MNTZNN for Solving Hybrid Double-Deck Dynamic Nonlinear Equation System Applied to Robot Manipulator Control.

Compared with conventional dynamic nonlinear equation systems, a hybrid double-deck dynamic nonlinear equation system (H3DNES) not only has multiple layers describing more different tasks in practice, but also has a hybrid nonlinear structure of solution and its derivative describing their nonlinear constraints. Its characteristics lead to the ability to describe more complicated problems involving multiple constraints, and strong nonlinear and dynamic features, such as robot manipulator tracking control. Besides, noises are inevitable in practice and thus strong robustness of models solving H3DNES is also necessary. In this work, a multilayered noise-tolerant zeroing neural network (MNTZNN) model is proposed for solving H3DNES. MNTZNN model has strong robustness and it solves H3DNES successfully even when noises exist in both the two layers of H3DNES. In order to develop the MNTZNN model, a new zeroing neural network (ZNN) design formula is proposed. It not only enables equations with respect to solutions to become equations with respect to the second-order derivatives of solutions but also makes the corresponding model have strong robustness. The robustness of the MNTZNN model is proved when parameters in the model satisfy a loose constraint and the error bounds are programmable via setting appropriate parameter values. Finally, the MNTZNN model is applied to the tracking control of the six-link planar robot manipulator and PUMA560 robot manipulator with hybrid nonlinear constraints of joint angle and velocity.

Magnetically driven capsules with multimodal response and multifunctionality for biomedical applications.

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule's global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Asymmetric magnetic levitation for density-based measurement and analysis.

BACKGROUND: Magnetic levitation (MagLev) based on negative magnetophoresis represents a promising technology for density-based analysis and manipulation of nonmagnetic objects. This approach has garnered considerable interest across multiple fields, such as chemistry, materials science, and biochemistry, primarily due to its inherent simplicity, precision, and cost-effectiveness. However, it is essential to recognize that frequently used MagLev configurations, including standard MagLev and axial MagLev, are not without their limitations. These configurations often struggle to strike a balance between levitation performance, ease of operation, and visibility. Therefore, it is necessary to develop a new MagLev configuration to address the aforementioned issue. RESULTS: This work describes the development of an innovative MagLev, termed "asymmetric MagLev", achieved by combining a ring magnet and a cylinder magnet as up-down asymmetric magnetic field sources. The asymmetric design overcomes the physical obstacles along the centerline of the standard MagLev, offering unique open-structure advantages, including easy handling of samples, the ability to observe samples from the top or bottom, and no restrictions on the container height. Meanwhile, comparative analysis reveals a considerable enhancement in the working distance of the asymmetric MagLev without significantly sacrificing the measurement range compared to the axial MagLev. Notably, the asymmetric MagLev achieves a remarkable sensitivity of up to about 1.8 × 104 mm (g cm-3)-1, surpassing the axial MagLev by approximately 30 times. Furthermore, experimental results validate the successful application of the asymmetric MagLev in density measurement and quality detection of small-sized objects. SIGNIFICANCE: This pioneering configuration represents the first utilization of up-down asymmetric magnets in the field of MagLev. Through the integration of an axially magnetized ring magnet and a cylinder magnet, the asymmetric MagLev design overcomes the limitations associated with conventional MagLev configurations. This innovative design exhibits outstanding operational capabilities and levitation performance, making it suitable for a wide range of applications in density-based measurement and analysis.

Neuroligin-3 activates Akt-dependent Nrf2 cascade to protect osteoblasts from oxidative stress.

Excessive oxidative stress will cause significant injury to osteoblasts, serving as one major pathological mechanism of osteoporosis. Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein and is expressed in the bone. We here explored its potential activity against hydrogen peroxide (H2O2)-induced oxidative injury in cultured osteoblasts. In primary murine and human osteoblasts, NLGN3 stimulation dose-dependently induced Akt, Erk1/2 and S6K activation. NLGN3 pretreatment ameliorated H2O2-induced cytotoxicity and death in osteoblasts. Moreover, H2O2-induced reactive oxygen species (ROS) production and oxidative injury were alleviated with NLGN3 pretreatment in cultured osteoblasts. Further studies showed that NLGN3 activated Nrf2 signaling cascade and induced Nrf2 protein Serine-40 phosphorylation, Keap1-Nrf2 dissociation, Nrf2 protein stabilization and nuclear translocation in osteoblasts. NLGN3 also increased antioxidant response element (ARE) activity and induced expression of Nrf2-ARE-dependent genes (HO1, GCLC and NQO1) in osteoblasts. Moreover NLGN3 mitigated osteoblast oxidative injury by dexamethasone or sodium fluoride (NaF). Nrf2 cascade activation is essential for NLGN3-induced cytoprotective activity in osteoblasts. Nrf2 shRNA or knockout (KO) abolished NLGN3-induced osteoblast cytoprotection against H2O2. Contrarily forced Nrf2 cascade activation by Keap1 KO mimicked NLGN3-induced anti-oxidative activity in murine osteoblasts. Importantly, NLGN3-induced Serine-40 phosphorylation and Nrf2 cascade activation were blocked by an Akt inhibitor MK-2206 or by Akt1 shRNA. Importantly, Akt inhibition, Akt1 silencing or Nrf2 S40T mutation largely inhibited NLGN3-induced osteoblast cytoprotection against H2O2. At last, we showed that NLGN3 mRNA and protein expression was significantly downregulated in necrotic bone tissues of dexamethasone-taken patients. Taken together, NLGN3 activated Akt-dependent Nrf2 cascade to protect osteoblasts from oxidative stress.

RcSPL1-RcTAF15b regulates the flowering time of rose (Rosa chinensis).

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 levels were substantially upregulated during the floral development period in CF and OF plants. Additionally, accumulation of 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 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. 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 that RcSPL1-RcTAF15b modulates the flowering time of rose plants.

Radial Magnetic Levitation and Its Application to Density Measurement, Separation, and Detection of Microplastics.

This work describes the development of radial magnetic levitation (MagLev) using two radially magnetized ring magnets to solve the problem of limited operational spaces in standard MagLev and the major shortcoming of a short working distance in axial MagLev. Interestingly and importantly, we demonstrate that for the same magnet size, this new configuration of MagLev doubles the working distance over the axial MagLev without significantly sacrificing the density measurement range, whether for linear or nonlinear analysis. Meanwhile, we develop a magnetic assembly method to fabricate the magnets for the radial MagLev, where multiple magnetic tiles with single-direction magnetization are used as assembly elements. On this basis, we experimentally demonstrate that the radial MagLev has good applicability in density-based measurement, separation, and detection and show its advantages in improving separation performance compared with the axial MagLev. The open structure of two-ring magnets and good levitation characteristics make the radial MagLev have great application potential, and the performance improvement brought by adjusting the magnetization direction of magnets provides a new perspective for the magnet design in the field of MagLev.

The Efficacy and Outcome of a Two-Staged Operation for Irreducible Knee Dislocation: A Prospective Short-Term Follow-Up.

Background: Irreducible knee dislocation (IKD) is a very rare but serious type of knee dislocation; it can lead to soft tissue necrosis due to incarceration of the medial structures and faces great difficulty in the postoperative rehabilitation, too. IKD needs careful pre-operative planning. There is no universal agreement about the appropriate surgical strategy for IKD. The purpose of this study was to investigate the clinical efficacy, safety, and outcome of the two-staged operation in treatment of IKD. Methods: IKD patients were included from June 1, 2016 to May 31, 2020. In the stage-1 surgery, acute reduction and extra-articular structure repair were performed. Following an intermediate rehabilitation, delayed cruciate ligament reconstructions were performed in stage-2. Physical examination, CT, MRI, and X-ray were performed during the pre-operative period. Knee function, joint stability, ligament laxity, knee range of motion (ROM), and alignment were accessed at follow-ups. The minimum and maximum follow-up times were 0.5 years and 1 year, respectively. Results: In total, 17 IKD patients were included. There were three subjects (17.65%) missing at the 1 year follow-up and the average follow-up was 11.18 ± 2.53 months. After stage-1, normal alignment and superior valgus/varus stability were restored in most subjects; however, a notable anterior-posterior instability still existed in most patients. The intermediate rehabilitation processed smoothly (6.94 ± 1.20 weeks), and all patients achieved knee ROM of 0-120° finally. At 0.5 years and 1 year follow-up after stage-2, all subjects had achieved normal knee stability, ROM, and satisfying joint function. No infection or DVT was observed. Conclusions: The two-staged operation for IKD has superior efficacy on knee stability and function, and it can facilitate the rehabilitation and achieve satisfactory short-term outcome.

Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in TNF-α-induced rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs) have functions in the pathogenesis of rheumatoid arthritis (RA) through the onset of synovitis, the growth of pannus and the destruction of cartilage and bone. The significant increase in the proliferation, migration and invasion of FLSs induces the onset and advancement of RA. To date, the exact function of corepressor element-1 silencing transcription factor (CoREST) in RA remains unclear, but its expression has been determined in RA synovial tissues. In this study, the effects of CoREST were investigated in a TNF-α-induced FLS activation model. Following the silencing of CoREST expression with small interfering (si)RNA, the viability and migration of FLSs were evaluated. Furthermore, the possible molecular mechanisms were explored by detecting the expression of key factors, including matrix metalloproteinases (MMPs), lysine-specific histone demethylase 1 (LSD1) and associated cytokines, via reverse transcription-quantitative PCR and western blotting. CoREST expression increased not only in the RA synovial tissues, but also in the TNF-α-induced FLS activation model. Following the silencing of CoREST in the FLSs treated with TNF-α, cell viability was inhibited, and the migratory capacity of FLSs was suppressed, which was accompanied by the reduced expression of MMP-3 and MMP-9. The expression of LSD1 was also downregulated. There was a notable decrease in the synthesis of interferon-γ and interleukin (IL)-17, while IL-10 expression was increased. The knockdown of CoREST inhibited the viability and migration of FLSs stimulated with TNF-α. Thus, the suppression of CoREST may have crucial roles in the occurrence and development of RA.

Assessment of muscle activity and fatigue during laparoscopic surgery.

BACKGROUND: Cumulative musculoskeletal stress during operative procedures can contribute to the development of chronic musculoskeletal injury among surgeons. This is a concern in laparoscopic specialties where trainees may incur greater risk by learning poor operative posture or technique early in training. This study conducted an initial investigation of the physical stress encountered during the conduct of foregut laparoscopic surgery. METHODS: Subjects were divided into two groups based on their surgical experience level, high experience (HE), consisting of two attending surgeons, and low experience (LE), consisting of two fellow surgeons and a surgical chief resident. Nine distinct foregut laparoscopic procedures were observed for data collection within these groups. Electromyographic (EMG) activity was collected at the bilateral neck, shoulders, biceps, triceps, and lower back for each procedure. Physical workload was measured using percent reference voluntary contractions (%RVC) for each surgeon's muscle activities. Fatigue development was assessed using the median frequency of EMG data between two consecutive cases. Subjects completed a NASA-TLX survey when surgery concluded. RESULTS: LE surgeons experienced higher levels of %RVC in the lower back muscles compared to HE surgeons. LE fatigue level was also higher than HE surgeons across most muscle groups. A decrease in median frequency in six of the ten muscle groups after performing two consecutive cases, the largest decrements being in the biceps and triceps indicated fatigue development across consecutive cases for both surgeon groups. CONCLUSION: Surgeons developed fatigue in consecutive cases while performing minimally invasive surgery (MIS). HE surgeons demonstrated a lower overall physical workload while also demonstrating different patterns in muscle work. The findings from this study can be used to inform further ergonomic studies and the data from this study can be used to develop surgical training programs focused on the importance of surgeon ergonomics and minimizing occupational injury risk.

Identification and validation of key long non-coding RNAs in resveratrol protect against IL-1ß-treated chondrocytes via integrated bioinformatic analysis.

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-1ß-treated chondrocytes. METHODS: In this experiment, high-throughput sequencing technique was performed to identify the differentially expressed lncRNAs, miRNAs, and mRNAs between IL-1ß-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.

Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. METHODS: Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. RESULTS: We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. CONCLUSION: In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

A field study on marching band members' workload assessment.

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.

Resveratrol alleviates the interleukin-1ß-induced chondrocytes injury through the NF-κB signaling pathway.

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-1ß (IL-1ß). 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-1ß 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-1ß by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1ß, 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-1ß. 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.

MiR-708 inhibits MC3T3-E1 cells against H2O2-induced apoptosis through targeting PTEN.

BACKGROUND: The 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. METHODS: MC3T3-E1 was co-cultured with H2O2 for 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. RESULTS: H2O2 (100 nM) could significantly induce the apoptosis of MC3T3-E1 cells. Moreover, H2O2 could significantly increase the MDA level and downregulated Gpx level. RT-PCR found that H2O2 significantly decrease the level of miR-708. Compared with H2O2 group, H2O2 + miR-708 mimic significantly decreased the apoptosis rate. CONCLUSIONS: miR-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.

The antidepressant-like effects of fluvoxamine in mice involve the mTOR signaling in the hippocampus and prefrontal cortex.

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.

Synthesis of 9-O-arylated berberines via copper-catalyzed CAr-O coupling reactions.

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.

microRNA-7 inhibition protects human osteoblasts from dexamethasone via activation of epidermal growth factor receptor signaling.

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.

Sitting versus standing makes a difference in musculoskeletal discomfort and postural load for surgeons performing vaginal surgery.

INTRODUCTION AND HYPOTHESIS: We compared musculoskeletal discomfort and postural load among surgeons in sitting and standing positions during vaginal surgery. MATERIALS AND METHODS: Assessment of discomfort and posture of the primary surgeons in both positions was performed at two institutions. The primary outcome was an increase in body discomfort score after surgery as determined from subjective responses using validated tools. The secondary outcome was the percentage of time spent in awkward body postures measured objectively and stratified into awkward postures for neck, trunk, and bilateral shoulder angles. Variables were compared between sitting and standing positions using Fisher's exact test for primary outcomes and Wilcoxon rank-sum test for secondary outcomes. RESULTS: Data were collected for 24 surgeries from four surgeons in sitting position and nine surgeries from nine surgeons in standing position. The standing surgeons reported a significant increase in discomfort postoperatively for bilateral wrists, thighs, and lower legs compared with the sitting surgeons. The median percentage of time spent in awkward postures was significantly lower for the trunk in the standing versus sitting position (median 0.3% vs 58.8%, p < 0.001) but was significantly higher for both shoulders in the standing versus the sitting position (right shoulder: median 17.8% vs 0.3%, p = 0.003; left shoulder: median 7.4% vs 0.2%, p = 0.003). CONCLUSION: Surgeons reported more discomfort in when performing vaginal surgery while standing. The postural load was worse for trunk but favorable for bilateral shoulders when seated. Such differences may impact a surgeon's decision to perform vaginal surgery seated rather than standing.