ONECUT2高表达介导胃癌复发患者5-FU化疗耐药

目的:探究One cut结构域家族成员2(ONECUT2)是否可以作为对5-FU耐药的胃癌复发患者的治疗靶点。方法:利用癌症基因组图谱(TCGA)数据库分析ONECUT2基因在胃癌患者及胃癌复发患者的表达情况。利用基因集富集分析(GSEA)评估TCGA数据库中ONECUT2表达量与药物代谢相关生物学过程的相关性。利用CCK-8细胞毒性实验评估胃癌细胞敲低或过表达ONECUT2对5-FU的耐药情况。分析30例胃癌术后复发患者ONECUT2表达量与5-FU治疗效果的相关性。结果:TCGA数据库分析显示,在经受过化疗且复发的胃癌患者中,ONECUT2高表达的患者无病间隔期(disease-free interval,DFI)更短。GSEA分析结果表明,ONECUT2高表达与异生药物代谢通路呈正相关,这提示可能与胃癌患者的耐药相关。体外实验中,敲低ONECUT2降低胃癌细胞对5-FU的半数抑制浓度(IC_(50))值;反之,过表达ONECUT2增加细胞对5-FU的IC_(50)值。30例胃癌复发患者对5-FU的药物敏感性与ONECUT2表达量相关。结论:胃癌复发患者的ONECUT2表达量更高,ONECUT2高表达与胃癌复发患者的5-FU耐药相关,可能是潜在的治疗靶点。

Instability mechanism of mining roadway passing through fault at different angles in kilometre-deep mine and control measures of roof cutting and NPR cables

The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and field experiments in the context of the Daqiang coal mine located in Shenyang, China. The stability control countermeasure of "pre-splitting cutting roof + NPR anchor cable"(PSCR-NPR) is simultaneously proposed. According to the different deformation characteristics of the roadway, the faults are innovatively classified into three types, with α of type I being 0°-30°, α of type II being 30°-60°, and α of type III being 60°-90°. The full-cycle stress evolution paths during mining roadway traverses across different types of faults are investigated by numerical simulation. Different pinch angles α lead to high stress concentration areas at different locations in the surrounding rock. The non-uniform stress field formed in the shallow surrounding rock is an important reason for the instability of the roadway. The pre-cracked cut top shifted the high stress region to the deep rock mass and formed a low stress region in the shallow rock mass. The high prestressing NPR anchor cable transforms the non-uniform stress field of the shallow surrounding rock into a uniform stress field. PSCR-NPR is applied in the fault-through roadway of Daqiang mine. The low stress area of the surrounding rock was enlarged by 3-7 times, and the cumulative convergence was reduced by 45%-50%. It provides a reference for the stability control of the deep fault-through mining roadway.

Hole cleaning evaluation and installation spacing optimization of cuttings bed remover in extended-reach drilling

In extended-reach or long-horizontal drilling,cuttings usually deposit at the bottom of the annulus.Once cuttings accumulate to a certain thickness,complex problems such as excessive torque and drag,tubing buckling,and pipe stuck probably occur,which results in a lot of non-productive time and remedial operations.Cuttings bed remover can efficiently destroy deposited cuttings in time through hydraulic and mechanical stirring effects.This paper aims to build a method for hole cleaning evaluation and installation spacing optimization of cuttings bed remover to improve the wellbore cleaning effect.Firstly,a Computational Fluid Dynamics approach with Eulerian—Eulerian multiphase model was utilized to investigate the mechanism of cuttings transportation,and a new type of cuttings bed remover was designed.Next,an evaluation method of hole cleaning effect of remover was established.After that,the effects of several drilling parameters on hole cleaning including flow rate of drilling fluid,rotational speed of drillpipe,rate of penetration,wellbore size,rheological property of drilling fluid,and remover eccentricity on the performance of cuttings bed remover were investigated.The results demonstrate that the new type of remover with streamline blade performs better than conventional removers.The efficiency of hole cleaning is greatly improved by increasing the rotational speed of drillpipe,flow rate of drilling fluid,remover eccentricity,and 6 rpm Fann dial reading for drilling fluid.While higher rate of penetration and large wellbore size result in worse hole cleaning.These findings can serve as an important guide for the structure optimization design of cuttings bed remover and installation spacing of removers.

Yield and Nutritive Values of Semi- and Non-Fall Dormant Alfalfa Cultivars under Late-Cutting Schedule in California’s Central Valley

California is one of the major alfalfa (Medicago sativa L) forage-producing states in the U.S, but its production area has decreased significantly in the last couple of decades. Selection of cultivars with high yield and nutritive value under late-cutting schedule strategy may help identify cultivars that growers can use to maximize yield while maintaining area for sustainable alfalfa production, but there is little information on this strategy. A field study was conducted to determine cumulative dry matter (DM) and nutritive values of 20 semi- and non-fall dormant (FD) ratings (FD 7 and FD 8 - 10, respectively) cultivars under 35-day cut in California’s Central Valley in 2020-2022. Seasonal cumulative DM yields ranged from 6.8 in 2020 to 37.0 Mg·ha−1 in 2021. Four FD 8 - 9 cultivars were the highest yielding with 3-yrs avg. DM greater than the lowest yielding lines by 46%. FD 7 cultivar “715RR” produced the highest crude protein (CP: 240 g·Kg−1) while FD 8 cultivar “HVX840RR” resulted in the highest neutral detergent fiber digestibility (NDFD: 484 g·Kg−1, 7% greater than the top yielding cultivars) but with DM yield intermediate. Yields and NDFD correlated positively but weakly indicating some semi- and non-FD cultivars performing similarly. These results suggest that selecting high yielding cultivars under 35-day cutting schedule strategy can be used as a tool to help growers to maximize yield while achieving good quality forages for sustainable alfalfa production in California’s Central Valley.

Unraveling engineering disturbance effects on deformation in red-bed mudstone railway cuttings:incorporating crack-facilitated moisture diffusion

Red-bed mudstone, prevalent in southwest China, poses a formidable challenge due to its hydrophilic clay minerals, resulting in expansion, deformation, and cracking upon exposure to moisture. This study addresses uplift deformation disasters in high-speed railways by employing a moisture diffusion-deformation-fracture coupling model based on the finite-discrete element method(FDEM). The model integrates the influence of cracks on moisture diffusion. The investigation into various excavation depths reveals a direct correlation between depth and the formation of tensile cracks at the bottom of the railway cutting. These cracks expedite moisture migration, significantly impacting the temporal and spatial evolution of the moisture field. Additionally, crack expansion dominates hygroscopic deformation, with the lateral coordinate of the crack zone determining peak vertical displacement. Furthermore, key factors influencing deformation in railway cuttings, including the swelling factor and initial moisture content at the bottom of the cutting, are explored. The number of tensile and shear cracks increases with greater excavation depth, particularly concerning shear cracks. Higher swelling factors and initial moisture contents result in an increased total number of cracks, predominantly shear cracks. Numerical calculations provide valuable insights, offering a scientific foundation and directional guidance for the precise prevention, control, prediction, and comprehensive treatment of mudstone-related issues in high-speed railways.

Assessing cutter-rock interaction during TBM tunnelling in granite:Large-scale standing rotary cutting tests and 3D DEM simulations

The widespread utilisation of tunnel boring machines(TBMs)in underground construction engineering requires a detailed investigation of the cutter-rock interaction.In this paper,we conduct a series of largescale standing rotary cutting tests on granite in conjunction with high-fidelity numerical simulations based on a particle-type discrete element method(DEM)to explore the effects of key cutting parameters on the TBM cutter performance and the distribution of cutter-rock contact stresses.The assessment results of cutter performance obtained from the cutting tests and numerical simulations reveal similar dependencies on the key cutting parameters.More specifically,the normal and rolling forces exhibit a positive correlation with penetration but are slightly influenced by the cutting radius.In contrast,the side force decreases as the cutting radius increases.Additionally,the side force shows a positive relationship with the penetration for smaller cutting radii but tends to become negative as the cutting radius increases.The cutter's relative effectiveness in rock breaking is significantly impacted by the penetration but shows little dependency on the cutting radius.Consequently,an optimal penetration is identified,leading to a low boreability index and specific energy.A combined Hertz-Weibull function is developed to fit the cutter-rock contact stress distribution obtained in DEM simulations,whereby an improved CSM(Colorado School of Mines)model is proposed by replacing the original monotonic cutting force distribution with this combined Hertz-Weibull model.The proposed model outperforms the original CSM model as demonstrated by a comparison of the estimated cutting forces with those from the tests/simulations.The findings from this work that advance our understanding of TBM cutter performance have important implications for improving the efficiency and reliability of TBM tunnelling in granite.

Ground response and failure mechanism of gob-side entry by roof cutting with hard main roof

This study is the result of long-term efforts of the authors’team to assess ground response of gob-side entry by roof cutting(GSERC)with hard main roof,aiming at scientific control for GSERC deformation.A comprehensive field measurement program was conducted to determine entry deformation,roof fracture zone,and anchor bolt(cable)loading.The results indicate that GSERC deformation presents asymmetric characteristics.The maximum convergence near roof cutting side is 458 mm during the primary use process and 1120 mm during the secondary reuse process.The entry deformation is closely associated with the primary development stage,primary use stage,and secondary reuse stage.The key block movement of roof cutting structure,a complex stress environment,and a mismatch in the supporting design scheme are the failure mechanism of GSERC.A controlling ideology for mining states,including regional and stage divisions,was proposed.Both dynamic and permanent support schemes have been implemented in the field.Engineering practice results indicate that the new support scheme can efficiently ensure long-term entry safety and could be a reliable approach for other engineering practices.

Cutting-edge Technological Innovation Outcome Displayed at 2024 Beijing Science and Technology Week

The 2024 National Science and Technology Week and Beijing Science and Technology Week opened in Shougang Park in Shijingshan District from May 25 to June 1.Under the theme of“Carrying forward the spirit of scientists and inspiring societal innovation,”this event focused on the new-generation IT technology,medical health,energy and technology,modern agriculture and intelligent manufacturing industries.

Road Layout Cuts Volume Evaluation by Electrical Resistivity Tomography: Case Study of Gagnoa-Gueyo-Bamenadou Road Project

A study of excavated material on the Gagnoa-Guéyo-Bamenadou road project in southwest Côte d’Ivoire was carried out using electrical resistivity tomography with a dipole-dipole configuration. This study aimed to determine the nature and volume of the studied cuts. Based on the cumulative distances of the longitudinal sections of the road alignment superimposed on the tomographic profiles, a cumulative volume of 104681 m3 of material was determined. This volume comprises 88557 m3 of soft cuts and 16,124 m3 of rocky cuts, which can be reused in specific embankment zones. This work may, therefore be useful in the characterization of cuts in a preliminary design study, in order to anticipate changes during the road’s development and asphalting.

Obstacles to the Integrated Care of Children Aged 6 to 59 Months Suffering from Acute and Severe Malnutrition at the Chu-Me and HATC of N’Djamena/Chad

Introduction: the problem of Severe Acute Malnutrition (SAM) and its consequences concern and challenge all social actors worldwide. The objective of the study was to identify the real obstacles that actors face in the integrated management of children aged 6 - 59 months suffering from SAM at the University Hospital of Mother and Child (CHUME) and the Chad-China Friendship Hospital (HATC) of N’Djamena. Methodology: this is a cross-sectional descriptive and interpretative study conducted from January to October 2023 at the CHUME and HATC of N’Djamena. It is based on questionnaires and direct observation of two hundred and thirty-six (236) parents or guardians of malnourished children admitted to these health facilities. All 236 agreed to participate freely in this study. Results: it appears from this study that the obstacles to the integrated management of malnourished children were: poor care-care relationship (26.7%) permanent product breaks (22.9%), the direct costs of services ranged from 30,000 to 60,000 FCFA (41.53%), drugs used for the treatment of patients came from the street (66.10%), malaria and anemia occupy an important place (27.5%), 57.2% respondents had monthly income below 60,000 CFAF. Conclusion: the present study carried out has identified the real bottlenecks to the integrated management of children suffering from SAM in the therapeutic nutritional units of the city of N’Djamena. .

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Factors Associated with Acute Respiratory Infections in Children Aged 0 - 5 Years in the Yénawa District of Cotonou (Benin) in 2023

Introduction: Acute respiratory infections remain one of the main causes of mortality in children aged 0 to 5. This work aimed to study the associated factors with the occurrence of acute respiratory infections in children 0 to 5 years old in Yénawa, Cotonou in 2023. Subjects and Method: It was an analytical cross-sectional study of children aged 0 - 5 years and their mothers in Yénawa, selected by four-degree random sampling. The sampling size, calculated using the Schwartz formula, was 126 children and 126 mothers. The dependent variable was the occurrence of acute respiratory infections. The independent variables were classified into four groups: socio-demographic and economic characteristics, behavioral factors, child-related factors, and environmental factors. Data collected by observation and questionnaire survey were analyzed using STATA version 15 software. Associated factors were investigated by bivariate analysis and multiple logistic regression, at the 5% significance level. Results: A total of 126 children aged 0 - 5 years and 126 mothers were surveyed, aged 23.5 (11 - 36) months and 30 (18 - 48) years respectively. The prevalence of acute respiratory infections was 74.60% (CI95% = 66.89 to 82.30). The associated factors were the mother’s age between 18 and 28 (OR = 10.77;CI95% = 1.89 to 61.27;p = 0.007), the use of charcoal/wood for cooking (OR = 7.36;IC = 1.99 to 27.10;p = 0.003)), children's poor personal hygiene (OR = 8.87;IC = 2.92 to 26.97;p 0.001)), and cohabitation with domestic animals (OR = 7.27;IC = 1.67 to 31.71;p = 0.015). Conclusion: Communicating with mothers about the factors identified will help reduce the prevalence of acute respiratory infections in children aged 0 to 5.

The Protective Effects of Flavonoids from Scutellaria Baicalensis Georgi Stems and Leaves on Oligodendrocyte Damage Induced by Aβ1-42

Aim: This study aimed to investigate the protective effects of flavonoids from the stem and leaves of Scutellaria baicalensis Georgi (SSFs) against Aβ1-42-induced oligodendrocytes (OL) damage. Methods: Immunofluorescence was used for the detection of myelin-associated glycoprotein (MAG), a characteristic protein of rat oligodendrocytes (OLN-93 cells). To evaluate the potential protective effects of SSFs on OLN-93 cells injured by Aβ1-42, an injury model was established by subjecting OLN-93 cells to Aβ1-42 exposed. Cell morphology was examined using an inverted microscope, while cell viability was assessed using the colorimetric method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Additionally, lactate dehydrogenase (LDH) was measured using the pyruvic acid reduction assay. The Ginkgo biloba leaf extract (GBE) injection was used as a positive control. Results: A total of >95% of the MAG immunofluorescence-positive cells were identified as oligodendrocytes. Gradually increasing concentrations of SSFs impaired the cells, and the maximum nondetrimental dose for OLN-93 cells was 75 mg/L. This study assessed the effects of SSFs on OLN-93 cells damaged by Aβ1-42. The results indicated that SSFs significantly improved OLN-93 cell morphological abnormal changes, increased the OLN-93 cell survival rate, and reduced LDH release. Conclusion: SSFs can alleviate Aβ1-42-induced damage of OL.

基于SPI-RRV指数中国气象干旱及其风险时空演变特征研究

为全面揭示变化环境下我国多维气象干旱特征,耦合气象干旱指数(SPI)和可靠性-回弹性-脆弱性(RRV)指数,提出了一种基于SPI-RRV指数的干旱风险评价方法,定量评价了中国气象干旱及其风险的时空演变特征。结果表明:SPI-RRV指数具有特征稳定和时空可比性强的特点,能够较为准确地评估气象干旱风险时空演变特征;南方平均干旱栅格比、干旱月占比和频次大于北方,湿润区和半湿润区干旱历时短、烈度大,半干旱区和干旱区干旱历时长、烈度相对较小;干旱高风险区转移具有显著年代际变化规律,空间上从西北向西南地区转移。

深部煤储层孔裂隙结构对煤层气赋存的影响-以鄂尔多斯盆地东缘大宁-吉县区块为例

深部煤储层孔隙–裂缝结构对深部煤层气资源潜力评价和勘探开发具有重要意义。选取鄂尔多斯盆地东缘大宁–吉县区块DJ57井本溪组5个煤岩样品为研究对象,在煤岩煤质参数测试的基础上,采用气体吸附法、高压压汞法和微米CT扫描等测试手段,对深部煤储层中的纳米级孔隙-微米级裂缝进行多尺度定量表征,综合评价不同尺度的孔裂隙结构特征。再结合渗透率和甲烷等温吸附试验,探讨了微观孔裂隙对深部煤储层中煤层气的赋存和渗流的影响。研究结果表明:基于多种孔隙表征方法对深部煤储层孔裂隙进行多尺度定量表征,其孔裂隙体积分布类型主要以“U”型为主,呈现出微孔与微裂缝并存双峰态,主要集中在0.3~1.5 nm和>100μm的范围内。其中,微孔(<2 nm)、介孔(2~50 nm)、宏孔(50 nm~10μm)和微裂缝(>10μm)体积平均分别占总孔裂隙体积的80.18%,6.70%,1.65%和11.47%。随着微孔发育而吸附气量呈增大的趋势,微孔可以提供大量吸附点位,为深部煤层气的吸附和赋存提供场所。随着微裂缝发育而游离气量呈增大的趋势,微裂缝可以提供大量储集空间,为深部煤层气的富集提供空间条件。此外,微裂缝在三维空间中相互连通,形成网状结构,连通性强。随着微裂缝越发育,煤储层渗透率越大,微裂缝增强了煤层气的渗流能力。纳米级孔隙和微米级裂隙发育特征分别控制着深部煤层气吸附能力和开发潜力。

水资源-能源-粮食-生态系统耦合协调及驱动力分析

为加深对我国水资源、能源、粮食、生态系统协同演变趋势的认识,构建水资源-能源-粮食-生态多维系统指标体系,运用耦合协调度模型对我国2005—2020年水资源-能源-粮食-生态系统耦合协调度进行评价,并采用多因素归因分析法进行驱动力分析。结果表明:我国水资源-能源-粮食-生态系统耦合协调度从2005年的0.55增长到2020年的0.84,各地区耦合协调度从勉强协调发展水平过渡到中级协调发展水平,各子系统对耦合协调度上升的驱动分别经历了由粮食子系统到生态子系统再到水资源子系统主导的过程;能源子系统的贡献率虽然比较小,但是未来可能是各地区提升水资源-能源-粮食-生态系统多维系统协调发展水平的突破口。

基于DEMATEL-ISM的水利工程EPC项目价值增值机理研究

采用设计-采购-施工(engineering-procurement-construction,EPC)总承包模式的水利工程项目日益增多,研究其价值增值机理有利于总承包方做好项目的价值管理。从水利工程EPC项目的价值链分析入手,基于文献和专家访谈得到23个价值增值影响因素。采用问卷调查方式得到各因素间的影响程度评分,用决策实验和评估实验(decision-making trial and evaluation laboratory,DEMATEL)法计算了各因素的中心度和原因度,结合解释结构模型(interpretative structural modeling,ISM)对数据进行分析,将价值增值因素划分为6类,构建了水利工程EPC项目价值增值的递阶模型,探究和揭示了项目价值增值的路径和机理。研究结果对水利工程EPC总承包方制订管理策略有一定启示作用。

基于混合式教学的“教-学-评”一体化实验教学体系探索

实验能力是医学专业研究生的重要科研能力,实验能力的培养与实验教学的方法与质量密切相关。文章针对传统实验教学受到时间和空间限制且评价指标较为单一的现状,提出构建基于线上自主学习和现场实践相结合的“教-学-评”一体化实验教学体系,建立覆盖课前线上自主学习、课堂现场实践、课后作业提交与考核教学全过程的评价体系,以评促学,以评促教,通过评价反馈激发学生的学习热情,改进教学内容和方法,不断探索与完善实验教学体系,提高实验教学质量,以期为培养具有实践能力与创新精神的医学科研人才发挥积极作用。

基于“心-脉-神”互言探讨肝心同治冠心病合并抑郁(双心疾病)的理论研究

双心疾病作为“血脉之心”与“神明之心”同病的复合疾病,已经成为现代社会影响人类健康的主流问题之一,其中的冠心病合并抑郁属于临床中常见的发病类型。冠心病是一种严重威胁健康的心血管疾病,焦虑和抑郁是其不良预后的潜在危险因素。冠心病合并抑郁属中医“胸痹”“郁证”范畴,“心藏脉,脉舍神”,心脏对生命活动具有重要的控制和调节作用,“从心论治”使机体心主神明、心主血脉功能正常发挥。心血管疾病与情志病是密不可分的,胸痹患者心脉不畅,肝失疏泄,痰瘀互结,气机郁滞加重,由此引发情志的改变。双心疾病与中医的“心主血脉”“心主神明”“肝主藏血”“肝主疏泄”功能失常密切相关,“心”与“肝”的状态失衡是导致疾病进展的主要因素,故“肝心同治”是调节关键病机-肝心失调的必由之法,以疏肝解郁、调气和血为主。基于对“从心论治”“心-脉-神”与“肝心同治”的理论探讨,结合现代科学技术,旨在为防治冠心病合并抑郁提供新的思路与机制预测。

基于UPLC-QTOF-MS解析苦荞黄酮组成及药理学网络分析

为优化苦荞黄酮提取工艺并明确其具体成分结构和含量及药理作用,本研究以四川省凉山彝族自治州甘洛县优质苦荞为研究对象,对超声提取苦荞黄酮工艺进行了优化,采用超高效液相色谱-四级杆-飞行时间质谱(UPLC-QTOF-MS)对主要黄酮成分进行结构鉴定,并采用超高效液相色谱-三重四级杆质谱联用仪对鉴定到的黄酮进行准确定量,同时利用中药系统药理学(TCMSP)系统分析其网络药理学特性。结果表明,超声辅助乙醇提取苦荞黄酮的最优条件为乙醇浓度90%(V/V)、超声功率140 W、超声温度70℃、超声时间60 min、提取溶剂与苦荞原料比50∶1(mL·g^(-1)),该条件下,提取液中共鉴定到黄酮16种,其中芦丁、表儿茶素和儿茶素含量分别达到115.81、72.99和23.08μg·mL^(-1)。这16种黄酮在防治心血管疾病、慢性炎症性疾病上具有重要作用。本研究可为苦荞精深加工综合利用尤其是功能性苦荞产品开发利用奠定基础。