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Bolt connection is commonly used to assemble shell structures in engineering fields. Prolonged external excitation can induce stick, slip, even separation states at the connection interface, leading to complex nonlinear dynamics in bolted shell structures. Understanding the dynamic mechanism of bolted joined shells under stick–slip-separation condition is crucial for the design and application of these structures. In this study, we aim to build the nonlinear dynamic model and reveal the vibration mechanism of bolted joined conical-cylindrical shells with stick–slip-separation behavior. During the development of the mechanical model of the bolt connection, the axial bilinear stiffness characteristics and interface friction behaviors are taken into account simultaneously, which could simulate the transition of the contact state at the connection interface. The rigid joint between the conical and cylindrical shells is realized via successive distributed artificial springs. Donnell's shell theory as well as the displacement assumption of Chebyshev polynomials are employed in theoretical modeling, and the governing equation is obtained by the Lagrange equation. In contrast with existing research and experimental data, the accuracy of the present theoretical model is validated. Both theoretical and experimental results indicate the frequency multiplication and dynamic softening phenomena as the excitation level increases. By the consideration of the stick-slip-separation behavior at the connection interface in the modeling, these nonlinear vibration behaviors can be effectively illustrated. Additionally, hysteresis characteristics are further investigated to explore frictional energy dissipation. The stick–slip-separation contact state at the connection interface under different excitation levels, bolt preloads and cone angles are also analyzed. The present investigation provides a basis for the design and health condition monitoring of bolted shell structures. [ABSTRACT FROM AUTHOR]

• A new strategy is proposed for vibration control of flexible pendulums. • We introduce a flywheel to control flexible pendulum vibration. • The control method has robustness and is effective for nonlinear forced vibration. • An experiment platform is built to validate the proposed control strategy. Flexible inverted pendulums have found wide applications in mechanical systems, but their stability is susceptible to external disturbances. In this study, a new strategy that employs a flywheel to suppress vibration of flexible inverted pendulums is proposed. We develop the theoretical dynamic model of flexible pendulums with a flywheel by the Euler-Bernoulli beam theory, where the axial displacement of the pendulum and geometric nonlinearities are considered. An active control method based on the Bézier trajectory is proposed, where the acceleration of the flywheel is set as the input. Additionally, the equivalent damping ratio of the system including flywheel's motion is derived. The relationship between the parameters in the control equation and the suppression effect is obtained through the simulation of the equivalent damping ratio. Then, an experimental platform is built. The experimental results show that the present control strategy has good suppression effect on the vibration of the flexible inverted pendulums when selecting appropriate parameters. Meanwhile, the results of anti-disturbance test show that the present method has a certain robustness. Finally, the simulation results show that this strategy is also effective for nonlinear forced vibration under different excitation frequencies. [ABSTRACT FROM AUTHOR]

• Vibrations of JCCSs with bolt loosening boundary are studied theoretically and experimentally. • Non-uniform arc constraint is established to simulate the bolt loosening boundary. • The developed model is reliable in estimating the dynamic behaviors of bolted JCCSs with different loosening degrees. • Experimental results validate the present theoretical model. This paper investigated the vibration characteristics of joined conical-cylindrical shells (JCCSs) with bolt loosening boundary conditions both theoretically and experimentally. The non-uniform arc constraint model is established to simulate the bolt loosening boundary conditions by the artificial spring technology, which can describe the actual bolt contact pressure distribution. Continuously distributed artificial springs are introduced to realize the connection of the conical and cylindrical shells. Donnell's shell theory and Chebyshev polynomials are adopted to establish the theoretical model, and the dynamic equation is derived from the Lagrange equation. The validity of the present model is verified by the available literature, hammer test and vibration shaker test. The results indicate that the maximum errors of natural frequencies and resonant displacements are less than 4.41% and 18.6%, respectively. It is found that bolt loosening has a significant effect on the fundamental frequency, but it gradually weakens with the increase of the mode order. Increasing bolt loosening degree can lead to an increment of resonant displacement. The developed model is reliable in estimating the dynamic behaviors of bolted JCCSs with different loosening degrees, and it contributes to providing guidance in the design and service process of combined shell structures. [ABSTRACT FROM AUTHOR]

Abstract: The nonlinear vibrations of a thin, elastic, laminated composite circular cylindrical shell, moving in axial direction and having an internal resonance, are investigated in this study. Nonlinearities due to large-amplitude shell motion are considered by using Donnell’s nonlinear shallow-shell theory, with consideration of the effect of viscous structure damping. Differently from conventional Donnell’s nonlinear shallow-shell equations, an improved nonlinear model without employing Airy stress function is developed to study the nonlinear dynamics of thin shells. The system is discretized by Galerkin’s method while a model involving four degrees of freedom, allowing for the traveling wave response of the shell, is adopted. The method of harmonic balance is applied to study the nonlinear dynamic responses of the multi-degrees-of-freedom system. When the structure is excited close to a resonant frequency, very intricate frequency–response curves are obtained, which show strong modal interactions and one-to-one-to-one-to-one internal resonance phenomenon. The effects of different parameters on the complex dynamic response are investigated in this study. The stability of steady-state solutions is also analyzed in detail. [Copyright &y& Elsevier]

Abstract: Angiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic agent in cancer, and in this study, we investigated the regulatory mechanisms of TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF levels. Phosphorylation of p44/42 MAPK, which was followed by increased expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these events could be ameliorated by addition with TNP-470 in time- and dose-dependent manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into culture supernatant. Furthermore, TNP-470 blockage of VEGF production in activated HSCs could be nullified by exogenous inoculation with prostaglandin E2. In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production. [Copyright &y& Elsevier]

The flexibility of insect wings and model wings in flapping-wing micro air vehicles (FWMAVs) is crucial to guarantee an economic flight. Since the wing deformation is bilaterally coupled with the aerodynamic force, conventional simulations on this fluid–structure interaction (FSI) problem mostly build up their models using computational fluid dynamics (CFD) and computational solid dynamics (CSD) methods, which requires high computational costs. Alternatively, an analytical model is proposed here for a quick estimate of the aerodynamic performance and passive deformation on flexible flapping wings. The deformation is simplified into a rigid-body rotation at the wing root, a spanwise twist, and a shortening along the span. The aerodynamic force is approximated by a predictive quasi-steady model and the spanwise twist is modeled using a quadratic polynomial. Results show that the introduction of wing flexibility can attenuate the lift generation due to the negative rotational lift and adverse translation–rotation coupling effect after each stroke reversal. The wing with moderate stiffness is recommended to achieve a high lift. An increase of aspect ratio and root cutoff can also enhance the dimensional lift generation, while the most economic wing design has an aspect ratio around 5 and no root cut-off. More importantly, the increase of flapping frequency can only result in a lift enhancement within certain limits. However, the power consumption keeps increasing as the frequency goes up, indicating a significant breakdown of performance. Our findings can uncover the role of wing flexibility in both insects and FWMAVs and therefore contribute to the design of FWMAVs. [ABSTRACT FROM AUTHOR]

In this paper, nonlinear static and dynamic behaviors of slightly curved cantilevered pipes conveying fluid under transverse base excitations are investigated. Incorporating geometrical and inertial nonlinearities, a new three-dimensional dynamic model is developed for the inextensible cantilevered pipe based on the Euler–Bernoulli beam theory. The resultant partial differential equations are discretized using the Galerkin method and solved utilizing the pseudo-arclength continuation technique and a time-integration method. The static equilibrium configuration, linear stability, and nonlinear response of the pipe are calculated for various cases, which allow us to investigate the effects of flow velocity, gravity coefficient, initial curvature amplitude and shape, and base-excitation amplitude and frequency. An emphasis is put on the importance of modal interactions on frequency-response and force-response relationships, evidencing the possible in-plane and out-of-plane transverse vibrations and identifying the preferred forms of pre- and post-instability behaviors. This study offers an efficient theoretical model for exploring the nonlinear forced response of slightly curved cantilevered pipes conveying fluid and provides a better insight for further investigations on the modal interaction in cantilevered pipe devices. [ABSTRACT FROM AUTHOR]

The overuse of fossil fuels has accelerated the desire for clean energy. Hydrogen energy has become an important energy on the world energy stage in the 21st century. Hydrogen production technology has also become the focus of attention. Based on the previous reported Ni-bib (bib ​= ​1,4-bis(1H-imidazole-1-yl) benzene), Ni-bibp (bibp ​= ​4,4′-bi(1H-imidazole-1-yl)-1,1′-biphenyl) with longer ligand was designed and synthesized by solvothermal method. Its molecular formula is {[Ni 4 (bibp) 4 (SO 4 2−) 4 (H 2 O) 8 ]} n. Ni-bibp-900 derived from high temperature pyrolysis can be used as bi-functional electrode material for HER (hydrogen evolution reaction) and UOR (urea oxidation reaction). For HER, the overpotential is −297mV at a current density of 10 ​mA ​cm−2. The Tafel slope of the Ni-bibp-900 is 153.3 ​mV·dec−1. For UOR, the overpotential is 1.4 ​V when the current density is 10 ​mA ​cm−2. The Tafel slope of the Ni-bibp-900 is 97.53 ​mV·dec−1. The performance of UOR and HER is better than that of Ni-bib-T. In addition, we also studied the effect of different doping amounts of zinc ions on HER. The results show that the HER performance is improved after doping zinc ion, which may be attributed to the sublimation of zinc ions during the pyrolysis process. Based on our previous reported Ni-bib, Ni-bibp with longer ligand was designed and synthesized by solvothermal method and the derived material Ni-bibp-900 after high temperature pyrolysis show better hydrogen evolution reaction (HER) and urea oxidation reaction (UOR) performance compared with Ni-bib-T. We also studied the effect of different doping amounts of zinc ions on the HER properties and we found that the electrocatalytic performance of Ni-bibp@Zn-900 (Ni: Zn ​= ​1:2) was obviously improved. [Display omitted] • Based on reported Ni-bib, Ni-bibp with longer ligand was designed and synthesized. • The derived Ni-bibp-900 show better HER and UOR performance. • We studied the effect of different doping amounts of zinc ions on HER properties. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a “glove-and-stocking” distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord, activation of microglia, but not astrocyte, was persistently observed until week five after the first cisplatin injection. Additionally, mRNA levels of inflammation related molecules including IL-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2 by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss. Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL-6, TNF-α, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti-inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin triggered persistent activation of spinal cord microglia through strengthening TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN intervention. [ABSTRACT FROM AUTHOR]

Clinical usage of opioids in pain relief is dampened by analgesic tolerance after chronic exposure, which is related to opioid-associated neuroinflammation. In the current study, which is based on a chronic morphine tolerance rat model and sustained morphine treatment on primary neuron culture, it was observed that Akt phosphorylation, cleaved-Caspase-1-dependent NALP1 inflammasome activation and IL-1β maturation in spinal cord neurons were significantly enhanced by morphine. Moreover, treatment with LY294002, a specific inhibitor of PI3k/Akt signaling, significantly reduced Caspase-1 cleavage, NALP1 inflammasome activation and attenuated morphine tolerance. Tail-flick tests demonstrated that pharmacological inhibition on Caspase-1 activation or antagonizing IL-1β dramatically blocked the development of morphine tolerance. The administration of an exogenous analogue of lipoxin, Aspirin-triggered Lipoxin (ATL), caused a decline in Caspase-1 cleavage, inflammasome activation and mature IL-1β production and thus attenuated the development of morphine tolerance by inhibiting upstream Akt phosphorylation. Additionally, treatment with DAMGO, a selective μ-opioid receptor peptide, significantly induced Akt phosphorylation, Caspase-1 cleavage and anti-nociception tolerance, all of which were attenuated by ATL treatment. Taken together, the present study revealed the involvement of spinal NALP1 inflammasome activation in the development of morphine tolerance and the role of the μ-receptor/PI3k–Akt signaling/NALP1 inflammasome cascade in this process. By inhibiting this signaling cascade, ATL blocked the development of morphine tolerance. [ABSTRACT FROM AUTHOR]

One zinc coordination polymer based on 5-(4-(tetrazol-5-yl) phenyl) m-phthalic acid (tpia) was synthesized. It was characterized by powder X-ray diffraction. Fluorescence titration experiments show that 1 is a multifunctional probe for metal ions and antibiotics. In addition, its electrocatalytic performance was improved and optimized by doping cobalt ions and pyrolysis, that is 1 -Co-700. 1 -Co-700 has a low initial potential (−423 ​mV), Tafel efficiency (101.9 ​mV·dec−1) and good cycle stability (stable after at least 1000 cycles). One new Zn-MOF was synthesized and could be as an excellent multifunctional probe for Fe3+, gatifloxacin and norfloxacin. Its HER performance was improved and optimized by doping cobalt ions. [Display omitted] • One new Zn-MOF was an excellent multifunctional probe. • It has a fluorescence quenching effect on Fe3+ in aqueous solution. • It has fluorescence quenching effects on antibiotics. • Its HER performance was improved and optimized by doping cobalt ions. [ABSTRACT FROM AUTHOR]

Abstract: This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Aβ fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of ‘mirror image’ pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain. [Copyright &y& Elsevier]

Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity and hepatotoxicity in fetal rats exposed to monocrotaline (MCT), a representative toxic PA. The aim of this study was to explore the underlying mechanism. 20 mg·kg−1·d−1 MCT was intragastrically given to pregnant Wistar rats from gestation day 9 to 20. CYP3As expression and pregnane X receptor (PXR) activation were specifically enhanced in female fetal liver. After MCT treatment, we also observed a significant increase of CYP3As expression in LO2 cells (high PXR level) or hPXR-transfected HepG2 cells (low PXR level). Employing hPXR and CYP3A4 dual-luciferase reporter gene assay, we confirmed the agonism effect of MCT on PXR-dependent transcriptional activity of CYP3A4. Agonism and antagonism of the androgen receptor (AR) either induced or blocked MCT-induced PXR activation, respectively. This study was the first report identifying that MCT served as PXR agonist to induce CYP3A expression. CYP3A induction may increase self-metabolic activation of MCT and subsequently lead to more severe hepatotoxicity in female fetus. While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity. Unlabelled Image • Gender differences in fetal MCT metabolism may due to female-specific CYP3A induction. • MCT is a PXR ligand and CYP3A inducer in both rat and human. • Cross talk between activated AR and PXR inhibits CYP3A induction by MCT in males. [ABSTRACT FROM AUTHOR]