A stable implicit nodal integration-based particle finite element method(N-PFEM)for modelling saturated soil dynamics

In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated soils.Our approach incorporates the nodal integration technique into a generalised Hellinger-Reissner(HR)variational principle,creating an implicit PFEM formulation.To mitigate the volumetric locking issue in low-order elements,we employ a node-based strain smoothing technique.By discretising field variables at the centre of smoothing cells,we achieve nodal integration over cells,eliminating the need for sophisticated mapping operations after re-meshing in the PFEM.We express the discretised governing equations as a min-max optimisation problem,which is further reformulated as a standard second-order cone programming(SOCP)problem.Stresses,pore water pressure,and displacements are simultaneously determined using the advanced primal-dual interior point method.Consequently,our numerical model offers improved accuracy for stresses and pore water pressure compared to the displacement-based PFEM formulation.Numerical experiments demonstrate that the N-PFEM efficiently captures both transient and long-term hydro-mechanical behaviour of saturated soils with high accuracy,obviating the need for stabilisation or regularisation techniques commonly employed in other nodal integration-based PFEM approaches.This work holds significant implications for the development of robust and accurate numerical tools for studying saturated soil dynamics.

An efficient parallel algorithm of variational nodal method for heterogeneous neutron transport problems

The heterogeneous variational nodal method(HVNM)has emerged as a potential approach for solving high-fidelity neutron transport problems.However,achieving accurate results with HVNM in large-scale problems using high-fidelity models has been challenging due to the prohibitive computational costs.This paper presents an efficient parallel algorithm tailored for HVNM based on the Message Passing Interface standard.The algorithm evenly distributes the response matrix sets among processors during the matrix formation process,thus enabling independent construction without communication.Once the formation tasks are completed,a collective operation merges and shares the matrix sets among the processors.For the solution process,the problem domain is decomposed into subdomains assigned to specific processors,and the red-black Gauss-Seidel iteration is employed within each subdomain to solve the response matrix equation.Point-to-point communication is conducted between adjacent subdomains to exchange data along the boundaries.The accuracy and efficiency of the parallel algorithm are verified using the KAIST and JRR-3 test cases.Numerical results obtained with multiple processors agree well with those obtained from Monte Carlo calculations.The parallelization of HVNM results in eigenvalue errors of 31 pcm/-90 pcm and fission rate RMS errors of 1.22%/0.66%,respectively,for the 3D KAIST problem and the 3D JRR-3 problem.In addition,the parallel algorithm significantly reduces computation time,with an efficiency of 68.51% using 36 processors in the KAIST problem and 77.14% using 144 processors in the JRR-3 problem.

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression.CONCLUSION VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal,and inhibits the dedifferentiated self-renewal of CCSCs.

Clinical outcomes in patients diagnosed with extra-nodal Hodgkin lymphoma: a 20-year retrospective analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database

Background:Hodgkin lymphoma refers to a malignancy of the lymphatic tissue.Extra-nodal Hodgkin lymphoma(ENHL)is a rare variant consisting of Hodgkin lymphoma occurring outside the lymphatic system.Studies investigating the epidemiology associated with ENHL are rare.Methods:618 ENHL cases were analyzed using the National Cancer Institute’s Surveillance,Epidemiology,and End Results(SEER)database(2000–2020).Demographics including sex,race/ethnicity,rural-urban continuum,age group(categorized as adolescent and young adult(AYA)if between years of 15 and 39,and adult if over the age of 40),and living status(alive/deceased)were examined,with survival status as the main outcome.Results:This study included 335 males(54.2%)and 283 females(45.8%).Of this total,47.9%were in the AYA group.In terms of ethnicity the distribution was 12.5%non-Hispanic Black,67.5%non-Hispanic White,5.2%non-Hispanic Asian/Pacific Islander,and 14.9%Hispanic.Bivariate analyses evidenced significant differences in survival by age group with 91.6%in AYA vs.72.4%in adults(P<0.001)alive by the end of the study period.Multivariable analyses identified age as a key predictor of survival,as the AYA patients had a lower odds ratio for death(odds ratio=0.25,P<0.001).In addition,survival outcomes were also impacted by race,with non-Hispanic Blacks showing higher survival probabilities.Regarding treatment,27.0%of patients underwent surgery,with 10.2%receiving post-surgery radiation,reducing odds of mortality(odds ratio=0.32,P=0.046).Conclusion:The background research as such,tends to affirm that these two factors–age and race are quite crucial in the prognosis as well as management of ENHL.Compared to adults,AYA patients had significantly lower odds of death,while non-Hispanic Black individuals exhibited reduced survival probabilities.It should be noted that 27.0%of patients underwent surgery with 10.2%receiving post-operative radiation which led to decrease in mortality rates.Thus,these results reiterate the necessity for tailor-made treatment methods according to demographic characteristics to boost patient outcomes effectively.For better ENHL care,future studies could shed light on these disparities and improve treatment regimens as needed.

Straight and twisted Weyl nodal line phonons in Ho2CF2 material

Based on first-principles calculations, symmetry analysis and model construction, we predict that Ho2CF2hosts both straight and twisted Weyl nodal lines in its bulk phonon spectrum. We identify that the top two phonon bands entangle with each other, forming two straight Weyl nodal lines on the K–H and K′–H′paths at the Brillouin zone(BZ) boundary,and six twisted Weyl nodal lines within the BZ. All the Weyl nodal lines along the kz direction and across the entire BZ.The symmetry analysis indicates that these Weyl nodal lines are protected by the PT symmetry and crystal symmetry. The Berry phase and drumhead-like nontrivial surface states are calculated. We also construct a tight-binding model to describe these nodal lines. Our work provides an excellent material platform for exploring the fascinating physics associated with straight and twisted Weyl nodal line phonons.

Number of involved nodal stations: a better lymph node classification for clinical stage IA lung adenocarcinoma

Background:With the popularization of lung cancer screening,more early-stage lung cancers are being detected.This study aims to compare three types of N classifications,including location-based N classification(pathologic nodal classification[pN]),the number of lymph node stations(nS)-based N classification(nS classification),and the combined approach proposed by the International Association for the Study of Lung Cancer(IASLC)which incorporates both pN and nS classification to determine if the nS classification is more appropriate for early-stage lung cancer.Methods:We retrospectively reviewed the clinical data of lung cancer patients treated at the Cancer Hospital,Chinese Academy of Medical Sciences between 2005 and 2018.Inclusion criteria was clinical stage IA lung adenocarcinoma patients who underwent resection during this period.Sub-analyses were performed for the three types of N classifications.The optimal cutoffvalues for nS classification were determined with X-tile software.Kaplan‒Meier and multivariate Cox analyses were performed to assess the prognostic significance of the different N classifications.The prediction performance among the three types of N classifications was compared using the concordance index(C-index)and decision curve analysis(DCA).Results:Of the 669 patients evaluated,534 had pathological stage N0 disease(79.8%),82 had N1 disease(12.3%)and 53 had N2 disease(7.9%).Multivariate Cox analysis indicated that all three types of N classifications were independent prognostic factors for prognosis(all P<0.001).However,the prognosis overlaps between pN(N1 and N2,P=0.052)and IASLC-proposed N classification(N1b and N2a1[P=0.407],N2a1 and N2a2[P=0.364],and N2a2 and N2b[P=0.779]),except for nS classification subgroups(nS0 and nS1[P<0.001]and nS1 and nS>1[P=0.006]).There was no significant difference in the C-index values between the three N classifications(P=0.370).The DCA results demonstrated that the nS classification provided greater clinical utility.Conclusion:The nS classification might be a better choice for nodal classification in clinical stage IA lung adeno-carcinoma.

Recent advances in treatment of nodal and gastrointestinal follicular lymphoma

Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.

Chiral symmetry protected topological nodal superconducting phase and Majorana Fermi arc

With an external in-plane magnetic field, we show the emergence of a topological nodal superconducting phase of the two-dimensional topological surface states. This nodal superconducting phase is protected by the chiral symmetry with a non-zero magnetic field, and there are corresponding Majorana Fermi arcs(also known as flat band Andreev bound states) connecting the two Majorana nodes along the edges, similar to the case of Weyl semimetal. The topological nodal superconductor is an intermediate phase between two different chiral superconductors, and is stable against the effects of substrates. The two-dimensional effective theory of the nodal superconducting phase also captures the low energy behavior of a three-dimensional lattice model which describes the iron-based superconductor with a thin film geometry. The localizations of the Majorana nodes can be manipulated through external in-plane magnetic fields, which may introduce a non-trivial topological Berry phase between them.

Fabrication of honeycomb AuTe monolayer with Dirac nodal line fermions

Two-dimensional honeycomb lattices show great potential in the realization of Dirac nodal line fermions(DNLFs).Here,we successfully synthesized a gold telluride(AuTe)monolayer by direct tellurizing an Au(111)substrate.Low energy electron diffraction measurements reveal that it is(2×2)AuTe layer stacked onto(3×3)Au(111)substrate.Moreover,scanning tunneling microscopy images show that the AuTe layer has a honeycomb structure.Scanning transmission electron microscopy reveals that it is a single-atom layer.In addition,first-principles calculations demonstrate that the honeycomb AuTe monolayer exhibits Dirac nodal line features protected by mirror symmetry,which is validated by angle-resolved photoemission spectra.Our results establish that monolayer AuTe can be a good candidate to investigate 2D DNLFs and provides opportunities to realize high-speed low-dissipation devices.

Nodal信号通路、Nodal纤毛与先天性心脏病研究进展

心脏的形成是非常复杂的过程,涉及多个基因及信号通路的时空表达。Nodal信号在心脏发育中发挥极其重要的作用,研究证实,信号通路中主要成员的变异参与多种先天性心脏病的发生。另外还发现,Nodal纤毛在心脏左右不对称形态的发生中发挥关键作用,部分是通过调控Nodal信号来诱导,Nodal纤毛的异常可引起一系列纤毛相关性先天性心脏病。本文阐述了Nodal信号通路、Nodal纤毛与先天性心脏病发病之间的关系。

人源Nodal成熟肽的原核表达及多克隆抗体的制备

目的:表达人Nodal成熟肽,免疫小鼠制备其多克隆抗体。方法:构建原核表达质粒pReceiver-hNodal,转化大肠杆菌BL21(DE3),经IPTG诱导表达His6-hNodal融合蛋白,融合蛋白经Ni-NTA树脂亲和纯化后,回收融合蛋白,免疫BALB/c小鼠制备多克隆抗体。通过间接ELISA、Westernblot和免疫细胞化学染色和间接免疫荧光等方法检测抗体的效价和特异性。结果:在大肠杆菌中高效表达了与预期理论值大小相符的Mr约13 000的人Nodal成熟肽的融合蛋白,通过免疫小鼠制备的多克隆抗体效价高、特异性强。结论:成功制备了抗人Nodal成熟肽多克隆抗体,为进一步深入研究Nodal在肿瘤发生发展过程中的生物学功能奠定了基础。

Nodal信号的研究进展

早期胚胎发育过程中 ,组织者能够诱导胚胎组织形成完整的体轴。研究表明细胞之间的信息交流是脊椎动物胚胎诱导作用的基础。Nodal作为早期胚胎诱导信号的关键成分 ,参与了中胚层和内胚层的形成、前 -后体轴的位置确定和左 -右体轴特化等一系列关键事件 ,表明Nodal信号在脊椎动物早期发育过程中具有重要作用。

斑马鱼胚胎中受Nodal信号调控基因的鉴定

Nodal信号在脊椎动物胚胎发育的中内胚层诱导、左右不对称性的建立、神经外胚层沿前后轴线的分化等方面起着重要的作用.为鉴定受Nodal信号调控的基因,特别是那些转录因子基因,通过将来自squint过量表达、缺失Nodal信号的MZoep突变体或野生型30%外包期胚胎的RNA与Affymetrix斑马鱼寡核苷酸芯片杂交.发现与野生型样本相比,在squint过量表达的样本中,265个转录本的表达显著增强(log2ratio>1),111个转录本的表达显著减弱(log2ratio<-1);在MZoep样本中,表达显著增强的(log2ratio>1)转录本有1495个,表达显著减弱(log2ratio<-1)的有550个.squint过量表达使26个转录因子基因的表达增强,11个转录因子基因的表达减弱;另一方面,MZoep突变体中表达增强的转录因子基因为69个,表达减弱的转录因子基因为30个.这些结果为进一步研究Nodal信号的转导机理和生物学功能提供了有益的数据.

膀胱移行细胞癌组织中Nodal的表达变化及意义

目的观察胚胎成形素Nodal在膀胱移行细胞癌(下称膀胱癌)组织中的表达情况,并探讨其临床意义。方法采用Western blot及RT-PCR方法分别检测17例膀胱癌组织及6例膀胱正常组织中Nodal蛋白及mRNA。17例膀胱癌病理分级:Ⅰ级5例、Ⅱ级7例、Ⅲ级5例;TNM分期:Ta期7例、T1期6例、T2～T4期4例。结果正常膀胱组织中没有检测到Nodal蛋白、mRNA的表达,17例肿瘤组织均存在Nodal蛋白及mRNA的阳性表达;且Nodal表达与肿瘤病理分级、临床分期有关,其分级、分期越高,Nodal表达亦越强,Ⅲ级>Ⅱ级(P<0.05)>Ⅰ级(P<0.01),T2～T4期>T1期>Ta期(P均<0.05)。结论膀胱癌组织中Nodal蛋白、mRNA呈高表达,其表达强弱与膀胱癌病理分级及临床分期有关。Nodal有望成为膀胱癌早期检测及治疗的重要靶点。

Nodal蛋白在肾细胞癌组织中的表达及意义

目的研究胚胎成形素Nodal蛋白在肾细胞癌组织中的表达情况,并探讨其临床意义。方法采用免疫组织化学、Western blot及Realtime PCR方法分别检测25例肾细胞癌组织及16例正常肾组织中Nodal mRNA、蛋白的表达,并检测微血管密度(MVD)指数,分析比较不同临床分期、组织学分级肾细胞癌组织中Nodal的表达情况及其与MVD之间的相关关系。结果肾细胞癌高表达Nodal mRNA基因及蛋白,且随着临床分期的升高及组织学分级的恶化,Nodal mRNA基因及蛋白表达水平不断上升;不同的临床分期及组织学分级中,Nodal蛋白的表达与MVD的变化趋势之间均存在明显的正相关关系。结论肾细胞癌高表达Nodal基因及蛋白,Nodal可能通过促进新生肿瘤血管生成促进肾癌的发展。

Nodal在肝细胞癌组织的表达与意义

目的研究上皮-间质转化现象调节基因Nodal在肝细胞癌中的表达及其意义。方法采用免疫组织化学染色法检测Nodal蛋白在肝癌组织、肝炎肝硬化组织和癌旁肝组织的表达。结果在95例肝细胞癌组织中,59例(62.1%)Nodal蛋白阳性,20例癌旁肝组织中4例(20.0%)阳性,12例肝炎肝硬化组织中2例(16.7%)阳性;Nodal蛋白表达的患者,肿瘤组织直径较大、血管侵袭率较高、Edmondson分级较高、TNM分期较晚(P<0.05)。结论Nodal与肝细胞癌的发生发展有关,可能作为肝细胞恶性变的重要预测指标。

Nodal基因的第一内含子中存在着顺式调控增强子元件

小鼠ｎｏｄａｌ基因是在胚胎发育时期表达的一个基因。它在原肠期起着重要作用，并且参与左一右体轴的决定［１，２］。４１３－ｄ小鼠胚胎于细胞系３５６３在ｎｏｄａｌ基因的第一内含子中含有单拷贝逆转录病毒的插入［３］。采用定量 ＲＮａｓｅ保护法比较了该细胞系及其母源 ＥＳ细胞 ＣＣＥ中ｎｏｄａｌ基因的表达量，ＣＣＥ细胞中ｎｏｄａｌ ｍＲＮＡ的含量是３５６３ＥＳ细胞含量的２．３倍。这一结果提示原病毒在ｎｏｄａｌ基因第一内含子中的整合降低了ｎｏｄａｌ ｍＲＮＡ的表达，其原因可能是病毒的插入破坏了ｎｏｄａｌ基因第一内含子中整合位点上的或其附近的顺式调控元件。为了验证这一推论，构建了一系列包含３５６３细胞系ｎｏｄａｌ基因的完整第一内含子及其部分片段的荧光素酶报告质粒，并以瞬时转化的方法测定了它们对报告基因转录活性的影响。该内含子５’端 ２．４ｋｂ ＤＮＡ片段亦足以使报告基因的转录活性提高 ８倍。这一结果表明：在 ｎｏｄａｌ基因的第一内含子中存在着控制ｎｏｄａｌ基因表达的顺式增强子元件。

Nodal与肿瘤:表达特征和功能分析

Nodal分子是胚胎发育中一个重要的形态发生素分子（Morphogen）,属于转化生长因子-β（Transforming growth factor-β, TGF-β）超家族成员.它在维持胚胎干细胞的未分化状态、诱导中胚层和形成内脏器官左右不对称性等过程中发挥重要作用[1].Nodal基因在胚胎发育早期高表达,而在胚胎晚期呈低表达,在成年正常个体中仅表达于少数几种生殖系统组织[2].最近研究表明Nodal分子在多种恶性肿瘤中表达,并与肿瘤的发生、发展、浸润和转移密切相关,说明Nodal分子可能作为肿瘤诊断的标志分子和靶向治疗的靶点.本文将综述Nodal分子的特点及其与肿瘤的关系.

激活Nodal信号通路促进小鼠胚胎干细胞向定型内胚层分化

目的：探讨激活Nodal信号通路在小鼠胚胎干细胞（embryonic stem cells,ESC）向定型内胚层（definitive endoderm,DE）分化中的作用,寻找小鼠ESC向DE分化的最佳培养体系。方法：根据培养基的不同,实验分为3组：胚胎干细胞组（基础培养＋LIF）、自然分化组（基础培养基）和activin A组（基础培养基＋50μg/L activin A）。细胞培养1~7 d,收集不同作用时点（1、3、5、7 d）的细胞及细胞爬片。用流式细胞术检测CXCR4阳性细胞的比例;免疫细胞化学法检测CXCR4蛋白的表达;Western blot检测OCT4及CXCR4蛋白的表达。结果：流式细胞术检测结果提示,随着培养时间的延长,CXCR4阳性细胞的比例,胚胎干细胞组在1~7 d无明显变化,自然分化组和activin A组逐渐增高,第5天达高峰（P〈0.05）,其中activin A组最高（P〈0.05）。细胞免疫组化结果显示CXCR4阳性细胞呈棕褐色或棕黄色。Western blot的结果提示,随着培养时间的延长,胚胎干细胞组OCT4和CXCR4蛋白表达无明显变化;自然分化组和activin A组的CXCR4蛋白的表达逐步增高,OCT4蛋白的表达逐步下降,第5天达高峰（P〈0.05）,其中activin A组的表达最明显（P〈0.05）。结论：在小鼠ESC分化过程中,在诱导培养的第5天,DE的比例最高。激活Nodal信号通路可以促进小鼠ESC向具有CXCR4分子标志的DE分化,有利于获取更多的DE细胞。

Nodal蛋白在胃腺癌组织中的表达及意义

目的探讨Nodal蛋白在胃腺癌组织中的表达情况及其与临床病理特征和生存期的关系。方法选择50例胃腺癌患者,随访生存期;取手术切除标本行免疫组织化学检测Nodal蛋白表达,标准评定采用半定量法。结果 50例胃腺癌组织中,46例Nodal阳性表达,阳性表达率为92.0%;Nodal蛋白表达与胃癌组织分化程度无相关性(P>0.05),与肿瘤是否发生血管浸润和淋巴结转移呈正相关(P<0.05)。Nodal蛋白表达≤25%组与表达>26%组比较,术后生存期存在统计学差异(P<0.05)。结论 Nodal蛋白在胃癌组织中高表达,胃癌组织中Nodal蛋白表达水平可作为评价生存期预后的有价值指标。