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.

Effects of different orthokeratology lens designs on slowing axial length elongation in children with myopia

AIM:To elucidate whether differences exist in the impact on retarding the elongation of axial length(AL)among children with myopia when utilizing orthokeratology(ortho-k)lenses employing the corneal refractive therapy(CRT)design versus those employing the vision shaping treatment(VST)design.METHODS:This retrospective clinical trial aimed to collect and analyze AL data from individuals who wore ortho-k lenses for three years.A total of 654 subjects were enrolled and prescribed one of the three specific brands of ortho-k lenses:CRT,Euclid,and Mouldway.The study’s primary focus was to compare the rates of AL elongation and myopic progression across these three brands of ortho-k lenses.RESULTS:In the 3-year follow-up,the AL elongation exhibited variations of 0.73±0.36 mm in the CRT lens group,0.59±0.37 mm in the Euclid lens group,and 0.63±0.38 mm in the Mouldway lens group.A noteworthy disparity emerged between the CRT and Mouldway groups(P<0.01),as well as between the CRT and Euclid groups(P<0.001).Additionally,it was observed that 32.1%of participants who wore CRT lenses experienced a decelerated progression of myopia,in contrast to 47.2%in the Euclid group and 44.4%in the Mouldway group.Statistical analyses revealed a statistically significant distinction between the CRT and Euclid groups(P<0.01),and similarly,the CRT group demonstrated a statistically significant difference when compared to the Mouldway group(P<0.05).CONCLUSION:Ortho-k lenses represent a pragmatic strategy for mitigating the advancement of myopia.In contradistinction to ortho-k lenses utilizing the CRT design,those employing the VST design exhibited a more favorable impact regarding retarding AL elongation.

Influence of axial stress on rockburst in deep tunnels: insight from model experiment

Frequent rockburst disasters in deep-buried engineering projects severely impact construction. To explore the influence of axial stress on rockburst in deep-buried tunnels, large-scale true triaxial rockburst experiments were conducted under four different axial stress ratio conditions (ηt, axial loading stress/vertical loading stress) using a self-developed true triaxial loading device under the condition of "pre-loading before excavation". The influence of axial stress on the rockburst process and failure characteristics in deep tunnels was studied using a combination of real-time video monitoring, rockburst debris sieving, and acoustic emission monitoring. The results indicate: (1) all four specimens subjected to different axial stress ratio loading conditions exhibited three stages of macroscopic failure: small particle ejection, flake spalling, and large fragment ejection. Ultimately, "V"-shaped notches appeared on both sides of the tunnel. (2) The failure stress, fragment volume, and fragment size distribution of the rockburst specimens exhibited a clear two-stage failure characteristic with increasing axial stress ratio. In the lower axial stress ratio stage (ηt ≤ 0.7), the increase in the axial stress ratio enhances lateral confinement, thereby increasing the crack initiation strength of the surrounding rock, inhibiting crack formation and propagation, and thus suppressing damage to the surrounding rock of the tunnel. In the higher axial stress ratio stage (ηt > 0.7), the increase in axial stress ratio makes the Poisson effect of the surrounding rock more pronounced, promoting the generation and propagation of cracks along the tunnel axis direction, thereby promoting damage to the surrounding rock. (3) Based on the analysis of acoustic emission parameters (fracture properties), it can be concluded that in the lower axial stress ratio stage (ηt ≤ 0.7), an increase in the axial stress ratio leads to a higher proportion of shear fracture in rockburst damage. Conversely, in the higher axial stress ratio stage (ηt > 0.7), the increase in axial stress ratio gradually reduces the proportion of shear fracture in rockburst damage.

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.

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.

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.

A numerical survey of parameters to reach ignition condition for axial compression of a large-sized field reversed configuration

Field reversed configuration(FRC)is widely considered as an ideal target plasma for magnetoinertial fusion.However,its confinement and stability,both proportional to the radius,will deteriorate inevitably during radial compression.Hence,we propose a new fusion approach based on axial compression of a large-sized FRC.The axial compression can be made by plasma jets or plasmoids converging onto the axial ends of the FRC.The parameter space that can reach the ignition condition while preserving the FRC's overall quality is studied using a numerical model based on different FRC confinement scalings.It is found that ignition is possible for a large FRC that can be achieved with the current FRC formation techniques if compression ratio is greater than 50.A more realistic compression is to combine axial with moderate radial compression,which is also presented and calculated in this work.

Impact of multifocal gas-permeable lens designs on short-term choroidal response, axial length, and retinal defocus profile

AIM:To investigate the impact of multifocal gas permeable contact lens(MFGPCL)in various add power and distance/near area allocation on short-term changes of choroidal thickness(ChT),axial length(AL),and retinal defocus profile in young adults.METHODS:Seventeen young adults(2 males and 15 females;age 23.17±4.48y)were randomly assigned to wear two designs binocularly with a one-week washout period in between.Total of four MFGPCL designs were assessed.All designs were distance-center that varied in two add power(+1.50 and 3.00 D)and/or two distance zone(DZ)diameters(1.50 and 3.00 mm;design A:DZ 1.5/add 3.0,B:DZ 1.5/add 1.5,C:DZ 3.0/add 3.0,D:DZ 3.0/add 1.5).ChT,AL,and peripheral refraction data were collected on each subject at baseline,on days 1 and 7 of MFGPCL daily wear.ChT was assessed in four quadrants using a spectraldomain optical coherence tomography.RESULTS:AL was shortened by-26±44μm with lens C,-18±27μm with lens D,-13±29μm with lens A,and-8±30μm with lens B(all P<0.05).A significant overall increase in ChT was observed with all 4 designs(lens A:+6±6μm,B:+3±7μm,C:+8±7μm,and D:+8±7μm).Temporal and superior choroid exhibited more choroidal thickening associated with MFGPCL.All designs induced significant relative peripheral myopia(RPM)beyond the central 20o across the horizontal meridian in both nasal and temporal fields(P<0.05).CONCLUSION:MFGPCLs show a significant influence on ChT and AL,which are associated with significant increase in RPM after short-term wear.The reliability and feasibility of quantifying short-term changes in ChT support its use as a promising marker for the long-term efficacy of myopia-controlling treatments.

Investigation of granite failure precursor under axial load using modified LSTM framework

Granite is usually composed of quartz,biotite,feldspar,and cracks,and the variation characteristics of these components could reflect the deformation and failure process of rock well.Taking granite as an example,the video camera was used to record the deformation and failure process of rock.The distribution of meso-components in video images was then identified.The meso-components of rock failure precursors were also discussed.Moreover,a modified LSTM(long short-term memory method)based on SSA(sparrow search algorithm)was proposed to estimate the change of meso-components of rock failure precursor.It shows that the initiation and expansion of cracks are mainly caused by feldspar and quartz fracture,and when the quartz and feldspar exit the stress framework,rock failure occurs;the second large increase of crack area and the second large decrease of quartz or feldspar area may be used as a precursor of rock failure;the precursor time of rock failure based on meso-scopic components is about 4 s earlier than that observed by the naked eye;the modified LSTM network has the strongest estimation ability for quartz area change,followed by feldspar and biotite,and has the worst estimation ability for cracks;when using the modified LSTM network to predict the precursors of rock instability and failure,quartz and feldspar could be given priority.The results presented herein may provide reference in the investigation of rock failure mechanism.

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.

Particle residence time distribution and axial dispersion coefficient in a pressurized circulating fluidized bed by using multiphase particle-in-cell simulation

The particle residence time distribution(RTD)and axial dispersion coefficient are key parameters for the design and operation of a pressurized circulating fluidized bed(PCFB).In this study,the effects of pressure(0.1-0.6 MPa),fluidizing gas velocity(2-7 m·s^(-1)),and solid circulation rate(10-90 kg·m^(-2)·s^(-1))on particle RTD and axial dispersion coefficient in a PCFB are numerically investigated based on the multiphase particle-in-cell(MP-PIC)method.The details of the gas-solid flow behaviors of PCFB are revealed.Based on the gas-solid flow pattern,the particles tend to move more orderly under elevated pressures.With an increase in either fluidizing gas velocity or solid circulation rate,the mean residence time of particles decreases while the axial dispersion coefficient increases.With an increase in pressure,the core-annulus flow is strengthened,which leads to a wider shape of the particle RTD curve and a larger mean particle residence time.The back-mixing of particles increases with increasing pressure,resulting in an increase in the axial dispersion coefficient.

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.

A Brief Introduction to the English Periodical of Contemporary Social Sciences

The English periodical of Contemporary Social Sciences is an English periodical founded by Sichuan Academy of Social Sciences and is published every two months.It was approved by the National Radio and Television Administration of the People’s Republic of China(formerly the State Administration of Press,Publication,Radio,Film and Television of the People’s Republic of China)in March 2016.

Parametric resonance of axially functionally graded pipes conveying pulsating fluid

Based on the generalized Hamilton's principle,the nonlinear governing equation of an axially functionally graded(AFG)pipe is established.The non-trivial equilibrium configuration is superposed by the modal functions of a simply supported beam.Via the direct multi-scale method,the response and stability boundary to the pulsating fluid velocity are solved analytically and verified by the differential quadrature element method(DQEM).The influence of Young's modulus gradient on the parametric resonance is investigated in the subcritical and supercritical regions.In general,the pipe in the supercritical region is more sensitive to the pulsating excitation.The nonlinearity changes from hard to soft,and the non-trivial equilibrium configuration introduces more frequency components to the vibration.Besides,the increasing Young's modulus gradient improves the critical pulsating flow velocity of the parametric resonance,and further enhances the stability of the system.In addition,when the temperature increases along the axial direction,reducing the gradient parameter can enhance the response asymmetry.This work further complements the theoretical analysis of pipes conveying pulsating fluid.

A Tabletop Nano-CT Image Noise Reduction Network Based on 3-Dimensional Axial Attention Mechanism

Nano-computed tomography(Nano-CT)is an emerging,high-resolution imaging technique.However,due to their low-light properties,tabletop Nano-CT has to be scanned under long exposure conditions,which the scanning process is time-consuming.For 3D reconstruction data,this paper proposed a lightweight 3D noise reduction method for desktop-level Nano-CT called AAD-ResNet(Axial Attention DeNoise ResNet).The network is framed by theU-net structure.The encoder and decoder are incorporated with the proposed 3D axial attention mechanism and residual dense block.Each layer of the residual dense block can directly access the features of the previous layer,which reduces the redundancy of parameters and improves the efficiency of network training.The 3D axial attention mechanism enhances the correlation between 3D information in the training process and captures the long-distance dependence.It can improve the noise reduction effect and avoid the loss of image structure details.Experimental results show that the network can effectively improve the image quality of a 0.1-s exposure scan to a level close to a 3-s exposure,significantly shortening the sample scanning time.