热激活的Vg1转基因文昌鱼品系构建及表型分析

[目的] Vg1作为Nodal信号通路的重要配体之一参与了早期胚胎发育过程中的背腹分化调控及左右不对称模式的建立.构建Vg1转基因文昌鱼品系以研究其在文昌鱼胚胎不同发育阶段的功能.[方法]结合Tol2转座子转基因系统和热敏启动子Hsp70构建文昌鱼BbHsp70-BfVg1稳定转基因品系;并用热激实验、表型统计和原位杂交等手段对该转基因品系的有效性进行评估.[结果]热激结果显示,在囊胚晚期热激处理Vg1转基因文昌鱼导致胚胎背腹轴形成异常;在原肠胚中期热激处理Vg1转基因文昌鱼导致胚胎原本左右不对称的器官变为对称分布.基因表达分析结果显示,在囊胚晚期热激F1代胚胎中有部分比例胚胎的Vg1呈现全身性表达,背部中胚层标记基因Gsc表达扩张,腹部标记基因Evx表达下调,神经标记基因SoxB1a向腹侧蔓延;在原肠胚中期热激F1代胚胎中有部分比例胚胎的左侧特异基因Pitx呈现两侧对称表达,左侧口前窝标记基因Pit呈现两侧对称表达.[结论]初步构建了一个能够实现实时热激活Vg1的文昌鱼稳定转基因品系,并为后续在文昌鱼中进行基因功能研究提供了一个新手段.

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.

Angle-resolved photoemission study of NbGeSb with non-symmorphic symmetry

We investigate the electronic structure of NbGeSb with non-symmorphic symmetry.We employ angle-resolved photoemission spectroscopy(ARPES)to observe and identify the bulk and surface states over the Brillouin zone.By utilizing high-energy photons,we identify the bulk Fermi surface and bulk nodal line along the direction X–R,while the Fermi surface of the surface state is observed by using low-energy photons.We observe the splitting of surface bands away from the high-symmetry point X.The density functional theory calculations on bulk and 1 to 5-layer slab models,as well as spin textures of NbGeSb,verify that the band splitting could be attributed to the Rashba-like spin–orbit coupling caused by space-inversion-symmetry breaking at the surface.These splitted surface bands cross with each other,forming two-dimensional Weyl-like crossings that are protected by mirror symmetry.Our findings provide insights into the two-dimensional topological and symmetry-protected band inversion of surface states.

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.

Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades

BACKGROUND Hepatosplenic T-cell lymphoma(HSTCL)is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes,representing less than one percent of non-Hodgkin lymphomas.Given its rarity,the true incidence of HSTCL is unknown and most data have been extrapolated through case reports.To the best of our knowledge,the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014,with a sample size of 122 patients.AIM To paint the most updated epidemiological picture of HSTCL.METHODS A total of 186 patients diagnosed with HSTCL,between 2000 and 2017,were ultimately enrolled in our study by retrieving data from the Surveillance,Epidemiology,and End Results database.We analyzed demographics,clinical characteristics,and overall mortality(OM)as well as cancer-specific mortality(CSM)of HSTCL.Variables with a P value<0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors,with a hazard ratio of greater than 1 representing adverse prog-nostic factors.CONCLUSION Overall,the outlook for this rare malignancy is very grim.In this retrospective cohort study of the United States population,non-Hispanic blacks and the elderly had a higher CSM.This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group,such as treatment delays,which have been shown to increase mortality in this racial/ethnic group for other cancers.

Evaluation of AVNRT & AVRT by Different Criteria: Old & New

The two most frequent causes of paroxysmal SVT are atrioventricular tachycardia (AVRT) and atrioventricular nodal re-entrant tachycardia (AVNRT). The purpose of this study was to assess the diagnostic efficacy of traditional and newly proposed ECG criteria in the identification of Avnrt and Avrt. Aim of the Study: The aim of this study was to evaluate Atrioventricular Nodal Reentrant Tachycardia (AVNRT) and Atrioventricular Re-entrant Tachycardia (AVRT) using both traditional and novel criteria. Methods: This prospective observational study was conducted at the Electrophysiology Unit, Department of Cardiology, National Institute of Cardiovascular Diseases (NICVD) in Dhaka, from February 2019 to January 2020. A total of 62 patients with Supraventricular Tachycardia (SVT) undergoing electrophysiology study (EPS) were included. Standard ECG criteria were applied for the differential diagnosis, and electrophysiological diagnoses were made using established criteria. Statistical analysis, including descriptive statistics and appropriate tests, was performed using SPSS 23.0. Result: In our study of 62 patients with Supraventricular Tachycardia (SVT), we found that 66.1% had AVNRT and 33.9% had AVRT. The mean age in AVNRT was higher than AVRT (41.3 ± 9.7 vs. 38.5 ± 14.3, p = 0.36) with statistically no significant difference, with similar gender distribution between AVNRT and AVRT groups. Classical AVNRT criteria were present in 30.6% of patients, and 45.2% showed a Pseudo R' wave in aVR. Additionally, 30.6% had an RP interval ≥100ms, more prevalent in AVRT patients (66.7%). Conclusion: Integrating traditional and novel criteria, including lead aVR analysis, enhances the electrocardiographic diagnosis of AVNRT and AVRT, offering a pathway to refined patient care.

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.

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.

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.

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.

Tubing Dimension Optimization for the Development of an Offshore Gasfield

L1 is one of the largest offshore gas fields currently under development.In order to optimize the related design,nodal analysis is applied(including proper consideration of the plant productivity,sensitivity to the tubing size,erosion effects,liquid carrying performance,and tubing string).As a result of such approach,it is shown that 13Cr material should be chosen as the appropriate tubing material.Moreover,3-1/2 inches 9.3 lb/ft N80 tubing,4-1/2 inches 12.75 lb/ft N80 tubing,5-1/2 inches 17 lb/ft N80 tubing should be used for a gas production rate under 80×10^(4)m^(3)/d,between 80×10^(4)m^(3)/d and 120×10^(4)m^(3)/d and above 120×10^(4)m^(3)/d,respectively.

A new method to evaluate integrated production system capacity in oil fields

To improve the design and management of an integrated production system(IPS),a set of mathematical models and workflows are developed for evaluating the capacity of an IPS at steady-state conditions.Combining the conservation laws with applicable multiphase fluid and choke models,these mathematical models are solved to characterize the hydraulics of an integrated system of reservoir,wells,chokes,flowlines,and separator at steady state.The controllable variables such as well count,choke size and separator pressure are adjusted to optimize the performance of the IPs at a specific time.It is found that increasing the well count can increase the bulk flow rate of the production network,but too many wells may increase the manifold pressure,leading to decline of single-well production.Increasing the choke size can improve the capacity of the IPs.The production of the IPs is negatively correlated with the separator pressure.With increasing separator pressure and decreasing choke size,the increment of total fluid production(the capacity of IPS)induced by increasing well count decreases.Validation tests with field examples show a maximum absolute deviation is 1.5%,demonstrating the robustness and validity of the proposed mathematical models and workflows.

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。

叶酸缺乏对斑马鱼体轴发育的影响

目的构建叶酸缺乏斑马鱼模型,观察叶酸缺乏斑马鱼胚胎的体轴发育情况,初步探讨叶酸缺乏导致胚胎体轴发育异常的机制。方法分别应用二氢叶酸还原酶(dhfr)抑制剂甲氨蝶呤(MTX)以及二氢叶酸还原酶(dhfr)基因阻抑技术,通过下调二氢叶酸还原酶功能构建叶酸缺乏斑马鱼模型。在胚胎发育至17 hpf时在显微镜下观察胚胎的体轴偏移情况。利用特异性探针通过胚胎整体原位杂交的方法标记肝脏、胰脏以及心脏,以观察其位于中线两侧的位置。利用胚胎整体原位杂交和Real-time PCR的方法检测与体轴发育密切相关的Nodal信号通路下游因子ntl和gsc的表达情况。结果叶酸缺乏组一定比例胚胎存在体轴偏移以及肝脏、胰脏和心脏左右轴异位。叶酸缺乏组Nodal信号通路下游因子ntl以及gsc的表达强度无明显变化,但表达的空间模式发生改变,提示轴中胚层发育紊乱。结论叶酸缺乏可导致斑马鱼胚胎体轴发育异常以及轴中胚层发育紊乱,但对Nodal信号通路无明显干扰作用。

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.

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.

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。