Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Mechanical Behavior Based on Aggregates Microstructure of Ultra-high Performance Concrete

We developed ultra-high performance concrete(UHPC)incorporating mullite sand and brown corundum sand(BCS),and the quartz sand UHPC was utilized to prepare for comparison.The properties of compressive strength,elastic modulus,ultrasonic pulse velocity,flexural strength,and toughness were investigated.Scanning electron microscopy and nanoindentation were also conducted to reveal the underlying mechanisms affecting macroscopic performance.Due to the superior interface bonding properties between mullite sand and matrix,the compressive strength and flexural toughness of UHPC have been significantly improved.Mullite sand and BCS aggregates have higher stiffness than quartz sand,contributing to the excellent elastic modulus exhibited by UHPC.The stiffness and volume of aggregates have a more significant impact on the elastic modulus of UHPC than interface performance,and the latter contributes more to the strength of UHPC.This study will provide a reference for developing UHPC with superior elastic modulus for structural engineering.

Straw mulching alters the composition and loss of dissolved organic matter in farmland surface runoff by inhibiting the fragmentation of soil small macroaggregates

Straw mulching is a widespread practice for reducing the soil carbon loss caused by erosion.However,the effects of straw mulching on dissolved organic matter(DOM)runoff loss from black soil are not well studied.How straw mulching affects the composition and loss of runoff DOM by changing soil aggregates remains largely unclear.Here,a straw mulching treatment was compared to a no mulching treatment(as a control)on sloping farmland with black soil erosion in Northeast China.We divided the soil into large macroaggregates(>2 mm),small macroaggregates(0.25-2 mm),and microaggregates(<0.25 mm).After five rain events,the effects of straw mulching on the concentration(characterized by dissolved organic carbon(DoC)and composition(analyzed by fluorescence spectroscopy)of runoff and soil aggregate DOM were studied.The results showed that straw mulching reduced the runoff amount by 54.7%.Therefore,although straw mulching increased the average DOc concentration in runoff,it reduced the total runoff DOM loss by 48.3%.The composition of runoff DOM is similar to that of soil,as both contain humic-like acid and protein-like components.With straw mulching treatment,the protein-like components in small macroaggregates accumulated and the protein-like components in runoff declined with rain events.Fluorescence spectroscopy technology may help in understanding the hydrological paths of rain events by capturing the dynamic changes of runoff and soil DOM characteristics.A variation partitioning analysis(VPA)indicated that the DOM concentration and composition of microaggregates explained 68.2%of the change in runoff DOM from no mulching plots,while the change in runoff DOM from straw mulching plots was dominated by small macroaggregates at a rate of 55.1%.Taken together,our results demonstrated that straw mulching reduces the fragmentation of small macroaggregates and the loss of microaggregates,thus effecting DOM compositions in soil and reducing the DOM loss in runoff.These results provide a theoretical basis for reducing carbon loss in sloping farmland.

High-efficiency Carbonation Modification Methods of Recycled Coarse Aggregates

To solve the problem of only surface carbonation and realize high-efficiency carbonation of recycled coarse aggregate,the method of carbonated recycled coarse aggregate with nano materials pre-soaking was first put forward.The carbonation effect of modified recycled coarse aggregate with three different carbonation methods was evaluated,and water absorption,apparent density and crush index of modified recycled coarse aggregate were measured.Combined with XRD,SEM,and MIP microscopic analysis,the high-efficiency carbonation strengthening mechanism of modified recycled coarse aggregate was revealed.The experimental results show that,compared with the non-carbonated recycled coarse aggregate,the physical and microscopic properties of carbonated recycled coarse aggregate are improved.The method of carbonation with nano-SiO_(2) pre-soaking can realize the high-efficiency carbonation of recycled coarse aggregate,for modified recycled coarse aggregate with the method,water absorption is reduced by 23.03%,porosity is reduced by 44.06%,and the average pore diameter is 21.82 nm.The high-efficiency carbonation strengthening mechanism show that the pre-socked nano-SiO_(2) is bound to the hydration product Ca(OH)_(2) of the old mortar with nano-scale C-S-H,which can improve the CO_(2) absorption rate,accelerate the carbonation reaction,generate more stable CaCO_(3) and nano-scale silica gel,and bond to the dense three-dimensional network structure to realize the bidirectional enhancement of nano-materials and pressurized carbonation.It is concluded that the method of carbonation with nano-SiO_(2) pre-soaking is a novel high-efficiency carbonation modification of recycled coarse aggregate.

"Three-in-One" Ecological Development and Efficient Utilization Model of Aggregates

Green mining and the formation of an effective and efficient development model have become key issues that aggregates enterprises around the world need to solve urgently.On the basis of analyzing the development status of aggregates industry in Xiluodu area,the paper studied the main problems faced in the construction of green aggregates mines at present,and proposed a"three-in-one"ecological,intelligent and efficient green mine construction model for"ecological development","green logistics"and"solid waste recycling"of aggregates.The study has certain theoretical value and practical significance for the construction of green aggregates mine in Xiluodu area.

TAX1BP1 and FIP200 orchestrate non-canonical autophagy of p62 aggregates for mouse neural stem cell maintenance

Autophagy plays a pivotal role in diverse biological processes,including the maintenance and differentiation of neural stem cells(NSCs).Interestingly,while complete deletion of Fip200 severely impairs NSC maintenance and differentiation,inhibiting canonical autophagy via deletion of core genes,such as Atg5,Atg16l1,and Atg7,or blockade of canonical interactions between FIP200 and ATG13(designated as FIP200-4A mutant or FIP200 KI)does not produce comparable detrimental effects.This highlights the likely critical involvement of the non-canonical functions of FIP200,the mechanisms of which have remained elusive.Here,utilizing genetic mouse models,we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1,primarily via TAX1BP1 in NSCs.Conditional deletion of Tax1bp1 in fip200hGFAP conditional knock-in(cKI)mice led to NSC deficiency,resembling the fip200hGFAP conditional knockout(cKO)mouse phenotype.Notably,reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation.Conversely,a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration.Furthermore,conditional deletion of Tax1bp1 in fip200hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200hGFAP cKO mice.Collectively,these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function,presenting novel therapeutic targets for neurodegenerative diseases.

Calcium carbonate promotes the formation and stability of soil macroaggregates in mining areas of China

We studied changes in the concentrations of aggregate-cementing agents after different reclamation times and with different fertilization regimes,as well as the formation mechanism of aggregates in reclaimed soil,to provide a theoretical basis for rapid reclamation of soil fertility in the subsidence area of coal mines in Shanxi Province,China.In this study,soil samples of 0–20 cm depth were collected from four fertilization treatments of a longterm experiment started in 2008:no fertilizer (CK),inorganic fertilizer (NPK),chicken manure compost (M),and50%inorganic fertilizer plus 50%chicken manure compost (MNPK).The concentrations of cementing agents and changes in soil aggregate size distribution and stability were analysed.The results showed that the formation of>2 mm aggregates,the aggregate mean weight diameter (MWD),and the proportion of>0.25 mm water-stable aggregates (WR_(0.25)) increased significantly after 6 and 11 years of reclamation.The concentration of organic cementing agents tended to increase with reclamation time,whereas free iron oxide (Fed) and free aluminium oxide(Ald) concentrations initially increased but then decreased.In general,the MNPK treatment signi?cantly increased the concentrations of organic cementing agents and CaCO_(3),and CaCO_(3) increased by 60.4%at 11 years after reclamation.Additionally,CaCO_(3) had the greatest effect on the stability of aggregates,promoting the formation of>0.25 mm aggregates and accounting for 54.4%of the variance in the proportion and stability of the aggregates.It was concluded that long-term reclamation is bene?cial for improving soil structure.The MNPK treatment was the most effective measure for increasing maize grain yield and concentration of organic cementing agents and CaCO_(3).

Substitution of Aggregates in Concrete and Mortar with Coltan Mining Waste: Mechanical, Environmental, and Economic Impact Case Study

The mining process involves drilling and excavation, resulting in the production of waste rock and tailings. The waste materials are then removed and stored in designated areas. This study aims to evaluate the mechanical strength and the environmental and economic impact of using Coltan Mining Waste (CMW) as a substitute for aggregates in concrete and mortar production. To achieve this, the CMW needs to be characterised. The Dreux Gorisse method was primarily used to produce concrete with a strength of 20 MPa at 28 days. The mortars, on the other hand, were formulated according to the NF P 18-452 standard. The environmental impact of using CMW as substitutes for natural aggregates in the production of concrete and mortar was analysed using SimaPro software. The results showed that mortars and concrete made with CMW have comparable compressive strengths to the reference mortar and concrete;reduce the negative impact on ecosystem quality, human health, resources, and climate change. It has also been shown that the substitution of aggregates by CMW reduces the cost of concrete and mortar as a function of the distance from the aggregate footprint.

西葫芦新品种京葫42的选育

京葫42是以抗病自交系865为母本,以820为父本配制而成的温室专用抗病西葫芦一代杂种。中早熟,生长势强,茎秆粗壮,低温弱光下连续结瓜能力强,抗白粉病、小西葫芦花叶病毒(ZYMV)、西瓜花叶病毒(WMV)和番木瓜花叶病毒(PRSV);商品瓜翠绿色,中长柱形,瓜条顺直,商品性好;每667 m^(2)产量12000 kg左右,适宜华北、西北、黄淮海和东北地区越冬温室栽培。

缺血性脑卒中后抑郁患者外周血CDC42、Th17细胞表达及与抑郁程度的相关性分析

目的观察缺血性脑卒中患者外周血细胞分裂周期蛋白42(CDC42)、辅助性T细胞17(Th17)表达并探究其表达与患者抑郁程度的相关性。方法选取2022年1月—2023年1月河北北方学院附属第一医院收治的200例缺血性脑卒中患者为观察组,另选取同期该院200例体检健康者为对照组。患者入院后均接受常规抗血小板聚集、降脂等对症支持治疗,并采用多感官刺激方案对患者进行干预。采用蒙哥马利抑郁评定量表评估患者的抑郁状态,并将患者分为无抑郁组116例、轻度抑郁组38例、中度抑郁组31例、重度抑郁组15例。比较各组医院焦虑抑郁量表(HADS)和简易精神状态评价量表(MMSE)评分,比较观察组干预前后日常生活活动能力(ADL)评分;检测各组外周血CDC42 mRNA、Th17细胞、调节性T细胞(Treg)、Th17/Treg表达。以Pearson相关系数分析HADS评分与患者外周血CDC42 mRNA、Th17细胞、Treg细胞、Th17/Treg表达水平的相关性。结果观察组HADS-A评分、HADS-D评分均高于对照组(P<0.05),MMSE评分低于对照组(P<0.05)。重度抑郁组HADS-A评分、HADS-D评分高于其他组(P<0.05),MMSE评分低于其他组(P<0.05);中度抑郁组HADS-A评分、HADS-D评分高于轻度抑郁组和无抑郁组(P<0.05),MMSE评分低于轻度抑郁组和无抑郁组(P<0.05);轻度抑郁组HADS-A评分、HADS-D评分高于无抑郁组(P<0.05),MMSE评分低于无抑郁组(P<0.05)。观察组外周血CDC42 mRNA、Treg细胞的表达水平低于对照组(P<0.05),外周血Th17细胞、Th17/Treg的表达水平高于对照组(P<0.05)。重度抑郁组Th17细胞、Th17/Treg表达水平高于其他组(P<0.05),Treg细胞表达水平低于另外组(P<0.05),中度抑郁组Th17细胞、Th17/Treg表达水平高于轻度抑郁组、无抑郁组(P<0.05),Treg细胞表达水平低于轻度抑郁组、无抑郁组(P<0.05),轻度抑郁组Th17细胞、Th17/Treg表达水平高于无抑郁组(P<0.05),Treg细胞表达水平低于无抑郁组(P<0.05)。观察组干预后HADS-A评分、HADS-D评分低于干预前(P<0.05),MMSE评分、ADL评分高于干预前(P<0.05)。观察组干预前后外周血CDC42 mRNA表达水平比较,差异无统计学意义(P>0.05)。观察组干预后外周血Th17细胞、Th17/Treg表达水平低于干预前(P<0.05),外周血Treg细胞表达水平高于干预前(P<0.05)。观察组患者外周血Th17细胞、Th17/Treg表达与HADS评分呈正相关(r=0.673、0.603,均P<0.05),外周血Treg细胞表达与HADS评分呈负相关(r=-0.586,P<0.05),外周血CDC42 mRNA与HADS评分无相关性(r=-0.375,P>0.05)。结论缺血性脑卒中患者外周血CDC42mRNA表达明显降低、Th17细胞表达明显升高,随着患者抑郁程度加重,Th17细胞表达逐渐升高,而CDC42mRNA表达与患者的抑郁程度无相关性,可通过合理的干预措施减轻抑郁情绪,防止病情加重。

血清Aβ1-42、P-Tau181和Hcy与帕金森病患者睡眠障碍的相关性

目的探讨血清Aβ1-42、P-Tau181和Hcy与帕金森病(PD)患者睡眠障碍的相关性。方法将80例PD患者根据匹兹堡睡眠质量指数(PSQI)评估结果分为睡眠正常组(<7分)和睡眠障碍组(≥7分)。采用单因素和多因素logistic回归分析血清Aβ1-42、P-Tau181和Hcy水平与PD患者睡眠障碍的相关性。采用受试者工作特征(ROC)曲线分析不同指标预测PD患者发生睡眠障碍的效能参数。结果单因素和多因素logistic回归分析发现血清Aβ1-42和Hcy分别是PD患者发生睡眠障碍的保护因素和独立危险因素(P<0.05)。血清Aβ1-42、Hcy水平预测PD伴睡眠障碍的AUC分别为0.757(95%CI:0.652~0.861)和0.796(95%CI:0.688~0.905)。结论PD患者血清Aβ1-42、Hcy水平与睡眠障碍密切相关,可作为临床诊断PD伴睡眠障碍的预测因子。

牛膝提取物含药血清对Aβ1-42诱导的神经元氧化应激和凋亡的调控机制研究

目的探讨牛膝提取物含药血清对β淀粉样蛋白1-42(amyloidβ-protein1-42,Aβ1-42)诱导的神经元氧化应激和凋亡的影响及作用机制。方法体外培养大鼠海马神经元,分为对照组,模型组(Aβ1-42诱导神经元),牛膝低、中、高剂量组(15、30、45μg/mL的牛膝提取物含药血清作用于Aβ1-42诱导的神经元),si-ZBTB20-AS1组[Aβ1-42诱导转染锌指和BTB结构域蛋白20的反义RNA小干扰RNA的神经元]和si-NC组(Aβ1-42诱导转染乱序无意义阴性序列的神经元)。ELISA法检测超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)含量,CCK-8法检测细胞存活率,流式细胞术检测细胞凋亡率,RT-qPCR法检测ZBTB20-AS1表达水平,Western blot法检测细胞增殖抗原Ki67和胱天蛋白酶-3(cysteine aspartic acid specific protease-3,Caspase-3)表达水平。结果与对照组比较,模型组SOD含量、细胞存活率、Ki67蛋白表达均降低(P<0.05),MDA含量、细胞凋亡率、BTB20-AS1表达、Caspase-3蛋白表达均升高(P<0.05)。与模型组比较,牛膝中、高剂量组SOD含量、细胞存活率、Ki67蛋白表达均升高(P<0.05),MDA含量、细胞凋亡率、BTB20-AS1表达、Caspase-3蛋白表达均降低(P<0.05)。与si-NC组比较,si-ZBTB20-AS1组SOD含量、细胞存活率、Ki67蛋白表达均升高(P<0.05),MDA含量、细胞凋亡率、BTB20-AS1表达、Caspase-3蛋白表达均降低(P<0.05)。结论牛膝提取物含药血清可能通过下调ZBTB20-AS1表达抑制Aβ1-42诱导的海马神经元氧化应激和凋亡。

细胞分裂周期蛋白42基因在肿瘤中的研究进展

细胞分裂周期蛋白42(cell division cycle 42,Cdc42)是小G蛋白Rho亚家族中的核心成员,最初在酿酒酵母中被发现。研究表明Cdc42可通过调控上皮形态和极性的发生,调节肌动球蛋白和微管细胞骨架的蛋白质的极化输送和脂质组成的变化,在细胞黏附、囊泡运输、凋亡、吞噬作用、细胞迁移和胞质分裂等细胞生理过程中发挥着关键作用[1]。

利用同异联系势分析法综合评价豫谷36、豫谷37和豫谷42

利用同异联系势分析方法,对2020~2021年国家华北夏谷区组谷子品种区域试验品种进行了分析,并对豫谷36、豫谷37和豫谷42进行分析评价,以期对谷子育种和生产有所帮助。

老年急性轻型缺血性脑卒中患者血清S100β蛋白、Aβ42表达水平与脑卒中后认知功能障碍的关系

目的 探讨老年急性轻型缺血性脑卒中(MIS)患者血清S100β蛋白、β-淀粉样蛋白(Aβ)42表达水平与脑卒中后认知功能障碍(PSCI)的相关性。方法 老年MIS患者91例按脑卒中3个月蒙特利尔认知评估(MoCA)量表评分分为PSCI组(MoCA评分<26分)39例与非PSCI组52例(MoCA评分≥26分)。比较两组入院时血清S100β蛋白、Aβ42水平,应用Logistic回归模型确定PSIC的独立影响因素,采用Pearson相关分析检验PSCI组血清S100β蛋白、Aβ42水平与MoCA评分的相关性,并应用受试者工作特征(ROC)曲线对S100β蛋白、Aβ42水平预测PSCI的能力进行评价。结果 相比非PSCI组,PSCI组年龄较大,糖化血红蛋白(HbA1c)水平较高,且血清S100β蛋白、Aβ42水平较高,差异有统计学意义(P<0.05)。多因素Logistic回归分析得出,年龄(OR=1.335)、血清S100β蛋白水平(OR=1.581)、血清Aβ42水平(OR=1.644)为PSCI的危险因素(P<0.05)。ROC曲线分析显示,入院时血清S100β蛋白、Aβ42水平预测PSCI的AUC分别为0.832、0.886,二者联合的AUC为0.944,相比单一指标均显著提高(P<0.05)。结论 血清S100β蛋白、Aβ42表达水平与老年MIS患者PSCI发生密切相关,二者联合可较好预测PSCI的发生。

棉花GhMYB42基因的克隆及原核表达

MYB转录因子对棉花的生长发育起到重要作用,而GhMYB42为MYB家族之一的转录因子同样具有一定的研究价值,因此,从棉花中克隆了GhMYB42基因的编码序列,并构建了原核表达载体。利用生物信息学方法对GhMYB42的核苷酸序列及氨基酸序列进行了分析,通过Gataway BP和LR反应,将GhMYB42基因的编码序列构建到原核表达载体pGEX-4T-1上,通过设置不同的IPTG诱导条件来确定IPTG诱导蛋白的最佳条件,最后利用Western Blot鉴定重组蛋白。结果显示,GhMYB42(XP_016732693.1)全长序列1508 bp,编码区长792 bp,编码263个氨基酸,预测分子量约为29.534 ku,等电点为5.18。氨基酸序列比对分析发现,MYB转录因子的序列相似率为80.62%,且GhMYB42蛋白N末端含有2个串联的SANT结构域,是一个R2R3转录因子。进化树分析结果显示,陆地棉MYB42蛋白与陆地棉中另一MYB蛋白(XP_012439547.1)相似性最高并在一个分支上。蛋白诱导时由于各个试验梯度结果差别不明显,因此,选择的条件为IPTG的终浓度0.2 mmol/L,温度37℃,时间3 h,蛋白溶解的温度和时间为37℃诱导3 h。Western Blot结果表明,重组蛋白的大小正确,最终成功获得了大小为55.54 ku的GhMYB42重组蛋白,后续将对该重组蛋白进行纯化及深入研究转录因子GhMYB42的功能。

西南麦区骨干亲本川麦42重要基因组区段的确定及其对衍生品种的遗传贡献

【目的】川麦42是利用人工合成六倍体小麦选育出的高产、广适的优异小麦品种,是西南麦区重要的骨干亲本,本研究通过明确川麦42重要基因组区段及其对衍生品种的遗传贡献,为西南麦区突破性品种培育提供分子设计依据。【方法】利用170个SSR和2268个DArT标记分析川麦42遗传组分在7个衍生品种中的分布与传递情况;根据已构建的遗传图谱和定位到的产量性状QTL,明确川麦42遗传组分对各个衍生品种的遗传贡献。【结果】川麦42遗传组分在7个一代衍生品种中分布与传递频率不同,其中川麦56、川麦58、川麦64、川麦104、川麦90和川麦91继承了50%以上的川麦42的遗传组分,平均为64%,高于理论值,而川麦92则低于25%。17条小麦染色体上的92个等位位点在川麦42衍生品种中具有较高的分布频率,得到稳定传递;对比已构建的川麦42遗传连锁图谱及其定位到的QTLs,发现位于2A、2B、4A、4D、5B、5D、5A、6D、7A和7D染色体上11个基因组区段与重要农艺性状QTL紧密连锁,其中4A、4D、5B、5D和7D染色体上川麦42单倍型可提高衍生品种的穗粒数、千粒重和小区产量;位于5B染色体Xgwm234~Xgwm371区段携带千粒重QTL,川麦42单倍型最高可增加千粒重2.21 g;位于4D、5D和7D染色体区段携带小区产量QTL,川麦42单倍型最高增产率分别为8.92%、6.33%、4.79%。【结论】携带产量性状增效QTL并且在衍生品种中能够高频传递的基因组区段是川麦42能够成为西南麦区骨干亲本的重要遗传基础,川麦42重要基因组区段的确定为西南麦区小麦骨干亲本选择及突破性品种的培育提供了重要的理论参考。

豆腐果苷对Aβ_(1-42)诱导阿尔茨海默病模型大鼠认知功能的影响

目的:探究豆腐果苷(HEL)对β淀粉样蛋白1-42(Aβ_(1-42))诱导阿尔茨海默病(AD)大鼠认知功能的影响。方法:24只SPF级健康雄性SD大鼠随机分成生理盐水(NS)组、Aβ_(1-42)+NS组、Aβ_(1-42)+HEL组、HEL组,每组6只。通过脑立体定位双侧海马区注射Aβ_(1-42)(5μg/μL)建立AD模型,注射3 d后Aβ_(1-42)+NS组和Aβ_(1-42)+HEL组分别给予生理盐水和豆腐果苷(50 mg/kg)灌胃治疗4周;作为对照,NS组和HEL组分别给予生理盐水和豆腐果苷(50 mg/kg)灌胃4周。治疗结束后通过Morris水迷宫实验对各组大鼠行为、认知能力进行评估;通过HE染色检测各组大鼠海马CA1区细胞的形态变化;采用免疫组化检测大鼠海马CA1区核因子-κB(NF-κB)表达情况;免疫印迹检测大鼠海马中淀粉前体样蛋白(APP)、NF-κB、肿瘤坏死因子(TNF-α)的表达水平。结果:(1)与NS组相比,Aβ_(1-42)+NS组大鼠逃逸潜伏期明显延长,穿越原平台次数和停留在原平台象限的时间均显著降低;海马CA1区细胞形态发生明显核固缩;APP、NF-κB、TNF-α表达显著升高(P<0.05)。(2)与Aβ_(1-42)+NS组相比,Aβ_(1-42)+HEL组大鼠逃逸潜伏期明显缩短,穿越原平台次数和原平台所在象限停留时间均明显增多。(3)海马CA1区细胞核固缩得到良好改善;APP、NF-κB、TNF-α表达明显降低(P<0.05)。(4)NS组和HEL组大鼠Morris水迷宫结果无显著差异,APP、NF-κB和TNF-α蛋白在海马CA1区均无明显变化。结论:豆腐果苷能够改善Aβ_(1-42)诱导AD大鼠认知功能,可能与抑制APP、NF-κB及TNF-α的蛋白表达有关。

Aβ42寡聚体对突触内外谷氨酸受体表达的影响

目的:通过体内外实验探讨阿尔茨海默病关键发病分子β-淀粉样蛋白42寡聚体(Aβ42Os)作用下离子型谷氨酸受体N-甲基-D-天冬氨酸受体(NMDAR)亚基(NR2A、NR2B和NR1)和代谢型谷氨酸受体5(mGluR5)在突触内外的表达分布变化。方法:(1)用不同浓度的Aβ42Os处理乳小鼠原代神经元,Western blot和免疫荧光染色检测原代神经元中mGluR5和NMDAR的表达和分布情况。(2)在C57BL/6小鼠侧脑室立体定位注射不同浓度的Aβ42Os,Western blot检测海马组织中mGluR5和NMDAR在突触内外的蛋白水平,以及mGluR5下游磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/AKT)信号通路相关蛋白、钙信号下游通路相关蛋白和突触相关蛋白的表达。结果:(1)高浓度Aβ42Os处理原代小鼠神经元增加mGluR5表达(P<0.01),减少NR2A、NR2B和NR1表达(P<0.01);引起mGluR5膜表面聚集,而使NR2A、NR2B和NR1膜表面表达分布减少。(2)高浓度Aβ42Os引起小鼠海马组织中突触mGluR5表达增加(P<0.01),NR2A(P<0.05)和NR2B(P<0.01)表达减少,突触外NR2B表达增加(P<0.01);抑制PI3K表达及AKT和细胞外信号调节激酶(ERK)磷酸化,过度激活钙/钙调蛋白依赖性蛋白激酶IIα(CaMKIIα);引起突触后致密蛋白95、亲棘蛋白(spinophilin)、突触小泡蛋白(synaptophysin)和微管相关蛋白2表达减少(P<0.01)。结论:(1)高浓度Aβ42Os引起神经元突触mGluR5过度聚集,NR2A、NR2B和NR1表达减少,而突触外NR2B表达增加。(2)高浓度Aβ42Os抑制PI3K/AKT和ERK信号通路,过度激活CaMKIIα通路,损伤突触结构。

缺血性脑小血管病患者血清3-NT、Aβ1-42、CX3CL1与认知功能障碍的相关性分析

目的探讨缺血性脑小血管病患者血清3-硝基酪氨酸(3-NT)、β淀粉样蛋白1-42(Aβ1-42)、趋化因子C-X3-C配体1(CX3CL1)与认知功能障碍的相关性。方法选取我院2022年12月至2023年12月收治的117例缺血性脑小血管病患者,分为认知正常组37例和认知障碍组80例,依据MoCA评分将认知障碍组分为轻度组23例、中度组27例、重度组30例,另选取30例同期健康体检者作为对照组。检测血清3-NT、Aβ1-42、CX3CL1水平,ROC曲线分析血清3-NT、Aβ1-42、CX3CL1检测诊断认知障碍的灵敏度和特异性。结果认知功能障碍组血清3-NT水平高于认知功能正常组和对照组,血清Aβ1-42、CX3CL1低于认知功能正常组和对照组(P<0.05);血清3-NT、Aβ1-42、CX3CL1异常表达与缺血性脑小血管病患者认知功能障碍有关(P<0.05);血清3-NT、Aβ1-42、CX3CL1联合检测诊断缺血性脑小血管病认知功能障碍的AUC值高于单项检测(Z_(3-NT-联合检测)=3.621,Z_(Aβ1-42-联合检测)=3.046,Z_(CX3CL1-联合检测)=2.075,P<0.05)。结论缺血性脑小血管病患者认知功能障碍与血清3-NT升高、Aβ1-42、CX3CL1降低有关。