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Objective To isolate, sequence, and identify biological characterization and complete genome sequencing of a virulent Staphylococcus aureus (S. aureus) bacteriophage vB_SauH_IME522. Methods A phage was isolated from sewage of PLA Chinese General Hospital using a clinically isolated S. aureus strain as host bacteria. The double-layer agar plate was used to determine the optimal multiplicity of infection (optimal MOI) and one-step growth curve. Phage morphology was observed by transmission electron microscopy after purification using sucrose gradient separation. Phage DNA was sequenced using the Illumina Miseq sequencing platform. The complete genome sequence was annotated, then comparative genomics and evolutionary analyses were performed. Results A lytic phage of S. aureus was isolated from hospital sewage and named as vB_SauH_IME522. The optimal MOI of the phage was 0.01. One step growth curve showed that its latent period and burst period were 20 and 200 min, respectively. The burst size was about 89 PFU/cell. Electron microscopy displayed the phage having an icosahedral head (70±1) nm and a long contractile tail (135±2) nm. Genome sequencing results showed that the total length of the phage genome was 140 246 bp and the G+C content accounted for 30.2%. The genomic annotation revealed that the phage contained 223 genes coding proteins, 164 putative promoters, 66 terminators, 4 tRNAs, and 7 resistance-related regions. Phylogenetic analysis suggested that the phage was a member of the genus Kayvirus within the subfamily Twortvirinae. Conclusion A lytic phage of S. aureus vB_SauH_IME522 is identified as a new member of the Twortvirinae subfamily, with strong lytic ability and short latent period.

Background: Three-dimensional (3D) chromatin architecture frequently altered in cancer. However, its changes during the pathogenesis of hepatocellular carcinoma (HCC) remained elusive. Methods: Hi-C and RNA-seq were applied to study the 3D chromatin landscapes and gene expression of HCC and ANHT. Hi-C Pro was used to generate genome-wide raw interaction matrices, which were normalized via iterative correction (ICE). Moreover, the chromosomes were divided into different compartments according to the first principal component (E1). Furthermore, topologically associated domains (TADs) were visualized via WashU Epigenome Browser. Furthermore, differential expression analysis of ANHT and HCC was performed using the DESeq2 R package. Additionally, dysregulated genes associated with 3D genome architecture altered were confirmed using TCGA, qRT-PCR, immunohistochemistry (IHC), etc. Results: First, the intrachromosomal interactions of chr1, chr2, chr5, and chr11 were significantly different, and the interchromosomal interactions of chr4–chr10, chr13–chr21, chr15–chr22, and chr16–chr19 are remarkably different between ANHT and HCC, which resulted in the up-regulation of TP53I3 and ZNF738 and the down-regulation of APOC3 and APOA5 in HCC. Second, 49 compartment regions on 18 chromosomes have significantly switched (A–B or B–A) during HCC tumorigenesis, contributing to up-regulation of RAP2A. Finally, a tumor-specific TAD boundary located on chr5: 6271000–6478000 and enhancer hijacking were identified in HCC tissues, potentially associated with the elevated expression of MED10, whose expression were associated with poor prognosis of HCC patients. Conclusion: This study demonstrates the crucial role of chromosomal structure variation in HCC oncogenesis and potential novel biomarkers of HCC, laying a foundation for cancer precision medicine development. [ABSTRACT FROM AUTHOR]

The flow characteristics in reciprocating pump-pipe system are inevitably subject to the interaction effects between pump and pipeline. In this paper, a parametric interaction model of flow characteristics in reciprocating pump-pipe system is presented by considering the coupling effect and leakage characteristics. The analytical solutions of the proposed interaction equations are deduced with the aid of the harmonic balance method. A testing platform of a simplex plunger reciprocating pump-pipe system is employed for validating the proposed model. The experimental tests under different operating conditions are used to compare the pressure pulsations and discharge flow rates from analytical solutions. It is observed that the analytical solutions are in good agreement with the test data and numerical results, and the prediction error is within 13%, thus validating the presented interaction model and analytical solutions. The interaction effects as well as the flow characteristics in reciprocating pump-pipe system are analyzed and discussed using the proposed model. It is found that the opening of flow control valve has remarkable influence on the relationship between flow rate and operating speed of reciprocating pump. The pressure pulsation within a pipe is closely related to and significantly affected by the plunger-to-cylinder clearance and the plunger stroke. [ABSTRACT FROM AUTHOR]

Functionally graded material (FGM) has an important application prospect in aircraft engineering, especially in smart aircraft. The dynamic behavior of FGM has been widely investigated so far but more work is needed for the porous FGM pipes conveying fluid. In this paper, a sensible pore distribution function related with the volume fraction of metal and ceramic is proposed for the dynamic modeling of porous FGM pipes conveying fluid. The maximum porosity and its corresponding position are taken into account in the present mechanical model. The material properties of the porous pipes are temperature dependent and can be affected by pore distribution. The governing equation of the porous FGM pipe is derived and then the exact solution of post buckling is obtained. The nonlinear primary resonance is determined by the multiple scale method. It is shown that the effect of the pore distribution is very significant on the post buckling behavior and nonlinear primary resonance of the porous FGM pipes. The current work is very helpful in understanding the influence of pore distribution on static and dynamic behavior of pores FGM structures in engineering practice. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by chronic, progressive, and fibrotic lung injury. Although remarkable progress has been made toward understanding the pathogenesis of PF, finding more effective treatments for this fatal disease remains a challenge. In this study, we describe an innovative macrophage‐based approach to deliver anti‐fibrotic protein to the lung and inhibit PF in a mouse model of bleomycin (BLM)‐induced lung injury. We engineered macrophages to continuously secrete three types of proteins: interleukin‐10, which prevents inflammation; TGFRcFc, a soluble truncated TGF‐βR2 that blocks TGF‐β; and CD147, which induces matrix metalloproteinases (MMPs) and causes collagen degradation. Infusing these engineered macrophages into the lungs of BLM‐induced PF mouse models in an optimal pattern significantly ameliorated PF in mice. Specifically, the most effective therapeutic outcome was achieved by infusing IL‐10‐secreting macrophages on day 1, followed by TGFRcFc‐secreting macrophages on day 7 and CD147‐secreting macrophages on day 14 into the same mice after BLM treatment. Our data suggest that macrophage‐based delivery of anti‐fibrotic proteins to the lungs is a promising therapy for fibrotic lung disorders. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a persistent and progressive respiratory disorder characterized by expiratory airflow limitation caused by chronic inflammation. Evidence has shown that COPD is correlated with neutrophil chemotaxis towards the airways, resulting in neutrophilic airway inflammation. This study aimed to evaluate neutrophil chemotaxis in bronchoalveolar lavage fluid (BALF) from COPD patients using a high-throughput nine-unit microfluidic platform and explore the possible correlations between neutrophil migratory dynamics and COPD development. The results showed that BALF from COPD patients induced stronger neutrophil chemotaxis than the Control BALF. Our results also showed that the chemotactic migration of neutrophils isolated from the blood of COPD patients was not significantly different from neutrophils from healthy controls, and neutrophil migration in three known chemoattractants (fMLP, IL-8, and LTB4) was not affected by glucocorticoid treatment. Moreover, comparison with clinical data showed a trend of a negative relationship between neutrophil migration chemotactic index (C. I.) in COPD BALF and patient's spirometry data, suggesting a potential correlation between neutrophil migration and the severity of COPD. The present study demonstrated the feasibility of using the microfluidic platform to assess neutrophil chemotaxis in COPD pathogenesis, and it may serve as a potential marker for COPD evaluation in the future. [ABSTRACT FROM AUTHOR]

In this paper, a pendulum-type metamaterial (PTM) is designed with a pendulum bob hinged at the primary mass. Considering the effect of geometric nonlinearity, the nonlinear dynamic equations of PTM unit cell are presented with the aid of the Bloch theorem. The analytical formula of dispersion equation is deduced to discuss the nonlinear internal resonance bandgap using the harmonic balance method. The obtained bandgap of the metamaterial is in good agreement with the numerical simulation result. The nonlinear geometric influence of pendulum on PTM bandwidth is significant. The bandgaps under different internal resonances are substantially different from each other due to the nonlinear effects. The upper boundaries of the frequency bandgap under 1:1/2 and 1:1/3 internal resonance rise nonlinearly to higher than those under linear and 1:1 internal resonance conditions. It shows that the impact of 1:1/2 and 1:1/3 internal resonance on the bandgap could be more obvious as the strong nonlinearity is taken into consideration. [ABSTRACT FROM AUTHOR]

Active vibration control of a smart FG (functionally graded) cylindrical shell conveying fluid in thermal environment is studied theoretically by using a laminated piezoelectric actuator. Velocity feedback control law is implemented to activate the piezoelectric actuator. Considering the electric-thermo-fluid-structure interaction effect, a nonlinear dynamic model of the smart fluid-conveying FG cylindrical shell is developed based on Hamilton’s principle and von-Karman type geometrical nonlinear relationship. The inviscid, incompressible, isentropic and irrotational fluid is coupled into governing equations using the linearized potential theory. The Galerkin’s method is used to obtain the nonlinear governing equations of motion of the coupled system. The multiple time scales approach is applied to solve the resulting governing equations for analysing the nonlinear dynamic characteristics of the coupled system. The influence of fluid flow velocity, feedback control gains of piezoelectric voltage, external excitation and material properties of FGM on the frequency-response curves of system are investigated. The results indicate that the piezoelectric voltage is an effective controlling parameter for vibration control of the system, and the flow velocity can effect significantly the vibration amplitude and nonlinearity of the coupled system.

The components of a pump–pipeline system are coupled and interact with each other, but the dynamic analysis of reciprocating pump valves is usually executed without considering the effects of pipeline. In this article, a theoretical study is carried out to investigate the interaction effects between pump and pipeline on the motions of suction and discharge valves. Based on the principle of force balance and the law of mass and energy conservation, a new dynamic model of reciprocating pump valves is presented in order to obtain the motions of pump valve and the flow characteristics of pipeline simultaneously. The computational results are compared with the prior experimental data and the computational fluid dynamics simulation results to validate the proposed model, and good agreement is obtained. With the proposed model, the influences of piping parameters as well as the interaction effects on dynamic behaviors of pump valves and discharge flow rate are analyzed and discussed. It is found that the error between computational and prior experimental maximum valve lifts is less than 5%, and the proposed model has higher precision than the Adolph model in predicting the actual working characteristics of pump valves. The lift of pump valve and the flow rate in pipe are coupled with each other because the cylinder pressure and the leakage are directly related to the working load and the pressure drop of pipeline. The flow resistance of pipe could reduce the maximum value of valve lift but has slight influence on the lag time of valve opening. With the increasing of spring stiffness, the maximum value of valve lift decreases nonlinearly. The variation characteristics of flow rate versus pump operating speed relationships are significantly influenced by the flow resistance of pipeline, which means that the piping effects are significant and non-negligible for the pump design. [ABSTRACT FROM AUTHOR]

Ball bearings are important mechanical components in high-speed turbomachinery that is liable for severe vibration and noise clue to the inherent nonlinearity of ball bearings. Using experiments and the numerical approach, the nonlinear dynamic behavior of a flexible rotor supported by ball bearings is investigated in this paper. An experimental ball bearing-rotor test rig is presented in order to investigate the nonlinear dynamic performance of the rotor systems, as the speed is beyond the first synchroresonance frequency. The finite element method and two-degree-of-freedom dynamic model of a ball bearing are employed for modeling the flexible rotor system. The discrete model of a shaft is built with the aid of the finite element technique, and the ball bearing model includes the nonlinear effects of the Hertzian contact force, bearing internal clearance, and so on. The nonlinear unbalance response is observed by experimental and numerical analysis. All of the predicted results are in good agreement with experimental data, thus validating the proposed model. Numerical and experimental results show that the resonance frequency is provoked when the speed is about twice the synchroresonance frequency, while the subharmonic resonance occurs due to the nonlinearity of ball bearings and causes severe vibration and strong noise. The results show that the effect of a ball bearing on the dynamic behavior is noticeable in optimum design and failure diagnosis of high-speed turbomachinery. [DOI: 10.1115/1.4000586] Keywords: ball bearing, rotor, experiment, nonlinear vibration

In this article, the coupling effects of the unbalanced magnetic pull and ball bearing on nonlinear vibration of the three-phase asynchronous motor are investigated with the experimental and numerical methods. A test rig of a motor whose rotor supported by ball bearings is used and a 2 degrees of freedom magnetic solid coupling dynamic model of the motor rotor system is presented. The nonlinear dynamic response and spectrum are obtained from experiments and numerical analysis. The numerical results are in good agreement with test data, thus validating the presented model. It is found that the unbalanced magnetic pull and ball bearing forces possess the significantly interactional and nonlinear influences on the rotor dynamic characteristics. Small magnetic pull could impact the nonlinear bearing-rotor system, resulting in remarkable changes in the dynamic characteristics of the system. The effects of rotational speed and the rotor mass eccentricity on dynamic behaviors of the motor are discussed, and the results show that the magnetic pull gradually increases the amplitude of the ball bearing-rotor system, and its effect decreases with the increment of the rotational speed and mass eccentricity. [ABSTRACT FROM AUTHOR]

The magnetic pull, bearing forces, and operating temperature, as important factors affecting motor performance, actually act together on the electric motor. In this study, the magnetic-solid-thermal coupling rotordynamic behaviors of a three-phase asynchronous motor are investigated via experiments and numerical analysis. A motor test platform controlled by a variable frequency converter is offered, and the experiments under multiworking conditions are carried out to explore the rotordynamic characteristics of the motor system. A rotordynamic modeling method of the magnetic-solid-thermal coupling system is presented for analyzing the coupling effect of the unbalanced magnetic pull (UMP), nonlinear ball bearing forces (NBB), and operating temperature on the motor rotordynamic behaviors. All of the predicted results coincide well with the experimental data to validate the presented model. Through experiments and numerical analysis, it is shown that the interaction of magnetic, structural, and thermal fields plays a significant role in the nonlinear vibration of the motor rotor. UMP, even with slight amplitudes at low rotating speeds, can induce a remarkable impact on the dynamic characteristics of the system on account of the nonlinear effect of ball bearing forces. The combined action of UMP and NBB on the thermal effect is more notable than that of single action. The effect of the unbalanced load gradually decreases with the increase of the temperature. The experimental and numerical results indicate that the magnetic-solid-thermal coupling influence is a noticeable issue in the optimum design, failure diagnosis, and operation maintenance of motor systems. [ABSTRACT FROM AUTHOR]

The dynamic characteristics of reciprocating pump–pipeline system are directly affected by the fluid–mechanism dynamic interaction related to the slider-crank mechanism, valves and pipes conveying fluid. In this article, the fluid–mechanism interaction and nonlinearities involved in the kinetic of slider-crank mechanism, the motions of pump valves and the dynamic transmission in pipeline are explored for the nonlinear dynamic modeling of reciprocating pump–pipeline interaction systems. The nonlinear fluid–mechanism coupling model and corresponding analysis procedure are presented for investigating the system dynamic characteristics at all operating conditions. An experiment platform consisting of a simplex plunger reciprocating pump and suction and discharge pipes with a flow control valve is established to validate the proposed model. By the comparisons of pressure pulsations under multi-working conditions, the results obtained from the proposed model show good agreement with the test data. The dynamic characteristic of pump, as well as the effects of interaction and nonlinearity on the flow pulsation, are studied with the proposed model. It is found that nonlinear factors such as joint clearance and nonlinear spring stiffness are of great importance to the lag characteristics of pump valves and the pressure pulsation of pump–pipe system. The amplitudes of pressure pulsation increase with the decrease of control valve opening nonlinearly, and the effect of flow control valve becomes significant when the opening is less than 40%. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) pose a significant threat to global public health. In present research, a total of 80 CRKP strains belonging to ST11 were collected with 70% (56 of 80 isolates) expressing a K47 capsular type. Thus, it is significant to prevent and control infections caused by these bacteria. Capsule depolymerases could degrade bacterial surface polysaccharides to reduce their virulence and expose bacteria to host immune attack. Previous studies have demonstrated the potential of phage-encoded depolymerases as antivirulent agents in treating CRKP infections in vitro and in vivo. Here, two capsule depolymerases (Dpo42 and Dpo43) derived from phage IME205 were expressed and characterized. Although both depolymerases act on strains with a capsular serotype K47, they are active against different subsets of strains, indicating subtle differences in capsule composition that exist within this serotype. The host range of phage IME205 matched to the sum of specificity range of Dpo42 and Dpo43. These two enzymes maintained stable activity in a relatively broad range of pH levels (pH 5.0–8.0 for Dpo42 and pH 4.0–8.0 for Dpo43) and temperatures (20–70°C). Besides, both Dpo42 and Dpo43 could make host bacteria fully susceptible to the killing effect of serum complement and display no hemolytic activity to erythrocytes. In summary, capsule depolymerases are promising antivirulent agents to combat CRKP infections. [ABSTRACT FROM AUTHOR]

The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study, we found that a capsule depolymerase Dpo48 could strip bacterial capsules, and the non-capsuled A. baumannii were significantly decreased in the presence of serum complement in vitro. Here, we further explored its potential as a therapeutic agent for controlling systemic infections caused by extensively drug-resistant A. baumannii. Prior to mammalian studies, the anti-virulence efficacy of Dpo48 was first tested in a Galleria mellonella infection model. Survival rate of Dpo48-pretreated bacteria or Dpo48 treatment group was significantly increased compared to the infective G. mellonella without treatment. Furthermore, the safety and therapeutic efficacy of Dpo48 to mice were evaluated. The mice treated with Dpo48 displayed normal serum levels of TBIL, AST, ALT, ALP, Cr, BUN and LDH, while no significant histopathology changes were observed in tissues of liver, spleen, lung, and kidney. Treatment with Dpo48 could rescue normal and immunocompromised mice from lethal peritoneal sepsis, with the bacterial counts in blood, liver, spleen, lung, and kidney significantly reduced by 1.4–3.3 log colony-forming units at 4 h posttreatment. Besides, the hemolysis and cytotoxicity assays showed that Dpo48 was non-homolytic to human red blood cells and non-toxic to human lung, liver and kidney cell lines. Overall, the present study demonstrated the promising potential of capsule depolymerases as therapeutic agents to prevent antibiotic-resistant A. baumannii infections. [ABSTRACT FROM AUTHOR]

Influenza virus (IAV) infection is a major cause of severe respiratory illness that affects almost every country in the world. IAV infections result in respiratory illness and even acute lung injury and death, but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully elucidated. In this study, the basic fibroblast growth factor 2 (FGF2) level was markedly increased in H1N1 virus-infected humans and mice. FGF2, which is predominately derived from epithelial cells, recruits and activates neutrophils via the FGFR2–PI3K–AKT–NFκB signaling pathway. FGF2 depletion or knockout exacerbated influenza-associated disease by impairing neutrophil recruitment and activation. More importantly, administration of the recombinant FGF2 protein significantly alleviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected mice. Based on the results from experiments in which neutrophils were depleted and adoptively transferred, FGF2 protected mice against IAV infection by recruiting neutrophils. Thus, FGF2 plays a critical role in preventing IAV-induced lung injury, and FGF2 is a promising potential therapeutic target during IAV infection. [ABSTRACT FROM AUTHOR]