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Rose (Rosa chinensis), which is an economically valuable floral species worldwide, has three types, namely once-flowering (OF), occasional or re-blooming (OR), and recurrent or continuous flowering (CF). However, the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown. In this study, we observed that the RcSPL1 transcript level was substantially upregulated during the floral development period in the CF and OF plants. Additionally, the accumulation of the RcSPL1 protein was controlled by rch-miR156. The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering. Furthermore, the transient overexpression of RcSPL1 in rose plants accelerated flowering, whereas the silencing of RcSPL1 had the opposite phenotype. Accordingly, the transcription levels of floral meristem identity genes (APETALA1, FRUITFULL, and LEAFY) were significantly affected by the changes in RcSPL1 expression. The RcTAF15b protein, which is an autonomous pathway protein, was revealed to interact with RcSPL1. The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering, respectively. Collectively, the study findings imply RcSPL1–RcTAF15b modulates the flowering time of rose plants.

Magnetic targeted drug delivery systems can improve drug utilization and reduce drug side effects. There are still many difficulties to be overcome in clinical practice. The main problems include providing large enough magnetic capture particles to concentrate drug-loaded magnetic micro-nanoparticles (MNPs) to the lesion site. The existing research focuses on the development of targeted carriers, and the magnet device has not formed a mature research system. Based on the recent development of magnet devices in recent years, this paper proposes the research direction of potential magnet devices. From the dynamic behavior of the particles under the magnetic field, the magnetic system and the mathematical model design direction of the optimized magnet are developed. This article describes the obstacles encountered in drug targeting in the study of magnet devices and summarizes the potential development of future magnet devices.

When kinematic control of robot manipulator is modeled as time-varying problems, control algorithms generated by solving time-varying problems perform well in the aspect of real-time control and control precision. However, conventional algorithms are based on relatively simple time-varying problems modeling and solving, and thus, it is difficult for them to solve more other problems while completing tracking task. In this work, the kinematic control of robot manipulator is first modeled as more complicated multilayered time-varying problem, which simultaneously formulates the tracking task and joint angle limits. Then, zeroing neural dynamics method is future investigated to find the equivalence of multilayers. Finally, three explicit solutions based on three discretization formulas are presented to solve the multilayered time-varying problem. The presented solutions not only complete the tracking task in real time with different precision, but also solve the problem of joint angle limits during the control process.

Electromagnetic forming (EMF) is a technology that uses Lorentz force to drive the deformation of light alloy. In the processing of small metal pipe fittings, attraction forming is beneficial to reduce the design requirements of forming coils and the application cost of actual tooling. However, the attractive dual-frequency current method requires strict matching between currents. This will lead to difficulty in controlling and changing the attractive force, thus reducing the uniformity of the deformation of the workpiece. To solve this problem, a field shaper is introduced to optimize the distribution of electromagnetic force and improve the uniformity of pipe forming. The finite element model including circuit field, electromagnetic field, and structure field was established, and the bulging of an aluminum alloy pipe fitting with a radius of 10 mm and a length of 40 mm under the action of 9-kV power supply was simulated. The results show that the deformation uniformity is increased by 15% and the degree of shape change is increased by 8.9% with the addition of field shaper. It is proved that field shaper can improve the uniformity of pipe fitting.

Generally, several mechanisms influenced the secondary injury chutes following acute spinal cord injury (SCI). Though current SCI therapeutic approaches mostly target single elements in the injury chutes, they have been mostly ineffective in clinical trials. The aim of this study was to design and develop a novel cerium oxide/silk fibroin (CeO2/SF) hydrogel material loaded with minocycline (MCN) and transplantation of olfactory ensheathing cells (OEC) for SCI treatment. The prepared CeO2/SF hydrogel has an advantageous porous morphological structure and CeO2 NPs were greatly encapsulated on the surface, which was confirmed by microscopic observations. The results of in vitro analyses established favourable biocompatibility of 94.65% and 89.45%, sustained drug release rate of 89% and 58%, and significant reduction in pro-inflammatory factors for the treatments using cerium oxide loaded silk fibroin (CSF) and CeO2 NPs, respectively. Meanwhile, the administration of MCN@OEC greatly provides an efficient improvement in BBB score, decreased bladder weight, and histological improvement after SCI when compared to the control. Therefore, the combined MCN and OEC-loaded CSF hydrogel sample could be proved as a low cost, safe, and potential material for the treatment of SCI.

BACKGROUND: Marching band activities consist of both physically and cognitively demanding tasks. The demands that this activity has on players has largely been unstudied. OBJECTIVE: The goal of this study was to investigate the effects of players’ experience level, role, and gender on the workload of marching band players via a field study. METHODS: Surveys were issued during one game day to the Oregon State University Marching Band (OSUMB) in the fall of 2017. Increments of discomfort ratings and workload ratings were gathered. The three independent variables were experience level (novice or experienced), role (leader or non-leader), and gender. RESULTS: Novice players had a higher discomfort for their left hand and a higher level of cognitive demand as opposed to experienced players. Leaders had a higher increment of discomfort in their neck and upper back, and higher workload ratings in their performance workload and overall weighted workload than the non-leaders. Gender had no effect on increment of discomfort and workload, but some trends were noted. CONCLUSIONS: This study indicates that players’ role and experience, but not gender, can influence their workloads and discomfort.

Background Osteoarthritis (OA) is a regular age-related disease that affects millions of people. Resveratrol (RSV) is a flavonoid with a stilbene structure with different pharmacological effects. The purpose of the experiment was to evaluate the protective role of RSV against the human OA chondrocyte injury induced by interleukin-1β (IL-1β). Methods Chondrocytes were isolated from OA patients and identified by type II collagen, safranin O staining, and toluidine blue staining. Differentially expressed genes in chondrocytes treated RSV were identified by RNA sequencing. Kyoto encyclopedia of genes and genomes (KEGG) pathway as well as gene ontology (GO) were further conducted through Metascape online tool. A cell counting kit-8 (CCK-8) assay was applied to discover the viability of chondrocytes (6, 12, 24, and 48 μM). Many genes associated with inflammation and matrix degradation are evaluated by real-time PCR (RT-PCR) as well as western blot (WB). The mechanism of RSV for protecting IL-1β induced chondrocytes injury was further measured through immunofluorescence and WB assays. Results A total of 845 differentially expressed genes (upregulated = 499, downregulated = 346) were found. These differentially expressed genes mainly enriched into negative regulation of catabolic process, autophagy, and cellular catabolic process, intrinsic apoptotic, apoptotic, and regulation of apoptotic signaling pathway, cellular response to abiotic stimulus, external stimuli, stress, and radiation. These differentially expressed genes were obviously enriched in NF-kB signaling pathway. RSV at the concentration of 48 μM markedly weakened the viability of the cells after 24 h of treatment (87% vs 100%, P < 0.05). No obvious difference was observed between the 6, 12, and 24 μM groups (106% vs 100%, 104% vs 100%, 103% vs 100%, P > 0.05). RSV (24 μM) also markedly depressed the levels of PGE2 and NO induced by IL-1β by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1β, including the MMP-13, MMP-3, and MMP-1 in human OA chondrocytes by 50%, 35%, and 33% respectively. On the other hand, RSV inhibited cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and inducible nitric oxide synthase (iNOs) expression (P < 0.05), while increased collagen-II and aggrecan levels (P < 0.05). From a mechanistic perspective, RSV inhibited the degradation of IκB-α as well as the activation of nuclear factor-kappa B (NF-κB) induced by IL-1β. Conclusion In summary, RSV regulates the signaling pathway of NF-κB, thus inhibiting inflammation and matrix degradation in chondrocytes. More studies should be focused on the treatment efficacy of RSV for OA in vivo.

BackgroundThe dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of postmenopausal osteoporosis (PO). MicroRNAs play an important role in regulating apoptosis of MC3T3-E1 cells. However, the role and potential mechanism of miR-708 for regulating H2O2-induced apoptosis is unknown. This study aimed to investigate the protective function of miR-708 in H2O2-induced apoptosis of MC3T3-E1 osteoblasts.MethodsMC3T3-E1 was co-cultured with H2O2for 8 h, then, flow cytometry, malondialdehyde (MDA), and glutathione peroxidase (Gpx) levels were measured to establish the oxidative model. MiRNA microarray was performed to assess differentially expressed miRNAs between control and H2O2-treated MC3T3-E1 cells. We then performed RT-PCR to identify the relative expression of miR-708 and PTEN. After transfected MC3T3-E1 with miR-708 mimics, flow cytometry, MDA, and Gpx level were performed to identify the apoptosis rate and oxidative stress in these groups. Furthermore, we small interfering RNA of PTEN to identify the role of PTEN in H2O2-induced apoptosis of MC3T3-E1 cells.ResultsH2O2(100 nM) could significantly induce the apoptosis of MC3T3-E1 cells. Moreover, H2O2could significantly increase the MDA level and downregulated Gpx level. RT-PCR found that H2O2significantly decrease the level of miR-708. Compared with H2O2group, H2O2+ miR-708 mimic significantly decreased the apoptosis rate.ConclusionsmiR-708 plays a protective role in H2O2-induced MC3T3-E1 osteoblasts apoptosis and its protective effect is proceeded by regulating ROS level and PTEN expression level.

Hybrid multilayered time-varying linear system is a challenging problem, which has complex structure and time-varying characteristics. In order to solve this complex problem, we use the method of zeroing neural network to analyze the equivalence between different layers. According to the equivalent results, a continuous zeroing neural network model is proposed. In order to satisfy real-time computation and facilitate the hardware implementation, a five-instant time-discretization formula with high accuracy is proposed for the discretization of continuous zeroing neural network model. Then, corresponding discrete zeroing neural network model is proposed to solve hybrid multilayered time-varying linear system. It is worth noting that discrete zeroing neural network model can predict future-instant solution and satisfy the real-time calculation. Numerical experimental results show the effectiveness of proposed model.

At present, solenoid (helical) coils are widely used in various researches, especially electromagnetic forming (EMF), due to their advantages of simple manufacture and high magnetic field strength. However, in the study of EMF, there are still some defects in the high precision calculation of solenoid coils in the magnetic field the main reason is that the solenoid coil is of non-axisymmetric structure, which is generally equivalent to the 2-D or 3-D axisymmetric structure in practical research. Not only can it ignore the effect of the pitch effect of the solenoid coil, but also causes a certain deviation in the calculation of the magnetic field. Hence, this paper establishes 5 helical coils and 3-D axisymmetric finite element coils models with different layers for comparative analysis. The simulation results show that the magnetic flux density distribution deviation of helical coil and the 3-D axisymmetric coil is small and can be ignored when the coil layers are 1 or 2 layers. However, the number of linear circles increasing, the deviation between the two increases obviously. Therefore, in the study of EMF, the effect of solenoid coil pitch effect on magnetic field calculation can be ignored when the layers, radius and pitch of helical coils are used less whereas the effect of solenoid coil pitch effect on magnetic field calculation must be considered when the layers, radius and pitch of helical coils are used more.

Time discretization is an important part of time-varying problems solving that determines convergence, real-time performance and accuracy for solution models. It is a challenging work compared with relatively simple derivative approximation due to unknown future information and stability constraint. To the best of the authors’s knowledge, no effective time discretization was developed other than Euler finite difference formula before recently development of ZeaD formulas. Existing work presents some ZeaD formulas including specific time-discretization formulas having third order accuracy. In this work, $N$ -instant general third-order-accuracy formula is proposed, and it leads to different general third-order-accuracy formulas when different instant number $N$ is considered. Stability and convergence are analyzed, and effective domains for parameters in 5-instant and 6-instant general third-order-accuracy formula are given to guarantee effective time discretization. Furthermore, $N$ -instant general third-order-accuracy formula is employed to solve time-varying optimization, and $N$ -instant general solution model is proposed. Finally, comparative experimental results are presented to substantiate the effectiveness and superiority of proposed general formulas and models.

Sustained dexamethasone (Dex) treatment could induce secondary osteoporosis, osteonecrosis, or even bone fractures. Dex can induce potent cytotoxicity in cultured human osteoblasts. The aim of this study was to test the potential role of microRNA-7 (miR-7), which targets the epidermal growth factor receptor (EGFR), in Dex-treated human osteoblasts. In OB-6, hFOB1.19, and primary human osteoblasts, miR-7 depletion by a lentiviral antagomiR-7 construct (LV-antagomiR-7) increased EGFR expression and downstream Akt activation, protecting cells from Dex-induced viability reduction, cell death, and apoptosis. In contrast, forced overexpression of miR-7 by a lentiviral miR-7 construct (LV-miR-7) inhibited EGFR expression and Akt activation, potentiating Dex-induced cytotoxicity in OB-6, hFOB1.19, and primary human osteoblasts. EGFR is the primary target of miR-7 in human osteoblasts. Luciferase activity of the EGFR 3-untranslated region was enhanced by LV-antagomiR-7, but decreased by LV-miR-7 in OB-6 cells. Further, LV-antagomiR-7-induced osteoblast cytoprotection against Dex was abolished by the EGFR inhibitors AG1478 and PD153035. Moreover, neither LV-antagomiR-7 nor LV-miR-7 was functional in EGFR-KO OB-6 cells. We also show that miR-7 is upregulated in the necrotic femoral head tissues of Dex-administered patients, correlating with EGFR downregulation. Together, we conclude that miR-7 inhibition protects human osteoblasts from Dex via activation of EGFR signaling.

Fibroblast-like synoviocytes (FLSs) play an essential role in rheumatoid arthritis (RA) by promoting synovitis, pannus growth and cartilage/bone destruction. Increased proliferation, migration and invasion of FLSs greatly contribute to RA initiation and progression. Dual-specificity tyrosine-regulated kinase 1A (Dyrk1A), a serine/threonine kinase, regulates MAPK pathway activation, and governs the proliferation and differentiation of neuronal progenitor cells and cancer cells. Till now, the expression and possible function of Dyrk1A in RA FLSs have not been explored. In this study, we detected an increased expression of Dyrk1A both in the synovial tissues of RA patients and in a TNF-α-induced FLSs activation model. CCK-8 and Edu assays revealed that Dyrk1A knockdown inhibited TNF-α-induced FLSs proliferation. Moreover, inhibiting Dyrk1A expression apparently prevented the migration and invasion capability of FLSs accompanied by a decreased MMP-3 and -9 expression. To investigate the molecular mechanism through which Dyrk1A modulates FLSs activities, we evaluated the effects of Dyrk1A on Spry2, a negativity modulator of ERK MAPK pathway. Western blot assay demonstrated that Dyrk1A silencing significantly increased Spry2 expression and suppressed the phosphorylation of ERK in TNF-α-treated FLSs. Taken together, our results indicated that Dyrk1A might promote FLSs proliferation, migration and invasion by suppressing Spry2 expression and activating the ERK MAPK signaling pathway in RA.

Background Long non-coding RNAs (lncRNAs) participate in regulation of gene transcription, but little is known about the correlation among resveratrol and lncRNAs. This study aimed to identify and validate the key lncRNAs in resveratrol protect against IL-1β-treated chondrocytes. Methods In this experiment, high-throughput sequencing technique was performed to identify the differentially expressed lncRNAs, miRNAs, and mRNAs between IL-1β-treated chondrocytes with or not resveratrol. Moreover, gene ontology and KEGG pathway of the differentially expressed genes were carried out by R software. Then, lncRNA-miRNA-mRNA network was constructed by Cytoscape software. Venn diagram was performed to identify the potentially target miRNAs of LINC00654. Then, real-time polymerase chain reaction (RT-PCR) was performed to validate the most significantly differentially expressed lncRNAs. Results Totally, 1016 differentially expressed lncRNAs were identified (493 downregulated) between control and resveratrol-treated chondrocytes. Totally, 75 differentially expressed miRNAs were identified (downregulated = 54, upregulated = 21). Totally, 3308 differentially expressed miRNAs were identified (downregulated = 1715, upregulated = 1593). GO (up) were as follows: skin development, response to organophosphorus. GO (down) mainly included visual perception, single fertilization, and sensory perception of smell. KEGG (up) were as follows: TNF signaling pathway and TGF-beta signaling pathway. KEGG (down) were as follows: viral protein interaction with cytokine and cytokine receptor. We identified that LINC00654 and OGFRL1 were upregulated in resveratrol-treated chondrocytes. However, miR-210-5p was downregulated in resveratrol-treated chondrocytes. Conclusion In sum, the present study for the first time detected the differential expressed lncRNAs involved in resveratrol-treated chondrocytes via employing bioinformatic methods.

Warm water cooling has been regarded as a promising method to improve the energy efficiency of water-cooled datacenters. In warm water-cooling systems, hot spots occur as a common problem where the hybrid cooling architecture integrating thermoelectric coolers (TECs) emerges as a new remedy. Equipped with this architecture, the inlet water temperature can be raised higher, which provides more opportunities for heat recycling. However, currently, the heat absorbed from the server components is ejected directly into the water without being recycled, which leads to energy wasting. In order to further improve the energy efficiency, we propose Heat to Power (H2P), an economical and energy-recycling warm water cooling architecture, where thermoelectric generators (TEGs) harvest thermal energy from the "used" warm water and generate electricity for reusing in datacenters. Specifically, we propose some efficient optimization methods, including an economical water circulation design, fine-grained adjustments of the cooling setting and dynamic workload scheduling for increasing the power generated by TEGs. We evaluate H2P based on a real hardware prototype and cluster traces from Google and Alibaba. Experiment results show that TEGs equipped with our optimization methods can averagely generate 4.349 W, 4.203 W, and 3.979 W (4.177 W averagely) electricity on one CPU under the drastic, irregular and common workload traces, respectively. The power reusing efficiency (PRE) can reach 12.8%~16.2% (14.23% averagely) and the total cost of ownership (TCO) of datacenters can be reduced by up to 0.57%.

Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

TNF receptor-associated factor 7 (TRAF7), is an E3 ubiquitin ligase for several proteins involved in the activation of TLR-dependent NF-kappaB signaling. TRAF7 links TNF receptor family proteins to signaling pathways, thus participates in regulating cell death and survival mediated by TNF family ligands. To date, the biological function of TRAF7 after spinal cord injury (SCI) is still with limited acquaintance. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of TRAF7 expression in the spinal cord. Our results showed that TRAF7 was up-regulated significantly after SCI, which was paralleled with the levels of the apoptotic protein active caspase-3. Immunofluorescent labeling showed that TRAF7 was co-localizated with active caspase-3 in neurons. To further investigate the function of TRAF7, an apoptosis model was established in primary neuronal cells. When TRAF7 was knocked down by specific short interfering RNA (siRNA), the protein levels of active caspase-3 and the number of apoptotic primary neurons were significantly decreased in our study. Taken together, our findings suggest that the change of TRAF7 protein expression plays a key role in neuronal apoptosis after SCI.

College marching band players expose to high physical and cognitive workloads; however, there is lack of understanding on this matter. The purposes of this study were to investigate the workloads associated with marching band performance and to evaluate the effect of players’ role (leader vs. non-leader) on their workload. Forty participants were recruited from the Oregon State University Marching Band (OSUMB). They were conducted to complete a set of surveys before and after their performance on a game day. Their body discomfort and subjective workload were assessed using Borg-CR10 and NASA-TLX, respectively. Results found leaders’ discomfort ratings at their neck and upper back areas were significantly higher (p

While increasing attention has been given to the prevalence of work-related musculoskeletal disorders (WMDs) among surgeons in various medical specialties, there is no quantitative information about the potential work-related risk factors that contribute to WMDs among vaginal surgeons in the operating room (OR). This study aimed to quantify the frequency and duration of awkward postures, as well as musculoskeletal discomfort experienced by primary and assistant vaginal surgeons during surgery in order to provide a first step of informing ergonomics interventions that reduce postural loading during surgery. Thirteen primary and 14 assistant surgeons were evaluated during 13 surgical cases. Surgeon pre- and post-operative musculoskeletal discomfort ratings were collected with surveys. During surgery, real-time observations systematically characterized the frequency and duration of awkward neck, trunk and shoulder postures using tablet-based ergonomics software. Surgeons experienced postoperative increases in musculoskeletal discomfort of the neck, wrists, hands, back and feet. Assistant surgeons experienced greater right and left shoulder discomfort than primary surgeons (p Relevance to industry Surgeons provide a valuable healthcare service to the public, but surgeons are at high risk of musculoskeletal problems due to their work demands. This study provides new information about the physical requirements of vaginal surgeries to inform ergonomics interventions that prevent work-related musculoskeletal disorders among primary and assistant surgeons.

After the presentation of second-order correlation ranging principles with quantum entanglement, the concept of quantum measurement is introduced to dynamic satellite precise orbit determination. Based on the application of traditional orbit determination models for correcting the systematic errors within the satellite, corresponding models for quantum orbit determination (QOD) are established. This paper experiments on QOD with the BeiDou Navigation Satellite System (BDS) by first simulating quantum observations of 1 day arc-length. Then the satellite orbits are resolved and compared with the reference precise ephemerides. Subsequently, some related factors influencing the accuracy of QOD are discussed. Furthermore, the accuracy for GEO, IGSO and MEO satellites increase about 20, 30 and 10 times, respectively, compared with the results from the resolution by measured data. Therefore, it can be expected that quantum technology may also bring delightful surprises to satellite orbit determination as have already emerged in other fields.

// Dawei Xu 1, * , Hao Zhu 2, * , Chengniu Wang 3 , Xinhui Zhu 1 , Genxiang Liu 2 , Chu Chen 1 and Zhiming Cui 1 1 Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, China 2 Department of Orthopaedics, The Fourth Affiliated Hospital of Nantong University, Yancheng, China 3 Basic Medical Research Centre, Medical College, Nantong University, Nantong, China * These author have contributed equally to this work Correspondence to: Zhiming Cui, email: zhimingcui_orthnt@163.com Keywords: osteoblast, hydrogen peroxide (H 2 O 2 ), Nrf2, microRNA-455, cullin 3 (Cul3) Received: May 05, 2017 Accepted: June 19, 2017 Published: July 22, 2017 ABSTRACT Over-production of hydrogen peroxide (H 2 O 2 ) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation. We demonstrate that microRNA-455 (“miR-455”) is a putative Cul3-targeting microRNA. Forced-expression of miR-455 in both hFOB1. 19 osteoblast cell line and primary human osteoblasts induced Cul3 degradation and Nrf2 protein stabilization, which led to subsequent transcription of ARE (anti-oxidant response element)-dependent genes ( NQO1 , HO1 and GCLC ). Cul3 silencing, by expressing miR-455 or targeted-shRNA, protected human osteoblasts from H 2 O 2 . Reversely, miR-455 anti-sense caused Cul3 accumulation and Nrf2 degradation, which exacerbated H 2 O 2 damages in hFOB1. 19 cells. Moreover, forced over-expression of Cul3 in hFOB1. 19 cells silenced Nrf2 and sensitized H 2 O 2 . Together, we propose that miR-455 activated Nrf2 signaling and protected human osteoblasts from oxidative stress possibly via targeting Cul3.

This study investigated the role of PDK1 in inflammatory response which is initiated by TNF-α and analyzed the association between PDK1 and RSK2. TNF-α were added into MH7A cells to induce inflammation condition. Through overexpressing or suppressing PDK1 in MH7A cells, the role of PDK1 in cell invasiveness and inflammatory factors was determined. Levels of MMPs protein and inflammatory cytokines were assessed with PDK1 siRNA and TNF-α treatment. Inhibition of RSK2 was used to investigate the function of RSK2 on PDK1-induced inflammation. The phosphorylation of RSK2 was detected when PDK1 was inhibited. Luciferase reporter assay was performed to detect the transcriptional activity of NF-κB. We found highly expressed PDK1 could promote cell invasion and secretion of IL-1β and IL-6 in MH7A cells. Inhibition of RSK2 reduced the PDK1-induced cell invasion and cytokines secretion in MH7A cells. In response to TNF-α, PDK1 could phosphorylate RSK2 and activated RSK2, then promoting the activation of NF-κB. This may be a possible therapeutic option of rheumatoid arthritis.

OCCUPATIONAL APPLICATIONS Ergonomics postural assessment in real-time (ErgoPART) is a new job analysis tool designed to systematically characterize the postural demands of performing surgery. Tasks, equipment, and procedures that require ergonomic intervention can be identified. ErgoPART can also be used to quantify the benefits of ergonomic interventions that reduce the frequency and duration of non-neutral postures. Preliminary tests, conducted in the context of vaginal surgery, indicate that the tool is easy to learn and may allow broad categories of neck, shoulder, and trunk postures to be coded reliably. ErgoPART is freely available for use.TECHNICAL ABSTRACT Background: Little quantitative information exists regarding the postural demands placed on surgeons in the operating room. One reason for this is the lack of minimally invasive tools available to characterize the duration and frequency of non-neutral postures during surgery. Purpose: The objective of this study was to develop an ergonomics job ...

Objective Mounting evidence demonstrates that inflammation plays an important role in the pathogenesis of osteoarthritis (OA). Milk fat globule–epidermal growth factor 8 (MFG-E8) is an important glycoprotein that is involved in anti-inflammatory responses. The present study was performed to assess the MFG-E8 levels in plasma and synovial fluid and explore the association between radiographic severity and MFG-E8 levels in patients with knee OA. Methods This study involved 138 healthy controls and 142 patients with knee OA. The MFG-E8 levels in plasma and synovial fluid were evaluated by enzyme-linked immunosorbent assay. The Kellgren and Lawrence classification was used for OA grading. Results The plasma MFG-E8 level was significantly lower in patients with knee OA than in healthy controls. The synovial fluid MFG-E8 level was significantly lower than the plasma level in patients with knee OA. More importantly, the MFG-E8 levels in synovial fluid and plasma were significantly and inversely associated with radiographic severity among patients with knee OA. Conclusions These results demonstrate that the levels of MFG-E8 in synovial fluid and plasma are inversely correlated with the radiographic severity of knee OA.

Recent studies have suggested that activation of the mammalian target of rapamycin (mTOR) signaling may be related to antidepressant actions. Although thought as a selective serotonin reuptake inhibitor (SSRI), the antidepressant mechanisms of fluvoxamine remain elusive. Therefore, this study aims to evaluate whether mTOR underlies the antidepressant-like effects of fluvoxamine. Male C57BL/6 J mice were subjected to 8 weeks of chronic unpredictable mild stress (CUMS) with fluvoxamine administered during the last 2 weeks. Western blotting analyses were then used to assess the expression of the mTOR signaling cascade in the hippocampus and prefrontal cortex (PFC) among all groups. The selective inhibitor of mTOR, rapamycin, was further used. It was found that fluvoxamine treatment fully reversed the effects of CUMS on the mTOR signaling in the hippocampus and PFC, and the usage of rapamycin significantly prevented the antidepressant-like effects of fluvoxamine in the CUMS model of depression. Taken together, the mTOR system is involved in the antidepressant mechanisms of fluvoxamine.

Berberine is a widely used antimicrobial agent in clinic. However, a high dosage is often required due to its low lipophilicity and bioavailability. The current study explores the structural modifications of berberines with potentially lipophilic aryl groups to address this problem. A series of 15 9-O-aryl-substituted berberines (3a–o) and one 9-O-phenylene-bridged berberine dimer (5) was synthesized by copper-catalyzed cross-coupling of tetrahydroberberrubine and aryl iodides, followed by oxidation with I2.

// Jian-bo Fan 1, 2, * , Wei Liu 1, * , Xin-hui Zhu 1 , Hong Yi 1 , Sheng-yu Cui 1 , Jian-ning Zhao 2 , Zhi-ming Cui 1 1 Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China 2 Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing 210008, Jiangsu, PR China * These authors have contributed equally to this work Correspondence to: Zhi-ming Cui, email: zhimingcuiorth@163.com Keywords: dexamethasone, osteoblastic cells, microRNA-25, PKCζ, AMP-activated protein kinase (AMPK) Received: July 27, 2016 Accepted: November 14, 2016 Published: November 29, 2016 ABSTRACT AMP-activated protein kinase (AMPK) activation could protect osteoblasts from dexamethasone (Dex). This study aims to provoke AMPK activation via microRNA downregulation of its negative regulator protein kinase C ζ (PKCζ). Results show that microRNA-25-5p (miR-25-5p) targets PKCζ’s 3’ untranslated regions (UTRs). Forced-expression of miR-25 downregulated PKCζ and activated AMPK in human osteoblastic cells (OB-6 and hFOB1.19 lines), which thereafter protected cells from Dex. Reversely, expression of antagomiR-25, the miR-25 inhibitor, upregulated PKCζ and inhibited AMPK activation, exacerbating Dex damages. Notably, PKCζ shRNA knockdown similarly activated AMPK and protected osteoblastic cells from Dex. AMPK activation was required for miR-25-induced osteoblastic cell protection. AMPKα shRNA or dominant negative mutation almost completely blocked miR-25-induced cytoprotection against Dex. Further studies showed that miR-25 expression increased NADPH activity and suppressed Dex-induced oxidative stress in osteoblastic cells. Such effects by miR-25 were abolished with AMPKα knockdown or mutation. Significantly, miR-25-5p level was increased in patients’ necrotic femoral head tissues, which was correlated with PKCζ downregulation and AMPK hyper-activation. These results suggest that miR-25-5p targets PKCζ and protects osteoblastic cells from Dex possibly via activating AMPK signaling.

// Jian-Bo Fan 1, 4, * , Jian-Wei Ruan 2, * , Wei Liu 1, * , Lun-Qing Zhu 3 , Xin-Hui Zhu 1 , Hong Yi 1 , Sheng-Yu Cui 1 , Jian-Ning Zhao 4 , Zhi-Ming Cui 1 1 The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China 2 The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China 3 The Center of Diagnosis and Treatment for Childrens’ Bone Disease, Childrens’ Hospital Affiliated to Soochow University, Suzhou 215000, Jiangsu, PR China 4 Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing 210008, Jiangsu, PR China * These authors have contributed equally to this work Correspondence to: Zhi-Ming Cui, email: zhimingcuiorth@163.com Keywords: dexamethasone (Dex), osteoblastic cells, microRNA-135b, AMP-activated protein kinase (AMPK), phosphatase 1E (Ppm1e) Received: July 07, 2016 Accepted: September 06, 2016 Published: September 20, 2016 ABSTRACT Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA (“miRNA”) downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b (“miR-135b”) targets the 3’ untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced-expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex.

Studies have shown that lobetyolin (LBT), a component of traditional Chinese herbal medicine, has many very good biological activities and functions. However, its side effects and toxicities have not been evaluated adequately. In this work, we investigated the effects of LBT in transgenic zebrafish. LBT treatments promoted angiogenesis and led to vascular morphological malformation in zebrafish embryos, although they were normal in appearance. Interestingly, our results indicated that LBT has a function of promoting nerve growth in the embryonic stage of zebrafish. We also treated the zebrafish with combretastatin A-4 (which resulted in neuronal apoptosis) and LBT simultaneously and found that LBT promoted nerve growth at higher concentrations. Taken together, our findings clearly display that LBT efficiently promotes angiogenesis, leading to vascular morphological malformation, has low toxicity, and notably promotes neuronal development in zebrafish.

The traditional PPP/INS system is still not used as widely as the DGNSS/INS system in precise applications, although no local reference stations are required. The main reason that prevents its use is that the traditional PPP/INS system is based on the float ambiguity solution, which leads to long convergence period and unstable positioning accuracy. We propose a tightly coupled ambiguity-fixed PPP/INS integration. First, the derivation of the observation model of the ambiguity-fixed PPP at the single-difference level using integer phase clock products from Center National d'Etudes Spatiales is presented in detail. Then the inertial navigation system model is presented. With these two models, the tightly coupled model of the PPP/INS integration is established. Finally, two carborne tests are used to evaluate the performance of the tight integration of ambiguity-fixed PPP and INS. Experimental results indicate that the proposed ambiguity-fixed PPP/INS integration is able to reach stable centimeter-level positioning after the first-fixed solution and its overall performance is comparable to that of the DGNSS/INS integration, and rapid re-convergence and re-fixing are achievable after a short period of GNSS outage for the PPP/INS integration.