Search

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.

The significant effect of the closed-detached response on the system is often ignored by traditional vibration control and energy-harvesting devices. In this study, we design a composite vibration energy-harvesting damper by combining the lever-type nonlinear energy sink, the three-spring quasi-zero stiffness structure, and the suspended magneto-electric energy harvester. The analytical as well as the numerical solutions are obtained using the harmonic balance method combined with the arc-length extension method as well as the Runge–Kutta method, respectively. Numerical solutions support analytical solutions. The presence of the closed-detached voltage makes composite system voltage harvesting more efficient. In addition, we investigate the performance of vibration control and energy harvesting by changing the dynamic parameters of the system such as attached mass, stiffness, and fulcrum position. Finally, when compared with the traditional absorber, the proposed absorber shows great improvement either in vibration control or in energy harvesting.

In this study, a simply supported functionally graded material beam with a giant magnetostrictive thin film (GMF) was selected as an energy harvester. Based on the theory of large deformation and the Villari effect of GMF, piston theory was used to simulate the dynamic equation of the whole structure under supersonic aerodynamic pressure and in a thermal environment by using Hamilton’s principle, and the energy harvesting effect of GMF was simulated by using a Runge–Kutta algorithm. Below the critical flutter velocity, the maximum voltage output and energy harvesting results were discussed as they were affected by external factors such as the geometric model of structure parameters, slenderness ratio, gradient index, number of turns of an electromagnetic coil, airflow velocity, and temperature. The electromechanical coupling coefficient $$ k_{{33}}$$ was 71%. The results show that this proposed harvester can achieve an optimal harvesting effect by adjusting the parameters appropriately, and collect energy in thermal and supersonic environments using the GMF, which provides power to sensors of the health monitoring system of the aircraft’s own structure.

In this paper, a novel negative stiffness inertial nonlinear energy sink (NSI-NES) is proposed. The main structure is simulated as a single-degree-of-freedom linear oscillator. Newton's second law is applied to derive the kinematic equations of the coupled system. Based on the Runge–Kutta numerical solution, the complex dynamical behaviors of the system coupled with the NSI-NES are explored. Moreover, the quasiperiodic solution exhibited a strongly modulated response (SMR). The steady-state response of the system is obtained using the Runge–Kutta and harmonic balance methods and is cross-corroborated. Compared with the inertial nonlinear energy sink (I-NES) and the positive stiffness inertial nonlinear energy sink (PSI-NES), the damping effects of the NSI-NES are highlighted based on various excitations. The results show that the NSI-NES has a damping effect of up to 90%. In addition, the effect of the NSI-NES parameters on the damping effect is discussed. In general, the negative stiffness element can significantly improve NES performance. Therefore, this study promotes the application of negative stiffness and inerter in engineering.

This work proposes on a novel continuum vibratory absorber that integrates a lever-type nonlinear energy sink (LNES) with asymmetric elastic boundary into viscoelastic Euler–Bernoulli beam condition to attenuate vibration. The steady-state response of the system is studied both numerically and analytically, and consistent results are found. In the process of studying the influences of the LNES coefficients, special attention is paid to the repetitious emergence of a closed detached response (CDR), which is firstly observed in the continuum system. It emphasizes that bifurcation of the system may take place many times. Meantime, it underscores that the amplitude-frequency response after adding the resonance absorber would diminish gradually, not abruptly. And the intimate connection between the existence of the CDR and the primary response is further investigated. The CDR could dramatically influence the peak of the resonance response and help to suppress the vibration. Furthermore, comparing with the same system coupled to the traditional NES, greater performance of the LNES is presented. It is valued that the vibration suppression scheme we proposed can play a significant role in vibration attenuation of a continuum system.

A nonlinear energy sink can achieve vibration reduction without changing the resonant frequency of the system. In this work, an improved nonlinear energy sink is proposed by integrating with an electromagnetic system. The vibration reduction performance is further enhanced and an energy harvesting function is achieved at the same time. The dynamic equations of the primary system with the improved nonlinear energy sink are established, and the electromagnetic analysis is performed. The steady-state response of the system is solved with the harmonic balance method and verified by numerical simulations. The integration of the electromagnetic system provides additional damping to the nonlinear energy sink, and the vibration reduction performances under the harmonic and the impulsive excitations are enhanced. At the same time, the vibrational energy is effectively harvested by the electromagnetic system. The integration of the electromagnetic system does not change the resonant frequency of the system and retains the targeted energy transfer characteristic. The proposed system is applicable to the nonlinear energy sink with originally insufficient damping, and the electromagnetic coupling coefficient is a key parameter affecting both the vibration reduction and the energy harvesting performances. This integrated system is expected to provide a new strategy for multifunctional devices.

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β-catenin destruction complex (GSK-3β and Axin), promotes the ubiquitination degradation of β-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

Nonlinear vibration absorbers have been widely used for vibration suppression of elastic structures, but they were usually placed within the structures. However, designing such a vibration damping device within an engineering structure is possibly difficult. In this paper, an inertial nonlinear energy sinks (NES) is mounted on the boundaries of the elastic beam to suppress its vibration. Although this vibration suppression approach is more in line with engineering requirements, it introduces nonlinear oscillators at boundaries. This brings certain difficulties to the structural vibration analysis and the optimal absorber design. An approximate analytical approach for the steady-state response is developed in this work and verified by numerical solutions. The comparison with the uncontrolled system demonstrates the high-efficiency vibration suppression of the inertial NES installed on the boundary. Besides, the optimization of the NES parameters is performed. Resonance amplitude of the elastic structure can be reduced by 98% with the optimized NES. In summary, this paper proposes a novel approach to suppress the bending vibration of elastic structures through boundary NESs. The vibration reduction effect is very significant, and it is more feasible to implement. Therefore, this work is helpful to study the vibration of elastic structures with nonlinear boundaries and to promote the application of nonlinear vibration absorbers. A boundary damping strategy is proposed to solve the problem of the difficulty of installing the vibration absorber in engineering. Introduce an inertial nonlinear energy sinks (NES) to reduce the weight of the shock absorber. The nonlinear boundary is separated and merged into the elastic beam vibration control equation to realize the decoupling of the continuum model. Resonance peak of the elastic structure can be reduced by 98% with the optimized NES. This work is helpful to study the vibration of elastic structures with nonlinear boundaries and to promote the application of nonlinear vibration absorbers.

NiTiNOL-steel wire rope (NiTi-ST) is a new vibration absorber with nonlinear stiffness and hysteretic damping. Although there are many studies on NiTi-ST nonlinear identification, there are few studies on vibration suppression for laminated structures with NiTi-ST. In the present work, the NiTi-ST is integrated with a composite laminated beam for structural vibration suppression for the first time. A coupling model of the composite laminated beam embedded with NiTi-ST is proposed. The nonlinear restoring force and hysteretic damping force of NiTi-ST are processed into polynomial form. The responses of the beam embedded with different NiTi-ST are investigated by the Galerkin discretization together with the harmonic balance method (HBM). The terms of the polynomial model are discussed. Two numerical methods are utilized for steady-state responses and numerical validations. Simulation results demonstrate the effectiveness of NiTi-ST. This vibration suppression method can be popularized for other laminated structures and contribute to vibration control in engineering fields.

Cancer stem cells (CSCs) have been implicated in tumorigenesis and tumor recurrence and metastasis are key therapeutic targets in cancer treatment. MicroRNAs display therapeutic potential by controlling the properties of CSCs; however, whether an association exists between miR-3682-3p and CSCs is unknown.To investigate the mechanism by which miR-3682-3p promotes stemness maintenance in hepatocellular carcinoma (HCC).MiR-3682-3p expression in HCC cell lines and 34 pairs of normal and HCC specimens was assayed by quantitative polymerase chain reaction. The functional role of miR-3682-3p was investigatedWe found that miR-3682-3p plays a key role in HCC pathogenesis by promoting HCC cell stemness. The upregulation of miR-3682-3p enhanced CSC spheroid-forming ability, side population cell fractions, and the expression of CSC factors in HCC cellsOur findings reveal a novel mechanism by which miR-3682-3p promotes stemness in HCC stem cells. Silencing miR-3682-3p may represent a novel therapeutic strategy for HCC.

Background Cholecystectomy is a common elective procedure for cholecystic diseases, including cholecystitis and cholelithiasis. Common bile duct injury is a major complication in both open and laparoscopic cholecystectomy (LC). The number of cholecystectomies performed has increased due to popularization and application of the laparoscopic technique, which has led to an increase in the number of bile duct injuries. Case summary A 65-year-old man presented to the General Surgery Department with a complaint of repeated right upper quadrant pain for 2 years that had worsened over the previous day. The patient had a history of gallstones and hypertension. A LC was performed; it was found that a biliary stricture of 53 h duration was caused by a ligature injury of the common bile duct during the LC. Another laparoscopic exploration was performed, and the stricture was released. Conclusion LC is a common surgical procedure, but if a complication occurs, it is important for the surgeon to consider another exploratory surgery.

Purpose When a manipulator captures an unknown space object, inertia parameters of endpoint payload should be timely obtained to handle possible unexpected parameter variations and monitor the system’s operating conditions. Therefore, this study aims to present an identification method for estimating the inertia parameter of the payload carried by a flexible two-link space manipulator. Design/methodology/approach The original nonlinear dynamics model of the manipulator is linearized at a selected working point. Subsequently, the system modal frequencies with and without payload are determined using the subspace identification algorithm, and the difference of these frequencies is computed. Furthermore, by adjusting the structural configuration of the manipulator, multiple sets of frequency differences are obtained. Therefore, the inertia parameters of the payload, i.e. the mass and the moment of inertia, can be derived from the frequency differences by solving a least-squares problem. Findings The proposed method can effectively estimate the payload parameters and has satisfactory identification accuracy. Practical implications The approach’s implementation provides a practical reference for determining inertia parameters of an unknown space target in the capture process. Originality/value The study proposes a novel method for identifying the inertia parameters of the payload of a flexible two-link space manipulator using the estimated system frequencies.

A nonlinear vibration isolation system is promising to provide a high-efficient broadband isolation performance. In this paper, a generalized vibration isolation system is established with nonlinear stiffness, nonlinear viscous damping, and Bouc-Wen (BW) hysteretic damping. An approximate analytical analysis is performed based on a harmonic balance method (HBM) and an alternating frequency/time (AFT) domain technique. To evaluate the damping effect, a generalized equivalent damping ratio is defined with the stiffness-varying characteristics. A comprehensive comparison of different kinds of damping is made through numerical simulations. It is found that the damping ratio of the linear damping is related to the stiffness-varying characteristics while the damping ratios of two kinds of nonlinear damping are related to the responding amplitudes. The linear damping, hysteretic damping, and nonlinear viscous damping are suitable for the small-amplitude, medium-amplitude, and large-amplitude conditions, respectively. The hysteretic damping has an extra advantage of broadband isolation.

Quasi-zero stiffness system has been widely used to isolate structural vibrations. However, its small dynamic stiffness may result in drastic low-frequency vibration. This is a curse of employing quasi-zero stiffness systems in engineering. In this paper, a nonlinear energy sink (NES) is used to overcome this difficulty. In order to reduce the additional weight of the NES, the mass of the NES is replaced by an inerter. By superposing the quasi-zero stiffness system and the inertial NES together, a combined vibration control technique is proposed. The equations of the motion of the primary structure and the combined control system are established. The steady-state response of the system is solved by the harmonic balance method and verified numerically. The suppression performance is evaluated based on the resonance suppression efficiency and the effective vibration isolation bandwidth. In addition, the parameters of the inertial NES are optimized. The results show that the combined control system has a better vibration control effect than the quasi-zero stiffness isolator. Specifically, the combined control system provides a smaller resonance amplitude and a wider vibration isolation band. In summary, the combined control scheme has both effects of the nonlinear isolation and the nonlinear absorption. Therefore, this paper proposes a vibration control technique that can achieve a wide band of vibration isolation and small vibration amplitude with a very little additional mass.

Nonlinear vibration absorption of a laminated composite beam is investigated with the account of complex environment (moisture and temperature). A passive efficient nonlinear energy sink (NES) vibration absorber is used to control the transverse vibration. The generalized Hamilton principle is applied to derive a dynamic model of the laminated composite beam coupled with the NES. Numerical simulations reveal the effects of temperature, moisture, and laying angle on natural frequencies. It is numerically found that the NES can rapidly reduce the vibration amplitude. Then, approximate analytical solutions are sought via the harmonic balance method. The approximate analytical solutions are confirmed by the numerical solutions. Amplitude–frequency response curves show that the NES can reduce the amplitude to very low values for various temperatures, moisture levels, and laying angles. In a certain ranges of the NES parameters, different control effects are determined via an approximate analysis. It is demonstrated that the NES is a promising approach to control vibration of a laminated composite beam in complex environment.

The nonlinear behaviors and vibration reduction of a linear system with nonlinear energy sink (NES) are investigated. The linear system is excited by a harmonic and random base excitation, consisting of a mass block, a linear spring, and a linear viscous damper. The NES is composed of a mass block, a linear viscous damper, and a spring with ideal cubic nonlinear stiffness. Based on the generalized harmonic function method, the steady-state Fokker-Planck-Kolmogorov equation is presented to reveal the response of the system. The path integral method based on the Gauss-Legendre polynomial is used to achieve the numerical solutions. The performance of vibration reduction is evaluated by the displacement and velocity transition probability densities, the transmissibility transition probability density, and the percentage of the energy absorption transition probability density of the linear oscillator. The sensitivity of the parameters is analyzed for varying the nonlinear stiffness coefficient and the damper ratio. The investigation illustrates that a linear system with NES can also realize great vibration reduction under harmonic and random base excitations and random bifurcation may appear under different parameters, which will affect the stability of the system.

Background Breast cancer is a common cancer among women in the world. However, its pathogenesis is still to be determined. The role and molecular mechanism of Nucleosome Assembly Protein 1 Like 1 (NAP1L1) in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for breast cancer treatment. Methods A bioinformatics analysis was conducted to determine the differential expression of NAP1L1 in breast cancer and find the potential biomarker that interacts with NAP1L1 and hepatoma-derived growth factor (HDGF). The expression of NAP1L1 in tissues was detected by using immunohistochemistry. Breast cancer cells were transfected with the corresponding lentiviral particles and siRNA. The efficiency of transfection was measured by RT-qPCR and western blotting. Then, MTT, Edu, plate clone formation, and subcutaneous tumorigenesis in nude mice were used to detect the cell proliferation in breast cancer. Furthermore, coimmunoprecipitation (Co-IP) assay and confocal microscopy were performed to explore the detailed molecular mechanism of NAP1L1 in breast cancer. Results In this study, NAP1L1 protein was upregulated based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Consistent with the prediction, immunohistochemistry staining showed that NAP1L1 protein expression was significantly increased in breast cancer tissues. Its elevated expression was an unfavorable factor for breast cancer clinical progression and poor prognosis. Stably or transiently knocking down NAP1L1 reduced the cell growth in vivo and in vitro via repressing the cell cycle signal in breast cancer. Furthermore, the molecular basis of NAP1L1-induced cell cycle signal was further studied. NAP1L1 interacted with the HDGF, an oncogenic factor for tumors, and the latter subsequently recruited the key oncogenic transcription factor c-Jun, which finally induced the expression of cell cycle promoter Cyclin D1(CCND1) and thus the cell growth of breast cancer. Conclusions Our data demonstrated that NAP1L1 functions as a potential oncogene via interacting with HDGF to recruit c-Jun in breast cancer.

This paper explores a new method for vibration control and energy harvesting by coupling a nonlinear energy sink (NES) with a cantilever beam containing giant magnetostrictive material. A mathematical model of the principal linear system under the action of an external harmonic force is established, and the dynamic equation of the system is derived using Newton’s second law, Hamilton’s principle, and nonlinear boundary conditions. The displacement responses of the system as functions of time and of frequency are obtained by using the Runge–Kutta method and harmonic balance method. The analytic results are found to be consistent with the numerical solution, confirming the accuracy and reliability of the calculated results. The frequency response and time response of the system with and without NES coupling, and with other parameters unchanged, were compared. The results show that the proposed structure can achieve excellent vibration suppression. The energy harvesting effect of the system as a function of time is also analyzed by the Runge–Kutta method, comparing results for different values of parameters such as NES mass, nonlinear spring stiffness, and damping coefficient. The results indicate that the proposed structure can achieve the desired effects of vibration reduction and energy harvesting, and that results can be optimized by adjusting the relevant parameters.

Integration of a vibration absorber and an energy harvester is a promising approach to achieve simultaneously vibration reductions and vibratory energy harvesting. The present work investigates random responses of a nonlinear energy sink (NES) combined with a giant magnetostrictive energy harvester (GMEH). When a structure is modeled as a one-degree-of-freedom oscillator subjected to a random excitation, the structure with the integrated NES-GMEH is governed by two simultaneous nonlinear stochastic differential equations coupled with a nonlinear algebraic equation. The Ferrari formula is applied to decouple the algebraic equations from the stochastic differential-algebraic equations. The resulting stochastic algebraic differential equations are transformed into the steady Fokker-Planck-Kolmogorov equations. A fourth finite difference scheme is used to solve numerically the FPK equations. The FPK equations based solutions are qualitatively verified via Monte Carlo simulations. The parametric effects on vibration suppression and electricity production are examined, where the electricity is indicated by the square expectations of voltage and power. The responses of the structure, the structure with the NES only and the structure with both NES-GMEH are compared under the same Gaussian white noise and system parameters. It is found that the integrated NES-GMEH system achieves the best vibration suppression. It is demonstrated that a properly designed NES-GMEH device can simultaneously suppress vibration and produce electricity under Gaussian white noise excitations.

A novel vibration isolation device called the nonlinear energy sink (NES) with NiTiNOL-steel wire ropes (NiTi-ST) is applied to a whole-spacecraft system. The NiTi-ST is used to describe the damping of the NES, which is coupled with the modified Bouc-Wen model of hysteresis. The NES with NiTi-ST vibration reduction principle uses the irreversibility of targeted energy transfer (TET) to concentrate the energy locally on the nonlinear oscillator, and then dissipates it through damping in the NES with NiTi-ST. The generalized vibration transmissibility, obtained by the root mean square treatment of the harmonic response of the nonlinear output frequency response functions (NOFRFs), is first used as the evaluation index to analyze the whole-spacecraft system in the future. An optimization analysis of the impact of system responses is performed using different parameters of NES with NiTi-ST based on the transmissibility of NOFRFs. Finally, the effects of vibration suppression by varying the parameters of NiTi-ST are analyzed from the perspective of energy absorption. The results indicate that NES with NiTi-ST can reduce excessive vibration of the whole-spacecraft system, without changing its natural frequency. Moreover, the NES with NiTi-ST can be directly used in practical engineering applications.

BACKGROUND Most eukaryocytes release nano vesicles (30-120 nm), named exosomes, to various biological fluids such as blood, lymph, and milk. Hepatocellular carcinoma (HCC) is one of the tumors with the highest incidence rate in primary malignant carcinoma of the liver. However, the mechanism of HCC proliferation remains elusive. In this study, we aim to explore whether HCC cell-derived exosomes affect the proliferation of cancer cells. MATERIAL AND METHODS Exosomes were isolated from HCC cells by ultracentrifugation and were visualized the phenotype by transmission electron microscopy. Cell proliferation was detected by Cell Counting Kit-8 assays and EdU (5-ethynyl-2-deoxyuridine) incorporation assays. Dual-luciferase assays were performed to validate the paired correlation of miR-155 and 3'-UTR of PTEN (gene of phosphate and tension homology deleted on chromosome 10). A xenograft mice model was constructed to verify the effect of exosome-mediated miR-155 on cell proliferation in vivo. RESULTS Our finding showed that miR-155 was enriched in exosomes released from HCC cells. The exosome-containing miR-155 transferred into new HCC targeted cells and lead to the elevation of HCC cells' proliferation. Besides, the exosomal miR-155 directly bound to 3'-UTR of PTEN leading to the reduction of relevant targets in recipient liver cells. The knockdown of PTEN attenuated the proliferation of HCC cells treated with the exosomal miR-155. Moreover, nude-mouse experiment results revealed a promotional effect of the exosomal miR-155 on HCC cell-acquired xenografts. CONCLUSIONS Our study indicated that exosomal-specific miR-155 transfers to adjacent and/or more distant cells and stimulates the proliferation of HCC cells.

When introduces nonlinearity into the system, there may be closed detached frequency response due to the bifurcation. This paper aims to provide the dynamical behaviors of a structure combined with a lever-type nonlinear energy sink (LNES). The structure subjected to periodic excitation is modeled as linear to stress the dynamical complexity driven only by the LNES. Depended on the numerical results, the global bifurcation analysis is proposed to expose the existence of periodic and aperiodic motion. The aperiodic motions are numerically identified via time history response, phase trajectories, Poincare maps, and power spectra. Besides, to trace the frequency response of the system, especially the closed detached response curves, the harmonic balance method is covered with the arc-length tracking continuation. The Floquet theory is utilized to settle the stability of frequency response and discovers the saddle-node (SN) bifurcation and the Neimark–Sacker (NS) bifurcation under the resonance response interaction. The investigation demonstrates that when SN bifurcation and NS bifurcation occur concurrently, it is a predictor that the closed detached frequency response may appear.

This paper presents nonlinear energy sink with giant magnetostrictive-piezoelectric material for energy harvesting of the whole-spacecraft vibration reduction system. The whole-spacecraft vibration attenuation system can effectively reduce vibration and achieve self-tuning enhanced energy harvesting range. The open-circuit voltage generated at low frequency is affected by the magnetic field force, alternating magnetic field and relative displacement. In order to acquire a steady periodic solution of the energy harvesting system, a combination of the harmonic balance method and pseudo arc length continuation technique is used. The numerical outcomes are consistent with the analytical outcomes in a certain range, which also proves the accuracy and reliability of the results. The amplitude and voltage of the energy harvesting system are analyzed by parameters such as cubic stiffness, viscous damping, and external excitation acceleration. In addition, this paper provides a new idea for broadband energy harvesting.

A nonlinear energy sink (NES) is a promising device to reduce structural vibrations. If a nonlinear energy sink moves vertically, in principle, its weight cannot be ignored together with the initial deformation due to the static equilibrium. The present work investigates dynamic effects of the weight on the vibration of a structure coupled with a nonlinear energy sink, which is modeled as a 2-degree-of-freedom system. Free vibration is numerically examined. Forced vibration is analytically explored via the method of harmonic balance with numerical validations. It is found that the freely vibrating frequency is larger than the natural frequency of the structure except for an unreasonably small NES mass if the weight is considered, while it is smaller if the weight is ignored. It is also found that the steady-state response of the primary structure in the case considering the weight is smaller than that in the case ignoring the weight, but the difference decreases with the increase of the excitation amplitude. The experimental results demonstrate that considering the weight leads to more accurate predictions.

A novel archetype of nonlinear energy sink (NES) enhanced by an inerter is proposed for vibration reduction of vibrating systems. The proposed NES-inerter suppressed vibration more effectively than a convenient NES measured by both energy dissipation and amplitude frequency responses. Complexification-averaging technique is applied to analyze a coupled system to find steady-state periodic solutions, and the analytical results are confirmed by numerical simulations. The analytical solutions are used to bifurcation analysis, and the results show that the saddle node and the Hopf bifurcations occur under a series of parameters in the steady-state responses. The effects of parameters, such as inertance, cubic stiffness, viscous damping, and amplitude of the external excitation, on the performance of the proposed NES are examined based on the analytical solutions. The investigation reveals that the optimal value of the inerter exists in a certain range.

A generalized transmissibility is proposed to evaluate nonlinear vibration absorbers. Due to possible existence of higher order harmonics and aperiodic motion, the root mean square is employed to define the transmissibility. The transmissibility beyond harmonic motion is applied to measure vibration reduction of a structure coupled with a nonlinear energy sink. Periodic steady-state responses of the coupled system are analytically predicted by the method of harmonic balance, and the stabilities of the responses are determined. The effects of parameters of the nonlinear energy sink on the transmissibility are explored based on harmonic balance solutions and numerical simulations. Phase portraits, Poincare map and frequency spectrum reveal that quasi-periodic motions occur when periodic responses are unstable. Finally, two evaluation approaches based on the energetics and the transmissibility are compared. The investigation demonstrates the quasi-periodic motion is an indication of the optimal transmissibility. The performance of nonlinear energy sink absorbers may be extremely sensitive to parameter variations.

This paper presents a new device integrating a nonlinear vibration absorber with a levitation magnetoelectric energy harvester for whole-spacecraft systems. This device effectively reduces vibration and has a stronger energy harvesting capability than the existing systems. It harvests energy from a wide frequency range and has a high output voltage. The harvested energy is determined by magnetic field strength, excitation frequency, and resistive load. The change in the magnetic field strength has the least impact on the output voltage. The vibration reduction effects and harvested energy of the system are analyzed with an approximate analytical method that combines the harmonic balance approach and the pseudo-arclength continuation algorithm. The results of the Runge–Kutta method are nearly consistent with those of the approximate analytical method. Moreover, the effects of the excitation frequency, resistive load, and parameters of the nonlinear energy sink on the system vibration response and energy harvesting are analyzed.

A novel type of a nonlinear energy sink is proposed by introducing a lever to reduce the necessary mass. The lever-type nonlinear energy sink is attached to a two-degree-of-freedom simplified model of whole-spacecraft subjected a harmonic excitation. The transmissibility is used to evaluate the performance of vibration reduction. The harmonic balance method with an alternating frequency time is applied to predict the variation of the transmissibility with the excitation frequency. The harmonic balance solutions are supported by the numerical results. It is found that the disappearance of closed detached resonance response may dramatically decrease the transmissibility. Besides, the quasi-periodic motion may be a predictor to generate the closed detached resonance. The harmonic balance solutions are used to examine the effects of the mass, the nonlinear stiffness and the fulcrum location. With a suitable fulcrum location, the lever-type nonlinear energy sink outperform a conventional nonlinear energy sink with same mass, damping and nonlinear stiffness.

Gastric cancer (GC) is a common cancer worldwide and its precise mechanism is largely unknown. The aim of the present study was to evaluate the expression levels of NOD-like receptor X1 (NLRX1), tumor necrosis factor receptor-associated factor 6 (TRAF6) and NF-κB in GC and normal gastric tissue samples to determine the association with the clinicopathological features of GC. GC and adjacent normal gastric tissues from 60 patients with GC were analyzed using immunohistochemistry and western blotting analysis. In addition, the association between NLRX1, TRAF6 and NF-κB expression levels were investigated by Spearman's correlation analysis. The results revealed that NLRX1 protein expression levels were downregulated in the GC tissues compared with the normal gastric tissues (P

In order to improve the harsh dynamic environment experienced by heavy rockets during different external excitations, this study presents a novel active variable stiffness vibration isolator (AVS-VI) used as the vibration isolation device to reduce excessive vibration of the whole-spacecraft isolation system. The AVS-VI is composed of horizontal stiffness spring, positive stiffness spring, parallelogram linkage mechanism, piezoelectric actuator, acceleration sensor, viscoelastic damping, and PID active controller. Based on the AVS-VI, the generalized vibration transmissibility determined by the nonlinear output frequency response functions and the energy absorption rate is applied to analyze the isolation performance of the whole-spacecraft system with AVS-VI. The AVS-VI can conduct adaptive vibration suppression with variable stiffness to the whole-spacecraft system, and the analysis results indicate that the AVS-VI is effective in reducing the extravagant vibration of the whole-spacecraft system, where the vibration isolation is decreased up to above 65% under different acceleration excitations. Finally, different parameters of AVS-VI are considered to optimize the whole-spacecraft system based on the generalized vibration transmissibility and the energy absorption rate.

Numerous studies have reported the important role of microRNAs (miRNAs) in human cancers. Although abnormal miR-29b expression has been linked to tumorigenesis in several cancers, its role in cholangiocarcinoma remains largely unknown. We found that miR-29b expression is frequently downregulated in human cholangiocarcinoma QBC939 cells and in clinical tumor samples. In cholangiocarcinoma patients, low miR-29b expression predicts poor overall survival. Overexpression of miR-29b in QBC939 cells inhibited proliferation, induced G1 phase cycle arrest, and promoted apoptosis. Methylation-specific PCR (MSP) analysis revealed a decreased methylation imprint at the promoter of the cell cycle inhibitor gene CDKN2B in cells overexpressing miR-29b. After identifying the DNA methyltransferase DNMT3B as a putative miR-29b target, luciferase reporter assays confirmed a suppressive effect of miR-29b on DNMT3B expression. Accordingly, we detected an inverse correlation between miR-29b and DNMT3B expression in clinical cholangiocarcinoma specimens. In QBC939 cells, DNMT3B overexpression promoted proliferation and inhibited apoptosis. DNMT3B silencing, in turn, led to increased CDKN2B expression. We also observed significant growth arrest in subcutaneous tumors formed in nude mice by QBC939 cells overexpressing miR-29b. These findings suggest miR-29b functions as a tumor suppressor in cholangiocarcinoma by relieving DNMT3B-mediated repression of CDKN2B expression.

Background: Until now, the novel coronavirus 2019 (SARS-CoV-2) has caused wide dissemination in China and other 72 countries, affecting more than 90,000 peoples. Global health systems are facing the unprecedented challenges. Here we shared the experiences and lessons in emergency responses and management from our hospital, a government-assigned regional anti-COVID-19 general hospital in Nanjing, Jiangsu Province, China. Methods: All measures were designed and taken based on three periodic strategies with different emphases, in response to the epidemic progress. Beginning on January 6, 2020, an emergency leadership committee with subsidiary companion teams were established in Phase Ⅰ. Proactive preparation like infrastructure modifications and personnel training were conducted. In Phase Ⅱ, no efforts were spared on special arrangements for outpatients, surgeries, and online medical services to cut the visitors density. With continuous drop of newly confirmed cases since mid-February, regular hospital operation recovered gradually (Phase Ⅲ). COVID-19 screening flow was tailored in each phase. Questionnaires for staffs’ mental status and satisfaction were also surveyed. Findings: Since January 16, three patients were diagnosed with SARS-CoV-2 infection in our hospital. No hospital employees were infected with COVID-19. There was no case of hospital-acquired COVID-19 infection for those who received medical care in the setting of both outpatient and inpatient. During the epidemics, 6·46% staffs suffered depression, 9·87% had anxiety, and 98% were satisfied with the hospital infection control work. Shortages in staffs and medical consumables, and limitation in space were the obstacles we encountered. Interpretation: As the outbreak was rapid and sudden, and great uncertainties in COVID-19 still remain, we faced substantial challenges and difficulties. As the cost of in-hospital transmission is unbearable, our experiences and lessons suggested that prompt actions should be taken immediately to decrease or eliminate potential in-hospital transmission. Experience shared herein may be useful for those facilities who are and who may engage in COVID-19. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.

Nonlinear isolators in the shape of a circular ring have been shown to have an advantage over linear isolators in that they allow low-frequency vibration isolation. These isolators have generally been assumed to possess linear viscous damping, which degrades the performance of the isolator at high frequencies. An alternative design is to make use of nonlinear damping, where the nonlinear behavior is achieved by placing linear dampers, so that they are orthogonal to the motion of the isolator. In this work, the performance of circular ring isolators with this type of damping is compared with the corresponding isolators exhibiting linear viscous damping only. It is found that the isolators with linear viscous damping perform better around the resonance frequencies, but the isolators with nonlinear damping perform better at high frequencies.

Manipulator systems are widely used in payload capture and movement in the ground/space operation due to their dexterous manipulation capability. In this study, a method for identifying the payload parameters of a flexible space manipulator using the estimated system of complex eigenvalue matrix is proposed. The original nonlinear dynamic model of the manipulator is linearized at a selected working point. Subsequently, the system state-space model and corresponding complex eigenvalue parameters are determined by the observer/Kalman filter identification algorithm using the torque input signal of the motor and the vibration output signals of the link. Therefore, the inertia parameters of the payload, that is, the mass and the moment of inertia, can be derived from the identified complex eigenvalue system and mode shapes by solving a least-squares problem. In numerical simulations, the proposed parameter identification method is implemented and compared with the classical recursive least-squares and affine projection sign algorithms. Numerical results demonstrate that the proposed method can effectively estimate the payload parameters with satisfactory accuracy.