Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

非小细胞肺癌EGFR基因少见突变P733L对第1代和第3代EGFR-TKI敏感性的研究

目的:探讨表皮生长因子受体(EGFR)基因少见突变P733L对第1代和第3代EGFR酪氨酸激酶抑制剂(EGFR-TKI)的敏感性。方法:通过四唑盐比色法和平板克隆实验分析EGFR L858R和P733L肺癌细胞对第1代和第3代EGFR-TKI的敏感性;通过Transwell实验分析第1代和第3代EGFR-TKI对EGFR L858R和P733L肺癌细胞迁移的抑制作用;通过检测凋亡蛋白分析第1代和第3代EGFR-TKI促进EGFR L858R和P733L肺癌细胞凋亡的作用。结果:第1代和第3代EGFR-TKI对EGFR L858R和P733L细胞的增殖、克隆形成和细胞迁移都有抑制作用。与EGFR野生型肺癌细胞相比,第1代和第3代EGFR-TKI处理后,EGFR L858R和P733L细胞的EGFR激酶活性受到抑制,细胞凋亡明显增加。结论:EGFR P733L突变细胞对第1代和第3代EGFR-TKI的敏感性与EGFR L858R突变细胞的敏感性相似,本研究为EGFR基因少见突变从EGFR-TKI治疗中获益提供了实验证据。

Effects of Nitrogen Fertilizer Management on Biological Traits and Physiological Indexes at Seedling Stage and Yield of Directly-sown Rapeseed(Brassica napus L.)

Field experiments were carried out to study the effects of different nitroge- napplication rates and application times on biological traits and physiological indexes of directly-sown rapeseed （Brassica napus L.） at the seedling stage and investigate the relationship between these biological traits or physiological indexes at the seedling stage and yield, so as to provide scientific theoretical support for high yield and efficient fertilization management in production of winter rapeseed. Field trials were conducted in Chengdu plain of Sichuan Province under rice-rapeseed rotation system during the period of 2011-2012. The nitrogen application rate trial consisted of five nitrogen levels （0, 90, 180, 270 and 360 kg/hm2） and the nitrogen application time trial included NTl（single application as base fertilized）, NT2 （bottom application ＋one time of topdressing at seedling stage） and NT3 （bottom application＋two times of topdressing at seedling stage） under the same nitrogen rate （225 kg/hm2）. The results indicated that compared with no nitrogen application （NO） treatment, the in- crease of nitrogen fertilizer is beneficial to the increase of biological traits including plant height, green leaf number, leaf area index and dry weight of rapeseed at the seedling stage, the improvement of physiological indexes including total nitrogen content, chlorophyll content and soluble protein content of functional leaves, and the reduction of soluble sugar content. Nitrogen rate was linearly correlated with various biological traits at the seedling stage and physiological indexes including total nitro- gen content, chlorophyll content and soluble sugar content in functional leaves over- a/I, but in parabolic correlation with soluble protein content. Under the same nitrogen rate, NT2 treatment exhibited biological traits remarkably or significantly higher than NT1 treatment and NT3 treatment. The nitrogen application times were linearly cor- related with the physiological indexes of functional leaves at the seedling stage. The various biological traits and physiological index of functional leaves at the seedlings stage were in quadratic function parabolic correlation with seed yield, and the corre- lation was significant （P〈0.05）. Therefore, under the rice-rapeseed rotation system in Chengdu plain, the economic rational nitrogen rate is 180-225 kg/hm2, and the mode of bottom application ＋ one time of topdressing （NT2） is suitable.

基于L型轮辐结构膜片的窄频光纤F-P声波传感器研究

光纤声传感器被广泛应用在工业、医疗等领域。为了提高光纤F-P声传感器的性能,本文提出了一种L型轮辐结构的F-P传感膜片。膜片的厚度为15μm、梁宽度为0.5 mm、中心膜片的半径为1 mm。膜片由激光加工技术在304不锈钢上刻蚀而成。实验对1000 Hz下的传感器灵敏度进行研究,将传感器应用于光声池共振频率为1600 Hz的光声光谱气体检测系统中,并实现对50~100×10^(-6)的乙炔(C_(2)H_(2))气体浓度测量。实验结果表明,该传感器在1000 Hz下的声压灵敏度为25.4 nm/Pa,传感器可实现的最小可探测声压(MDP)为38.2μPa/Hz^(1/2)@1 kHz,声压信噪比为76.8 dB。实验所得到的光声光谱二次谐波信号的峰值与乙炔浓度呈现良好的线性关系,乙炔浓度的响应度为1.8 pm/10^(-6)。该传感器在光声光谱等单频声信号检测领域具有广泛的应用前景。

P和L波段的典型地物雷达散射系数的研究

能够反映地物散射特性的雷达散射系数应用前景广泛,具有重要的学术价值。国内外对于L波段同极化和交叉极化雷达散射系数的差值的相关研究较少,且暂无公开的P波段典型地物的雷达散射系数数据,为了弥补这一现状,文章结合国内外实测数据分析了P波段和L波段雷达散射系数和入射角的变化关系,并对L波段和P波段典型地物的雷达散射系数进行了比较。结果表明:L波段HH极化和HV极化雷达散射系数的差值随着入射角的增大而减小,在40°入射角时,典型地物的差值在10~13 dB;P波段典型地物雷达散射系数随着入射角的增加而减小,且比L波段小1~2 dB;P波段HH极化和HV极化雷达散射系数差值随着入射角的增大而减小。文章的研究为P、L波段雷达的遥感应用积累了数据,为极化SAR反演目标信息提供帮助和借鉴。

CircRTN4调节miR-224-5p/MYT1L轴对胶质母细胞瘤细胞恶性生物学行为的影响

目的:探讨环状RNA(CircRNA)RTN4调节微小RNA(miR)-224-5p/髓磷脂转录因子1样(MYT1L)轴对胶质母细胞瘤(GM)细胞恶性生物学行为的影响。方法:以对数生长期的U251细胞进行设置分组:空白组、阴性对照(sh NC)组、沉默circRTN4 shRNA(sh circRTN4)组、sh circRTN4+抑制剂对照(inhibitor NC)组、sh circRTN4+miR-224-5p抑制剂(miR-224-5p inhibitor)组。Transwell实验、流式细胞术、CCK-8、qRT-PCR、Western blot以及双荧光素酶分别检测细胞迁移与侵袭、凋亡、增殖、CircRTN4、miR-224-5p、MYT1L mRNA表达、增殖蛋白(ki-67)、凋亡蛋白(cleaved Caspase-3)、MYT1L蛋白表达以及miR-224-5p分别与CircRTN4、MYT1L靶向关系验证;qRT-PCR检测GM细胞系U118、U87、U251和LN229细胞及正常人星形胶质细胞系NHA细胞中CircRTN4、miR-224-5p、MYT1L mRNA表达水平。结果:U118、U87、U251和LN229细胞中CircRTN4、MYT1L mRNA表达较NHA细胞显著增加,miR-224-5p表达显著下降(P<0.05);miR-224-5p分别与CircRTN4、MYT1L的有靶向关系。与空白组、sh NC组相比,sh circRTN4组迁移、侵袭数、24h、48h A450值、ki-67、CircRTN4、MYT1L mRNA及蛋白表达显著降低,凋亡率、cleaved Caspase-3表达显著增加(P<0.05);与sh circRTN4+inhibitor NC组相比,sh circRTN4+miR-224-5p inhibitor组迁移、侵袭数、24h、48h A450值、ki-67、MYT1L mRNA及蛋白表达显著增加,凋亡率、cleaved Caspase-3表达显著下降(P<0.05),CircRTN4表达无统计学差异(P>0.05),体内实验证明干扰CircRTN4可显著抑制移植瘤裸鼠肿瘤质量(P<0.05)。结论:沉默CircRTN4调节miR-224-5p/MYT1L轴抑制GM细胞恶性生物学行为。

P/L波段大带宽轻质柔性超材料吸波体

为了适应现代武器设备在低频端的应用和对于吸波性能的要求,基于电磁超材料理论,利用电磁谐振特性设计了一种在P/L波段工作的大带宽轻质柔性吸波体。当电磁波入射到该新型吸波体,根据电磁感应作用机理,会在吸波体表面产生感应电流,通过装载集总电阻的方式,可将入射电磁波的能量转化为热能,从而实现对于电磁波的有效吸收。对于吸波体单元结构形状和尺寸的设计使得该吸波体具有两处谐振频点,并通过多谐振频率的耦合进一步展宽吸波带宽。仿真和实测结果验证了吸波体的优良性能。其工作频段为382~1419.4 MHz,相对带宽为140.9%,吸波层厚度仅为0.2 mm,在保证大带宽的同时具有重量轻、可共形的优点,在转台曲面吸波、雷达隐身等领域具有广阔的应用前景。

MyD88L265P及CD79B基因突变对原发性中枢神经系统淋巴瘤预后的影响

目的探究MyD88L265P及CD79B基因突变对原发性中枢神经系统淋巴瘤(PCNSL)患者预后的影响。方法收集2018年8月-2020年11月于兰州大学第二医院经开颅手术或立体定位活检术确诊的18例免疫功能正常(无HIV感染及免疫抑制药服用病史)的PCNSL患者临床资料进行回顾性分析。分别采用实时荧光定量PCR和一代基因测序技术检测18例PCNSL患者肿瘤组织中MyD88L265P和CD79B基因突变情况。针对可能与PCNSL首次无疾病进展生存期(PFS)和总生存期相关的指标行单因素分析,并采用Cox回归进行多因素分析。结果18例PCNSL肿瘤组织MyD88L265P突变率为38.9%,CD79B突变率为33.3%,MyD88L265P/CD79B共突变率为27.8%。单因素分析结果显示,病灶多发、病灶深部受累、肿瘤组织CD79B突变患者的PFS时间更短(P<0.05);多因素分析结果显示,病灶深部受累(HR=0.135,95%CI 0.023~0.799,P<0.05)、肿瘤组织CD79B突变(HR=0.149,95%CI 0.028~0.800,P<0.05)是PCNSL患者预后不良的独立危险因素。结论本组PCNSL患者肿瘤组织MyD88L265P、CD79B突变频率较高,这两种基因突变尤其是CD79B突变可能与PCNSL不良预后相关。

Assessment of Photochemical Reflectance Index as a Tool for Evaluation of Chlorophyll Fluorescence Parameters in Cotton and Peanut Cultivars Under Water Stress Condition

The relationships between photochemical reflectance index （PRI） and the chlorophyll fluorescence parameters were examined to assess suitability of PRI as a remote-sensing tool for the chlorophyll fluorescence parameters. A greenhouse experiment was conducted using cotton and peanut crops under water stress condition. Five cotton and six peanut cultivars were grown using Andosole soil in pots maintained at two water levels; the control and water stress treatment （WS） of 100 and 50% of the daily transpiration, respectively. Higher non-photochemical quenching （NPQ） was exhibited by peanut than that of cotton by the water stress. On the other hand, the decreases of the actual quantum yield of photosystem II （△F/F＇m） and PRI by the water stress in cotton were larger than those in peanut. There were positively significant correlation coefficients between PRI and △F/F＇m in cotton at noon and in the afternoon including the control and WS. The correlations of PRI with NPQ were negatively significant at noon and in the afternoon for cotton, and in the afternoon for peanut. No clear relationship was found among these parameters in the morning probably due to the diurnal increase in global solar radiation. It was concluded that there would be a possibility to detect the effects of water stress on △F/F＇m and NPQ by PRI with some exceptions, although PRI could not note varietals differences in △F/F＇m and NPQ for each treatment.

Relationship of 2 100-2 300 nm Spectral Characteristics of Wheat Canopy to Leaf Area Index and Leaf N as Affected by Leaf Water Content

The effects of leaf water status in a wheat canopy on the accuracy of estimating leaf area index (LAI) and N were determined in this study using extracted spectral characteristics in the 2 000-2 300 nm region of the short wave infrared (SWI) band. A newly defined spectral index, relative adsorptive index in the 2000-2300 nm region (RAI2000-2300), which can be calculated by RAI2000-2300 = (R2224 - R2054) (R2224 + R2054)-1 with R being the reflectance at 2224 or 2054 nm, was utilized. This spectral index, RAI2000-2300, was significantly correlated (P < 0.01) with green LAI and leaf N concentration and proved to be potentially valuable for monitoring plant green LAI and leaf N at the field canopy scale. Moreover, plant LAI could be monitored more easily and more successfully than plant leaf N. The study also showed that leaf water had a strong masking effect on the 2 000-2 300 nm spectral characteristics and both the coefficient between RAI2000-2300 and green LAI and that between RAI2000-2300 and leaf N content decreased as leaf water content increased.

△P index with different gas compositions for instantaneous outburst prediction in coal mines

In this study we measured the △P(initial speed of gas emission) index with different gas concentrations of carbon dioxide(pure CO2,90% CO2+10% CH4,67% CO2+33% CH4,50% CO2+50% CH4,30% CO2+10% CH4 and pure CH4) of coal samples from the No.2 coal seam in the Yaojie Coal Mine,Gansu province,China.The effect of carbon dioxide concentration,gas composition,coal strength and particle size of coal samples on the △P index was investigated.The experimental results show that with gas of various compositions,the △P value of three samples were clearly different.The △P index of coal samples A,B and C(0.2～0.25 mm) were 4,6 and 7 with pure CH4 and 22,30 and 21 when pure CH4 was used.Carbon dioxide concentration affects the △P index markedly.The △P index increases with an increase in carbon dioxide concentration,especially for coal B.Hence,the △P index and K(another outburst index) values tested only with pure CH4 for prediction of the danger of outburst is not accurate.It is important to determine the initial speed of gas emission given the gas composition of the coal seam to be tested for exact outburst prediction.

基于P-L双重特征提取的PEMFC系统故障诊断方法

针对质子交换膜燃料电池系统故障诊断问题,提出基于P-L双重特征提取的故障诊断方法。使用P-L双重特征提取对预处理后的样本数据进行特征提取,通过冗余变量剔除与二次特征提取,最大程度保留分类特征并有效降低样本数据维度。利用二叉树多类支持向量机与极限学习机对二维故障特征向量进行分类实现故障诊断。通过实例验证,对比线性判别分析的特征提取效果,P-L双重特征提取可使相同分类器测试集诊断准确率提高21.19%,诊断准确率达99.27%,实现了PEMFC系统膜干、氢气供应故障的精准快速诊断。

基于改进L-P法的块系岩体摆型波与准共振机理分析

块系岩体中摆型波具有非线性特征,导致难以解释其频谱特征及准共振现象机理。针对此问题,建立了考虑三次项的摆型波非线性振动模型,利用改进的L-P法与振型叠加法,求得多自由度强非线性振动的近似解析解,一定程度上解释了试验观测到块系岩体摆型波的非线性现象机理。结果表明,块体系统振动频率可表示为输入能量的高次多项式,随能量增大振动频率呈非单调变化;各谐振频率之间的比例与系统构造有关,近似满足√2的整数倍比例关系。通过建立摆型波的层次构造模型,得出准共振是摆型波在不同尺度块体之间跃迁的标志。

基于AHP-DEMATEL法的外来入侵植物风险评估指标体系确立

通过对外来物种风险评估的影响因素进行对比和筛选,统筹指标体系的科学性、重要性、实用性和可移植性,选取决定风险产生的关键因素,构建外来植物风险评估的典型指标体系。从入侵性、适生性、扩散性、危害性4个纬度建立基于AHP-DEMATEL法的外来入侵植物风险度量数学模型,用以揭示因素之间的相互依赖关系,识别并量化因素之间的直接和间接影响,并利用构建的评估体系和生态位模型对印加孔雀草在中国的风险性进行分析。结果表明:经济危害、防除难度、国内重视程度、耐逆性是导致入侵植物风险性系数升高的重要因素,印加孔雀草在我国的综合风险评估值P为0.82,属于高度风险性有害植物,需要在适生区建立监测预警体系,阻截该植物的扩散蔓延,以保护生态环境和农业可持续发展。

Exogenous calcium enhances the physiological status and photosynthetic capacity of rose under drought stress

Drought(water shortage)can substantially limit the yield and economic value of rose plants(Rosa spp.).Here,we characterized the effect of exogenous calcium(Ca^(2+))on the antioxidant system and photosynthesis-related properties of rose under polyethylene glycol 6000(PEG6000)-induced drought stress.Chlorophyll levels,as well as leaf and root biomass,were significantly reduced by drought;drought also had a major effect on the enzymatic antioxidant system and increased concentrations of reactive oxygen species.Application of exogenous Ca^(2+)increased the net photosynthetic rate and stomatal conductance of leaves,enhanced water-use efficiency,and increased the length and width of stomata following exposure to drought.Organ-specific physiological responses were observed under different concentrations of Ca^(2+).Application of 5 mmol·L^(-1)Ca^(2+)promoted photosynthesis and antioxidant activity in the leaves,and application of 10 mmol·L^(-1)Ca^(2+)promoted antioxidant activity in the roots.Application of exogenous Ca^(2+)greatly enhanced the phenotype and photosynthetic capacity of potted rose plants following exposure to drought stress.Overall,our findings indicate that the application of exogenous Ca^(2+)enhances the drought resistance of roses by promoting physiological adaptation and that it could be used to aid the cultivation of rose plants.

Using Crop Management Scenario Simulations to Evaluate the Sensitivity of the Ohio Phosphorus Risk Index

Phosphorus (P) risk indices are commonly used in the USA to estimate the field-scale risk of agricultural P runoff. Because the Ohio P Risk Index is increasingly being used to judge farmer performance, it is important to evaluate weighting/scoring of all P Index parameters to ensure Ohio farmers are credited for practices that reduce P runoff risk and not unduly penalized for things not demonstrably related to runoff risk. A sensitivity analysis provides information as to how sensitive the P Index score is to changes in inputs. The objectives were to determine 1) which inputs are most highly associated with P Index scores and 2) the relative impact of each input variable on resultant P Index scores. The current approach uses simulations across 6134 Ohio point locations and five crop management scenarios (CMSs), representing increasing soil disturbance. The CMSs range from all no-till, which is being promoted in Ohio, rotational tillage, which is a common practice in Ohio to full tillage to represent an extreme practice. Results showed that P Index scores were best explained by soil test P (31.9%) followed by connectivity to water (29.7%), soil erosion (13.4%), fertilizer application amount (11.3%), runoff class (9.5%), fertilizer application method (2.2%), and finally filter strip (2.0%). Ohio P Index simulations across CMSs one through five showed that >40% scored <15 points (low) while <1.5% scored >45 points (very high). Given Ohio water quality problems, the Ohio P Index needs to be stricter. The current approach is useful for Ohio P Index evaluations and revision decisions by spatially illustrating the impact of potential changes regionally and state-wide.

一类漂移系数分段连续的随机微分方程驯服Euler方法的L^(p)收敛率

本文研究一类漂移系数分段连续的标量随机微分方程的驯服Euler方法的L^(p)收敛率.更确切地说,本文在漂移系数是分段连续的并且呈多项式增长,扩散系数是Lipschitz连续的并且在漂移系数的间断点处不为0的假设下,证明方程具有唯一的强解,并且对于任意的p∈[1,∞),驯服Euler方法的L^(p)收敛阶都可以达到1/2.此外,本文还提供一个数值算例来验证理论结果.

喉癌肿瘤组织NOC2L、p53表达及其临床价值研究

目的检测喉癌肿瘤组织中NOC2L、p53 mRNA表达并研究其临床价值。方法选取2020年1月—2022年1月武汉大学附属同仁医院诊治的喉癌患者103例(喉癌组)和喉良性疾病患者57例(对照组)。采用实时荧光定量聚合酶链反应检测组织NOC2L、p53 mRNA表达。比较喉癌不同临床病理特征中肿瘤组织NOC2L、p53 mRNA表达差异。受试者工作特征(ROC)曲线分析肿瘤组织NOC2L、p53表达预测喉癌患者预后不良的价值;多因素Cox回归模型分析喉癌预后不良的危险因素;Kaplan-Meier模型分析NOC2L、p53表达对喉癌生存期的影响。结果与对照组比较,喉癌组患者NOC2L表达升高,p53表达降低(t/P=19.307/<0.001、13.726/<0.001)。组织学分级3级、原发肿瘤大小≥3 cm、转移淋巴结数N2~3、远处转移M1及TNM分期Ⅲ~Ⅳ期喉癌患者肿瘤组织NOC2L mRNA表达高于组织学分级1~2级、原发肿瘤大小<3 cm、转移淋巴结数N0~1、远处转移M0及TNM分期Ⅰ~Ⅱ期患者(t/P=3.681/0.001、4.167/<0.001、2.554/0.012、4.005/<0.001、3.228/<0.001),p53 mRNA表达低于组织学分级1~2级、原发肿瘤大小<3 cm、转移淋巴结数N0~1、远处转移M0及TNM分期Ⅰ~Ⅱ期患者(t/P=4.162/<0.001、4.789/<0.001、4.053/<0.001、3.492/<0.001、3.724/<0.001);NOC2L、p53及二者联合预测喉癌预后不良的AUC分别为0.756、0.712、0.917,二者联合优于各自单独预测效能(Z=7.238、8.102,P<0.001)。NOC2L≥0.73、p53≤0.65、组织学分级3级、原发肿瘤大小≥3 cm、转移淋巴结数N2~3、远处转移M1及TNM分期Ⅲ~Ⅳ期为喉癌预后不良的独立危险因素[HR(95%CI)=5.328(1.455~9.201)、4.200(1.279~7.122)、1.992(1.127~2.857)、2.164(1.099~3.299)、2.228(1.304~3.152)、2.406(1.131~3.681)、2.514(1.278~3.762)];NOC2L≥0.81且p53≤0.54喉癌患者中位生存期显著低于NOC2L<0.81或p53>0.54患者中位生存期(Log Rankχ^(2)=9.033,P<0.001)。结论喉癌患者NOC2L及p53表达与病情严重程度及生存期显著相关,可为喉癌病情及预后评估提供客观证据,NOC2L及p53联合检测可显著提高其临床价值。

MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.