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Notoginsenoside R1 Functionalized Gelatin Hydrogels to Promote Reparative Dentinogenesis 三七皂苷R1功能化明胶水凝胶促进修复性牙本质形成
Pub Date : 2020-09-22 DOI: 10.2139/ssrn.3677352
Lei Wang, Hui Fu, Wenwen Wang, Yi Liu, Xumin Li, Jijing Yang, Lingli Li, Gang Wu, Yihuai Pan
Pulp-capping materials are commonly adopted in the clinic to form reparative dentin and thus protect dental pulp tissues from cases of deep caries, accidentally exposed pulps or partial pulpotomy. Some traditional pulp capping materials used in the clinic include calcium hydroxide and mineral trioxide aggregates. However, there are limitations to thin restorative dentin, and a long period of time is needed to cause degenerative changes in dental pulp. In this paper, injectable colloidal gels were developed to induce the formation of reparative dentin through a simple UV method from methacrylic acid functionalized gelatin loaded with notoginsenoside R1 (Gel-MA/NGR1). The results of the physicochemical property examinations showed that the prepared Gel-MA/NGR1 hydrogel possessed an appropriate interconnected porous microarchitecture with a pore size of 10.5 micrometres and suitable mechanical properties with a modulus of 50-60 kPa, enabling cell adhesion and proliferation. The hydrogel remained hydrophilic with sustained drug release performance. In addition, Gel-MA/NGR1 significantly enhanced the odontogenetic differentiation of mouse dental papilla cells by elevating the expression levels of the dentinogenic markers ALP and OCN and extracellular matrix mineralization. In vivo stimulation was carried out by injecting the precursors into the predrilled alveolar cavity of Sprague-Dawley rats followed by immediate in situ UV crosslinking. The results showed that Gel-MA/NGR1 has a strong capacity to promote reparative dentin formation. Haematoxylin & eosin, Masson, and immunohistochemical staining (DMP-1, DSPP, OCN and RUNX2) and micro-CT were employed to illustrate the effectiveness of dentinogenesis, and the relative volumes of calcification were found to have increased ∼175-fold. All of the results showed that the Gel-MA/NGR1 hydrogel promoted reparative dentin formation, which suggests that this hydrogel provides great potential as a pulp-capping material to induce dentin formation.
临床上常用盖髓材料来形成修复性牙本质,从而保护牙髓组织不受深部龋、意外暴露牙髓或部分截髓的影响。临床上常用的传统盖髓材料包括氢氧化钙和矿物三氧化物聚集体。然而,薄化修复牙本质存在局限性,且需要较长时间才能引起牙髓的退行性改变。本文以三七皂苷R1 (Gel-MA/NGR1)为载体,采用简单的紫外法制备了可注射胶体凝胶,诱导修复牙本质的形成。理化性质测试结果表明,制备的Gel-MA/NGR1水凝胶具有合适的互连多孔微结构,孔径为10.5微米,力学性能为50-60 kPa,有利于细胞粘附和增殖。水凝胶保持亲水性,具有持续的药物释放性能。此外,Gel-MA/NGR1通过提高牙本质标志物ALP和OCN的表达水平和细胞外基质矿化水平,显著增强了小鼠牙乳头细胞的成牙分化。通过将前体注射到Sprague-Dawley大鼠的预钻孔肺泡腔中,然后立即原位UV交联进行体内刺激。结果表明,Gel-MA/NGR1具有较强的促进修复性牙本质形成的能力。采用血红素和伊红、马松、免疫组织化学染色(DMP-1、DSPP、OCN和RUNX2)和显微ct来说明牙本质形成的有效性,发现钙化的相对体积增加了~ 175倍。以上结果表明,凝胶- ma /NGR1水凝胶促进修复性牙本质的形成,表明该水凝胶作为牙本质覆盖材料在诱导牙本质形成方面具有很大的潜力。
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引用次数: 16
A Novel Study of Lichen Planopilaris Among Different Iranian Ethnicities based on Computer-aided Programs 基于计算机辅助程序的伊朗不同民族扁平苔藓新研究
Pub Date : 2020-08-31 DOI: 10.5121/ijcsit.2020.12407
Maryamsadat Nejadghaderi
Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it. The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
一种疾病的人口统计学研究可以揭示该疾病在特定人群中的特征,并将帮助医生获得更准确的认识。伊朗人口中PlanoPilaris (LPP)的人口统计是未知的。本研究的目的是描述伊朗人群中扁平苔藓的临床、人口统计学和组织病理学结果。
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引用次数: 0
Covalent Self-Assembly of PEG and Heparin Improves Biological Performance of Electrospun Vascular Grafts for Carotid Artery Replacement 聚乙二醇和肝素共价自组装提高电纺丝血管移植物颈动脉置换术的生物学性能
Pub Date : 2020-07-17 DOI: 10.2139/ssrn.3647647
T. Zhu, Hongbing Gu, Hongmei Zhang, Hongsheng Wang, Huitang Xia, X. Mo, Jinglei Wu
Rapid endothelialization of small-diameter vascular grafts remains a significant challenge in clinical practice. In addition, compliance mismatch causes intimal hyperplasia and finally leads to graft failure. To achieve compliance match and rapid endothelialization, we synthesized low-initial-modulus poly(ester-urethane)urea (PEUU) elastomer and prepared it into electrospun tubular grafts and then functionalized the grafts with poly(ethylene glycol) (PEG) and heparin via covalent self-assembly. The PEG- and heparin-functionalized PEUU (PEUU@PEG-Hep) graft had comparable mechanical properties with the native blood vessel. In vitro data demonstrated that the grafts are of great cytocompatibility and blood compatibility. Covalent self-assembly of PEG and heparin significantly promoted the adhesion, spreading, and proliferation of human umbilical vein endothelial cells (HUVECs) and upregulated the expression of vascular endothelial cell-related genes, as well as increased the capability of grafts in preventing platelet deposition. In vivo assessments indicated good biocompatibility of the PEUU@PEG-Hep graft as it did not induce severe immune responses. Replacement of resected carotid artery with the PEUU@PEG-Hep graft in a rabbit model showed that the graft was capable of rapid endothelialization, initiated vascular remodeling, and maintained patency. This study demonstrates the synergistic effects of compliance match and efficacious antithrombosis of synthetic grafts for blood vessel regeneration.
在临床实践中,小直径血管移植的快速内皮化仍然是一个重大挑战。此外,顺应性错配导致内膜增生,最终导致移植物失败。为了实现顺应性匹配和快速内皮化,我们合成了低初始模量聚(酯-聚氨酯)尿素(PEUU)弹性体,并将其制备成电纺丝管状接枝,然后用聚乙二醇(PEG)和肝素通过共价自组装对接枝进行功能化。聚乙二醇和肝素功能化的PEUU (PEUU@PEG-Hep)移植物具有与天然血管相当的机械性能。体外实验结果表明,移植物具有良好的细胞相容性和血液相容性。聚乙二醇与肝素共价自组装显著促进人脐静脉内皮细胞(HUVECs)的粘附、扩散和增殖,上调血管内皮细胞相关基因的表达,增强移植物抗血小板沉积能力。体内评估表明PEUU@PEG-Hep移植物具有良好的生物相容性,因为它不会引起严重的免疫反应。在兔模型中,用PEUU@PEG-Hep移植物替代切除的颈动脉,表明移植物能够快速内皮化,启动血管重塑,并保持通畅。本研究证明了顺应性匹配和有效抗血栓形成对血管再生的协同作用。
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引用次数: 0
Do Patent Systems Deter Innovation in a Genetically Modified Seed Research? 专利制度会阻碍转基因种子研究的创新吗?
Pub Date : 2020-05-31 DOI: 10.2139/ssrn.3614876
Yeongbin Kim
This paper empirically examines the relationship between research exemptions – which are mechanisms in patent law that provide shelter to researchers using patented inventions for scientific research from infringement claims – and innovation. We analyze a 2002 court decision (Madey v. Duke University) that has dramatically limited the scope of research exemptions in the United States. The court decision provides us with a quasi-natural policy experiment we leverage to empirically estimate the effects of this policy change on innovation. We use data on patents in the area of genetically modified organisms. Employing a difference-in-difference estimation approach, we find statistically significant evidence that this policy change led to a marked decrease in research conducted in the United States. However, we find no significant effect in research conducted in countries with more liberal research exemptions. Our results suggest that there is a negative relationship between research exemptions and genetically modified seed patents. We also find that U.S. researchers still engage in co-invention with their domestic peers, suggesting that they have not yet strategically adapted to this policy change and new research environment. The oligopolistic market structure of the genetically modified seed industry may stifle an active relocation of research abroad, thereby hindering innovation.
本文从实证角度考察了研究豁免与创新之间的关系。研究豁免是专利法中的一种机制,为使用专利发明进行科学研究的研究人员提供庇护,使其免受侵权索赔。我们分析了2002年的一项法院判决(Madey诉杜克大学),该判决极大地限制了美国研究豁免的范围。法院的判决为我们提供了一个准自然的政策实验,我们利用它来经验地估计这一政策变化对创新的影响。我们使用转基因生物领域的专利数据。采用差中差估计方法,我们发现统计上显著的证据表明,这一政策变化导致在美国进行的研究显著减少。然而,我们发现在研究豁免更自由的国家进行的研究没有显著的影响。研究结果表明,研究豁免与转基因种子专利之间存在负相关关系。我们还发现,美国研究人员仍然与国内同行进行共同发明,这表明他们尚未从战略上适应这一政策变化和新的研究环境。转基因种子产业的寡头垄断市场结构可能会扼杀国外研究的积极转移,从而阻碍创新。
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引用次数: 0
Extraction Endocardium and Epicardium of Left Ventricle using Internal and External Energy Terms of Signed Distance Function in Cardiac MRI 利用心脏MRI内、外能量项的符号距离函数提取左心室心内膜和心外膜
Pub Date : 2020-05-01 DOI: 10.2139/ssrn.3646233
S. Pawar, S. Dhanure
For clinical detection of cardiac function such as ejection fraction, end-systolic volume and end-diastolic volume used MRI (Magnetic Resonance Images). These functions were evaluated from experts manually or semi-automatically, they were time-consuming and tedious. This paper applies the automatic evolution of inner contour and outer contour on the MICCAI 2012 database of cardiac MRI. This paper gives optimistic results in terms of the boundary line and cross-section area of the epicardium and endocardium of the left ventricle. This paper will be useful for experts to quantify the endocardium and epicardium for Cardiac Vascular Diseases (CVD) type.
临床检测心功能如射血分数、收缩期末期容积和舒张末期容积采用MRI(磁共振成像)。这些功能由专家手动或半自动评估,耗时且繁琐。本文将内轮廓和外轮廓的自动演化应用于MICCAI 2012心脏MRI数据库。本文对左心室心外膜和心内膜的边界线和横截面积给出了乐观的结果。本文将有助于专家对心血管疾病(CVD)类型的心内膜和心外膜进行量化。
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引用次数: 0
STIM1 a Calcium Sensor Promotes the Assembly of an ECM that Contains Extracellular Vesicles and Factors that Modulate Mineralization STIM1钙传感器促进含有细胞外囊泡和调节矿化因子的ECM的组装
Pub Date : 2020-04-15 DOI: 10.2139/ssrn.3568118
Yinghua Chen, Rahul Koshy, Anne George
Bone and dentin development requires temporal and spatial deposition of calcium phosphate mineral. Several proteins work in coordination and contribute to this tightly regulated process. STIM1 (Stromal interaction molecule 1) is one such protein that has been recently identified to function in bone and enamel mineralization. STIM1 is a calcium sensor localized on the ER membrane and is well recognized for its physiological role in maintaining calcium homeostasis. We have demonstrated earlier that DMP1 stimulation of preosteoblasts and preodontoblasts stimulate calcium release from internal Ca2+ stores and this store depletion is sensed by STIM1. Store-operated calcium entry (SOCE) is one of the major Ca2+ influx mechanisms following store depletion in the ER. To demonstrate a role for STIM1 in dentin matrix mineralization, we generated transgenic DPSCs in which STIM1 was either overexpressed or silenced. These cells were characterized for their differentiation potential by gene expression analysis, Alizarin Red staining and the topology of the matrix examined by Field Emission Scanning Electron Microscopy (FESEM). Results suggest upregulation of genes involved in mineralization and increased calcium deposition with STIM1 overexpression. FESEM results demonstrate that STIM1 overexpression resulted in release of large amount of extracellular microvesicles and promoted matrix mineralization. Interestingly, knockdown of STIM1 resulted in release of fewer microvesicles and less mineral deposits in the ECM. Reduced dentin thickness, malformed and highly porous alveolar bone of STIM-1 null mice confirmed the role of STIM1 in the formation of calcified tissues. Overall, STIM1 is a crucial molecule in biomineralization as STIM1 can influence intracellular Ca2+ oscillations and thus provide a signal for activation of upstream and downstream effectors to promote precursor cell differentiation and matrix mineralization.
骨和牙本质的发育需要磷酸钙矿物的时空沉积。几种蛋白质协同工作,促进这一严格调控的过程。STIM1(基质相互作用分子1)是一种最近被发现在骨和牙釉质矿化中起作用的蛋白质。STIM1是一种定位于内质网膜上的钙传感器,其在维持钙稳态中的生理作用已得到广泛认可。我们之前已经证明,DMP1刺激成骨前细胞和成牙前细胞刺激钙从内部Ca2+储存中释放,这种储存消耗被STIM1感知。储存操作钙进入(SOCE)是内质网储存耗尽后Ca2+内流的主要机制之一。为了证明STIM1在牙本质基质矿化中的作用,我们产生了STIM1过表达或沉默的转基因DPSCs。通过基因表达分析、茜素红染色和场发射扫描电镜(FESEM)观察基质的拓扑结构,对这些细胞的分化潜力进行了表征。结果表明,参与矿化和钙沉积的基因上调与STIM1过表达。FESEM结果表明,STIM1过表达导致细胞外微泡大量释放,促进基质矿化。有趣的是,抑制STIM1导致ECM中微囊泡的释放减少,矿物质沉积减少。STIM-1缺失小鼠牙本质厚度减少,牙槽骨畸形和高度多孔,证实了STIM1在钙化组织形成中的作用。总的来说,STIM1是生物矿化的关键分子,因为STIM1可以影响细胞内Ca2+振荡,从而为上游和下游效应物的激活提供信号,以促进前体细胞分化和基质矿化。
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引用次数: 0
Using Waste Carbon Feedstocks to Produce Chemicals 利用废碳原料生产化学品
Pub Date : 2020-04-07 DOI: 10.1089/ind.2020.29217.ern
Elizabeth R. Nesbitt
Emerging carbon capture utilization (CCU) technologies potentially allow chemical companies and other manufacturers to capture waste carbon—in the form of carbon monoxide (CO) and/or carbon dioxide...
新兴的碳捕获利用(CCU)技术有可能使化工公司和其他制造商以一氧化碳(CO)和/或二氧化碳的形式捕获废碳……
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引用次数: 2
Feature Extraction Techniques for Iris Recognition System: A Survey 虹膜识别系统特征提取技术综述
Pub Date : 2020-03-01 DOI: 10.21276/ijircst.2020.8.2.5
A. Y.A, A. O
The extraction of features involves the method of converting the original pixel values of an image to more meaningful, useful and measurable information that can be used in other techniques, such as image processing, pattern recognition and machine learning. The feature extraction plays a predominant role in iris recognition in which also the recognition rate is determined. The effective recognition accuracy, reduction of mis-classification of two iris templates mostly depends on feature extraction techniques. An efficient iris recognition system requires that the discriminating information presents in an iris pattern to be accurately obtained. This paper performed a literature review on different techniques of feature extraction of iris recognition. The recommendation was made on how these techniques can be further enhanced to produce an effective iris recognition system.
特征提取涉及将图像的原始像素值转换为更有意义、有用和可测量的信息的方法,这些信息可用于其他技术,如图像处理、模式识别和机器学习。特征提取是虹膜识别的关键,也是决定虹膜识别率的关键。有效的识别精度和减少两种虹膜模板的误分类主要依赖于特征提取技术。高效的虹膜识别系统要求准确地获取虹膜图案中所呈现的识别信息。本文对虹膜识别中不同的特征提取技术进行了综述。建议如何进一步加强这些技术,以产生有效的虹膜识别系统。
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引用次数: 6
In Vitro and in Vivo Studies of Selective Laser Melting-Mediated Surface Concave Microwell Treatment to Enhance Osteogenesis and Osseointegration of Nanohydroxyapatite/Polyamide 66 Implants 选择性激光熔化介导的表面凹微孔治疗促进纳米羟基磷灰石/聚酰胺66种植体成骨和骨整合的体内外研究
Pub Date : 2020-01-01 DOI: 10.2139/ssrn.3684929
Yafeng Wen, Yanan Xu, Weikang Zhao, Jun Wu, Qiming Yang, Sinan Chen, Kai Li, B. Qiao
The structural and functional combination of an implant and living bone is greatly influenced by the surface characteristics of the implant. To enhance the implant-bone interface regarding the osteointegration of nanohydroxyapatite/polyamide66 (nHA/PA66) material, concave microwells that were 100 μm, 200 μm and 400 μm in size (denoted by P100, P200, and P400, respectively) were prepared on the nHA/PA66 substrate surface by selective laser melting (SLM) technology. The surface characteristics of these samples were analyzed by scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), 3D scanning laser microscopy and static water contact angle measurements. We examined the effects of different concave microwell sizes on the adhesion, proliferation and osteogenesis of C3H10T1/2 cells in vitro by cell counting kit-8 (CCK-8), SEM, alkaline phosphatase assay, alizarin red staining, and western blot, and continued our evaluating through micro-CT, histological analysis and push-out tests to verify the osseointegration ability in vivo. P100, P200 and P400 surface modification led to significant increases in concave microwell diameter, depth and surface roughness, and the contact angle measurements showed that only the hydrophilicity of P100 microwells was improved. In vitro testing revealed that P100 microwells could effectively promote the adhesion, proliferation and osteogenic differentiation of C3H10T1/2 cells; in vivo studies further confirmed that P100 microwells significantly increased new bone volume, enhanced bone remodeling, and improved material-bone interface bonding force and instigated rapid osteointegration of nHA/PA66 with host bone. However, these phenomena were not observed for P200 and P400 microwells. Overall, P100 was associated with improved cell adhesion, proliferation and osteogenic differentiation in vitro and greater implant fixation in vivo. These results suggest that surface concave microwell treatment of nHA/PA66 material through SLM technology provides a fast, simple and effective method for clinical applications involving bone tissue regeneration.
种植体和活骨的结构和功能组合很大程度上受种植体表面特性的影响。为了增强纳米羟基磷灰石/聚酰胺66 (nHA/PA66)材料骨整合的种植-骨界面,采用选择性激光熔化(SLM)技术在nHA/PA66衬底表面制备了尺寸分别为100 μm、200 μm和400 μm的凹微孔(分别用P100、P200和P400表示)。采用扫描电镜(SEM)、能量色散x射线能谱仪(EDS)、三维扫描激光显微镜和静态水接触角测量等方法分析了样品的表面特征。通过细胞计数试剂盒-8 (CCK-8)、扫描电镜(SEM)、碱性磷酸酶试验、茜素红染色、western blot等检测不同凹孔大小对C3H10T1/2细胞体外粘附、增殖和成骨的影响,并通过显微ct、组织学分析和推出试验继续进行评价,验证其体内骨整合能力。P100、P200和P400的表面改性导致凹孔直径、深度和表面粗糙度显著增加,接触角测量结果表明,只有P100微孔的亲水性得到改善。体外实验表明,P100微孔能有效促进C3H10T1/2细胞的粘附、增殖和成骨分化;体内研究进一步证实P100微孔显著增加新骨体积,增强骨重塑,提高材料-骨界面结合力,促进nHA/PA66与宿主骨快速骨整合。而在P200和P400微孔中没有观察到这些现象。总的来说,P100与体外细胞粘附、增殖和成骨分化的改善以及体内更大的植入物固定有关。这些结果表明,采用SLM技术对nHA/PA66材料进行表面凹微孔处理,为骨组织再生的临床应用提供了一种快速、简单、有效的方法。
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引用次数: 0
Remodeling of Aligned Fibrous Extracellular Matrix by Encapsulated Cells Under Mechanical Stretching 机械拉伸作用下被包裹细胞对排列纤维细胞外基质的重塑
Pub Date : 2020-01-01 DOI: 10.2139/ssrn.3542979
D. Pei, Mengqi Wang, Wenfang Li, Meiwen Li, Qian Liu, Rui Ding, Jing Zhao, Ang Li, Feng Xu, Guorui Jin
Extracellular matrix remodeling is essential for the development and functions of connective tissues (e.g., heart, muscle and periodontal ligament), where ECM is generally with highly anisotropic features and under mechanical stimulation. However, the nature of how cells remodel their surrounding ECM under mechanical stimulation remains elusive. Herein, we encapsulated human periodontal ligament stem cells (hPDLSCs) within the aligned rat collagen scaffold labeled with fluorescein isothiocyanate (FITC) and provided continuous mechanical stimulation by magnetic stretching. Through tracking the FITC-labeled rat collagen scaffold and the newly secreted human type I collagen, we studied the mechanism of aligned ECM remodeling by encapsulated cells under mechanical stretching. We found that the aligned topography combined with magnetic stretching could significantly promote initial ECM degradation and new ECM secretion: the expression of matrix metalloproteinase 1 and 9 are significantly higher, and the elastic modulus increases from 50 kPa to 75 kPa as compared to the random collagen scaffold encapsulating hPDLSCs. Therefore, we decipher that cells remodel their surrounding ECM under continuous stretching through degradation and then secretion of new ECM to integrate with the aligned ECM and maintain tissue functions. Our study holds great potential in optimization of biomaterial scaffold design for clinical translation.
细胞外基质重塑对于结缔组织(如心脏、肌肉和牙周韧带)的发育和功能至关重要,其中ECM通常具有高度各向异性的特征,并受到机械刺激。然而,细胞如何在机械刺激下重塑其周围ECM的本质仍然是难以捉摸的。在这项研究中,我们将人牙周韧带干细胞(hPDLSCs)包裹在用异硫氰酸荧光素(FITC)标记的排列大鼠胶原支架中,并通过磁拉伸提供连续的机械刺激。通过对fitc标记的大鼠胶原支架和新分泌的人I型胶原的跟踪,我们研究了机械拉伸下被包被细胞对ECM排列重构的机制。我们发现,与随机胶原支架包封hPDLSCs相比,排列的地形结合磁拉伸可以显著促进ECM的初始降解和新ECM的分泌:基质金属蛋白酶1和9的表达显著提高,弹性模量从50 kPa增加到75 kPa。因此,我们解释了细胞通过降解和分泌新的ECM来重塑其周围的ECM,从而与排列的ECM整合并维持组织功能。我们的研究在优化临床翻译用生物材料支架设计方面具有很大的潜力。
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引用次数: 1
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EngRN: Biomaterials (Topic)
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