鼻咽癌中Period2下调ERK/MAPK磷酸化水平的机制

目的探讨生物钟基因Period2在鼻咽癌中下调ERK/MAPK磷酸化水平的分子机制。方法用慢病毒对细胞进行感染,构建细胞系。采用Label-free蛋白质组学检测方法对PER2蛋白表达进行验证。采用不同浓度的ERK通路激活剂Ceramide C6干预各组细胞,MTT检测各组细胞的增殖能力,筛选最佳药物浓度和作用时间。采用ERK通路激活剂Ceramide C6干预细胞,正常对照组采用等剂量药物溶剂进行处理,分为6组。Western blot检测各组细胞PER2、ERK、p38MAPK、p-ERK、p-p38MAPK蛋白的表达。流式细胞术检测细胞周期,Transwell实验检测各组细胞侵袭能力,进一步明确PER2调控ERK、MAPK磷酸化的机制。用免疫组化检测PER2、p-ERK在人体鼻咽癌样本中的表达,并分析PER2、p-ERK与鼻咽癌临床特点的相关性。结果蛋白质组学检测结果示PER2过表达组的PER2蛋白表达明显高于阴性病毒对照组和空白对照组(P<0.05)。Top 20差异蛋白显示MAPK3在PER2过表达组和对照组差异有统计学意义(P<0.05)。MTT实验结果:不同药物浓度处理后,根据每组细胞抑制率,得出最佳的药物作用浓度10μmol/L,最佳处理时间24 h。WB结果显示PER2过表达下调p-ERK、p-p38MAPK蛋白表达,ERK通路激活剂Ceramide C6干预后,在PER2-OE组中ERK、p38MAPK蛋白水平无明显变化,但p-ERK、p-p38MAPK蛋白表达水平上调,干预前后差异有统计学意义(P<0.01)。细胞周期实验结果显示:ERK通路激活剂Ceramide C6干预各组细胞后,使细胞在G1期的比例明显增加,而在G2期数量减少。Transwell实验结果显示PER2过表达抑制细胞侵袭能力,此种现象不能被磷酸激酶逆转。在鼻咽癌组织、鼻咽部黏膜中PER2蛋白、p-ERK蛋白表达阳性率差异有统计学意义(P<0.05)。PER2蛋白表达与肿瘤的T分期相关(P<0.05)。在鼻咽癌组织中PER2蛋白与p-ERK蛋白表达相关(P<0.05)。结论PER2过表达下调ERK/MAPK磷酸化水平,可能不是直接作用于ERK和p38MAPK的磷酸化位点,而是与调控ERK和p38MAPK的关键节点有关。鼻咽癌组织中PER2蛋白呈低表达,p-ERK蛋白呈高表达,两者相关,并且与肿瘤的发生、发展关系密切。

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

Preweaning period is a critical window for rumen microbial regulation of average daily gain in Holstein heifer calves

Background Rumen bacterial groups can affect growth performance,such as average daily gain(ADG),feed intake,and efficiency.The study aimed to investigate the inter-relationship of rumen bacterial composition,rumen fermentation indicators,serum indicators,and growth performance of Holstein heifer calves with different ADG.Twelve calves were chosen from a trail with 60 calves and divided into higher ADG(HADG,high pre-and post-weaning ADG,n=6)and lower ADG(LADG,low pre-and post-weaning ADG,n=6)groups to investigate differences in bacterial composition and functions and host phenotype.Results During the preweaning period,the relative abundances of propionate producers,including g_norank_f_Butyricicoccaceae,g_Pyramidobacter,and g_norank_f_norank_o_Clostridia_vadin BB60_group,were higher in HADG calves(LDA>2,P<0.05).Enrichment of these bacteria resulted in increased levels of propionate,a gluconeogenic precursor,in preweaning HADG calves(adjusted P<0.05),which consequently raised serum glucose concentrations(adjusted P<0.05).In contrast,the relative abundances of rumen bacteria in post-weaning HADG calves did not exert this effect.Moreover,no significant differences were observed in rumen fermentation parameters and serum indices between the two groups.Conclusions The findings of this study revealed that the preweaning period is the window of opportunity for rumen bacteria to regulate the ADG of calves.

Ultrafast dynamics of femtosecond laser-induced high spatial frequency periodic structures on silicon surfaces

Femtosecond laser-induced periodic surface structures(LIPSS)have been extensively studied over the past few decades.In particular,the period and groove width of high-spatial-frequency LIPSS(HSFL)is much smaller than the diffraction limit,making it a useful method for efficient nanomanufacturing.However,compared with the low-spatial-frequency LIPSS(LSFL),the structure size of the HSFL is smaller,and it is more easily submerged.Therefore,the formation mechanism of HSFL is complex and has always been a research hotspot in this field.In this study,regular LSFL with a period of 760 nm was fabricated in advance on a silicon surface with two-beam interference using an 800 nm,50 fs femtosecond laser.The ultrafast dynamics of HSFL formation on the silicon surface of prefabricated LSFL under single femtosecond laser pulse irradiation were observed and analyzed for the first time using collinear pump-probe imaging method.In general,the evolution of the surface structure undergoes five sequential stages:the LSFL begins to split,becomes uniform HSFL,degenerates into an irregular LSFL,undergoes secondary splitting into a weakly uniform HSFL,and evolves into an irregular LSFL or is submerged.The results indicate that the local enhancement of the submerged nanocavity,or the nanoplasma,in the prefabricated LSFL ridge led to the splitting of the LSFL,and the thermodynamic effect drove the homogenization of the splitting LSFL,which evolved into HSFL.

ON THE STABILITY OF PERIODIC SOLUTIONS OF PIECEWISE SMOOTH PERIODIC DIFFERENTIAL EQUATIONS

In this paper,we address the stability of periodic solutions of piecewise smooth periodic differential equations.By studying the Poincarémap,we give a sufficient condition to judge the stability of a periodic solution.We also present examples of some applications.

Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages phenotype.In a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Tuning Second Chern Number in a Four-Dimensional Topological Insulator by High-Frequency Time-Periodic Driving

Floquet engineering has attracted considerable attention as a promising approach for tuning topological phase transitions.We investigate the effects of high-frequency time-periodic driving in a four-dimensional(4D)topological insulator,focusing on topological phase transitions at the off-resonant quasienergy gap.The 4D topological insulator hosts gapless three-dimensional boundary states,characterized by the second Chern number C_(2).We demonstrate that the second Chern number of 4D topological insulators can be modulated by tuning the amplitude of time-periodic driving.This includes transitions from a topological phase with C_(2)=±3 to another topological phase with C_(2)=±1,or to a topological phase with an even second Chern number C_(2)=±2,which is absent in the 4D static system.Finally,the approximation theory in the high-frequency limit further confirms the numerical conclusions.

Sinensetin protects against periodontitis through binding to Bach1 enhancing its ubiquitination degradation and improving oxidative stress

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Solitons and Their Biperiodic Pulsation in Ultrafast Fiber Lasers Based on CB/GO

The carbon black(CB)is introduced to manufacture CB/graphene oxide(GO)composite material to mitigate limitations of GO as a saturable absorber with the excellent performance in ultrafast fiber lasers.At a central wavelength of 1555.5 nm,the stable mode-locked pulse with width of 656 fs,repetition rate of 20.16 MHz,and high signal-to-noise ratio of 82.07 dB is experimentally obtained.Additionally,experimental observations for pulsation phenomena of vector biperiodic solitons combining period-1 and period-17,period-2 and period-32,period-3 and period-36 are verified via simulations.

Periodic signal extraction of GNSS height time series based on adaptive singular spectrum analysis

Singular spectrum analysis is widely used in geodetic time series analysis.However,when extracting time-varying periodic signals from a large number of Global Navigation Satellite System(GNSS)time series,the selection of appropriate embedding window size and principal components makes this method cumbersome and inefficient.To improve the efficiency and accuracy of singular spectrum analysis,this paper proposes an adaptive singular spectrum analysis method by combining spectrum analysis with a new trace matrix.The running time and correlation analysis indicate that the proposed method can adaptively set the embedding window size to extract the time-varying periodic signals from GNSS time series,and the extraction efficiency of a single time series is six times that of singular spectrum analysis.The method is also accurate and more suitable for time-varying periodic signal analysis of global GNSS sites.

Elastic wave insulation and propagation control based on the programmable curved-beam periodic structure

Curved-beams can be used to design modular multistable metamaterials(MMMs)with reprogrammable material properties,i.e.,programmable curved-beam periodic structure(PCBPS),which is promising for controlling the elastic wave propagation.The PCBPS is theoretically equivalent to a spring-oscillator system to investigate the mechanism of bandgap,analyze the wave propagation mechanisms,and further form its geometrical and physical criteria for tuning the elastic wave propagation.With the equivalent model,we calculate the analytical solutions of the dispersion relations to demonstrate its adjustability,and investigate the wave propagation characteristics through the PCBPS.To validate the equivalent system,the finite element method(FEM)is employed.It is revealed that the bandgaps of the PCBPS can be turned on-and-off and shifted by varying its physical and geometrical characteristics.The findings are highly promising for advancing the practical application of periodic structures in wave insulation and propagation control.

Optimal design for rubber concrete layered periodic foundations based on the analytical approximations of band gaps and mapping relations

The seismic performance of rubber concrete-layered periodic foundations are significantly influenced by their design,in which the band gaps play a paramount role.Aiming at providing better designs for these foundations,this study first proposes and validates the analytical formulas to approximate the bounds of the first few band gaps.In addition,the mapping relations linking the frequencies of different band gaps are presented.Furthermore,an optimal design method for these foundations is developed,which is validated through an engineering example.It is demonstrated that ensuring the superstructure’s resonance zones are completely covered by the corresponding periodic foundation’s band gaps can achieve satisfactory vibration attenuation effects,which is a good strategy for the design of rubber concrete layered periodic foundations.

Interference-induced suppression of particle emission from a Bose-Einstein condensate in lattice with time-periodic modulations

Emission of matter-wave jets from a parametrically driven condensate has attracted significant experimental and theoretical attention due to the appealing visual effects and potential metrological applications.In this work,we investigate the collective particle emission from a Bose-Einstein condensate confined in a one-dimensional lattice with periodically modulated interparticle interactions.We give the regimes for discrete modes,and find that the emission can be distinctly suppressed.The configuration induces a broad band,but few particles are ejected due to the interference of the matter waves.We further qualitatively model the emission process and demonstrate the short-time behaviors.This engineering provides a way to manipulate the propagation of particles and the corresponding dynamics of condensates in lattices,and may find application in the dynamical excitation control of other nonequilibrium problems with time-periodic driving.

Four-to Six-Year Periodic Variation of Arctic Sea-Ice Extent and Its Three Main Driving Factors

Besides the rapid retreating trend of Arctic sea-ice extent(SIE),this study found the most outstanding low-frequency variation of SIE to be a 4-6-year periodic variation.Using a clustering analysis algorithm,the SIE in most ice-covered regions was clustered into two special regions:Region-1 around the Barents Sea and Region-2 around the Canadian Basin,which were located on either side of the Arctic Transpolar Drift.Clear 4-6-year periodic variation in these two regions was identified using a novel method called“running linear fitting algorithm”.The rate of temporal variation of the Arctic SIE was related to three driving factors:the regional air temperature,the sea-ice areal flux across the Arctic Transpolar Drift,and the divergence of sea-ice drift.The 4-6-year periodic variation was found to have always been present since 1979,but the SIE responded to different factors under heavy and light ice conditions divided by the year 2005.The joint contribution of the three factors to SIE variation exceeded 83%and 59%in the two regions,respectively,remarkably reflecting their dynamic mechanism.It is proven that the process of El Niño-Southern Oscillation(ENSO)is closely associated with the three factors,being the fundamental source of the 4-6-year periodic variations of Arctic SIE.

Resilience assessment and optimization method of city road network in the post-earthquake emergency period

The post-earthquake emergency period,which is a sensitive time segment just after an event,mainly focuses on saving life and restoring social order.To improve the seismic resilience of city road networks,a resilience evaluation method used in the post-earthquake emergency period is proposed.The road seismic damage index of a city road network can consider the influence of roads,bridges and buildings along the roads,etc.on road capacity after an earthquake.A function index for a city road network is developed,which reflects the connectivity,redundancy,traffic demand and traffic function of the network.An optimization model for improving the road repair order in the post-earthquake emergency period is also developed according to the resilience evaluation,to enable decision support for city emergency management and achieve the best seismic resilience of the city road network.The optimization model is applied to a city road network and the results illustrate the feasibility of the resilience evaluation and optimization method for a city road network in the post-earthquake emergency period.

Frequency-dependent viscoelasticity effects on the wave attenuation performance of multi-layered periodic foundations

In this paper,layered periodic foundations(LPFs)are numerically examined for their responses to longitudinal and transverse modes in the time and frequency domains.Three different unit-cells,i.e.,2-layer,4-layer,and 6-layer unit-cells,comprising concrete/rubber,concrete/rubber/steel/rubber,and concrete/rubber/steel/rubber/lead/rubber materials,respectively,are taken into account.Also,the viscoelasticity behavior of the rubber is modeled with two factors,i.e.,a frequency-independent(FI)loss factor and a linear frequency-dependent(FD)loss factor.Following the extraction of the complex dispersion curves and the identification of the band gaps(BGs),the simulations of wave transmission in the time and frequency domains are performed using the COMSOL software.Subsequent parametric studies evaluate the effects of the rubber viscoelasticity models on the dispersion curves and the wave transmission for the longitudinal and transverse modes.The results show that considering the rubber viscoelasticity enhances the wave attenuation performance.Moreover,the transverse-mode damping is more sensitive to the viscoelasticity model than its longitudinal counterpart.The 6-layer unit-cell LPF exhibits the lowest BG,ranging from 4.8 Hz to 6.5 Hz.

Oriental Reed Warblers do not abandon Common Cuckoo chicks during prolonged nestling periods

The Oriental Reed Warbler(Acrocephalus orientalis)is one of the most commonly used hosts for the parasitic Common Cuckoo(Cuculus canorus).However,as hosts that feed unrelated parasitic nestlings may suffer extra reproductive costs,they may be less willing to care for nestlings that have prolonged nestling periods.To test this hypothesis,the duration of feeding by Oriental Reed Warblers under natural conditions for their own nestlings was compared with the duration of feeding under natural conditions for Common Cuckoo nestlings and for artificially prolonged cuckoo nestlings.The results showed that Oriental Reed Warblers did not starve,drive away,or desert any of the nestlings in the experiment,and neither parent was left alone.Our experimental study indicates that both Oriental Reed Warbler parents were willing to care for nestlings with a prolonged nestling period(up to 30 days,twice the average duration time that the Oriental Reed Warblers fed their own chicks in natural conditions).However,further experiments and observations are required in other host bird species to examine whether both parents or one of the parents may exhibit the behavior of abandoning nestlings with a prolonged nestling period.

3D Printing of Periodic Porous Metamaterials for Tunable Electromagnetic Shielding Across Broad Frequencies

The new-generation electronic components require a balance between electromagnetic interference shielding efficiency and open structure factors such as ventilation and heat dissipation.In addition,realizing the tunable shielding of porous shields over a wide range of wavelengths is even more challenging.In this study,the well-prepared thermoplastic polyurethane/carbon nanotubes composites were used to fabricate the novel periodic porous flexible metamaterials using fused deposition modeling 3D printing.Particularly,the investigation focuses on optimization of pore geometry,size,dislocation configuration and material thickness,thus establishing a clear correlation between structural parameters and shielding property.Both experimental and simulation results have validated the superior shielding performance of hexagon derived honeycomb structure over other designs,and proposed the failure shielding size(D_(f)≈λ/8-λ/5)and critical inclined angle(θf≈43°-48°),which could be used as new benchmarks for tunable electromagnetic shielding.In addition,the proper regulation of the material thickness could remarkably enhance the maximum shielding capability(85-95 dB)and absorption coefficient A(over 0.83).The final innovative design of the porous shielding box also exhibits good shielding effectiveness across a broad frequency range(over 2.4 GHz),opening up novel pathways for individualized and diversified shielding solutions.

Estimation of peak wave period from surface texture motion in videos

Wave information retrieval from videos captured by a single camera has been increasingly applied in marine observation.However,when the camera observes ocean waves at low grazing angles,the accurate extraction of wave information from videos will be affected by the interference of the fine ripples on the sea surface.To solve this problem,this study develops a method for estimating peak wave periods from videos captured at low grazing angles.The method extracts the motion of the sea surface texture from the video and obtains the peak wave period via the spectral analysis.The calculation results captured from real-world videos are compared with those obtained from X-band radar inversion and tracking buoy movement,with maximum deviations of 8%and 14%,respectively.The analysis of the results shows that the peak wave period of the method has good stability.In addition,this paper uses a pinhole camera model to convert the displacement of the texture from pixel height to actual height and performs moving average filtering on the displacement of the texture,thus conducting a preliminary exploration of the inversion of significant wave height.This study helps to extend the application of sea surface videos.

Cranial ultrasound in perioperative period of acute severe traumatic brain injury

Objective To observe the value of cranial ultrasound for perioperative patients with acute severe traumatic brain injury(sTBI).Methods Data of 55 sTBI patients who underwent craniotomy were retrospectively analyzed.The patients were divided into observation group(n=15)and control group(n=40)according to received perioperative cranial ultrasound or not.The general data and surgical data were compared between groups,and ultrasonic data of observation group were analyzed.Results The proportions of good prognosis 1 and 6 months after operation in observation group were both higher than those in control group,while the incidence of cerebral infarction in observation group was lower than that in control group(all P<0.05).No significant difference of general data nor other surgical data was found between groups(all P>0.05).Acute encephalocele occurred in 1 case in observation group during operation,and cranial ultrasound accurately showed the contralateral secondary epidural hematoma.Increased intracranial pressure in different degrees were found in all 15 cases(15/15,100%)in observation group after operation with transcranial color coded Doppler(TCCD)or transcranial Doppler(TCD),while cerebral vascular spasm was observed in 5 cases(5/15,33.33%),among them 4 cases(4/5,80.00%)were diagnosed cerebral infarction based on CT examination.Conclusion Cranial ultrasound could be used to evaluate changes of sTBI in perioperative period and guide adjusting treatment strategy in time,being valuable for reducing risk of postoperative cerebral infarction and improving prognosis.