The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

Nucleotide-binding domain,leucine-rich repeat,and pyrin domaincontaining protein 3 inflammasome:From action mechanism to therapeutic target in clinical trials

The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.

MINIMUM SIZE OF 180 DEGREE DOMAINS IN FERROELECTRIC THIN FILMS COVERED BY ELECTRODES

Ferroelectric domain switching under low voltage or short pulses is of interest for the development of high-density random access memory （FRAM） devices. Being necessarily very small in size, instability and back switching often occur when the external voltage is removed, which creates serious problems. In this investigation, a general approach to determine the minimum size of ferroelectric domain to avoid back switching was developed, and as an example, a 180° domain in a ferroelectric thin film covered by the upper and lower electrodes was considered in detail. We note that our approach is generally applicable to many other fields, including phase transformation, nucleation and expansion of dislocation loops in thin films, etc.

抗桥粒芯蛋白1、3抗体及大疱性类天疱疮180、230抗体联合检测诊断大疱性皮肤病的应用价值

目的 探讨抗桥粒芯蛋白1、3(Dsg1、3)抗体及大疱性类天疱疮180、230(BP180、230)抗体联合检测在大疱性皮肤病临床诊断中的应用价值。方法 自2020年3月至2023年1月,纳入郑州大学第一附属医院收治的经组织病理结果、直接免疫荧光检测确诊的大疱性皮肤病患者88例为观察组,选取本院同期健康体检者76名为对照组。分析两组Dsg1、Dsg3、BP180、BP230抗体的阳性检出情况;分析观察组血清Dsg1、Dsg3、BP180、BP230抗体标本诊断类型占比及观察组不同年龄组大疱性皮肤病疾病类型阳性率占比;绘制ROC曲线分析Dsg1、Dsg3、BP180、BP230抗体单一及联合检测对大疱性皮肤病的诊断价值。结果 两组血清Dsg1、Dsg3、BP180、BP230抗体阳性率比较差异具有统计学意义(P<0.05)。据Dsg1、Dsg3、BP180、BP230抗体检测结果,诊断类型:BP、PV、PF、PF+BP、PV+BP阳性率分别为32.95%、20.45%、11.36%、7.95%、3.41%。其中BP阳性率占比最高,PV+BP阳性率占比最低,两者比较差异具有统计学意义(P<0.05)。>60岁组BP阳性率高于≤60岁组,PV及PF阳性率低于≤60岁组,差异有统计学意义(P<0.05)。Dsg1、Dsg3、BP180、BP230抗体联合检测对大疱性皮肤病灵敏度、特异度分别为91.02%、88.66%,AUC(95%CI)为0.821(0.745~0.911),均高于上述抗体单一检测(P<0.05)。结论 Dsg1、Dsg3、BP180、BP230抗体在大疱性皮肤病诊断中具有重要参考价值,且联合检测可提高诊断的准确性;大疱性皮肤病患者年龄和抗体类型之间也存在一定的关联,联合检测Dsg1、Dsg3、BP180、BP230抗体有助于大疱性皮肤病进行更精细的诊断和治疗。

玉米转录因子ZmEREB180调控根系生长发育及耐逆的功能研究

AP2/ERF(APETALA2/ethylene-responsive factor)转录因子是植物中最大的转录因子家族之一,在调控植物生长发育、响应逆境胁迫、调节激素信号转导和物质代谢等多种生物学过程中发挥着重要作用。目前AP2/ERF超家族基因在许多植物物种中的生物学功能已经得到验证,但对玉米(Zea mays L.)中AP2/ERF基因的结构和功能的研究报道较少。前期工作中我们发现,ZmEREB180(ethylene-responsive element binding)转录因子,在鉴定的玉米六叶期(V6)、十二叶期(V12)和抽雄期(VT)等关键发育时期,根系中的表达量均存在显著差异;通过组织表达分析发现该基因主要在玉米根系中表达,且在幼根中的表达量显著高于成熟根,推测该基因可能参与玉米根系生长发育调控。本研究克隆了ZmEREB180(Gene ID:100192457)基因,结合生物信息学分析、实时荧光定量PCR(RT-qPCR)、亚细胞定位和转基因拟南芥(Arabidopsis thaliana L.)株系的耐逆表型鉴定等生物学手段,初步分析了该基因的表达模式和生物学功能。该基因包含2个外显子,编码序列全长1023 bp,编码340个氨基酸,具有AP2/ERF家族所特有的保守结构域;该基因在玉米根系中表达量最高,且在高盐、干旱、高氮和低氮等胁迫处理条件下的玉米根部皆有不同程度的诱导表达,其中,低氮处理较高氮处理具有更高的表达量和更快的响应速率;在含0.10、0.15 mol L^(-1)NaCl以及0.15、0.20和0.30 mol L^(-1)甘露醇(mannitol)的1/2 MS固体培养基上,转ZmEREB180基因拟南芥的主根长度均显著长于野生型;土壤环境中,高盐和干旱胁迫条件下的转基因植株比野生型拟南芥具有更健康的生长状态、更高的绿叶率、更低的丙二醛含量和更高的过氧化物酶活性。转录因子ZmEREB180可能在调控玉米根系生长发育方面具有积极的促进作用,并且能增强玉米植株对高盐、干旱、渗透、低氮等逆境胁迫的耐受性。本研究为下一步鉴定转录因子ZmEREB180在玉米中的生物学功能和分子机制奠定了良好的基础。

选择性360°和180°微脉冲激光小梁成形术治疗原发性开角型青光眼的效果差异研究

对比选择性360°和180°微脉冲小梁成形术(MLT)对原发性开角型青光眼患者治疗的效果差异。方法 将2020年2月到2023年2月到我院治疗的80例原发性开角型青光眼患者根据入院单双日分为观察组(单日组41例)和对照组(双日组39例)。分别行360°微脉冲小梁成形术和180°微脉冲小梁成形术进行治疗,对比疗效差异。结果 ①两组患者术前、术后1h、术后1d、6个月眼压无差异(P>0.05);术后1周、术后1个月、3个月有差异(P<0.05);②两组患者术前、术后1h、术后1d、术后1周、术后1个月、3个月、6个月患眼视力水平无明显差异(P>0.05)。结论 选择性360°和选择性180°MLT都能提升原发性开角型青光眼患者的视力水平,降低眼压,可根据患者的需求辩证的选择。

Phase field simulation of the 180°domain-switching process in PbTiO_3 single crystal under an antiparallel electric field

The process of 180°domain switching in PbTiO_3 single crystal under an antiparallel electric field was investigated by the three-dimensional phase field simulation,especially the effect of electric field on the type and duration of domain switching.It is found that the polarization reversal of domains takes place under an antiparallel electric field in PbTiO_3 single crystal.The results of the phase field simulation indicate that there is only 90°domain switching under a weak electric field.With the rise of the electric field,180°domain switching appears.If the electric field is strengthened further,90°domain switching disappears and the duration of domain switching is shortened.

竖缝式鱼道90°~180°转弯段水力特性及优化研究

受鱼道进出口位置、工程地质、枢纽布置等因素限制,鱼道工程需要布置不同角度的转弯段池室,以适应复杂多变工程环境。采用数值模拟的方法,研究了同侧竖缝式鱼道不同转角α(90°≤α≤180°)的转弯段池室流场分布规律,并对不同转角池室提出了系统的优化措施。结果表明,当转弯角度α大于90°时,均出现主流冲击外侧边壁,池室中部伴有大尺度回流区的现象,并随着转弯段角度α增大,主流冲击程度加剧,回流区尺度也进一步扩大。针对上述流场问题,采用加设整流导板的措施进行优化,提出转弯角度α介于90°~140°之间时,整流较好的导板位置α_(0)/α值由1/4.0增加至1/2.8,当α介于140°~180°之间时,α_(0)/α值基本稳定于1/2.8~1/3.0之间,即随着转弯角度α的逐渐增加,较优的α_(0)/α值呈现先增加后趋于稳定的变化趋势,可为转弯段结构相似布置鱼道优化设计提供参考。

南海180℃超高温CO_(2)环境下水泥石强度衰退机理

南海莺琼盆地不但要面临180℃的超高温,还要面临高浓度CO_(2)的挑战。然而,加砂水泥水化产物在超高温CO_(2)环境下变化复杂,导致其强度衰退机理仍不清楚。因此,对超高温CO_(2)环境中改性水泥石的力学性能、矿物组成及微观形貌进行分析。结果表明:随着腐蚀时间的延长,水泥石的腐蚀深度一直增大,抗压强度一直降低,渗透率先降低后增大,SiO_(2)和C_(2)SH含量一直降低,C_(6)S_(6)H和CaCO_(3)含量一直增大,C_(6)S_(6)H的形貌由堆积的针状向着片状和块状转变。腐蚀初期,C_(2)SH和C_(6)S_(6)H被腐蚀生成CaCO_(3)和少量无定形SiO_(2),同时部分C_(2)SH会转变为更耐腐蚀的C_(6)S_(6)H,该阶段导致水泥石渗透率降低,C-S-H凝胶的聚合度增大。腐蚀后期,C_(6)S_(6)H和其他C-S-H凝胶被大量腐蚀,且CaCO_(3)溶解,使水泥石渗透率增大,C-S-H凝胶聚合度降低,导致水泥石抗压强度大幅降低。

Elastocaloric Effect in PbTiO3 Thin Films with 180°Domain Structure:A Phase Field Study

The elastocalorie effect of PbTiO3 thin films with 180° domain structure is studied using the phase field method. The influence of external stress σ33, misfit strain μm and domain wall energy on the adiabatic temperature change （ △ Tσ） at room temperature are carried out. The calculation results indicate that ｜△Tσ｜ increases as ｜σ33｜ or ｜μm｜ increases. The largest △ Tσ wlue of--7.81（ is obtained at σ33 = 2 GPa and Um =-0.02. Furthermore, the domain switching behaviors under different gradient coeffcients are different, and finally affect the elastocaloric effect in PTO thin films. These results could provide a guide to choose the substrate and the preparation process in experiments.

转录组分析揭示荷叶离褶伞菌多糖LDS-1抗小鼠S180肿瘤的分子机制

以荷叶离褶伞菌多糖LDS-1、甘露聚糖肽和空白对照作用下的小鼠S180肿瘤细胞为研究材料,运用RNA-Seq测序技术进行生物信息学分析,结果显示LDS-1组、甘露聚糖肽组和空白对照组分别获得8.27、 8.35和8.97 G的分析数据.高表达基因(FPKM>2 200)分析显示LDS-1主要通过下调Rplp1基因调控细胞分裂,将S180细胞停滞在G1期以抑制其分裂.差异基因分析结果显示LDS-1主要通过上调Alb、 Timp4、 Apoa1基因调节蛋白表达或者细胞黏连性,抑制S180肿瘤细胞迁移.KEGG(京都基因与基因组百科全书)通路富集结果显示, LDS-1抑制S180肿瘤生长的关键基因主要富集在过氧化物酶体增殖物激活受体(PPAR)信号通路中,上游Fabp3基因下调,激活下游Apoa1、Slc27a2和Adipoq等多个基因上调,调控S180细胞的脂质代谢和胆固醇代谢. LDS-1能够通过调控高表达关键基因Rplp1,差异表达关键基因Alb、 Timp4、 Apoa1,以及PPAR信号通路抑制S180肿瘤细胞的增殖分裂、能量获取和迁移侵袭.

Diabetic retinopathy identification based on multi-sourcefree domain adaptation

AIM:To address the challenges of data labeling difficulties,data privacy,and necessary large amount of labeled data for deep learning methods in diabetic retinopathy(DR)identification,the aim of this study is to develop a source-free domain adaptation(SFDA)method for efficient and effective DR identification from unlabeled data.METHODS:A multi-SFDA method was proposed for DR identification.This method integrates multiple source models,which are trained from the same source domain,to generate synthetic pseudo labels for the unlabeled target domain.Besides,a softmax-consistence minimization term is utilized to minimize the intra-class distances between the source and target domains and maximize the inter-class distances.Validation is performed using three color fundus photograph datasets(APTOS2019,DDR,and EyePACS).RESULTS:The proposed model was evaluated and provided promising results with respectively 0.8917 and 0.9795 F1-scores on referable and normal/abnormal DR identification tasks.It demonstrated effective DR identification through minimizing intra-class distances and maximizing inter-class distances between source and target domains.CONCLUSION:The multi-SFDA method provides an effective approach to overcome the challenges in DR identification.The method not only addresses difficulties in data labeling and privacy issues,but also reduces the need for large amounts of labeled data required by deep learning methods,making it a practical tool for early detection and preservation of vision in diabetic patients.

邹敬园双杠“后上转体180°成倒立”动作的运动学虚拟再现

分析双杠奥运冠军邹敬园在2023年全国体操冠军赛中的“后上转体180°成倒立”的运动学特征。通过三维录像解析法和3D虚拟现实技术,对邹敬园的动作进行数据采集和分析。发现各阶段重心速度和关节角度变化清晰,但未完全成倒立,仍有提升空间。尽管邹敬园的动作水平很高,但在上摆和转体阶段需进一步加强髋关节和肩关节的协调性,优化重心轨迹,以提高动作完成质量和稳定性。

Estimation-free spatial-domain image reconstruction of structured illumination microscopy

Structured illumination microscopy(SIM)achieves super-resolution(SR)by modulating the high-frequency information of the sample into the passband of the optical system and subsequent image reconstruction.The traditional Wiener-filtering-based reconstruction algorithm operates in the Fourier domain,it requires prior knowledge of the sinusoidal illumination patterns which makes the time-consuming procedure of parameter estimation to raw datasets necessary,besides,the parameter estimation is sensitive to noise or aberration-induced pattern distortion which leads to reconstruction artifacts.Here,we propose a spatial-domain image reconstruction method that does not require parameter estimation but calculates patterns from raw datasets,and a reconstructed image can be obtained just by calculating the spatial covariance of differential calculated patterns and differential filtered datasets(the notch filtering operation is performed to the raw datasets for attenuating and compensating the optical transfer function(OTF)).Experiments on reconstructing raw datasets including nonbiological,biological,and simulated samples demonstrate that our method has SR capability,high reconstruction speed,and high robustness to aberration and noise.

脉冲电流对轧辊用AD180高碳半钢材料力学性能及组织的影响

为分析电流处理对轧辊材料的影响规律,通过改变电流密度和处理时间来调整AD180高碳半钢的微观组织和力学性能。使用万能拉伸试验机对电流处理后的试样进行单轴拉伸实验,并对试样进行SEM断口截面分析和EBSD微观表征,研究其力学性能和微观组织的变化规律。拉伸结果表明,在电流密度11.88 A·mm-2、通电5 min时,试样的综合性能最好,屈服强度提高6.5%,抗拉强度提高12.1%,伸长率提高了25.4%。通过断口截面分析发现,拉伸试样均为脆性断裂,未通电试样存在大量孔洞缺陷,而合适的电流密度和通电时间可以促进试样内部孔洞缺陷的“愈合”,其中,电流密度为11.88 A·mm^(-2)、通电5 min时,试样断口上的缺陷最少。EBSD微观表征结果表明,脉冲电流使试样在较低温度下发生了再结晶,细化了晶粒。由此可见,脉冲电流可以改善试样内部的组织结构和治愈微缺陷,提高其综合力学性能。

Fast solution to the free return orbit's reachable domain of the manned lunar mission by deep neural network

It is important to calculate the reachable domain(RD)of the manned lunar mission to evaluate whether a lunar landing site could be reached by the spacecraft. In this paper, the RD of free return orbits is quickly evaluated and calculated via the classification and regression neural networks. An efficient databasegeneration method is developed for obtaining eight types of free return orbits and then the RD is defined by the orbit’s inclination and right ascension of ascending node(RAAN) at the perilune. A classify neural network and a regression network are trained respectively. The former is built for classifying the type of the RD, and the latter is built for calculating the inclination and RAAN of the RD. The simulation results show that two neural networks are well trained. The classification model has an accuracy of more than 99% and the mean square error of the regression model is less than 0.01°on the test set. Moreover, a serial strategy is proposed to combine the two surrogate models and a recognition tool is built to evaluate whether a lunar site could be reached. The proposed deep learning method shows the superiority in computation efficiency compared with the traditional double two-body model.

草黄口蘑多糖对S180荷瘤小鼠抗肿瘤活性分子机制研究

多糖作为口蘑属真菌的主要功能成分之一,具有免疫调节、抗氧化及抗肿瘤等活性。为明确草黄口蘑多糖的结构特征及其对S180荷瘤小鼠抗肿瘤活性相关分子机制,该研究以草黄口蘑子实体经热水浸提法提取的草黄口蘑多糖[Tricholoma lascivum (Fr.)Gillet polysaccharide,TLG-1]为实验材料,初步解析TLG-1结构,以S180荷瘤小鼠为模型检测体内抗肿瘤活性,并采用转录组测序技术对S180肿瘤组织总RNA进行测序分析。结果表明,TLG-1重均分子质量为13 442 Da,由木糖、甘露糖、葡萄糖和半乳糖4种单糖组成,其比例为1.57∶1.45∶2.84∶4.14。TLG-1可显著抑制荷瘤小鼠S180肿瘤的生长(P<0.01),抑瘤率为53.8%。转录组测序分析显示,TLG-1能显著上调mt-Co1、Prlr、Foxa1以及下调Pitx2、Rplp1、Eef1a1及Lgals1等基因,影响S180肿瘤细胞的代谢途径,调控细胞周期并抑制上皮间质转化过程。基因本体富集分析表明,TLG-1可激活细胞因子介导的信号通路,引发细胞免疫。京都基因与基因组百科全书富集分析显示,在Jak-STAT信号通路中的Il21、Il12rb2、Il12b、Il2ra、Il2rb、Il2rg、Il15ra和Ifng等基因显著上调,通过转换肿瘤相关巨噬细胞表型及分泌干扰素-γ等,增强小鼠抗肿瘤免疫应答。该研究结果为草黄口蘑多糖的开发和利用提供了一定的理论基础。

Slope displacement prediction based on multisource domain transfer learning for insufficient sample data

Accurate displacement prediction is critical for the early warning of landslides.The complexity of the coupling relationship between multiple influencing factors and displacement makes the accurate prediction of displacement difficult.Moreover,in engineering practice,insufficient monitoring data limit the performance of prediction models.To alleviate this problem,a displacement prediction method based on multisource domain transfer learning,which helps accurately predict data in the target domain through the knowledge of one or more source domains,is proposed.First,an optimized variational mode decomposition model based on the minimum sample entropy is used to decompose the cumulative displacement into the trend,periodic,and stochastic components.The trend component is predicted by an autoregressive model,and the periodic component is predicted by the long short-term memory.For the stochastic component,because it is affected by uncertainties,it is predicted by a combination of a Wasserstein generative adversarial network and multisource domain transfer learning for improved prediction accuracy.Considering a real mine slope as a case study,the proposed prediction method was validated.Therefore,this study provides new insights that can be applied to scenarios lacking sample data.

Delineating homogeneous domains of fractured rocks using topological manifolds and deep learning

Determining homogeneous domains statistically is helpful for engineering geological modeling and rock mass stability evaluation.In this text,a technique that can integrate lithology,geotechnical and structural information is proposed to delineate homogeneous domains.This technique is then applied to a high and steep slope along a road.First,geological and geotechnical domains were described based on lithology,faults,and shear zones.Next,topological manifolds were used to eliminate the incompatibility between orientations and other parameters(i.e.trace length and roughness)so that the data concerning various properties of each discontinuity can be matched and characterized in the same Euclidean space.Thus,the influence of implicit combined effect in between parameter sequences on the homogeneous domains could be considered.Deep learning technique was employed to quantify abstract features of the characterization images of discontinuity properties,and to assess the similarity of rock mass structures.The results show that the technique can effectively distinguish structural variations and outperform conventional methods.It can handle multisource engineering geological information and multiple discontinuity parameters.This technique can also minimize the interference of human factors and delineate homogeneous domains based on orientations or multi-parameter with arbitrary distributions to satisfy different engineering requirements.