基于网络药理学和分子对接技术的2,3-吲哚醌抗少弱精症机制研究

为研究2,3-吲哚醌(isatin, ISA)治疗少弱精症的可能作用靶点和作用机制,基于公共数据库分别获取ISA作用靶点和少弱精症相关疾病靶点,确定交集靶点,采用Cytoscape软件获取核心靶点。通过GO功能富集和KEGG通路分析交集靶点,采用分子对接预测ISA与靶点蛋白的结合能力。研究结果显示,ISA干预少弱精症主要涉及氧化应激、细胞凋亡和炎症等生物学过程,并与p53信号通路、细胞衰老通路和IL-17信号通路密切相关;经筛选确定8个核心靶点,ISA与其中6个核心靶点稳定结合。这表明,ISA可能通过作用于核心靶点CASP3、TP53、ESR1、PTGS2、TNF和ANXA5,调控p53信号通路和IL-17信号通路发挥抗少弱精症作用。

SSZ-13分子筛在二甲醚羰基化反应中的机理研究和空间限域效应

乙醇作为一种绿色清洁的燃料替代品和油品添加剂,在全球有广泛的市场需求.利用合成气经乙酸甲酯(MA)合成乙醇的工艺路线,因其原子经济性、产品选择性高、反应条件温和等优势而备受关注.其中,二甲醚(DME)羰基化是该路线的关键步骤之一.研究证实,具有8元环(8-MR)孔道结构的硅铝酸盐微孔分子筛可以在较低的反应温度下高选择性催化二甲醚羰基化反应.目前,研究者已经对丝光沸石(MOR)、镁碱沸石(FER)等分子筛进行了全面深入的分析,但对SSZ-13等菱沸石(CHA型)的研究有限,缺乏SSZ-13上主、副反应催化机理的阐释,并且忽略了沸石独特的笼状结构在反应中的空间限域效应.本文结合实验和理论计算确定了SSZ-13分子筛催化DME羰基化的活性位点,并探究了孔道的限域效应.通过负载具有不同尺寸的Na^(+)和Cs^(+)实现了对不同通道中Brönsted酸位点(BAS)的选择性屏蔽.酸性质表征和密度泛函理论(DFT)计算结果表明,在较低的负载量下,Na^(+)优先取代SSZ-13的6元环(6-MR)中的BAS,而Cs^(+)由于其较大的离子半径只能与8-MR中的BAS发生交换,从而实现了对SSZ-13不同孔道中酸分布的调控.负载不同金属量以及金属种类的样品活性研究表明,当6-MR中BAS减少时,DME转化率基本不变;而当8-MR中BAS被离子交换时,DME转化率明显下降.随后,将未经金属改性的、具有不同硅铝比的母体SSZ-13样品的MA生成速率与其8-MR中BAS的数量相关联,发现两者呈较好的线性关系,说明SSZ-13的8-MR中BAS为DME羰基化的活性中心.同时,DFT计算了DME在不同孔道BAS上的解离能,结果表明DME更容易在8-MR的BAS上解离从而进行后续反应.随后,探究了SSZ-13笼的空间限域效应对主副反应的影响机制.通过比较金属负载量相近的Na/H-SSZ-13和Cs/H-SSZ-13上CO插入甲氧基形成烯酮的反应势垒,证实了较大尺寸金属离子的引入增加了主反应速控步的能垒.为了揭示空间限域对副反应的影响,比较了反应后催化剂的热重、气质联用等表征结果,并利用密度泛函理论计算了副反应的关键物种(七甲基苯正离子)在Na/H-SSZ-13和Cs/H-SSZ-13上的吸附能,证实了SSZ-13的笼状结构体积是影响MA选择性的关键因素.金属负载后SSZ-13笼空间减少,可以有效地抑制副反应关键物种的形成,从而提高主反应选择性.综上,本文不仅对SSZ-13分子筛催化二甲醚羰基化反应机理进行了全面解析,并通过实验设计,改变了SSZ-13分子筛的孔道结构和笼结构空间,突出了分子筛限域效应在二甲醚羰基化反应中的重要作用.本文研究结果为设计具有较高选择性的沸石催化剂提供一定的参考.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

PTCD引导下体外震波碎石联合ERCP治疗改道术后困难胆管结石2例

背景经内镜逆行胰胆管造影术(endoscopic retrograde cholan-gio pancreatography,ERCP)是目前治疗胆管结石的常规手段,但对于改道术后的患者,由于乳头位置改变、胆管插管困难等原因,ERCP成功率有所下降,需探索更为合适的治疗方案.病例简介本文报道2例改道术后的困难胆管结石,在经经皮肝穿刺胆道引流术(percutaneous transhepatic cholangio-graphy drainage,PTCD)引导下进行体外震波碎石(ex-tracorporeal shock wave lithotripsy,ESWL)联合ERCP治疗,取得良好的治疗效果.结论对于一些高龄、基础条件差的困难胆管结石患者,常规ERCP失败后可尝试使用PTCD解除梗阻、充分引流,待一般情况好转后,择期ESWL联合ERCP取石,可取得不错的治疗效果.

轻质可排阻磁性分子印迹聚合物的制备及选择性分离和检测牛奶中痕量四环素

关注牛奶安全这一国计民生问题,将分子印迹前沿技术引入本科实验课堂,设计了一个综合实验。融合分子印迹、蛋白质排阻、磁性分离等技术制备得到磁性分子印迹聚合物,考察其性能,并以其作为固相萃取吸附剂,结合高效液相色谱,建立直接选择性检测牛奶样品中痕量四环素的新方法。本实验涉及材料化学、分析化学、仪器分析、食品化学等多学科知识,培养学生的科学素养、综合解决复杂问题的能力和创新性思维。印迹材料的设计和磁性分离过程富有创新性和趣味性,整个实验过程成本低廉、易操作、安全性高。通过本实验,学生能够了解分子印迹前沿技术,学习新检测方法的建立,巩固实验基础操作,提高数据采集和分析能力,加深对组分-性能-应用关系的理解。

早发性与晚发性结直肠癌临床特征比较及预后的分析

结直肠癌(colorectal cancer,CRC)是全球常见的消化系肿瘤,发病率位于世界第3,病死率位居世界第2,近年来结直肠癌总的发病率及病死率有所下降,但早发性结直肠癌(early-onset colorectal cancer,EOCRC)呈整体增长趋势.通常把<50岁诊断的结直肠癌定义为EOCRC,与晚发性结直肠癌(late-onset colorectal cancer,LOCRC)相比,其具有独特的临床特征,且预后较差.本文就EOCRC的临床特征及预后进行简要述评.

The occurrence characteristics of oil in shales matrix from organic geochemical screening data and pore structure properties:An experimental study Author links open overlay panel

The occurrence characteristics of shale oil are of great significance to the movability of shale oil.In this study,the occurrence characteristics of oil in the shale matrix at Funing Formation shale in Subei Basin were quantitatively evaluated by organic geochemistry and microscopic pore structure characterization experiments.The Multiple Isothermal Stages Pyrolysis(MIS)experiment results show that the content of total oil,adsorbed oil,and free oil in the shales are 3.15-11.25 mg/g,1.41-4.95 mg/g,and 1.74-6.51 mg/g,respectively.among which the silicon-rich shale has the best oil-bearing.The relative content of free oil shows an increasing trend in pores with pore diameters greater than 3 nm.When the relative content of free oil reaches 100%,the pore size of silicon-rich shale is about 200 nm,while that of calcium-rich shale,clay-rich shale,and siliceous mixed shale is about 10 nm.The occurrence law of adsorbed oil is opposite to that of free oil,which indicates that shale oil will occur in the pores and fractures in a free state in a more extensive pore size range(>200 nm).This study also enables us to further understand the occurrence characteristics of shale oil under the interaction of occurrence state and occurrence space.

Estimating shear strength of high-level pillars supported with cemented backfilling using the HoekeBrown strength criterion

Deep metal mines are often mined using the high-level pillars with subsequent cementation backfilling(HLSCB)mining method.At the design stage,it is therefore important to have a reasonable method for determining the shear strength of the high-level pillars(i.e.cohesion and internal friction angle)when they are supported by cemented backfilling.In this study,a formula was derived for the upper limit of the confining pressure σ3max on a high-level pillar supported by cemented backfilling in a deep metal mine.A new method of estimating the shear strength of such pillars was then proposed based on the Hoek eBrown failure criterion.Our analysis indicates that the horizontal stress σhh acting on the cemented backfill pillar can be simplified by expressing it as a constant value.A reasonable and effective value for σ3max can then be determined.The value of s3max predicted using the proposed method is generally less than 3 MPa.Within this range,the shear strength of the high-level pillar is accurately calculated using the equivalent MohreCoulomb theory.The proposed method can effectively avoid the calculation of inaccurate shear strength values for the high-level pillars when the original HoekeBrown criterion is used in the presence of large confining pressures,i.e.the situation in which the cohesion value is too large and the friction angle is too small can effectively be avoided.The proposed method is applied to a deep metal mine in China that is being excavated using the HLSCB method.The shear strength parameters of the high-level pillars obtained using the proposed method were input in the numerical simulations.The numerical results show that the recommended level heights and sizes of the high-level pillars and rooms in the mine are rational.

Micro segment analysis of supercritical methane thermal-hydraulic performance and pseudo-boiling in a PCHE straight channel

The printed circuit heat exchanger(PCHE) is receiving wide attention as a new kind of compact heat exchanger and is considered as a promising vaporizer in the LNG process. In this paper, a PCHE straight channel in the length of 500 mm is established, with a semicircular cross section in a diameter of 1.2 mm.Numerical simulation is employed to investigate the flow and heat transfer performance of supercritical methane in the channel. The pseudo-boiling theory is adopted and the liquid-like, two-phase-like, and vapor-like regimes are divided for supercritical methane to analyze the heat transfer and flow features.The results are presented in micro segment to show the local convective heat transfer coefficient and pressure drop. It shows that the convective heat transfer coefficient in segments along the channel has a significant peak feature near the pseudo-critical point and a heat transfer deterioration when the average fluid temperature in the segment is higher than the pseudo-critical point. The reason is explained with the generation of vapor-like film near the channel wall that the peak feature related to a nucleateboiling-like state and heat transfer deterioration related to a film-boiling-like state. The effects of parameters, including mass flow rate, pressure, and wall heat flux on flow and heat transfer were analyzed.In calculating of the averaged heat transfer coefficient of the whole channel, the traditional method shows significant deviation and the micro segment weighted average method is adopted. The pressure drop can mainly be affected by the mass flux and pressure and little affected by the wall heat flux. The peak of the convective heat transfer coefficient can only form at high mass flux, low wall heat flux, and near critical pressure, in which condition the nucleate-boiling-like state is easier to appear. Moreover,heat transfer deterioration will always appear, since the supercritical flow will finally develop into a filmboiling-like state. So heat transfer deterioration should be taken seriously in the design and safe operation of vaporizer PCHE. The study of this work clarified the local heat transfer and flow feature of supercritical methane in microchannel and contributed to the deep understanding of supercritical methane flow of the vaporization process in PCHE.

NbN quantum dots anchored hollow carbon nanorods as efficient polysulfide immobilizer and lithium stabilizer for Li-S full batteries

The shuttle effect of lithium polysulfides(LiPSs)and uncontrollable lithium dendrite growth seriously hinder the practical application of lithium-sulfur(Li-S)batteries.To simultaneously address such issues,monodispersed Nb N quantum dots anchored on nitrogen-doped hollow carbon nanorods(NbN@NHCR)are elaborately developed as efficient Li PSs immobilizer and Li stabilizer for high-performance Li-S full batteries.Density functional theory(DFT)calculations and experimental characterizations demonstrate that the sulfiphilic and lithiophilic NbN@NHCR hybrid can not only efficiently immobilize the soluble Li PSs and facilitate diffusion-conversion kinetics for alleviating the shuttling effect,but also homogenize the distribution of Li+ions and regulate uniform Li deposition for suppressing Li-dendrite growth.As a result,the assembled Li-S full batteries(NbN@NHCR-S||Nb N@NHCR-Li)deliver excellent long-term cycling stability with a low decay rate of 0.031%per cycle over 1000 cycles at high rate of 2 C.Even at a high S loading of 5.8 mg cm^(-2)and a low electrolyte/sulfur ratio of 5.2μL mg^(-1),a large areal capacity of 6.2 mA h cm^(-2)can be achieved in Li-S pouch cell at 0.1 C.This study provides a new perspective via designing a dual-functional sulfiphilic and lithiophilic hybrid to address serious issues of the shuttle effect of S cathode and dendrite growth of Li anode.

Full-domain collaborative deployment method of multiple interference sources and evaluation of its deployment effect

This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the attacker and the capability to defend the GNSS during navigation countermeasures.Key evaluation indicators for the jamming effect of GNSS suppressive and deceptive jamming sources are first created,their evaluation models are built,and their detection procedures are sorted out,as the basis for determining the deployment principles.The principles for collaboratively deploying multi-jamming sources are developed to obtain the deployment structures(including the required number,structures in demand,and corresponding positions)of three single interference sources required by collaboratively deploying.Accordingly,simulation and hardware-in-loop testing results are presented to determine a rational configuration of the collaborative deployment of multi-jamming sources in the set situation and further realize the full-domain deployment of an interference network from ground,air to space.Varied evaluation indices for the deployment effect are finally developed to evaluate the deployment effect of the proposed configuration and further verify its reliability and rationality.

A Railway Fastener Inspection Method Based on Abnormal Sample Generation

Regular fastener detection is necessary to ensure the safety of railways.However,the number of abnormal fasteners is significantly lower than the number of normal fasteners in real railways.Existing supervised inspectionmethods have insufficient detection ability in cases of imbalanced samples.To solve this problem,we propose an approach based on deep convolutional neural networks(DCNNs),which consists of three stages:fastener localization,abnormal fastener sample generation based on saliency detection,and fastener state inspection.First,a lightweight YOLOv5s is designed to achieve fast and precise localization of fastener regions.Then,the foreground clip region of a fastener image is extracted by the designed fastener saliency detection network(F-SDNet),combined with data augmentation to generate a large number of abnormal fastener samples and balance the number of abnormal and normal samples.Finally,a fastener inspection model called Fastener ResNet-8 is constructed by being trained with the augmented fastener dataset.Results show the effectiveness of our proposed method in solving the problem of sample imbalance in fastener detection.Qualitative and quantitative comparisons show that the proposed F-SDNet outperforms other state-of-the-art methods in clip region extraction,reaching MAE and max F-measure of 0.0215 and 0.9635,respectively.In addition,the FPS of the fastener state inspection model reached 86.2,and the average accuracy reached 98.7%on 614 augmented fastener test sets and 99.9%on 7505 real fastener datasets.

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

Co-doped BaFe_(2)As_(2) Josephson junction fabricated with a focused helium ion beam

Josephson junction plays a key role not only in studying the basic physics of unconventional iron-based superconductors but also in realizing practical application of thin-film based devices,therefore the preparation of high-quality iron pnictide Josephson junctions is of great importance.In this work,we have successfully fabricated Josephson junctions from Co-doped BaFe_(2)As_(2)thin films using a direct junction fabrication technique which utilizes high energy focused helium ion beam(FHIB).The electrical transport properties were investigated for junctions fabricated with various He^(+)irradiation doses.The junctions show sharp superconducting transition around 24 K with a narrow transition width of 2.5 K,and a dose correlated foot-structure resistance which corresponds to the effective tuning of junction properties by He^(+)irradiation.Significant J_c suppression by more than two orders of magnitude can be achieved by increasing the He^(+)irradiation dose,which is advantageous for the realization of low noise ion pnictide thin film devices.Clear Shapiro steps are observed under 10 GHz microwave irradiation.The above results demonstrate the successful fabrication of high quality and controllable Co-doped BaFe_(2)As_(2)Josephson junction with high reproducibility using the FHIB technique,laying the foundation for future investigating the mechanism of iron-based superconductors,and also the further implementation in various superconducting electronic devices.

Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren’s syndrome through inhibiting the TLR/NF-κB pathway

Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.

Application of BOPPPS + Mind Maps to Improve Clinical Competence of General Practitioner Residents: Taking Cough as an Example

Objective:To analyze the importance of general practitioner residents using the combined teaching method(BOPPPS+mind maps).Methods:From September 2023 to August 2024,a study was conducted with 6 control group participants receiving traditional teaching and 6 observation group participants receiving the combined teaching method(BOPPPS+mind maps).The study analyzed various indicators between the two groups(including mind map scores and assessment results).Results:Compared with the control group,the assessment scores of the observation group were significantly higher(P<0.05).Conclusion:The application of the combined teaching method(BOPPPS+mind maps)by general practitioner residents can significantly improve their comprehensive abilities.

5-FU和角膜绷带镜在翼状胬肉切除联合自体角膜缘干细胞移植术中的应用

目的:评价翼状胬肉切除联合自体角膜缘干细胞移植术(ALSCT)中联合应用5-氟尿嘧啶(5-FU)和角膜绷带镜治疗翼状胬肉的临床疗效。方法:随机对照临床试验。纳入2021-05/2022-11秦皇岛市海港医院眼科收治的翼状胬肉患者71例71眼:A组23眼行翼状胬肉切除联合ALSCT,B组24眼于术中局部浸润和术后结膜下注射5-FU,C组24眼联合应用5-FU的同时并于术后配戴角膜绷带镜。比较三组患者术后1、3、7、14d的舒适度评分,术后1、3、7、14d,1mo的角膜愈合情况,术后3~6mo的手术疗效和并发症发生率。结果:术后1、3、7d舒适度评分和术后1、3d角膜愈合情况比较,C组患者优于A、B两组。三组间术后14d的舒适度评分和术后14d、1mo的角膜愈合情况比较无差异。随访3~6mo,A组有3眼复发,B组1眼复发,C组无复发。三组患者术后并发症发生率比较无差异。结论:联合应用5-FU和术后配戴角膜绷带镜可以优化翼状胬肉切除联合ALSCT术后眼部体验,加快角膜上皮修复,并提高的手术成功率。

吲哚醌抗帕金森病药理作用研究进展

帕金森病(Parkinson′s disease,PD)是一种神经退行性病变,治疗药物主要有拟多巴胺药和抗胆碱药两大类,多巴胺类及其增效剂现有长足发展,包括单胺氧化酶-B(monoamine oxidase B,MAO-B)抑制剂、儿茶酚-氧位-甲基转移酶抑制剂、麦角类和非麦角类多巴胺(dopamine,DA)受体激动剂、DA前体药物,中药大麻类和吲哚醌等。吲哚醌作为内源特异抗老化酶MAO-B抑制剂,有多种药理活性,其机制还涉及多种蛋白调节的活性。

时空叙事视角下红歌歌词的多维解读与价值内化机理

红色歌曲记录了特定时空的家国故事,是传播中华民族精神,构建集体记忆,引发情感共鸣的宏大叙事。基于人文主义认识论,借助NVivo11软件,采用扎根理论、自然语言处理方法及LDA模型从时空叙事视角分析歌词文本的维度结构及其价值内化机理。结果表明:1)红歌歌词文本可分为时间、空间、记忆和精神4个维度,其中时间和空间是显性维度,而记忆和精神则是时空中的隐喻维度,呈现时空表现隐喻至时空表征的关联路径。2)红歌的价值内化体现为受众对多维度信息的接收、比对、叠加、重构、升华等系列过程,从而构建符合社会主流价值的思想和意识。3)红歌歌词的价值内化机理是政治话语、文化基因和现代性作用于媒介、教育、主体和社会等因素上的连锁反应。

The complete reference genome for grapevine (Vitis vinifera L.) genetics and breeding

Grapevine is one of the most economically important crops worldwide.However,the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres,limiting the accessibility of the repetitive sequences,the centromeric and telomeric regions,and the study of inheritance of important agronomic traits in these regions.Here,we assembled a telomere-to-telomere(T2T)gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads.The T2T reference genome(PN_T2T)is 69 Mb longer with 9018 more genes identified than the 12X.v0 version.We annotated 67%repetitive sequences,19 centromeres and 36 telomeres,and incorporated gene annotations of previous versions into the PN_T2T assembly.We detected a total of 377 gene clusters,which showed associations with complex traits,such as aroma and disease resistance.Even though PN40024 derives from nine generations of selfing,we still found nine genomic hotspots of heterozygous sites associated with biological processes,such as the oxidation–reduction process and protein phosphorylation.The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.