were all higher than that of GS or PD. US7 may be a feasible tool to assess the therapeutic response in RA patients.

Indirect comparison of teriparatide, denosumab, and oral bisphosphonates for the prevention of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.

OBJECTIVE: This study aims to compare the efficacy of teriparatide, denosumab, and oral bisphosphonates for reducing fracture risk in postmenopausal women with osteoporosis. METHODS: We searched the literature, via PubMed, Medline, Embase, and the Cochrane Library, to screen citations from January 1996 to October 2014 for inclusion in this study. A mixed-treatment comparison meta-analysis within a Bayesian framework was performed by WinBUGS version 1.4.3 software. The proportions of women with vertebral fractures and women with nonvertebral fractures were analyzed. RESULTS: Our meta-analysis results indicated that all of the therapies-except etidronate-achieved a statistically significant reduction of fractures compared with placebo. Teriparatide and denosumab were more effective than alendronate and risedronate for reducing vertebral fracture (teriparatide vs alendronate: odds ratio [OR], 1.76; 95% CI, 1.03-2.98; teriparatide vs risedronate: OR, 1.92; 95% CI, 1.13-3.19; denosumab vs alendronate: OR, 1.67; 95% CI, 1.06-2.67; denosumab vs risedronate: OR, 1.84; 95% CI, 1.16-2.92). Teriparatide, denosumab, alendronate, and risedronate also reduced the risk of nonvertebral fracture compared with placebo. Results of subgroup analysis showed that denosumab (OR, 0.6; 95% CI, 0.37-0.98), alendronate (OR, 0.61; 95% CI, 0.39-0.96), and risedronate (OR, 0.63; 95% CI, 0.46-0.86) can reduce the risk of hip fracture and that risedronate (OR, 0.59; 95% CI, 0.4-0.88) can also reduce the risk of upper-arm fracture. CONCLUSIONS: Teriparatide, denosumab, alendronate, and risedronate are effective in reducing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. Furthermore, denosumab, alendronate, and risedronate can reduce the risk of hip fracture, and risedronate can also reduce the risk of upper-arm fracture.

Angiogenic growth factors inhibit chondrocyte ageing in osteoarthritis: potential involvement of catabolic stress-induced overexpression of caveolin-1 in cellular ageing.

OBJECTIVE: Recently, attention has been attracted by the finding that overexpression of caveolin-1 induces cellular senescence in age-related diseases. We aimed to ascertain whether angiogenic growth factors (AGFs) can inhibit interleukin (IL)-1beta-induced senescence in human chondrocytes by downregulation of caveolin-1. METHODS: We investigated the intracellular signalling pathways involved in chondrocyte ageing. Human chondrocytes were isolated from the articular cartilage of patients undergoing arthroplastic knee surgery in osteoarthritis (OA). Chondrocytes were stimulated with or without IL-1beta (10 ng/mL) in the presence or absence of vascular endothelial growth factor, basic fibroblast growth factor or hepatocyte growth factor (20 ng/mL). After 72-h incubation, we observed the expression of caveolin-1 in human chondrocytes by immunohistochemistry, and analysed the protein levels of caveolin-1 by Western blot. We examined the time-course of phosphorylation patterns of mammalian mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K) by Western blot, and used several specific protein kinase inhibitors to evaluate the involvement of the intracellular signalling pathways. Also, chondrocyte replicative lifespan was analyzed in the presence or absence of AGFs. RESULTS: Treatment with AGFs inhibited IL-1beta-induced overexpression of caveolin-1 in human OA chondrocytes. Treatment with AGFs all down-regulated protein levels of IL-1beta-accelerated expression of caveolin-1 in chondrocytes. IL-1beta significantly decreased the cellular replicative lifespan in chondrocytes. Treatment with AGFs prevented the IL-1beta-induced shortening of chondrocyte replicative lifespan. The specific inhibitors for MAPK/extracellular signal-regulated kinase and PI3-K cancelled the AGF-induced downregulation of overexpression of caveolin-1. CONCLUSION: Our results suggest that AGFs downregulated IL-1beta-induced chondrocyte ageing and overexpression of caveolin-1 in human chondrocytes, which is mediated by kinase cascades involving the p42/44 MAP kinase and PI3-K/Akt signalling pathways.

TLR9/TLR7-triggered downregulation of BDCA2 expression on human plasmacytoid dendritic cells from healthy individuals and lupus patients.

Plasmacytoid dendritic cells (pDCs) can produce a large amount of interferon-alpha (IFN-alpha) upon exposure to TLR9 or TLR7 agonists. Human pDCs have been shown to play an important role in the pathogenesis of systemic lupus erythematosus (SLE) through increased production of IFN-alpha. So, how to negatively regulate activation of pDCs and how to evaluate the activation of pDC in SLE patients attract much attention. BDCA2 is selectively expressed on human pDCs, acting as a hallmark of human pDCs. In this study, we showed that BDCA2 expression on pDCs decreased along maturation of pDCs, and TLR7 or TLR9 agonists could further significantly downregulate pDCs to express BDCA2, suggesting that the activated pDCs exhibit decreased expression of BDCA2. Functionally, BDCA2 ligation significantly inhibited upregulation of CD40, CD86 and CCR7 expression, IFN-alpha, IFN-beta and IL-6 production by pDCs stimulated with CpG ODN. Moreover, BDCA2 ligation suppressed CpG ODN-activated pDCs to mediate Th1 response, including T cell proliferation, IFN-gamma production, and CD4(+)CCR5(+)Th1 development, confirming that BDCA2 is a negative regulator of TLR9-dependent activation of human pDCs. BDCA2 expression on pDCs from SLE patients decreased significantly but IFN-alpha production of these patients increased markedly as compared to that from healthy donors. Therefore, these results suggest that downregulation of BDCA2 expression on pDCs may reflect the activation of pDCs accumulated in SLE patients, and may be one marker for indication of the disease activity of SLE patients.

Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis, and gout in Shanghai, China: a COPCORD study.

OBJECTIVE: To carry out a cross-sectional survey on prevalence of musculoskeletal symptoms, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout. METHODS: In Shanghai, 4 communities comprising 7603 inhabitants over 15 years of age in an urban population were randomly selected from 13 communities. Interviews were conducted from September 1997 to March 1998 by trained physicians using the COPCORD Core Questionnaire. Physical and radiographic examinations and serologic tests were carried out when required to classify categories of rheumatic diseases. The diagnoses of RA, systemic lupus erythematosus (SLE), and gout were based on American Rheumatism Association criteria. The diagnosis of AS strictly followed the modified New York criteria of 1984. Crude prevalence rates were standardized according to a standard Chinese population for age and sex structure. RESULTS: A total of 6584 adults (3394 women, 3190 men) were interviewed, and response rate was 86.6%. The age and sex standardized prevalence rate of rheumatic symptoms at any site amounted to 13.3% (95% CI 12.5-14.1%). Symptoms occurred more frequently in the following sites: knee 7.0% (95% CI 6.4-7.6%), lower back 5.6% (95% CI 5.0-6.2%), shoulder 4.7% (95% CI 4.2-5.2%), and neck 2.4% (95% CI 2.0-2.8%). Women complained of rheumatic symptoms more frequently than men. The standardized rates of RA, AS, gout, symptomatic knee osteoarthritis, and soft tissue rheumatism were 0.28% (95% CI 0.15-0.41%), 0.11% (95% CI 0.03-0.19%), 0.22% (95% CI 0.11-0.33%), 4.1% (95% CI 3.6-4.6%), and 3.4% (95% CI 3.0-3.8%), respectively. Two cases of SLE, one case of dermatomyositis, and one case of systemic sclerosis were found. CONCLUSION: Compared with rates in European and Western countries the prevalence rates of RA, AS, and gout are low in Shanghai, China, although the prevalence rates of rheumatic symptoms are high.