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。

基于softmax的加权Double Q-Learning算法

强化学习作为机器学习的一个分支,用于描述和解决智能体在与环境的交互过程中,通过学习策略以达成回报最大化的问题。Q-Learning作为无模型强化学习的经典方法,存在过估计引起的最大化偏差问题,并且在环境中奖励存在噪声时表现不佳。Double Q-Learning(DQL)的出现解决了过估计问题,但同时造成了低估问题。为解决以上算法的高低估问题,提出了基于softmax的加权Q-Learning算法,并将其与DQL相结合,提出了一种新的基于softmax的加权Double Q-Learning算法(WDQL-Softmax)。该算法基于加权双估计器的构造,对样本期望值进行softmax操作得到权重,使用权重估计动作价值,有效平衡对动作价值的高估和低估问题,使估计值更加接近理论值。实验结果表明,在离散动作空间中,相比于Q-Learning算法、DQL算法和WDQL算法,WDQL-Softmax算法的收敛速度更快且估计值与理论值的误差更小。

基于Dueling Double DQN的交通信号控制方法

为了提高交叉口通行效率缓解交通拥堵,深入挖掘交通状态信息中所包含的深层次隐含特征信息,提出了一种基于Dueling Double DQN(D3QN)的单交叉口交通信号控制方法;构建了一个基于深度强化学习Double DQN(DDQN)的交通信号控制模型,对动作-价值函数的估计值和目标值迭代运算过程进行了优化,克服基于深度强化学习DQN的交通信号控制模型存在收敛速度慢的问题;设计了一个新的Dueling Network解耦交通状态和相位动作的价值,增强Double DQN(DDQN)提取深层次特征信息的能力;基于微观仿真平台SUMO搭建了一个单交叉口模拟仿真框架和环境,开展仿真测试;仿真测试结果表明,与传统交通信号控制方法和基于深度强化学习DQN的交通信号控制方法相比,所提方法能够有效减少车辆平均等待时间、车辆平均排队长度和车辆平均停车次数,明显提升交叉口通行效率。

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.

Influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel

The influence of variable viscosity and double diffusion on the convective stability of a nanofluid flow in an inclined porous channel is investigated.The DarcyBrinkman model is used to characterize the fluid flow dynamics in porous materials.The analytical solutions are obtained for the unidirectional and completely developed flow.Based on a normal mode analysis,the generalized eigenvalue problem under a perturbed state is solved.The eigenvalue problem is then solved by the spectral method.Finally,the critical Rayleigh number with the corresponding wavenumber is evaluated at the assigned values of the other flow-governing parameters.The results show that increasing the Darcy number,the Lewis number,the Dufour parameter,or the Soret parameter increases the stability of the system,whereas increasing the inclination angle of the channel destabilizes the flow.Besides,the flow is the most unstable when the channel is vertically oriented.

Double contrast-enhanced ultrasonography improves diagnostic accuracy of T staging compared with multi-detector computed tomography in gastric cancer patients

BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.

Enhancing the stability of Ni Fe-layered double hydroxide nanosheet array for alkaline seawater oxidation by Ce doping

Electrocatalytic hydrogen production from seawater holds enormous promise for clean energy generation.Nevertheless,the direct electrolysis of seawater encounters significant challenges due to poor anodic stability caused by detrimental chlorine chemistry.Herein,we present our recent discovery that the incorporation of Ce into Ni Fe layered double hydroxide nanosheet array on Ni foam(Ce-Ni Fe LDH/NF)emerges as a robust electrocatalyst for seawater oxidation.During the seawater oxidation process,CeO_(2)is generated,effectively repelling Cl^(-)and inhibiting the formation of Cl O-,resulting in a notable enhancement in the oxidation activity and stability of alkaline seawater.The prepared Ce-Ni Fe LDH/NF requires only overpotential of 390 m V to achieve the current density of 1 A cm^(-2),while maintaining long-term stability for 500 h,outperforming the performance of Ni Fe LDH/NF(430 m V,150 h)by a significant margin.This study highlights the effectiveness of a Ce-doping strategy in augmenting the activity and stability of materials based on Ni Fe LDH in seawater electrolysis for oxygen evolution.

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.

Correction to:Theoretical analysis of the double-differential cross-sections of neutron,proton,deuteron,^(3)He,and α for the p+^(6)Li reaction

Correction to:Nuclear Science and Techniques(2024)35:61 https://doi.org/10.1007/s41365-024-01421-5 In this article,the figures were wrongly numbered.The Fig.7 and 8 should have been Fig.11 and 12.The Fig.9,10,11,and 12 should have been 7,8,9 and 10.The original article has been corrected.

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.

Diagnosis of indirectly driven double shell targets with point-projection hard x-ray radiography

We present an application of short-pulse laser-generated hard x rays for the diagnosis of indirectly driven double shell targets. Coneinserted double shell targets were imploded through an indirect drive approach on the upgraded SG-II laser facility. Then, based on thepoint-projection hard x-ray radiography technique, time-resolved radiography of the double shell targets, including that of their near-peakcompression, were obtained. The backlighter source was created by the interactions of a high-intensity short pulsed laser with a metalmicrowire target. Images of the target near peak compression were obtained with an Au microwire. In addition, radiation hydrodynamicsimulations were performed, and the target evolution obtained agrees well with the experimental results. Using the radiographic images, arealdensities of the targets were evaluated.

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.

Defective Nickel-Iron Layered Double Hydroxide for Enhanced Photocatalytic NO Oxidation with Significant Alleviation of NO2 Production

Photocatalysis offers a sustainable means for the oxidative removal of low concentrations of NOx(NO,NO2,N2O,N2O5,etc.)from the atmosphere.Layered double hydroxides(LDHs)are promising candidate photocatalysts owing to their unique layered and tunable chemical structures and abundant surface hydroxide(OH)moieties,which are hydroxyl radical(OH)precursors.However,the practical applications of LDHs are limited by their poor charge-separation ability and insufficient active sites.Herein,we developed a facile N_(2)H_(4)-driven etching approach to introduce dual Ni^(2+)and OHvacancies(Niv and OHv,respectively)into NiFe-LDH nanosheets(hereafter referred to as NiFe-LDH-et)to facilitate improved charge-carrier separation and active Lewis acidic site(Fe^(3+)and Ni^(2+)exposed at OHv)formation.In contrast to inert pristine LDH,NiFe-LDH-et actively removed NO under visible-light illumination.Specifically,Ni_(76)Fe_(24)-LDH-et etched with 1.50 mmol·L^(-1)N_(2)H_(4)solution removed 32.8%of the NO in continuously flowing air(NO feed concentration:500 parts per billion(ppb))under visible-light illumination,thereby outperforming most reported catalysts.Experimental and theoretical data revealed that the dual vacancies promoted the production of reactive oxygen species(O_(2)·^(-)andOH)and the adsorption of NO on the LDH.In situ spectroscopy demonstrated that NO was preferentially adsorbed at Lewis acidic sites,particularly exposed Fe^(3+)sites,converted into NO+,and subsequently oxidized to NO3without the notable formation of the more toxic intermediate NO2,thereby alleviating risks associated with its production and emission.

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.

Young's double slit interference with vortex source

The fast and convenient demultiplex of optical vortex(OV) mode is crucial for its further application. We propose a novel approach that combines classic Young's doublet with an OV source to effectively identify the OV mode through the analysis of interference patterns. The interference patterns of the OV source incident on the double slits can be perfectly illustrated by using both the classical double-slit interference method and the Huygens–Fresnel principle. The interference fringes will twist along the negative or positive direction of x axis when topological charge(TC)l>0 or l<0, and the degree of the movement varies with the TC, allowing for a quantitative display of the OV characteristics through the interference patterns. Additionally, we deduce analytically that the zeroth-order interference fringe has a linear relationship with the TC and the vertical position. These findings highlight the ability to identify the OV mode by analyzing the interference patterns produced by Young's doublet.

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.