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。

Research on θ -Intuitionistic Fuzzy Homomorphism Theory

Fuzzy homomorphism is an important research content of fuzzy group theory, different fuzzy mappings will produce different fuzzy homomorphisms. In this paper, the fuzzy homomorphism of groups is generalized. Firstly, the θ-intuitionistic fuzzy mapping is defined, and the θ-intuitionistic fuzzy homomorphism of groups is obtained. The properties of intuitionistic fuzzy subgroups and intuitionistic fuzzy normal subgroups are studied under the θ-intuitionistic fuzzy homomorphism of groups, and the fundamental theorem of θ-intuitionistic fuzzy homomorphism is proved.

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。

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.

抑制SHP2和FGFR2调控RAS/ERK及PI3K/AKT通路治疗FGFR2融合胃癌

目的:探究共抑制成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)和Src同源2结构域的蛋白酪氨酸磷酸酶2(Src homology region 2-containing protein tyrosine phosphatase 2,SHP2)在FGFR2融合胃癌中的应用前景与作用机制。方法:构建过表达TACC2-FGFR2融合基因与对照慢病毒载体的人胃癌细胞系MKN45ACC2T-FGFR2、MKN45NC、NUGC4TACC2-FGFR2、NUGC4NC,分别用FGFR2抑制剂AZD4547、SHP2抑制剂SHP099或联药进行处理,通过细胞计数试剂盒(CCK-8)、划痕实验检测肿瘤细胞的增殖、迁移能力。以不同处理方式作用于MKN45TACC2-FGFR2、MKN45NC1 h或48 h后,采用Western blot法检测FGFR2、SHP2以及下游RAS/ERK、PI3K/AKT信号通路变化。结果:在MKN45TACC2-FGFR2与NUGC4TACC2-FGFR2中联用AZD4547与SHP099可以比单药更显著地抑制肿瘤细胞的增殖与迁移。药物处理1 h后,相较于AZD4547单药,联药在MKN45TACC2-FGFR2中进一步抑制了RAS/ERK、PI3K/AKT信号通路。药物处理48 h与1 h相比,AZD4547单药组中磷酸化FGFR与磷酸化SHP2出现了反馈性激活,且始终不能抑制RAS/ERK通路,但联药组可以持续地抑制上游的FGFR2、SHP2信号以及下游的RAS/ERK、PI3K/AKT通路。结论:共抑制FGFR2和SHP2可以通过下调RAS/ERK及PI3K/AKT通路有效抑制FGFR2融合胃癌,为FG-FR2融合突变胃癌患者带来新的治疗模式。

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.

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.

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.

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.

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.

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.

Analysis of the spatiotemporal trends and influencing factors of Hyphantria cunea in China

In recent years,the situation of the Hyphantria cunea(Drury)(Lepidoptera:Erebidae),infestation in China has been serious and has a tendency to continue to spread.A comprehensive analysis was carried out to examine the spa-tial distribution trends and influencing factors of H.cunea.This analysis involved integrating administrative division and boundary data,distribution data of H.cunea,and envi-ronmental variables for 2021.GeoDetector and gravity analysis techniques were employed for data processing and interpretation.The results show that H.cunea exhibited high aggregation patterns in 2021 and 2022 concentrated mainly in eastern China.During these years,the focal point of the infestation was in Shandong Province with a spread towards the northeast.Conditions such as high vegetation density in eastern China provided favorable situations for growth and development of H.cunea.In China,the spatial distribution of the moth is primarily influenced by two critical factors:precipitation during the driest month and elevation.These play a pivotal role in determining the spread of the species.Based on these results,suggestions are provided for a mul-tifaceted approach to prevention and control of H.cunea infestation.

Mixing characteristics of three-cylinder valve-controlled energy recovery device based on liquid piston

The isobaric energy recovery device can significantly reduce the energy consumption of the seawater reverse osmosis system by recycling the residual pressure energy of high-pressure concentrated brine.Three-cylinder valve-controlled energy recovery device(TC-ERD)solves the fluid pulsation of traditional two-cylinder devices,but the use of a“liquid piston”exacerbates the mixing between brine and seawater.Herein,the evolutionary law of“liquid piston”and the relationship between volumetric mixing degree and operating conditions are explored.The results show that the“liquid piston”first axially expands and then gradually stabilizes,isolating the brine and seawater.Additionally,as long as the volume utilization ratio(U_(R))of the pressure exchange cylinder remains constant,there will not be much difference in the volumetric mixing degree after stabilization of the“liquid piston”(Vm-max)regardless of changes in the processing capacity(Q)and cycle time(T_(0)).Therefore,the equation for Vm-max with respect to the operating parameters(Q,T_(0))is derived,which can not only predict the Vm-max of the TCERD,but also provide an empirical reference for the design of other valve-controlled devices with“liquid piston”.When the Vm-max is 6%,the efficiency of the TC-ERD at design conditions(30 m^(3)·h^(-1),5.0 MPa)is 97.53%.

Effects of Rattling Behavior of K and Cd Atoms along Different Directions in Anisotropic KCdAs on Lattice Thermal Transport and Thermoelectric Properties

We employ advanced first principles methodology,merging self-consistent phonon theory and the Boltzmann transport equation,to comprehensively explore the thermal transport and thermoelectric properties of KCdAs.Notably,the study accounts for the impact of quartic anharmonicity on phonon group velocities in the pursuit of lattice thermal conductivity and investigates 3ph and 4ph scattering processes on phonon lifetimes.Through various methodologies,including examining atomic vibrational modes and analyzing 3ph and 4ph scattering processes,the article unveils microphysical mechanisms contributing to the lowκL within KCdAs.Key features include significant anisotropy in Cd atoms,pronounced anharmonicity in K atoms,and relative vibrations in non-equivalent As atomic layers.Cd atoms,situated between As layers,exhibit rattling modes and strong lattice anharmonicity,contributing to the observed lowκL.Remarkably flat bands near the valence band maximum translate into high PF,aligning with ultralowκL for exceptional thermoelectric performance.Under optimal temperature and carrier concentration doping,outstanding ZT values are achieved:4.25(a(b)-axis,p-type,3×10^(19)cm^(−3),500 K),0.90(c-axis,p-type,5×10^(20)cm^(−3),700 K),1.61(a(b)-axis,n-type,2×10^(18)cm^(−3),700 K),and 3.06(c-axis,n-type,9×10^(17)cm^(−3),700 K).

Ultra-soft Desorption Assisted Mass Spectrometry using Picosecond Infrared Laser for the Detection of lons in the Liquid Surface

To identify the species in liquid surface using mass spectrometry,we must eliminate or reduce interferences during the vaporization or desorption of the species from the liquid surface.It is much more challenging to isolate the ionic,larger species from the liquid surface,because of the frangible structures and the higher solvation energies of those species.Here we demonstrate a new mass spectrometry in which the ionic species at the liquid surface can be desorbed with ultrasoft infrared picosecond laser pulses while the liquid surface is not breached.This laser desorption assisted mass spectrometry is not only a powerful tool to detect the fragile species but also promising to investigate vibrational energy transfer dynamics in the liquid surface.

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.

Half-integer Shapiro steps in MgB_(2) focused He ion beam Josephson junctions

Half-integer microwave induced steps(Shapiro steps)have been observed in many different Josephson junction systems,which have attracted a lot of attention because they signify the deviation of current phase relation(CPR)and uncover many unconventional physical properties.In this article,we first report the discovery of half-integer Shapiro steps in MgB_(2)focused He ion beam(He-FIB)Josephson junctions.The half-integer steps'dependence on microwave frequency,temperature,microwave power,and magnetic field is also analyzed.We find that the existence of half-integer steps can be controlled by the magnetic field periodically,which is similar to that of high temperature superconductor(HTS)grain boundary junctions,and the similarity of the microstructures between gain boundary junctions and He-FIB junctions is discussed.As a consequence,we mainly attribute the physical origin of half-integer steps in MgB_(2)He-FIB junctions to the model that a He-FIB junction is analogous to a parallel junctions'array.Our results show that He-FIB technology is a promising platform for researching CPR in junctions made of different superconductors.

Structural characterization and mechanisms of macrophage immunomodulatory activity of a novel polysaccharide with a galactose backbone from the processed Polygonati Rhizoma

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-b-D-Galp-(1]9/4,6)-b-D-Galp-(1/4)-a-D-GalpA-(1/4)-a-D-GalpA-(1/4)-aD-Glcp-(1/4,6)-a-D-Glcp-(1/4)-a/b-D-Glcp,with a branch chain of R1:b-D-Galp-(1/3)-b-D-Galp-(1/connected to the/4,6)-b-D-Galp-(1/via O-6,and a branch chain of R2:a-D-Glcp-(1/6)-a-D-Glcp-(1/connected to the/4,6)-a-D-Glcp-(1/via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1b and TNF-a),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 mM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing。