Subharmonic resonance of a clamped-clamped buckled beam with 1:1 internal resonance under base harmonic excitations

The subharmonic resonance and bifurcations of a clamped-clamped buckled beam under base harmonic excitations are investigated.The nonlinear partial integrodifferential equation of the motion of the buckled beam with both quadratic and cubic nonlinearities is given by using Hamilton’s principle.A set of second-order nonlinear ordinary differential equations are obtained by spatial discretization with the Galerkin method.A high-dimensional model of the buckled beam is derived,concerning nonlinear coupling.The incremental harmonic balance(IHB)method is used to achieve the periodic solutions of the high-dimensional model of the buckled beam to observe the nonlinear frequency response curve and the nonlinear amplitude response curve,and the Floquet theory is used to analyze the stability of the periodic solutions.Attention is focused on the subharmonic resonance caused by the internal resonance as the excitation frequency near twice of the first natural frequency of the buckled beam with/without the antisymmetric modes being excited.Bifurcations including the saddle-node,Hopf,perioddoubling,and symmetry-breaking bifurcations are observed.Furthermore,quasi-periodic motion is observed by using the fourth-order Runge-Kutta method,which results from the Hopf bifurcation of the response of the buckled beam with the anti-symmetric modes being excited.

The m6A reader YTHDF2 alleviates the inflammatory response by inhibiting IL-6R/JAK2/STAT1 pathway-mediated high-mobility group box-1 release

Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation,is connected to pathogenic and physiological processes in eukaryotes,but its effect on sepsis is still unknown.We aimed to discover the effects and mechanisms of YTHDF2 in sepsis.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and western blot analyses were used to measure the expression of YTHDF2,the interleukin 6 receptor(IL-6R),high-mobility group box-1(HMGB1),Janus kinase 2(JAK2)and signal transducer and activator of transcription 1(STAT1)under different in vitro conditions.Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1,IL-6,IL-1βand tumor necrosis factor-α.To confirm that YTHDF2 specifically targets IL-6R mRNA,RNA immunoprecipitation and dual-luciferase reporter assays were performed.Finally,we utilized a mouse model of lipopolysaccharide(LPS)-induced sepsis to verify the effects of YTHDF2 in vivo.Results:According to our findings,YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells.Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells.Mechanistically,YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA,thereby inhibiting HMGB1 release.In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis.Conclusions:In summary,these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway,indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.

Multi-omics revealed the mechanism of feed efficiency in sheep by the combined action of the host and rumen microbiota

This study was conducted to investigate potential regulatory mechanisms of feed efficiency(FE)in sheep by linking rumen microbiota with its host by the multi-omics analysis.One hundred and ninety-eight hybrid female sheep(initial body weight=30.88±4.57 kg;4-month-old)were selected as candidate sheep.Each test sheep was fed in an individual pen for 60 days,and the residual feed intake(RFI)was calculated.The ten candidate sheep with the highest RFI were divided into the Low-FE group,and the ten with the lowest RFI were divided into the High-FE group,all selected for sample collection.The RFI,average daily gain and average daily feed intake were highly significantly different between the two experimental groups(P<0.05).Compared with Low-FE group,the insulin-like growth factor-1 and very low-density lipoprotein in serum and the propionate in rumen significantly increased in High-FE group(P<0.01),but the acetate:propionate ratio in rumen significantly decreased in High-FE group(P¼0.034).Metagenomics revealed Selenomonas ruminantium,Selenomonas sp.and Faecalibacterium prausnitzii were key bacteria,and increased abundance of the genes encoding the enzymes for cellulose degradation and production of propionate in High-FE group.The results of proteomics and section showed the rumen papilla length and expression of carbonic anhydrase and Na^(+)/K^(+)-ATPase were significantly higher in High-FE group(P<0.05).On the other hand,the acetyl-CoA content significantly increased in the liver of High-FE group(P¼0.002).The relative expression levels of insulin-like growth factor-1 and apolipoprotein A4 genes were significantly up-regulated in the liver of High-FE group(P<0.05),but relative expression level of monoacylglycerol O-acyltransferase 3 gene was significantly down-regulated(P¼0.037).These findings provide the mechanism by which the collaborative interaction between rumen microbiota fermentation and host uptake and metabolism of fermentation products impacts feed efficiency traits in sheep.