1,3,5-Tris(2H-tetra­zol-5-ylmeth­oxy)­benzene

The title compound, C12H12N12O3, was obtained by the hydro­thermal reaction of 1,3,5-tricyano­methoxy­benzene and (CH3)3SiN3. The mol­ecule is almost planar, with an r.m.s. deviation of 0.0976 Å from the plane through all atoms in the mol­ecule. The three tetra­zole rings make dihedral angles of 13.09 (19), 2.01 (19) and 11.56 (18)° with one another and corresponding angles of 8.66 (17), 5.44 (16) and 3.51 (17)° with the central benzene ring. In the crystal structure, inter­molecular N—H⋯N hydrogen bonds form well separated one-dimensional planar sheets

Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats

Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophageassociated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs. Copyright © 2015 by The American Association of Immunologists, Inc

Progesterone Attenuates Temporomandibular Joint Inflammation Through Inhibition of NF-κB Pathway in Ovariectomized Rats

Sex hormones may contribute to the symptomatology of female-predominant temporomandibular disorders (TMDs) inflammatory pain. Pregnant women show less symptoms of TMDs than that of non-pregnant women. Whether progesterone (P4), one of the dominant sex hormones that regulates multiple biological functions, is involved in symptoms of TMDs remains to be explored. Freund\u27s complete adjuvant were used to induce joint inflammation. We evaluated the behavior-related and histologic effects of P4 and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the synovial membrane. Primary TMJ synoviocytes were treated with TNF-α or IL-1β with the combination of P4. Progesterone receptor antagonist RU-486 were further applied. We found that P4 replacement attenuated TMJ inflammation and the nociceptive responses in a dose-dependent manner in the ovariectomized rats. Correspondingly, P4 diminished the DNA-binding activity of NF-κB and the transcription of its target genes in a dose-dependent manner in the synovial membrane of TMJ. Furthermore, P4 treatment showed decreased mRNA expression of proinflammatory cytokines, and partially reversed TNF-α and IL-1β induced transcription of proinflammatory cytokines in the primary synoviocytes. Moreover, progesterone receptor antagonist RU-486 partially reversed the effects of P4 on NF-κB pathway. In conclusion, progesterone ameliorated TMJ inflammation through inhibition of NF-κB pathway. © 2017 The Author(s)

InAlN/GaN MOSHEMTs with high drain current of 2.3 A/mm high on/off ratio of 1012 and low SS of 64 mV/dec enabled by atomic-layer-epitaxial MgCaO as gate dielectric

Summary form only given. Recently, GaN-based high-electron-mobility-transistor (HEMT) has demonstrated its promise in high frequency, high power and low noise electronic devices. The lattice matched InAlN/GaN HEMT structure provides a higher 2D electron density than AlGaN/GaN due to a larger bandgap offset and minimized short-channel-effects due to its thinner barrier. However, because of its several-nm thin barrier, those devices usually suffer from high gate leakage and interface trap issues, the device off-state performance is degraded and thereby the off-state breakdown voltage is decreased. Therefore, finding a good method to reduce the gate leakage and interface trap density is of great importance to improve the device off-state performance. In this study, we use atomic layer epitaxial MgCaO as gate dielectric to fabricate sub-100nm InAlN/GaN MOSHEMTs with significantly improved maximum drain current, current on/off ratio and low subthreshold swing.Chemistry and Chemical Biolog

Thin film modeling of crystal dissolution and growth in confinement

We present a continuum model describing dissolution and growth of a crystal contact confined against a substrate. Diffusion and hydrodynamics in the liquid film separating the crystal and the substrate are modeled within the lubrication approximation. The model also accounts for the disjoining pressure and surface tension. Within this framework, we obtain evolution equations which govern the non-equilibrium dynamics of the crystal interface. Based on this model, we explore the problem of dissolution under an external load, known as pressure solution. We find that in steady-state, diverging (power-law) crystal-surface repulsions lead to flat contacts with a monotonic increase of the dissolution rate as a function of the load. Forces induced by viscous dissipation then surpass those due to disjoining pressure at large enough loads. In contrast, finite repulsions (exponential) lead to sharp pointy contacts with a dissolution rate independent on the load and on the liquid viscosity. Ultimately, in steady-state the crystal never touches the substrate when pressed against it, independently from the nature of the crystal-surface interaction due to the combined effects of viscosity and surface tension

Adenosine A2A Receptors Mediate Anti-Inflammatory Effects of Electroacupuncture on Synovitis in Mice with Collagen-Induced Arthritis

To study the role of adenosine A2A receptor (A2AR) in mediating the anti-inflammatory effect of electroacupuncture (EA) on synovitis in collagen-induced arthritis (CIA), C57BL/6 mice were divided into five treatment groups: Sham-control, CIA-control, CIA-EA, CIA-SCH58261 (A2AR antagonist), and CIA-EA-SCH58261. All mice except those in the Sham-control group were immunized with collagen II for arthritis induction. EA treatment was administered using the stomach 36 and spleen 6 points, and stimulated with a continuous rectangular wave for 30 min daily. EA treatment and SCH58261 were administered daily from days 35 to 49 (n=10). After treatment, X-ray radiography of joint bone morphology was established at day 60 and mouse blood was collected for ELISA determination of tumor necrosis factor alpha (TNF-α) levels. Mice were sacrificed and processed for histological examination of pathological changes of joint tissue, including hematoxylin-eosin staining and immunohistochemistry of A2AR expression. EA treatment resulted in significantly reduced pathological scores, TNF-α concentrations, and bone damage X-ray scores. Importantly, the anti-inflammatory and tissue-protective effect of EA treatment was reversed by coadministration of SCH58261. Thus, EA treatment exerts an anti-inflammatory effect resulting in significant protection of cartilage by activation of A2AR in the synovial tissue of CIA

Repeated Electroacupuncture Persistently Elevates Adenosine and Ameliorates Collagen-Induced Arthritis in Rats

The aim of this paper was to investigate the effect of repeated electroacupuncture (EA) over 21 days on the adenosine concentration in peripheral blood of rats with collagen-induced arthritis (CIA). Wistar rats were divided into three groups of 6 animals each: sham-control, CIA-control, and CIA-EA. We determined the adenosine concentration in peripheral blood and assessed pathological changes of ankle joints. Quantitative reverse-transcription-polymerase chain reaction was used to determine mRNA levels of ecto-5′-nucleotidase (CD73), adenosine deaminase (ADA), and tumor necrosis factor-alpha (TNF-α). Immunohistochemical staining was used to detect expression of ADA and CD73 in synovial tissue. Repeated EA treatment on CIA resulted in the persistence of high concentrations of adenosine in peripheral blood, significantly reduced pathological scores, TNF-α mRNA concentrations, and synovial hyperplasia. Importantly, EA treatment led to a significant increase in CD73 mRNA levels in peripheral blood but was associated with a decrease of CD73 immunostaining in synovial tissue. In addition, EA treatment resulted in a significant decrease of both ADA mRNA levels in peripheral blood and ADA immunostaining in synovial tissue. Thus, repeated EA treatment exerts an anti-inflammatory and immunoregulatory effect on CIA by increasing the concentration of adenosine. The mechanism of EA action may involve the modulation of CD73 and ADA expression levels

PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization

published_or_final_versio

Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1

BACKGROUND: HBO1 (histone acetyltransferase binding to ORC1) is a histone acetyltransferase (HAT) which could exert oncogenic function in breast cancer. However, the biological role and underlying mechanism of HBO1 in breast cancer remains largely unknown. In the current study, we aimed to investigate the role of HBO1 in breast cancer and uncover the underlying molecular mechanism. METHODS: Immunohistochemistry was applied to detect HBO1 protein expression in breast cancer specimens (n = 112). The expression of protein level was scored by integral optical density (IOD) for further statistical analyses using SPSS. Real-time PCR was used to simultaneously measure mRNA levels of HBO1. The HBO1 protein expression in breast cancer cells was confirmed by western blot. RESULTS: HBO1 was highly expressed in breast cancer tissues and significantly correlated with estrogen receptor α (ERα) (p < 0.001) and progestational hormone (PR) (p = 0.002). HBO1 protein level also correlated positively with histology grade in ERα positive tumors (p = 0.016) rather than ERα negative tumors. 17β-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ERα RNAi. E2-increased HBO1 protein expression was significantly suppressed by treatment with inhibitor of MEK1/2 (U0126) in T47 D and MCF-7 cells. CONCLUSIONS: HBO1 was an important downstream molecule of ERα, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2