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Cellular and Molecular Mechanism of Cell Proliferation in Human Gastric Cancer Drug-Resistant Cells After Hyperthermia and Cisplatin: Role of mRNAs and Long-Non-coding RNAs. 高热和顺铂作用下人胃癌耐药细胞增殖的细胞和分子机制:mRNA 和长非编码 RNA 的作用。
IF 1.2 Pub Date : 2022-05-01 DOI: 10.5152/tjg.2022.20845
Firoozeh Abolhasani Zadeh, Mina AkbariRad, HuoJun Lian, Ying Wei, Jing Yang, Xiaoke Feng, Reza Akhavan-Sigari

Background: Since thermo-chemotherapy was suggested as an effective treatment for gastric cancer, we aimed to evaluate the effects of hyperthermia combined with cisplatin (DDP) on the inhibition of human gastric cancer drug-resistant cells in vitro and explore its possible mechanisms.

Methods: SGC-7901/DDP cells were cultured and divided into control, cisplatin, hyperthermia, and hyperthermia combined with cispla- tin groups. Hyperthermia was done at 42°C, 44°C, 46°C, 48°C, and 50°C for 12 h, 24 h, 36 h; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay detected the proliferation of SGC-7901/DDP at different time and temperature, and the apoptotic rate of SGC-7901/DDP cells was evaluated by using Annexin staining assay. High-throughput Chromatin immunoprecipitation (ChIP)- seq was applied to test long non-coding RNA expression in SGC-7901/DDP cells. Then, real-time fluorescence quantitative polymerase chain reaction was used to verify the expression of long non-coding RNA in all groups.

Results: Double staining showed that hyperthermia combined with cisplatin increased the rate of early apoptosis of SGC-7901/DDP cells. Long non-coding RNA high-throughput ChIP-seq showed a significantly larger amount of long non-coding RNAs and mRNAs in the cells treated with hyperthermia combined cisplatin group in comparison with the control group. We observed that the upregulated mRNAs and long non-coding RNAs were highly related to immune system response and CD95 signaling pathway in nucleus, and down- regulated mRNAs and long non-coding RNA were highly related to Mammalian target of rapamycin (mTOR) and Tumor necrosis factor (TNF) receptor signaling pathway in cytoplasm.

Conclusion: Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.

背景:由于热化疗被认为是治疗胃癌的一种有效方法,我们旨在评估热化疗联合顺铂(DDP)在体外对人胃癌耐药细胞的抑制作用,并探讨其可能的机制:方法:培养 SGC-7901/DDP 细胞,将其分为对照组、顺铂组、热疗组和热疗联合顺铂组。热疗温度分别为42℃、44℃、46℃、48℃和50℃,时间分别为12小时、24小时和36小时;3-(4,5-二甲基噻唑-2-基)-2,5-二苯基- 2H-溴化四氮唑(MTT)检测不同时间和温度下SGC-7901/DDP细胞的增殖情况,Annexin染色检测SGC-7901/DDP细胞的凋亡率。应用高通量染色质免疫沉淀(ChIP)- seq检测SGC-7901/DDP细胞中长非编码RNA的表达。然后,采用实时荧光定量聚合酶链反应来验证各组长非编码 RNA 的表达:结果:双重染色显示,热疗联合顺铂增加了 SGC-7901/DDP 细胞的早期凋亡率。长非编码 RNA 高通量 ChIP-seq 结果显示,与对照组相比,热疗联合顺铂治疗组细胞中的长非编码 RNA 和 mRNA 数量明显增加。我们观察到,上调的mRNA和长非编码RNA与细胞核中的免疫系统反应和CD95信号通路高度相关,而下调的mRNA和长非编码RNA与细胞质中的哺乳动物雷帕霉素靶标(mTOR)和肿瘤坏死因子(TNF)受体信号通路高度相关:结论:热疗联合顺铂可逆转人胃癌耐药细胞中大量mRNA和长非编码RNA的表达。抑制人胃癌耐药细胞增殖的分子机制可能与CD95、mTOR和TNF受体信号通路中长非编码RNA和mRNA的上调有关。
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引用次数: 0
Deep learning techniques to classify agricultural crops through UAV imagery: a review. 通过无人机图像对农作物进行分类的深度学习技术:综述。
IF 4.5 Pub Date : 2022-01-01 Epub Date: 2022-03-05 DOI: 10.1007/s00521-022-07104-9
Abdelmalek Bouguettaya, Hafed Zarzour, Ahmed Kechida, Amine Mohammed Taberkit

During the last few years, Unmanned Aerial Vehicles (UAVs) technologies are widely used to improve agriculture productivity while reducing drudgery, inspection time, and crop management cost. Moreover, they are able to cover large areas in a matter of a few minutes. Due to the impressive technological advancement, UAV-based remote sensing technologies are increasingly used to collect valuable data that could be used to achieve many precision agriculture applications, including crop/plant classification. In order to process these data accurately, we need powerful tools and algorithms such as Deep Learning approaches. Recently, Convolutional Neural Network (CNN) has emerged as a powerful tool for image processing tasks achieving remarkable results making it the state-of-the-art technique for vision applications. In the present study, we reviewed the recent CNN-based methods applied to the UAV-based remote sensing image analysis for crop/plant classification to help researchers and farmers to decide what algorithms they should use accordingly to their studied crops and the used hardware. Fusing different UAV-based data and deep learning approaches have emerged as a powerful tool to classify different crop types accurately. The readers of the present review could acquire the most challenging issues facing researchers to classify different crop types from UAV imagery and their potential solutions to improve the performance of deep learning-based algorithms.

在过去几年里,无人驾驶飞行器(UAV)技术被广泛应用于提高农业生产率,同时减少繁重的劳动、检查时间和作物管理成本。此外,它们还能在几分钟内覆盖大片区域。由于技术进步显著,基于无人机的遥感技术越来越多地用于收集有价值的数据,这些数据可用于实现许多精准农业应用,包括作物/植物分类。为了准确处理这些数据,我们需要强大的工具和算法,如深度学习方法。最近,卷积神经网络(CNN)已成为图像处理任务的强大工具,取得了令人瞩目的成果,成为视觉应用领域最先进的技术。在本研究中,我们回顾了最近应用于基于无人机的作物/植物分类遥感图像分析的基于卷积神经网络的方法,以帮助研究人员和农民根据他们研究的作物和使用的硬件来决定应该使用哪种算法。融合不同的无人机数据和深度学习方法已成为准确分类不同作物类型的有力工具。通过本综述,读者可以了解研究人员在利用无人机图像对不同作物类型进行分类时所面临的最具挑战性的问题,以及提高基于深度学习的算法性能的潜在解决方案。
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引用次数: 0
Large-scale osteocyte lacunar morphological analysis of transiliac bone in normal and osteoporotic premenopausal women 绝经前正常和骨质疏松妇女髂骨的骨细胞腔隙形态分析
Pub Date : 2021-12-14 DOI: 10.1101/2021.12.13.21267731
Elliott Goff, A. Cohen, E. Shane, R. Recker, G. Kuhn, R. Müller
Bone's adaptation ability is governed by the network of embedded osteocytes that inhabit individual crevasses called lacunae. The morphology of these lacunae and their resident osteocytes are known to change with age and diseases such as postmenopausal osteoporosis. However, it is unclear whether alterations in lacunar morphology are present in younger populations with osteoporosis. To investigate this, we implemented a previously validated methodology to image and quantify the three-dimensional morphometries of lacunae on a large scale (26.2 million cells) with ultra-high-resolution micro-computed tomography (microCT) in transiliac bone biopsies from three groups of premenopausal women: control n=39; idiopathic osteoporosis (IOP) n=45; idiopathic low BMD (ILBMD) n=19. Important lacunar morphometric parameters were measured in both trabecular and cortical bone: lacunar density (Lc.N/BV), lacunar porosity (Lc.TV/BV), lacunar number (Lc.N), lacunar volume (Lc.V), lacunar surface area (Lc.S), lacunar alignment (Lc.{theta}), lacunar stretch (Lc.St), lacunar oblateness (Lc.Ob), lacunar equancy (Lc.Eq), and lacunar sphericity (Lc.Sr). These were then compared against each other and also with previously measured tissue morphometries including: bone volume density (BV/TV), trabecular separation (Tb.Sp), trabecular number (Tb.N), and trabecular thickness (Tb.Th), structure model index (SMI), cortical porosity (Ct.Po) and cortical pore spacing (Ct.Sp). We detected no differences in lacunar morphology between the IOP, ILBMD and healthy premenopausal women. In contrast, we did find significant differences between lacunar morphologies in cortical and trabecular regions within all three groups, which was consistent with our previous findings on a subgroup of the healthy group. Furthermore, we discovered strong correlations between Lc.Sr from both trabecular and cortical regions with the measured BV/TV. The findings and comprehensive lacunar dataset we present here will be a crucial foundation for future investigations of the relationship between osteocyte lacunar morphology and disease.
骨的适应能力是由嵌入的骨细胞网络控制的,这些骨细胞居住在称为骨陷窝的单个裂缝中。这些腔隙及其骨细胞的形态会随着年龄和疾病(如绝经后骨质疏松症)而改变。然而,尚不清楚腔隙形态的改变是否存在于年轻骨质疏松症人群中。为了研究这一点,我们采用了一种先前经过验证的方法,利用超高分辨率显微计算机断层扫描(microCT)对三组绝经前妇女的经髂骨活检进行了大规模(2620万个细胞)的腔隙三维形态成像和量化:对照组n=39;特发性骨质疏松症(IOP) n=45;特发性低骨密度(ILBMD) n=19。测量骨小梁和骨皮质的重要腔隙形态测量参数:腔隙密度(Lc. n /BV)、腔隙孔隙度(Lc. tv /BV)、腔隙数量(Lc. n)、腔隙体积(Lc. v)、腔隙表面积(Lc. s)、腔隙对准度(Lc.{θ})、腔隙拉伸度(Lc. st)、腔隙平坦度(Lc. ob)、腔隙等距(Lc. eq)和腔隙球形度(Lc. sr)。然后将这些数据相互比较,并与先前测量的组织形态测量进行比较,包括:骨体积密度(BV/TV)、小梁分离(Tb.Sp)、小梁数量(Tb.N)和小梁厚度(Tb.Th)、结构模型指数(SMI)、皮质孔隙度(Ct.Po)和皮质孔隙间距(Ct.Sp)。我们在IOP、ILBMD和健康绝经前妇女之间没有发现腔隙形态的差异。相比之下,我们确实发现在所有三组中,皮层和小梁区域的腔隙形态存在显著差异,这与我们之前在健康组亚组中的发现一致。此外,我们发现Lc。小梁和皮质区的Sr与测量的BV/TV。我们在这里提出的研究结果和全面的腔隙数据集将为未来研究骨细胞腔隙形态与疾病之间的关系奠定重要的基础。
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引用次数: 10
Multidirectional basketball activities load different regions of the tibia: A subject-specific muscle-driven finite element study. 多向篮球活动对胫骨不同区域的负荷:一项受试者特定肌肉驱动的有限元研究。
Pub Date : 2021-06-20 DOI: 10.31224/osf.io/5c8ba
Chenxi Yan, Ryan J. Bice, Jeffrey W. Frame, S. Warden, M. Kersh
The tibia is a common site for bone stress injuries, which are believed to develop from microdamage accumulation to repetitive sub-yield strains. There is a need to understand how the tibia is loaded in vivo to understand how bone stress injuries develop and design exercises to build a more robust bone. Here, we use subject-specific, muscle-driven, finite element simulations of 11 basketball players to calculate strain and strain rate distributions at the midshaft and distal tibia during six activities: walking, sprinting, lateral cut, jumping after landing, changing direction from forward-to-backward sprinting, and changing direction while side shuffling. Maximum compressive strains were at least double maximum tensile strains during the stance phase of all activities. Sprinting and lateral cut had the highest compressive (-2862 ± 662 με and -2697 ± 495 με, respectively) and tensile (973 ± 208 με and 942 ± 223 με, respectively) strains. These activities also had the highest strains rates (peak compressive strain rate = 64,602 ± 19,068 με/s and 37,961 ± 14,210 με/s, respectively). Compressive strains principally occurred in the posterior tibia for all activities; however, tensile strain location varied. Activities involving a change in direction increased tensile loads in the anterior tibia. These observations may guide preventative and management strategies for tibial bone stress injuries. In terms of prevention, the strain distributions suggest individuals should perform activities involving changes in direction during growth to adapt different parts of the tibia and develop a more fatigue resistant bone. In terms of management, the greater strain and strain rates during sprinting than jumping suggests jumping activities may be commenced earlier than full pace running. The greater anterior tensile strains during changes in direction suggest introduction of these types of activities should be delayed during recovery from an anterior tibial bone stress injury, which have a high-risk of healing complications.
胫骨是骨应力损伤的常见部位,据信这种损伤从微损伤积累发展为重复的亚屈服应变。需要了解胫骨在体内的负载情况,以了解骨应力损伤是如何发展的,并设计训练来构建更强健的骨骼。在这里,我们使用针对11名篮球运动员的特定主题、肌肉驱动的有限元模拟来计算六项活动中胫骨中段和远端的应变和应变速率分布:步行、短跑、侧向切入、落地后跳跃、从前向冲刺变为后向冲刺以及侧边洗牌时改变方向。在所有活动的站立阶段,最大压缩应变至少是最大拉伸应变的两倍。冲刺和侧向切入的抗压强度最高(-2862 ± 662με和-2697 ± 分别为495με)和拉伸(973 ± 208με和942 ± 223με)菌株。这些活性也具有最高的应变率(峰值压缩应变率 = 64602 ± 19068με/s和37961 ± 分别为14210με/s)。所有活动的压缩应变主要发生在胫骨后部;但拉伸应变的位置不同。涉及方向改变的活动增加了胫骨前部的拉伸负荷。这些观察结果可以指导胫骨应力损伤的预防和管理策略。在预防方面,应变分布表明,个体应在生长过程中进行涉及方向变化的活动,以适应胫骨的不同部位,并形成更耐疲劳的骨骼。在管理方面,短跑期间的应变率和应变率高于跳跃,这表明跳跃活动可能比全速跑更早开始。在方向改变过程中更大的前部拉伸应变表明,在胫骨前部应力损伤的恢复过程中,应推迟引入这些类型的活动,这具有愈合并发症的高风险。
{"title":"Multidirectional basketball activities load different regions of the tibia: A subject-specific muscle-driven finite element study.","authors":"Chenxi Yan, Ryan J. Bice, Jeffrey W. Frame, S. Warden, M. Kersh","doi":"10.31224/osf.io/5c8ba","DOIUrl":"https://doi.org/10.31224/osf.io/5c8ba","url":null,"abstract":"The tibia is a common site for bone stress injuries, which are believed to develop from microdamage accumulation to repetitive sub-yield strains. There is a need to understand how the tibia is loaded in vivo to understand how bone stress injuries develop and design exercises to build a more robust bone. Here, we use subject-specific, muscle-driven, finite element simulations of 11 basketball players to calculate strain and strain rate distributions at the midshaft and distal tibia during six activities: walking, sprinting, lateral cut, jumping after landing, changing direction from forward-to-backward sprinting, and changing direction while side shuffling. Maximum compressive strains were at least double maximum tensile strains during the stance phase of all activities. Sprinting and lateral cut had the highest compressive (-2862 ± 662 με and -2697 ± 495 με, respectively) and tensile (973 ± 208 με and 942 ± 223 με, respectively) strains. These activities also had the highest strains rates (peak compressive strain rate = 64,602 ± 19,068 με/s and 37,961 ± 14,210 με/s, respectively). Compressive strains principally occurred in the posterior tibia for all activities; however, tensile strain location varied. Activities involving a change in direction increased tensile loads in the anterior tibia. These observations may guide preventative and management strategies for tibial bone stress injuries. In terms of prevention, the strain distributions suggest individuals should perform activities involving changes in direction during growth to adapt different parts of the tibia and develop a more fatigue resistant bone. In terms of management, the greater strain and strain rates during sprinting than jumping suggests jumping activities may be commenced earlier than full pace running. The greater anterior tensile strains during changes in direction suggest introduction of these types of activities should be delayed during recovery from an anterior tibial bone stress injury, which have a high-risk of healing complications.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"116392"},"PeriodicalIF":0.0,"publicationDate":"2021-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44168894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Osteophyte size and location on hip DXA scans are associated with hip pain: Findings from a cross sectional study in UK Biobank 髋关节DXA扫描上骨赘的大小和位置与髋关节疼痛有关:来自UK Biobank的横断面研究结果
Pub Date : 2021-04-26 DOI: 10.1101/2021.04.26.21255905
B. Faber, R. Ebsim, F. Saunders, M. Frysz, C. Lindner, J. Gregory, R. Aspden, N. C. Harvey, G. Davey Smith, T. Cootes, J. Tobias
Objective It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method. Methods Hip DXAs were obtained from UK Biobank. An automated method was developed to obtain minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to provide a measure of rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires. Results 6,807 hip DXAs were examined. rHOA was present in 353 [5.2%] individuals and was associated with hip pain [OR 2.07 (95% CI 1.54-2.80)] and hospital diagnosed OA [5.73 (2.89-11.36)]. Total osteophyte area and mJSW were associated with hip pain [1.29 (1.21-1.36), 0.84 (0.77-0.92) respectively] in unadjusted models. After mutually adjusting and adding demographic covariates, total osteophyte area continued to have strong evidence of association with hip pain [1.31 (1.23-1.39)] but mJSW did not [0.95 (0.87-1.04)]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.19 (1.13-1.26), 1.22 (1.15-1.29), 1.21 (1.14-1.28) respectively]. Conclusion The relationship between DXA-derived rHOA and prevalent hip pain is explained by osteophyte area rather than mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.
目的髋关节骨关节炎(rHOA)的不同影像学表现如何导致髋关节疼痛尚不清楚。我们使用一种新型的双能x线吸收测量法(DXA)检测了rHOA(包括其单个成分)与髋关节疼痛之间的关系。方法从英国生物银行(UK Biobank)获得髋关节DXAs。开发了一种自动方法,从股骨头和髋臼周围的点获得最小关节间隙宽度(mJSW)。髋臼外侧、股骨头上、股骨头下骨赘部位手工取骨。骨赘和关节间隙狭窄(JSN)的半定量测量相结合,提供rHOA的测量。通过问卷调查,采用逻辑回归来检验这些变量与髋关节疼痛之间的关系。结果共检查髋部DXAs 6807例。353例(5.2%)患者存在rHOA,并与髋关节疼痛相关[OR 2.07 (95% CI 1.54-2.80)]和医院诊断的OA[5.73(2.89-11.36)]。在未调整的模型中,总骨赘面积和mJSW与髋关节疼痛相关[分别为1.29(1.21-1.36)和0.84(0.77-0.92)]。在相互调整和加入人口统计学协变量后,总骨赘面积仍然与髋关节疼痛有很强的相关性[1.31(1.23-1.39)],而mJSW则没有[0.95(0.87-1.04)]。髋臼、股骨上、下骨赘区均与髋关节疼痛独立相关[分别为1.19(1.13-1.26)、1.22(1.15-1.29)、1.21(1.14-1.28)]。结论dxa源性rHOA与髋关节普遍疼痛的关系与骨赘面积有关,而与mJSW无关。不同位置的骨赘与髋关节疼痛表现出重要的、潜在独立的关联,可能反映了不同的生物力学途径。
{"title":"Osteophyte size and location on hip DXA scans are associated with hip pain: Findings from a cross sectional study in UK Biobank","authors":"B. Faber, R. Ebsim, F. Saunders, M. Frysz, C. Lindner, J. Gregory, R. Aspden, N. C. Harvey, G. Davey Smith, T. Cootes, J. Tobias","doi":"10.1101/2021.04.26.21255905","DOIUrl":"https://doi.org/10.1101/2021.04.26.21255905","url":null,"abstract":"Objective It remains unclear how the different features of radiographic hip osteoarthritis (rHOA) contribute to hip pain. We examined the relationship between rHOA, including its individual components, and hip pain using a novel dual-energy x-ray absorptiometry (DXA)-based method. Methods Hip DXAs were obtained from UK Biobank. An automated method was developed to obtain minimum joint space width (mJSW) from points placed around the femoral head and acetabulum. Osteophyte areas at the lateral acetabulum, superior and inferior femoral head were derived manually. Semi-quantitative measures of osteophytes and joint space narrowing (JSN) were combined to provide a measure of rHOA. Logistic regression was used to examine the relationships between these variables and hip pain, obtained via questionnaires. Results 6,807 hip DXAs were examined. rHOA was present in 353 [5.2%] individuals and was associated with hip pain [OR 2.07 (95% CI 1.54-2.80)] and hospital diagnosed OA [5.73 (2.89-11.36)]. Total osteophyte area and mJSW were associated with hip pain [1.29 (1.21-1.36), 0.84 (0.77-0.92) respectively] in unadjusted models. After mutually adjusting and adding demographic covariates, total osteophyte area continued to have strong evidence of association with hip pain [1.31 (1.23-1.39)] but mJSW did not [0.95 (0.87-1.04)]. Acetabular, superior and inferior femoral osteophyte areas were all independently associated with hip pain [1.19 (1.13-1.26), 1.22 (1.15-1.29), 1.21 (1.14-1.28) respectively]. Conclusion The relationship between DXA-derived rHOA and prevalent hip pain is explained by osteophyte area rather than mJSW. Osteophytes at different locations showed important, potentially independent, associations with hip pain, possibly reflecting the contribution of distinct biomechanical pathways.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"153 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44274248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Bone Geometry and Microarchitecture Deficits in Children with Alagille Syndrome. 儿童Alagille综合征的骨几何结构和微结构缺陷。
Pub Date : 2019-07-31 DOI: 10.1530/boneabs.7.p63
J. Kindler, Ellen L. Mitchell, D. Piccoli, A. Grimberg, M. Leonard, K. Loomes, B. Zemel
Alagille syndrome (ALGS) is an autosomal dominant disorder attributed to mutations in the Notch signaling pathway. Children with ALGS are at increased risk for fragility fracture of unknown etiology. Our objective was to characterize bone mass, geometry, and microarchitecture in children with ALGS. This was a cross-sectional study of 10 children (9 females), ages 8-18 years, with a clinical diagnosis of ALGS. Bone density was assessed via DXA (Hologic Discovery A) at several skeletal regions. Tibia trabecular and cortical bone was assessed via pQCT (Stratec XCT 2000) at the distal 3% and 38% sites, respectively. Tibia bone microarchitecture was assessed via HR-pQCT (Scanco XtremeCT II) at an ultradistal site located at 4% of tibia length and a cortical site at 30% of tibia length. Z-scores were calculated for DXA and pQCT measures. In the absence of XtremeCT II HR-pQCT reference data, these outcome measures were descriptively compared to a sample of healthy children ages 5-20 years (n=247). Anthropometrics and labs were also collected. Based on one-sample t-tests, mean Z-scores for height and weight (both p<0.05), were significantly less than zero. DXA bone Z-scores were not significantly different from zero, but were highly variable. For pQCT bone measures, Z-scores for total bone mineral content at the distal 3% site and cortical bone mineral content, cortical area, and cortical thickness at the distal 38% site were significantly less than zero (all p<0.05). There was good correspondence between pQCT measures of cortical thickness Z-scores and DXA Z-scores for aBMD at the whole body less head, 1/3 radius, and femoral neck (all p<0.05). Compared to healthy children, those with ALGS generally had lower trabecular number and greater trabecular separation despite having greater trabecular thickness (measured via HR-pQCT). Bilirubin and bile acids, markers of hepatic cholestasis, were associated with poorer bone measures. For example, greater bilirubin was associated with lower trabecular number (Spearman's rho [ρ]=-0.82, p=0.023) and greater trabecular separation (ρ=0.82, p=0.023) measured via HR-pQCT, and greater bile acids were associated with lower cortical area measured via pQCT (ρ=-0.78, p=0.041) and lower serum insulin-like growth factor-1 (ρ=-0.86, p=0.002). In summary, deficits in cortical bone size and trabecular bone microarchitecture were evident in children with ALGS. Further investigation is needed to understand the factors contributing to these skeletal inadequacies, and the manner in which these deficits contribute to increased fracture risk.
Alagille综合征(ALGS)是一种常染色体显性遗传病,归因于Notch信号通路突变。患有ALGS的儿童发生原因不明的脆性骨折的风险增加。我们的目的是表征ALGS儿童的骨量、几何形状和微结构。这是一项横断面研究,10名儿童(9名女性),年龄8-18岁,临床诊断为ALGS。在几个骨骼区域通过DXA (Hologic Discovery A)评估骨密度。胫骨小梁和皮质骨分别通过pQCT (strategy XCT 2000)在远端3%和38%的位置进行评估。通过HR-pQCT (Scanco XtremeCT II)在位于胫骨长度4%的超远端部位和位于胫骨长度30%的皮质部位评估胫骨骨微结构。计算DXA和pQCT测量的z分数。在缺乏XtremeCT II HR-pQCT参考数据的情况下,将这些结局指标与5-20岁健康儿童样本(n=247)进行描述性比较。还收集了人体测量和实验室数据。基于单样本t检验,身高和体重的平均z分数(p均<0.05)显著小于零。DXA骨z评分与0无显著差异,但差异很大。对于pQCT骨测量,远端3%部位的总骨矿物质含量和远端38%部位的皮质骨矿物质含量、皮质面积和皮质厚度的z评分均显著小于零(均p<0.05)。pQCT测量的皮质厚度z -评分与全身、1/3半径和股骨颈的aBMD的DXA z -评分之间有很好的对应关系(均p<0.05)。与健康儿童相比,ALGS患者的小梁数量更少,小梁分离更大,尽管小梁厚度更大(通过HR-pQCT测量)。胆红素和胆汁酸,肝脏胆汁淤积的标志,与较差的骨质测量有关。例如,高胆红素与低小梁数(Spearman's ρ= -0.82, p=0.023)和高小梁分离(ρ=0.82, p=0.023)相关,高胆红酸与pQCT测量的低皮质面积(ρ=-0.78, p=0.041)和低血清胰岛素样生长因子-1 (ρ=-0.86, p=0.002)相关。总之,在ALGS儿童中,皮质骨大小和骨小梁微结构的缺陷是明显的。需要进一步的研究来了解导致这些骨骼缺陷的因素,以及这些缺陷导致骨折风险增加的方式。
{"title":"Bone Geometry and Microarchitecture Deficits in Children with Alagille Syndrome.","authors":"J. Kindler, Ellen L. Mitchell, D. Piccoli, A. Grimberg, M. Leonard, K. Loomes, B. Zemel","doi":"10.1530/boneabs.7.p63","DOIUrl":"https://doi.org/10.1530/boneabs.7.p63","url":null,"abstract":"Alagille syndrome (ALGS) is an autosomal dominant disorder attributed to mutations in the Notch signaling pathway. Children with ALGS are at increased risk for fragility fracture of unknown etiology. Our objective was to characterize bone mass, geometry, and microarchitecture in children with ALGS. This was a cross-sectional study of 10 children (9 females), ages 8-18 years, with a clinical diagnosis of ALGS. Bone density was assessed via DXA (Hologic Discovery A) at several skeletal regions. Tibia trabecular and cortical bone was assessed via pQCT (Stratec XCT 2000) at the distal 3% and 38% sites, respectively. Tibia bone microarchitecture was assessed via HR-pQCT (Scanco XtremeCT II) at an ultradistal site located at 4% of tibia length and a cortical site at 30% of tibia length. Z-scores were calculated for DXA and pQCT measures. In the absence of XtremeCT II HR-pQCT reference data, these outcome measures were descriptively compared to a sample of healthy children ages 5-20 years (n=247). Anthropometrics and labs were also collected. Based on one-sample t-tests, mean Z-scores for height and weight (both p<0.05), were significantly less than zero. DXA bone Z-scores were not significantly different from zero, but were highly variable. For pQCT bone measures, Z-scores for total bone mineral content at the distal 3% site and cortical bone mineral content, cortical area, and cortical thickness at the distal 38% site were significantly less than zero (all p<0.05). There was good correspondence between pQCT measures of cortical thickness Z-scores and DXA Z-scores for aBMD at the whole body less head, 1/3 radius, and femoral neck (all p<0.05). Compared to healthy children, those with ALGS generally had lower trabecular number and greater trabecular separation despite having greater trabecular thickness (measured via HR-pQCT). Bilirubin and bile acids, markers of hepatic cholestasis, were associated with poorer bone measures. For example, greater bilirubin was associated with lower trabecular number (Spearman's rho [ρ]=-0.82, p=0.023) and greater trabecular separation (ρ=0.82, p=0.023) measured via HR-pQCT, and greater bile acids were associated with lower cortical area measured via pQCT (ρ=-0.78, p=0.041) and lower serum insulin-like growth factor-1 (ρ=-0.86, p=0.002). In summary, deficits in cortical bone size and trabecular bone microarchitecture were evident in children with ALGS. Further investigation is needed to understand the factors contributing to these skeletal inadequacies, and the manner in which these deficits contribute to increased fracture risk.","PeriodicalId":93913,"journal":{"name":"Bone","volume":"1 1","pages":"115576"},"PeriodicalIF":0.0,"publicationDate":"2019-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47172523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Sex differences in the longitudinal associations between body composition and bone stiffness index in European children and adolescents. 欧洲儿童和青少年身体组成和骨僵硬指数之间纵向关联的性别差异。
Pub Date : 2019-07-31 DOI: 10.1530/boneabs.7.p107
Lan Cheng, H. Pohlabeln, W. Ahrens, P. Russo, T. Veidebaum, C. Chadjigeorgiou, D. Molnár, G. Eiben, S. de Henauw, L. Moreno, A. Page, A. Hebestreit
Fat mass (FM) and fat free mass (FFM) may influence bone health differentially. However, existing evidences on associations between FM, FFM and bone health are inconsistent and vary according to sex and maturity. The present study aims to evaluate longitudinal associations between FM, FFM and bone stiffness index (SI) among European children and adolescents with 6 years follow-up. A sample of 2468 children from the IDEFICS/I.Family was included, with repeated measurements of SI using calcaneal quantitative ultrasound, body composition using skinfold thickness, sedentary behaviors and physical activity using self-administrated questionnaires. Regression coefficients (β) and 99%-confidence intervals (99% CI) were calculated by sex-specified generalized linear mixed effects models to analyze the longitudinal associations between FM and FFM z-scores (zFM and zFFM) and SI percentiles, and to explore the possible interactions between zFM, zFFM and maturity. Baseline zFFM was observed to predict the change in SI percentiles in both boys (β = 4.57, 99% CI: 1.36, 7.78) and girls (β = 3.42, 99% CI: 0.05, 6.79) after 2 years. Moreover, baseline zFFM (β = 8.72, 99% CI: 3.18, 14.27 in boys and β = 5.89, 99% CI: 0.34, 11.44 in girls) and the change in zFFM (β = 6.58, 99% CI: 0.83, 12.34 in boys and β = 4.81, 99% CI: -0.41, 10.02 in girls) were positively associated with the change in SI percentiles after 6 years. In contrast, a negative association was observed between the change in zFM and SI percentiles in boys after 6 years (β = -3.70, 99% CI: -6.99, -0.42). Besides, an interaction was observed between the change in zFM and menarche on the change in SI percentiles in girls at 6 years follow-up (p = .009), suggesting a negative association before menarche while a positive association after menarche. Our findings support the existing evidences for a positive relationship between FFM and SI during growth. Furthermore, long-term FM gain was inversely associated with SI in boys, whereas opposing associations were observed across menarche in girls.
脂肪量(FM)和无脂肪量(FFM)可能对骨骼健康产生不同的影响。然而,关于FM、FFM与骨骼健康之间关系的现有证据是不一致的,并且根据性别和成熟度而不同。本研究旨在评估欧洲6岁儿童和青少年的FM、FFM和骨硬度指数(SI)之间的纵向相关性 年随访。来自IDEFICS/I的2468名儿童样本。纳入家庭,使用跟骨定量超声重复测量SI,使用皮褶厚度重复测量身体成分,使用自我管理问卷重复测量久坐行为和体育活动。通过性别指定的广义线性混合效应模型计算回归系数(β)和99%置信区间(99%CI),以分析FM和FFM z评分(zFM和zFFM)与SI百分位数之间的纵向关联,并探索zFM、zFFM与成熟度之间可能的相互作用。观察基线zFFM来预测两个男孩的SI百分位数的变化(β = 4.57,99%CI:1.36,7.78)和女孩(β = 3.42,99%置信区间:0.05,6.79) 年。此外,基线zFFM(β = 8.72,99%CI:3.18,14.27男孩和β = 5.89,99%CI:0.34,11.44)和zFFM的变化(β = 6.58,99%置信区间:男孩0.83,12.34,β = 4.81,99%的CI:女孩为-0.41,10.02)与6后SI百分位数的变化呈正相关 年。相反,男孩6岁后zFM和SI百分位数的变化呈负相关 年(β = -3.70,99%CI:6.99,-0.42)。此外,在zFM和月经初潮之间观察到女孩6岁时SI百分位数的变化 年随访(p = .009),表明在月经初潮前呈负相关,而在月经初初潮后呈正相关。我们的研究结果支持了生长过程中FFM和SI之间正相关的现有证据。此外,男孩的长期FM增益与SI呈负相关,而女孩的月经初潮则相反。
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引用次数: 5
Growth, enzymatic glutathione peroxidase activity and biochemical status of juvenile barramundi (Lates calcarifer) fed dietary fermented soybean meal and organic selenium. 以发酵豆粕和有机硒为饲料的金目鲈幼鱼的生长、酶谷胱甘肽过氧化物酶活性和生化状况。
IF 2.9 Pub Date : 2017-06-01 Epub Date: 2016-12-27 DOI: 10.1007/s10695-016-0331-2
I Ilham, Ravi Fotedar

Solvent-extracted soybean meal (SBM) was fermented using baker's yeast Saccharomyces cerevisae at 30 °C for 5 days. Four isonitrogenous and isocaloric diets containing 75% SBM protein, either fermented or non-fermented (SBM and FSBM), and supplemented or not with organic Se (OS) (SBMOS and FSBMOS), were fed to triplicate groups of juvenile barramundi (Lates calcarifer) (initial weight of 5 g) for 75 days. A fishmeal (FM)-based diet formulated for juvenile barramundi was used as a reference diet. The growth of fish was significantly affected by either the interaction of SBM type or by the OS level. In fish fed diets supplemented with OS (SBMOS and FSBMOS), final weight (FW), specific growth rate (SGR) and weight gain (WG) were higher in fish fed the fermented SBM (FSBMOS) than in those fed the non-fermented SBM (SBMOS). The apparent digestibility coefficient (ADC) of protein was higher in the fish fed the fermented SBM, either supplemented or unsupplemented with OS. However, there were no significant differences in the ADC of dry matter (DM) and lipids among the tested diets and in comparison to the reference diet. The haematocrit and leucocrit of fish fed the FSBMOS diet were lower than those of fish fed the FM diet. Furthermore, glutathione peroxidase (GPx) activity was significantly influenced by OS supplementation in the experimental diets; GPx activity was greater in the fish fed diets supplemented with OS. Creatinine kinase (CK) of all groups of fish was higher than the CK of those fed the reference diet. These results suggest that with a proper nutritional level, OS supplementation may act as an important factor in enzymatic GPx activity and in the haematology and blood biochemistry status of juvenile barramundi fed fermented SBM-based diets, encouraging improvement of the overall growth performance.

使用面包酵母在 30 °C 下发酵溶剂提取的豆粕(SBM)5 天。将含有 75% SBM 蛋白质的发酵或未发酵(SBM 和 FSBM)、添加或不添加有机硒(OS)(SBMOS 和 FSBMOS)的四种等氮等热量日粮喂给一式三组的金目鲈幼鱼(初始体重为 5 克),喂养 75 天。以鱼粉(FM)为基础配制的幼鱼日粮作为参考日粮。鱼类的生长受到 SBM 类型或 OS 水平的交互影响。在饲喂添加 OS 的日粮(SBMOS 和 FSBMOS)的鱼类中,饲喂发酵 SBM(FSBMOS)的鱼类的最终体重(FW)、特定生长率(SGR)和增重(WG)均高于饲喂非发酵 SBM(SBMOS)的鱼类。饲喂发酵 SBM(添加或不添加 OS)的鱼的蛋白质表观消化系数(ADC)更高。然而,不同试验日粮的干物质(DM)和脂类的表观消化系数与参考日粮相比没有明显差异。饲喂 FSBMOS 日粮的鱼的血细胞比容和白细胞比容低于饲喂 FM 日粮的鱼。此外,谷胱甘肽过氧化物酶(GPx)的活性受试验日粮中补充 OS 的显著影响;喂食补充 OS 的日粮的鱼的 GPx 活性更高。各组鱼的肌酸激酶(CK)均高于饲喂参考日粮的鱼。这些结果表明,在营养水平适当的情况下,补充 OS 可作为一个重要因素,促进以发酵 SBM 为基础的日粮饲喂的幼年金目鲈的 GPx 酶活性以及血液学和血液生化状况,从而提高其整体生长性能。
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引用次数: 1
The equilibrium of ubiquitination and deubiquitination at PLK1 regulates sister chromatid separation. PLK1 的泛素化和去泛素化平衡调节姐妹染色单体的分离。
IF 8 Pub Date : 2017-06-01 Epub Date: 2017-02-10 DOI: 10.1007/s00018-017-2457-5
Junjun Liu, Chuanmao Zhang

PLK1 regulates almost every aspect of mitotic events, including mitotic entry, spindle assembly, chromosome alignment, sister chromatid segregation, metaphase-anaphase transition, cytokinesis, etc. In regulating the chromosome alignment and sister chromatid segregation, PLK1 has to be localized to and removed from kinetochores at the right times, and the underlying mechanism that regulates PLK1 both spatially and temporally only became clearer recently. It has been found that deubiquitination and ubiquitination of PLK1 are responsible for its localization to and dissociation from the kinetochores, respectively. The equilibrium of this ubiquitination and deubiquitination plays an important role in regulating proper chromosome alignment and timely sister chromatid segregation. Here, we summarize and discuss the recent findings in investigating the spatial and temporal regulation of PLK1 during chromosome alignment and sister chromatid segregation.

PLK1几乎调控有丝分裂事件的各个方面,包括有丝分裂进入、纺锤体组装、染色体排列、姐妹染色单体分离、中期-后期转变、细胞质分裂等。在调节染色体排列和姐妹染色单体分离的过程中,PLK1必须在合适的时间定位到着丝点并从着丝点移出,而调控PLK1在空间和时间上的潜在机制直到最近才变得更加清晰。研究发现,PLK1的去泛素化和泛素化分别是其定位于着丝点和从着丝点分离的原因。这种泛素化和去泛素化的平衡在调节染色体正确排列和姐妹染色单体及时分离中起着重要作用。在此,我们总结并讨论了PLK1在染色体排列和姐妹染色单体分离过程中时空调控的最新研究结果。
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引用次数: 0
The Enigma of Poor Performance by Adults With Cochlear Implants. 佩戴人工耳蜗的成年人表现不佳之谜。
IF 2.1 Pub Date : 2016-12-01 DOI: 10.1097/MAO.0000000000001211
Aaron C Moberly, Chelsea Bates, Michael S Harris, David B Pisoni

Objective: Considerable unexplained variability and large individual differences exist in speech recognition outcomes for postlingually deaf adults who use cochlear implants (CIs), and a sizeable fraction of CI users can be considered "poor performers." This article summarizes our current knowledge of poor CI performance, and provides suggestions to clinicians managing these patients.

Method: Studies are reviewed pertaining to speech recognition variability in adults with hearing loss. Findings are augmented by recent studies in our laboratories examining outcomes in postlingually deaf adults with CIs.

Results: In addition to conventional clinical predictors of CI performance (e.g., amount of residual hearing, duration of deafness), factors pertaining to both "bottom-up" auditory sensitivity to the spectro-temporal details of speech, and "top-down" linguistic knowledge and neurocognitive functions contribute to CI outcomes.

Conclusions: The broad array of factors that contribute to speech recognition performance in adult CI users suggests the potential both for novel diagnostic assessment batteries to explain poor performance, and also new rehabilitation strategies for patients who exhibit poor outcomes. Moreover, this broad array of factors determining outcome performance suggests the need to treat individual CI patients using a personalized rehabilitation approach.

目的:使用人工耳蜗(CI)的语后聋成人在语音识别结果方面存在大量无法解释的差异和巨大的个体差异,相当一部分 CI 用户可被视为 "表现不佳者"。本文总结了我们目前对 CI 差异表现的认识,并为管理这些患者的临床医生提供了建议:方法:本文回顾了有关听力损失成人语音识别变异性的研究。方法:本文回顾了有关成人听力损失患者语音识别变异性的研究,并通过我们实验室最近对使用人工耳蜗的语后聋成人患者的研究结果进行了补充:结果:除了 CI 性能的传统临床预测因素(如残余听力、耳聋持续时间)外,"自下而上 "的听觉灵敏度对语音的频谱-时间细节以及 "自上而下 "的语言知识和神经认知功能都是影响 CI 效果的因素:影响成人 CI 用户语音识别能力的一系列因素表明,新型诊断评估电池既有可能解释不良表现,也有可能为表现出不良结果的患者提供新的康复策略。此外,决定结果表现的一系列因素表明,有必要采用个性化康复方法来治疗个别 CI 患者。
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引用次数: 0
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