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。

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.

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.

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.

Frontier and Evolution of Marketing Discipline Based on Scientific Metrological Analysis of Top 4 Marketing Periodicals in 2009-2013

Using scientific metrological method,this paper analyzed all literature published by top 4 marketing periodicals( JCR,JM,JMR,and MS) in 2009- 2013. It is intended to find out hot issues and frontier topics of current marketing research through cluster analysis of key words,get to know cooperation and exchange of organizations through analysis of organization cooperative network,explore new topics of marketing researches with the aid of analysis of abrupt change words,and explore evolution path and development rules of marketing researches through co-citation network analysis.

The Eighth Working Meeting of Serial Periodicals of the People's Medical Publishing House and the Meeting of the Ninth Editorial Board of the Chinese Journal for Clinicians and the Second Editorial Board of Global Health Journal were successfully convened

On March 15,2019,in order to study and implement General Secretary Xi Jinping's speech on deepening reform and cultivating worldclass scientific and technological journals,the eighth working meeting of serial periodicals of the People's Medical Publishing House (PMPH),meeting of the ninth editorial board of the Chinese Journal for Clinicians,and the second editorial board of the Global Health Journal were held in Beijing.

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89 1-01 Investigation of SingleMoFeSCubane-Like Cluster Compounds——Ⅲ.TheConversion of Linear Trinuclear Cluster into SingleCubane Cluster and the Structure ofMoFeS(EtNCS)CHCN Reaction ofFe(DMF)[(FeCl)MoS] and EtNCSNa in DMF re-sults in conversion of the linear trinuclear cluster into thesingle cabane—like cluster,MoFeS(EtNCS),thestructure of which has been determined.The influence ofthe ligand—related redox process and the ligation modeon the conversion reaction and the product are discussed.

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CONTENTS1.Extractive Metallurgy(9～16)2.Metal Material and Technology(5～9)3.Semiconductor(9～17)4.Metal Physics(5～8)5.Chemical Analysis and Physical Testing(5～11)92 1-9 Determination of Trace Selenium in High-Puri-ty Copper by Polarographic Catalytic Wave after Enrichmentand Separation with Sulfhydrl-Cotton A novel procedure

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93-1-38 Chemical Dispersion of MoOand TiOat Interface of MoO/TiOThe dispersion capacity ofMoOand TiOat the interface of MoO/TiOcal-cined at 500℃ for 5h was studied by XRD and FT-IR dif-ference spectra.There is about one monolayer ofnon-crystalline phase of MoOand TiOat the interface.

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CONTENTS1.Extractive Metallurgy(40～43)2.Metal Materials and Technology(30～32)3.Semiconductors(38～40)4.Metal Physics(24～26)5.Chemical Analysis and Physical Testing(38～39)93-1-40 Study of Pt-Ga/AlOCatalysts Ⅱ.Ef-fect of Ga on the Surface Structure and Acidity of the Cata-lysts The effect of Ga on the surface structure of sup-port and the acidity of Pt-Ga/AlOcatalysts was studiedby using EPMA,XRD,IR,physical adsorption,frontaladsorption of basic gases and cumene cracking.The results

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891—11 Polymerization of Conjugated Dienes withMixed Catalyst of Rare Earth and Other Transition MetalsⅠ.Butadiene Polymerization in the Presence of(NdCl+FeCl).nphen-AIH(i-Bu)Catalytic systemThe mixed catalyst(NdCl+FeCl).nphen with differentFe/Nd ratios was prepared by means of co-precipitation,and the polymerization of butadiene with the catalyst systemcomposed of(NdCl+FeCl).nphen and AIH(i-Bu)was

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90 1-1 Liquidus of NdCl-MgCl-LiCl SystemThe liquidus of ternary system NdCl-MgCl-LiCl hasbeen determined by means of DTA.It was found that thereare two surfaces corresponding to the primary crystallizationof NdCland α-(MgCl,LiCl) respectively,and anunivariant line related to the secondary crystallization with aminimun poin M(68.5 wt% NdCl.2.7 wt% MgCl,28.8wt% LiCl.441℃) in the system.Zheng Chaogui et al.,ActaMetallurgica Sinica.25(1989),No.1,B69.

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CONTENTS1.Extractive Metallurgy(36～37)2.Metal Material and Technology(26～27)3.Semiconductor(34～35)4.Metal Physics(21)5.Chemical Analysis and Physical Testing(35)

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92 1-1 Study on the Adsorption of HPdCland Me-tallic Ions on AlOThe adsorption of HPdCland me-tallic ions on AlOand their dependence have been studied.The adsorption isotherms of HPdCl, HPtCl, HAuCland Cu(NO), Co(NO), Ni(NO)on AlOwere all ofLangmuir type. The amount of HPdCladsorbed onAlOwas decreased by pre-impregnation with metallic ions.

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contents1.Extractive Metallurgy(17～23)2.Metal Material and Technology(7～10)3.Semiconductor(15～21)4.Metal Physics(7～9)5.Chemical Analysis and Physical Testing(14～19)89 1-17 Preparation of High- Voltage andHigh-Capacitance Tantalum Powder with CarbonReducing The technology of preparing high-voltage andhigh-eapacitance tantalum powder with carbon reducing has

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92 1-29 Role of Ceria in Non-precious Metal OxideCatalysts I. The Oxygen Properties of Cu and Ce OxidesSupported on γ-AlOThe reaction between Hand oxy-gen of Cu-O/ γ-AlO(Ⅰ), Ce-O/ γ-AlO(Ⅱ) was studiedby TPR method. The TPR spectra of (Ⅰ) show the peaks at

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89 1-24 Sulfur-Resistant Titanium Oxide BasedCatalysts for Deep Oxidation The poisonous effect ofSOon Ti-Cu. Ti-Mn oxides catalysts for the deepoxidation of toluene was investigated by means of infraredspectroscopy and X-ray photoelectron spectroscopy. It wasfound that the poisoning of the catalyst at lower temperaturewas caused by the SOadsorption, and the activity of thepoisoned catalyst could be regenerated. The kinetics of thedeep oxidation of toluene over Ti-Cu oxide catalyst before

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.