Deficiency of sorting nexin 10 prevents bone erosion in collagen-induced mouse arthritis through promoting NFATc1 degradation.

OBJECTIVE: Periarticular and subchondral bone erosion in rheumatoid arthritis caused by osteoclast differentiation and activation is a critical index for diagnosis, therapy and monitoring of the disease. Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation of endosomal sorting, has been implicated to play an important clinical role in malignant osteopetrosis. Here we studied the roles and precise mechanisms of SNX10 in the bone destruction of collagen-induced arthritis (CIA) mice. METHODS: The role of SNX10 in bone destruction was evaluated by a CIA mice model which was induced in male SNX10(-/-) mice and wild type littermates. The mechanism was explored in osteoclasts induced by receptor activator of nuclear factor κB ligand from bone marrow mononuclear cells of wild type and SNX10(-/-) mice. RESULTS: SNX10 knockout prevented bone loss and joint destruction in CIA mice with reduced serum levels of TNF-α, interleukin 1ß and anticollagen IgG 2α antibody. SNX10 deficiency did not block osteoclastogenesis, but significantly impaired osteoclast maturation and bone-resorption function by disturbing the formation of actin belt. The production of TRAP, CtsK and MMP9 in SNX10(-/-) osteoclasts was significantly inhibited, and partially restored by SNX10 overexpression. We further demonstrated that the degradation of NFATc1 was accelerated in SNX10(-/-) osteoclasts causing an inhibition of integrin ß3-Src-PYK2 signalling. CONCLUSIONS: Our study discloses a crucial role and novel mechanism for SNX10 in osteoclast function, and provides evidence for SNX10 as a promising novel therapeutic target for suppression of immune inflammation and bone erosion in rheumatoid arthritis.

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

[Application of grading evaluation on facial nerve function of Bell's palsy treated with electroacupuncture].

OBJECTIVE: To explore the correlation of facial nerve injury degree with facial contraction degree induced by electric stimulation in the treatment of Bell's palsy with electroacupuncture, and the significance in elec tric reaction grading evaluation. METHODS: Sixty-eight cases of Bell's palsy were enrolled. The positive and negative electrodes of the acupuncture treatment apparatus were attached to the needle handles at the 3 groups of points, named Taiyang (EX-HN 5)-Yangbai(GB 14), Xiaguan (ST 7)-Quanliao (SI 18) and Heliao (LI 19)-Jiachengjiang (Extra). The disperse-dense wave was applied. According to the severity of local muscle contraction after needling, the electric reaction was divided into 4 grades, named superior, moderate, poor and no reaction. After acupuncture and electroacupuncture, the efficacy was evaluated in accordance with the different electric reaction grades. METHODS: The curative rate was 100.0% (44/44) in patients with superior electric reaction, was 100.0% (7/7) in patients with moderate electric reaction, was 18.2% (2/11) in patients with poor electric reaction and was 0 (0/6) in patients with noelectric reaction. The difference was significant statistically in comparison of 4 groups (P<0.01). The superiority correlation presented between the efficacy and electric reaction grade (P< 0.001). The higher the superiority of electric reaction grade was, the better the efficacy was. The difference in the efficacy among different electric reaction grades was significant statistically (P<0.001). And the course of treatment was the shortest for those with the high superiority of electric reaction. CONCLUSION: The reaction grade of electric stimulation is conform to the facial nerve injury grading in Bell's palsy. The contraction degree of facial mimetic muscle induced by electroacupuncture stimulation is closely correlated with severity of disease. Based on the electric reaction, the facial nerve injury severity can be understood generally and the prognosis be judged.

Extracellular signal-regulated kinases (ERK) inhibitors from Aristolochia yunnanensis.

Six new sesquiterpenoids, aristoyunnolins A-F (1-6), an artifact of isolation [7-O-ethyl madolin W (7)], and 12 known analogues were isolated from stems of Aristolochia yunnanensis. The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 2, 3, 5-7, 9, 14, and 17 were determined by the modified Mosher's method and CD analysis. Compounds 1-19 were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways. Among three MAPKs (ERK1/2, JNK, and p38), compounds 1, 4, 10-13, 16, 18, and 19 exhibited selective inhibition of the phosphorylation of ERK1/2. Compounds 16 and 19 were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway.

[Characteristics of courtship calls of Microhyla ornata (Anura: Microhylidae)].

During breeding season in May, 2012, we recorded and analyzed the courtship calls and the acoustic parameters of the male Microhyla ornate in Lishui, Zhejiang province using an IC recorder (SX950) and the sound software Praat. We observed that the male M. ornate produced calls characterized by a single harmonic call structure, multiple pulses (7, 9-16) and spindle amplitudes. Analyses of the calls revealed several interesting findings: the dominant frequency of all calls ranged from 1.22-4.09 kHz (n=233); their average values composed of different numbers of pulses were similar and that call duration increased with numbers of pulses; and pulse duration among different multi-pulse call groups was nearly identical, but it was equal or less in the last pulse than other pulses. By contrast, our analyses also showed that pulse interval was negatively correlated with call duration, i.e. the shorter in call duration, the longer in pulse interval among the different numbers of pulses call groups. Within the 7-pulse call group, calls exhibited the largest in pulse interval and the smallest in pulse rate, while those calls in 16-pulse were the opposite. Except that the 7- and 16-pulse call groups were both significantly different in pulse rate with other multi-pulse call groups, we found that pulse rates expressed different variations between pair-wise comparisons of the remaining call groups. As for call intensity, significant differences were only found between the 16-pulse call group and the other call groups, while pairwise comparisons of the remaining groups were not significant. After conducting our initial analyses, we compared the calls of the M. ornate population from Lishui with populations from five other localities-Hangzhou, Xuancheng, Karnoor, Bajipe and Padil-and found that the call structures were similar among the different populations, being single harmonic, while we observed differences in call dominant frequency, call duration, pulse duration and pulse rate among the six populations. This research should prove useful to in furthering our understanding of the acoustic properties of species-specific calls as well as their behavior and the evolution of their communication, thereby providing a robust insight into the reproductive traits among different geographical populations of a species.

Expression of MAGE-A11 in breast cancer tissues and its effects on the proliferation of breast cancer cells.

The melanoma-associated antigen (MAGE) genes are commonly expressed in tumors, but the function of many of these genes remains unknown. Here, we investigated the expression of one family member, MAGE-A11, in breast cancer tissues and corresponding adjacent normal tissues. MAGE-A11 expression was assessed in breast cancer tissues and adjacent normal tissues from 100 women by immunohistochemistry. MAGE-A11 was significantly more highly expressed in breast tumors (56% of samples) compared to normal tissues (0%; P<0.05). Additionally, its expression in breast tumors was investigated in relation to various clinicopathological features, including patient age, tumor stage and volume, and lymph node metastasis. MAGE-A11 protein expression was correlated with expression of the human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER)-ß (P<0.05), but not with age, pathological type, histological grade, clinical stage, tumor size or lymph node metastasis, or ER-α, progesterone receptor (PR) or amplified in breast cancer 1 (AIB-1) expression. To determine how its expression affects cancer cell proliferation in vitro, MCF-7 human breast cancer cells were transfected with pCMV-AC-MAGE-A11-GFP. MTT colorimetry and colony-forming assays indicated that MAGE-A11 overexpression significantly increased breast cancer cell proliferation and the ability to form colonies (P<0.05). These findings indicate that MAGE-A11, similarly to HER-2 and ER-ß, may be an important diagnostic or prognostic indicator in breast cancer and potentially promotes tumor proliferation.

Sesquiterpenoids from Curcuma wenyujin with anti-influenza viral activities.

Five sesquiterpenoids, 1α,8α-epidioxy-4α-hydroxy- 5αH-guai-7(11),9-dien- 12,8-olide. (1), 8,9-seco-4ß-hydroxy-1α,5ßH-7(11)-guaen-8,10-olide (2), 8α-hydroxy-1α, 4ß,7ßH-guai-10(15)-en- 5ß,8ß-endoxide(3), 7ß,8α-dihydroxy-1α,4αH-guai-10(15)-en-5ß,8ß-endoxide(4) and 7-hydroxy-5(10),6,8-cadinatriene-4-one(5), together with seven known analogs were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D NMR techniques, and the structures of 1 and 2 were confirmed by single-crystal X-ray diffraction experiment. Compounds 1-10 and 12 showed significant in vitro antiviral activity against the influenza virus A with IC50 values ranged from 6.80 to 39.97 µM, and SI values ranged from 6.35 to 37.25.

Power density of piezoelectric transformers improved using a contact heat transfer structure.

Based on contact heat transfer, a novel method to increase power density of piezoelectric transformers is proposed. A heat transfer structure is realized by directly attaching a dissipater to the piezoelectric transformer plate. By maintaining the vibration mode of the transformer and limiting additional energy losses from the contact interface, an appropriate design can improve power density of the transformer on a large scale, resulting from effective suppression of its working temperature rise. A prototype device was fabricated from a rectangular piezoelectric transformer, a copper heat transfer sheet, a thermal grease insulation pad, and an aluminum heat radiator. The experimental results show the transformer maintains a maximum power density of 135 W/cm(3) and an efficiency of 90.8% with a temperature rise of less than 10 °C after more than 36 h, without notable changes in performance.

Coupled torsional and longitudinal vibrations of piezoelectric fiber actuator with helical electrodes.

The vibration characteristics of a piezoelectric fiber actuator with helical electrodes are studied theoretically and experimentally. Its working principle indicates that the torsional, longitudinal, and tangential deformations of the fiber are coupled. A simplified dynamic model is deduced to investigate the properties of the coupled vibrations and their corresponding equivalent circuits are also provided. Resonant frequencies and mechanical coupling coefficients in free-free boundary condition are calculated. The trends of resonant frequencies as functions of the electrode helical angle and fiber length are discussed and validated in experiments.