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This paper focuses on the problem of stochastic instability resulting from the action of dissipation and random excitations. The energy–momentum theorem is extended from deterministic Hamiltonian systems to stochastic Hamiltonian systems, and then a weak energy–momentum method is presented for stochastic instability analysis of random systems suffering destabilizing effects of dissipation and random excitations. The presented method combines the stochastic averaging procedure to formulate the equivalent systems of random systems for obtaining the stochastic instability criteria in probability, and can be applied to a class of systems including random gyroscopic systems with positive or negative definite potential energy. As an example, the stochastic instability conditions of a Lagrange top subjected to random vertical support excitations are formulated to express the stochastic instability induced by dissipation and random excitations. [ABSTRACT FROM AUTHOR]

Abstract: The performance of a ball bearing–rotor system is often limited by the occurrence of subharmonic resonance with considerable vibration and noise. In order to comprehend the inherent mechanism and the feature of the subharmonic resonance, a symmetrical rotor system supported by ball bearings is studied with numerical analysis and experiment in this paper. A 6DOF rotordynamic model which includes the non-linearity of ball bearings, Hertzian contact forces and bearing internal clearance, and the bending vibration of rotor is presented and an experimental rig is offered for the research of the subharmonic resonance of the ball bearing–rotor system. The dynamic response is investigated with the aid of orbit and amplitude spectrum, and the non-linear system stability is analyzed using the Floquet theory. All of the predicted results coincide well with the experimental data to validate the proposed model. Numerical and experimental results show that the resonance frequency is provoked when the speed is in the vicinity of twice synchroresonance frequency, while the rotor system loses stability through a period-doubling bifurcation and a period-2 motion i.e. subharmonic resonance occurs. It is found that the occurrence of subharmonic resonance is due to the together influence of the non-linear factors, Hertzian contact forces and internal clearance of ball bearings. The effect of unbalance load on subharmonic resonance of the rotor system is minor, which is different from that of the sliding bearing–rotor system. However, the moment of couple has an impact influence on the subharmonic resonances of the ball bearing–rotor system. The numerical and experimental results indicate that the subharmonic resonance caused by ball bearings is a noticeable issue in the optimum design and failure diagnosis of a high-speed rotary machinery. [Copyright &y& Elsevier]

Abstract: The stochastical axial loads, to which the rotor system of the turbomachine is usually subjected, are due to the aerodynamic forces, hydrodynamic forces, preload and so on. The modeling of rotor systems subjected to stochastical axial loads is presented as stochastically excited and dissipated Hamiltonian systems. The stochastic averaging method for quasi-integrable-Hamiltonian systems is applied to obtain the averaged equations and the expression for the largest Lyapunov exponent is formulated. The necessary and sufficient conditions for the almost sure asymptotic stability of the rotor system are presented approximately. The largest Lyapunov exponent is evaluated and employed to determine the region of almost sure asymptotic stability of rotor systems with random axial loads. It is found that the angular motion plays a key role in almost sure asymptotic stability of rotor systems. The effects of the spectral density of random axial load and the polar mass moments of inertia on stochastic stability of the rotor system are significant. [Copyright &y& Elsevier]

• The electro-thermo-fluid-structure interaction effect is considered in dynamic model. • The shell is subjected to piezoelectric parametric excitation and external excitation. • Multiple scales method is utilized to analyze the nonlinear behaviors of system. • The effect of interaction of modes on the nonlinear dynamic behavior is discussed. • Effects of fluid velocity, piezoelectric voltage, temperature of system are explored. Nonlinear vibrations of a fluid-conveying functionally graded (FG) cylindrical shell with piezoelectric actuator layer and subjected to external excitation and piezoelectric parametric excitation are analyzed theoretically. Considering the electric-thermo-fluid-structure interaction effect, a nonlinear dynamic model of fluid-conveying FG cylindrical shell with piezoelectric actuator layer is developed based on Hamilton's principle and von-Karman geometrical nonlinearity. The inviscid, incompressible, isentropic and irrotational fluid is coupled into governing equations using the linearized potential theory. The nonlinear coupled differential governing equations of system are obtained by using Galerkin's method with two modes. The developed coupled model is validated by comparing with the prior data and good agreements are observed. Multiple scales method is used to obtain nonlinear dynamic behaviors of the coupled system in case of 1:2 internal resonance, primary parametric resonance and 1/2 subharmonic resonance. The effects of three coupling cases between two modes on the dynamic behaviors of system are explored. Considering strongly coupled effect between two modes, the effect of external excitation, damping coefficient, piezoelectric harmonic voltage, fluid flow velocity, temperature and volume fraction exponent of FG cylindrical shell on the frequency-response curves are investigated. The influence of detuning parameters on force-amplitude response and voltage-amplitude response of system are also discussed. [ABSTRACT FROM AUTHOR]

• Phage–antibiotic synergy (PAS) is a promising strategy for bacterial infections. • The treatment order of PAS combinations plays a pivotal role in bacterial killing. • Simultaneous phage–colistin treatment could suppress the emergence of phage-resistant mutants. • Simultaneous phage–colistin treatment could mitigate colistin resistance. Bacteriophage (phage) therapy, exploiting phages which are the natural enemies of bacteria, has been re-introduced to treat multidrug-resistant (MDR) bacterial infections. However, some intrinsic drawbacks of phages are overshadowing their clinical use, particularly the narrow host spectrum and rapid emergence of resistance upon treatment. The use of phage–antibiotic combinations exhibiting synergistic bacterial killing [termed 'phage–antibiotic synergy' (PAS)] has therefore been proposed. It is well reported that the types and doses of phages and antibiotics are critical in achieving PAS. However, the impact of treatment order has received less research attention. As such, this study used an Acinetobacter baumannii phage vB_AbaM-IME-AB2 and colistin as a model PAS combination to elucidate the order effects in-vitro. While application of the phage 8 h before colistin treatment demonstrated the greatest antibacterial synergy, it failed to prevent the development of phage resistance. On the other hand, simultaneous application and antibiotic followed by phage application were able to suppress/delay the development of resistance effectively, and simultaneous application demonstrated superior antibacterial and antibiofilm activities. Further in-vivo investigation is required to confirm the impact of treatment order on PAS. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI), a persistent lung inflammatory response syndrome, may evolve into acute respiratory distress syndrome (ARDS). Characterized by rapid onset, critical features, and a complex etiology, ALI remains a challenging critical respiratory disease. Recently, mesenchymal stem cells (MSCs) have provided a new solution for the treatment of ALI. We built a lipopolysaccharide (LPS)-induced ALI model in mice. After treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs), FTY720, or a combination of hUC-MSCs and FTY207, the lung inflammatory response was apparently attenuated. To understand the mechanism underlying MSCs treatment of ALI at the genetic level, significant differentially expressed long non-coding RNAs (lncRNAs) between the treatment and model groups were analyzed using microarray technology. Moreover, genetic gene prediction, gene ontology (GO) analysis, pathway analysis, and transcription factor (TF) prediction were carried out. The results showed that a total of 66 lncRNAs were differentially expressed in all three treatment groups, including 8 up-regulated and 58 down-regulated lncRNAs. LncRNA A_30_P01029806 and A_30_P01029194, which were down-regulated, were involved in the signaling pathways closely related to ALI. Through further TF analysis, we identified several significant TFs which lay a foundation for revealing the mechanism underlying lncRNAs treatment of ALI. LncRNA A_30_P01029806 and A_30_P01029194 may serve as candidate biomarkers in the diagnosis and treatment of ALI. • 66 lncRNAs were differentially expressed in all three treatment groups. • Two lncRNAs were involved in the signaling pathways closely related to ALI. • Several significant TFs related to the two lncRNAs were identified through TF prediction. • The two lncRNAs may serve as candidate biomarkers in the diagnosis and treatment of ALI. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is one of the major Gram-negative bacterial pathogens causing hospital-acquired multidrug-resistant infections, and the antimicrobial treatment options are scarce. The lack of available antimicrobials has prompted the development of alternative strategies for the treatment of these infections. In this study, a K. pneumoniae bacteriophage (vB_KpnP_IME321) targeting a KN1 capsular type strain, Kp409, was isolated, characterized and sequenced. This bacteriophage has a latent period of 20 min and a burst size of approximately 410 pfu/cell. It contained 49 predicted open reading frames, of which ORF42 was identified as encoding the putative capsule depolymerase. The enzyme expressed and purified in the Escherichia coli BL21 system, namely Dp42, could depolymerize the capsular polysaccharide of Kp409 and form translucent halos on the plates. The phage-encoded depolymerase could increase the inhibitory effect of serum on the growth of bacteria in vitro. Pre-treated with Dp42 rescued 100% of mice following lethal Kp409 challenge, and administration of this enzyme after infection significantly increased survival rates of infected mice in the animal experiment. In conclusion, the phage-encoded depolymerase Dp42 represents a potential alternative strategy for controlling infections mediated by K. pneumoniae expressing the KN1 capsular polysaccharide. [ABSTRACT FROM AUTHOR]

Abstract Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) refer to acute and progressive hypoxic respiratory failure caused by non-cardiogenic factors, which is a common condition occurring in critically ill patients with widespread pulmonary inflammation. Use of a single medication or target cannot treat ALI/ARDS. Mesenchymal stem cells (MSCs) and FTY720, as an analogue of sphingosine-1-phosphate (S1P), can mitigate lipopolysaccharide (LPS)-induced inflammatory lung injury. In this investigation, the clinical efficacy of MSCs alone, FTY720 alone, and a MSC and FTY720 combination in the treatment of LPS-induced lung injury was evaluated in mouse models. The experimental results demonstrated that both MSCs and FTY720 alleviate lung injuries in mice. The combined application of MSCs and FTY720 yielded higher clinical efficacy in mitigating lung injuries compared with use of MSCs or FTY720 alone. Transcriptomic analysis was performed using an Agilent gene expression chip. By analyzing the differences in gene expression of lung tissues between treated and non-treated ALI/ARDS mice, Gene Ontology and Pathway terms related to ALI/ARDS treatment were identified. Moreover, the target genes which might play a pivotal role in the treatment of ALI/ARDS were also detected, thus providing a theoretical basis for multi-target or multi-drug combined treatment of ALI/ARDS and lay a solid foundation for clinical treatment of ALI/ARDS. Highlights • This investigation analyze the differences in gene expression of lung tissues between MSCs, FTY720, MSC and FTY720 combination treated ALI/ARDS mice. • Gene Ontology and Pathway terms related to ALI/ARDS treatment were identified. • The target genes which might play a pivotal role in the treatment of ALI/ARDS were also detected. • This investigation provide a theoretical basis for multi-target or multi-drug combined treatment of ALI/ARDS and lay a solid foundation for clinical treatment of ALI/ARDS. [ABSTRACT FROM AUTHOR]

Objectives Heteroresistance is a phenomenon in which there are various responses to antibiotics from bacterial cells within the same population. Here, we isolated and characterised an imipenem heteroresistant Acinetobacter baumannii strain (HRAB-85). Methods The genome of strain HRAB-85 was completely sequenced and analysed to understand its antibiotic resistance mechanisms. Population analysis and multilocus sequence typing were performed. Results Subpopulations grew in the presence of imipenem at concentrations of up to 64 μg/mL, and the strain was found to belong to ST208. The total length of strain HRAB-85 was 4,098,585 bp with a GC content of 39.98%. The genome harboured at least four insertion sequences: the common IS Aba1 , IS Aba22 , IS Aba24 , and newly reported IS Aba26 . Additionally, 19 antibiotic-resistance genes against eight classes of antimicrobial agents were found, and 11 genomic islands (GIs) were identified. Among them, GI3, GI10, and GI11 contained many ISs and antibiotic-resistance determinants. Conclusions The existence of imipenem heteroresistant phenotypes in A. baumannii was substantiated in this hospital, and imipenem pressure, which could induce imipenem-heteroresistant subpopulations, may select for highly resistant strains. The complete genome sequencing and bioinformatics analysis of HRAB-85 could improve our understanding of the epidemiology and resistance mechanisms of carbapenem-heteroresistant A. baumannii . [ABSTRACT FROM AUTHOR]

[Display omitted] With the emergence of multidrug resistance (MDR) bacteria, wound infection continues to be a challenging problem and represents a considerable healthcare burden. This study aims to evaluate the applicability of a phage loaded thermosensitive hydrogel in managing wound infections caused by MDR Acinetobacter baumannii , using IME-AB2 phage and MDR-AB2 as the model phage and bacteria, respectively. Excellent storage stability of the IME-AB2 phage in a ~18 wt% Poloxamer 407 (P407) hydrogel solution was first demonstrated with negligible titer loss (~0.5 log) in 24 months at 4 °C. The incorporated phage was released in a sustained manner with a cumulative release of 60% in the first 24 h. The in vitro bacterial killing efficiency of phage gel and phage suspension at 37 °C demonstrated >5 log 10 CFU/ml reduction against A. baumannii. A comparable biofilm elimination capacity was also noted between the phage gel and phage suspension (59% and 45% respectively). These results suggested that the incorporation of phage into the hydrogel not only had insignificant impacts on the bacterial killing efficiency of phage, but also act as a phage depot to maintain higher phage titer at the infectious site for a prolong period for more effective treatment. We also found that the hydrogel formulation significantly suppressed microbial survival in an ex vivo wound infection model using pig skin (90% reduction in bacterial counts was achieved after 4 h treatment). In summary, our results demonstrated that the P407-based phage-loaded thermosensitive hydrogel is a simple and promising phage formulation for the management of wound infections. [ABSTRACT FROM AUTHOR]

• It is the first prospective observational study for clearance of COVID-19. • The history of hypertension is risk factor for prolonged COVID-19 viral clearance. • Elevated IL-6 and NK cells level might be related to clearance of COVID-19. Clearance of COVID-19 from the human body has not been established. Our study collected the laboratory test results from patients and analyzed the correlation between early changes in serum indices and the virus clearance by univariable and multivariable COX regression models, with an aim to explore the risk factors for prolonged viral clearance. The study included 61 patients with COVID-19 treated at the Fifth Medical Center of PLA General Hospital in Beijing from 20 January 2020 to 20 February 2020. We set the total observation of the disease course to 20 days and the patients were divided into two groups (prolonged group, > 20d vs. normal group, ≤ 20d). The 48 patients with COVID-19 included in this study, 13 remained positive for viral nucleic acid monitoring 20 days after onset. The median for virus clearance was 16 days (range, 6–35 days). The results showed that hypertension, a lactate dehydrogenase level > 211.5 U/L, an interleukin 6 (IL-6) level > 12.5 pg/ml, and a NK lymphocyte percentage > 0.5% were associated with prolonged viral clearance. Therefore, we showed that a history of hypertension, an elevated IL-6 level, and an elevated percentage of NK cells were risk factors for prolonged viral clearance. [ABSTRACT FROM AUTHOR]