CAGEs

笼子
  • 文章类型: Journal Article
    碳硼烷研究领域不断发展,导致各种应用的结晶多孔材料的建设和发展。此外,创新的合成方法在这一领域正在扩大。自2007年首次报道碳硼烷基结晶多孔材料(CCPMs)以来,碳硼烷配体的合成,特别是通过创新的方法,hasconsistentlyposedasignificantchallengeindiscoveringnewstructureofCCPMs.ThispaperprovidesacomprehensivesummaryofrecentadvancesinvarioussyntheticapproachesforCCPMs,以及它们在不同领域的应用。预计主要挑战和未来机遇将刺激CCPM领域的进一步多学科发展。
    The field of carborane research has witnessed continuous development, leading to the construction and development of a diverse range of crystalline porous materials for various applications. Moreover, innovative synthetic approaches are expanding in this field. Since the first report of carborane-based crystalline porous materials (CCPMs) in 2007, the synthesis of carborane ligands, particularly through innovative methods, has consistently posed a significant challenge in discovering new structures of CCPMs. This paper provides a comprehensive summary of recent advances in various synthetic approaches for CCPMs, along with their applications in different domains. The primary challenges and future opportunities are expected to stimulate further multidisciplinary development in the field of CCPMs.
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  • 文章类型: Journal Article
    杂配PdnAnBn装配类中的两个新的结构基序,即syn-cis-Pd3A3B3碗和碗-(syn)或鞍形(反)顺式Pd4A4B4环被引入。所有的十个例子共享一个共同的更长的基于芴酮的双单齿配体,配备间吡啶供体基团。戒指尺寸(3-vs.4元)和构象偏好(碗与鞍座)通过选择较短的配体来控制。这些带有对吡啶供体,不同的芳香骨架(苯,噻吩或硒酚),并且没有或小或大体积的内面体取代基,通过不同的效应(配体角度,电荷分布或骨干散装)。此外,芴酮配体的发光在形成的结构中是保守的。发射强度以及主客体性质取决于向内指向函数。所有Pd3A3B3组件均显示为结合手性客体BINOL双磺酸盐,从而将其手性赋予整个主体-客体复合物。这导致客体诱导的圆二色性(CD)和圆偏振发光(CPL),其不对称因子glum高达10-3。
    Two new structural motifs within the class of heteroleptic PdnAnBn assemblies, namely syn-cis-Pd3A3B3 bowls and bowl- (syn) or saddle- (anti) shaped cis-Pd4A4B4 rings are introduced. All of the ten examples share a common longer fluorenone-based bis-monodentate ligand, equipped with meta-pyridine donor groups. The ring size (3- vs. 4-membered) and conformational preference (bowl vs. saddle) are controlled by the choice of the shorter ligand. These carry para-pyridine donors, different aromatic backbones (benzene, thiophene or selenophene) and either no or small or bulky endohedral substituents, serving to control the nuclearity of the heteroleptic rings through different effects (ligand angle, charge distribution or backbone bulk). Moreover, the luminescence of the fluorenone ligand is conserved in the formed architectures. Emission intensity as well as host-guest properties vary depending on the inward-pointing functions. All Pd3A3B3 assemblies are shown to bind chiral guest BINOL bis-sulfonate which imparts its chirality to the entire host-guest complex. This results in a guest-induced circular dichroism (CD) and circularly polarized luminescence (CPL) with dissymmetry factor glum up to 10-3.
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  • 文章类型: Journal Article
    已知组蛋白脱乙酰酶9(HDAC9)在各种癌症中上调。癌症相关抗原(CAGE)是在抗癌药物耐药性中起重要作用的癌症/睾丸抗原。本研究旨在探讨CAGE和HDAC9与抗癌药物耐药的关系。具有抗癌药物抗性表型的AGSR细胞显示比正常AGS细胞更高水平的CAGE和HDAC9。CAGEs调控AGS和AGSR细胞中HDAC9的表达。CAGEs直接调控HDAC9的表达。雷帕霉素,自噬的诱导剂,AGS中HDAC9表达增加,而氯喹降低AGSR细胞中HDAC9的表达。HDAC9的下调降低了自噬通量,入侵,迁移,和AGSR细胞中的肿瘤球状体形成潜力。TargetScan分析预测miR-512是HDAC9的负调节因子。miR-512模拟物降低CAGE和HDAC9的表达水平。miR-512模拟物也降低了自噬通量,入侵,迁移,和AGSR细胞的肿瘤球体形成潜力。AGSR的培养基增加了AGS中HDAC9的表达和自噬通量。人重组CAGE蛋白增加AGS细胞中HDAC9的表达。AGSR细胞显示出比AGS细胞更高的致瘤潜能。总之,我们的结果表明,CAGE-HDAC9-miR-512可以调节抗癌药物的耐药性,细胞增殖,和自噬通量。我们的研究结果有助于理解HDAC9在抗癌药物耐药性中的分子作用。
    Histone deacetylase 9 (HDAC9) is known to be upregulated in various cancers. Cancer-associated antigens (CAGEs) are cancer/testis antigens that play an important role in anti-cancer drug resistance. This study aimed to investigate the relationship between CAGEs and HDAC9 in relation to anti-cancer drug resistance. AGSR cells with an anti-cancer drug-resistant phenotype showed higher levels of CAGEs and HDAC9 than normal AGS cells. CAGEs regulated the expression of HDAC9 in AGS and AGSR cells. CAGEs directly regulated the expression of HDAC9. Rapamycin, an inducer of autophagy, increased HDAC9 expression in AGS, whereas chloroquine decreased HDAC9 expression in AGSR cells. The downregulation of HDAC9 decreased the autophagic flux, invasion, migration, and tumor spheroid formation potential in AGSR cells. The TargetScan analysis predicted that miR-512 was a negative regulator of HDAC9. An miR-512 mimic decreased expression levels of CAGEs and HDAC9. The miR-512 mimic also decreased the autophagic flux, invasion, migration, and tumor spheroid forming potential of AGSR cells. The culture medium of AGSR increased the expression of HDAC9 and autophagic flux in AGS. A human recombinant CAGE protein increased HDAC9 expression in AGS cells. AGSR cells displayed higher tumorigenic potential than AGS cells. Altogether, our results show that CAGE-HDAC9-miR-512 can regulate anti-cancer drug resistance, cellular proliferation, and autophagic flux. Our results can contribute to the understanding of the molecular roles of HDAC9 in anti-cancer drug resistance.
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  • 文章类型: Journal Article
    分子构建块,能够采用几种强烈偏离的构象,在刺激响应自组装的发展中特别感兴趣。短吖啶酮基桥接配体的显着结构灵活性,配备两个单齿异喹啉供体,在本文中,其用于组装令人惊讶的多样化系列的协调驱动的Pd(II)架构。首先,它可以形成高度扭曲的Pd2L4螺旋,可转化为相应的中间位置,受温度控制,反阴离子和溶剂的选择。第二,它还允许形成异位笼,来自配体与Pd(II)阳离子的混合物,或通过同质组装的笼到笼转化。这里,基于吖啶酮的配体耐受以发散或会聚的排列携带其供体的反配体,因为它可以将自己的配位位点旋转90°,并通过形状互补在结构上适应两种情况。第三,只有一只手臂旋转近180°,配体可以采用S形构象,并形成前所未有的C6h对称Pd6L12锯齿形六元环。
    Molecular building blocks, capable of adopting several strongly deviating conformations, are of particular interest in the development of stimuli-responsive self-assemblies. The pronounced structural flexibility of a short acridone-based bridging ligand, equipped with two monodentate isoquinoline donors, is herein exploited to assemble a surprisingly diverse series of coordination-driven Pd(II) architectures. First, it can form a highly twisted Pd2L4 helicate, transformable into the corresponding mesocate, controlled by temperature, counter anion and choice of solvent. Second, it also allows the formation of heteroleptic cages, either from a mix of ligands with Pd(II) cations or by cage-to-cage transformation from homoleptic assemblies. Here, the acridone-based ligand tolerates counter ligands that carry their donors either in a diverging or converging arrangement, as it can rotate its own coordination sites by 90° and structurally adapt to both situations via shape complementarity. Third, by a near 180° rotation of only one of its arms, the ligand can adopt an S-shape conformation and form an unprecedented C6h-symmetric Pd6L12 saw-toothed six-membered ring.
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  • 文章类型: Journal Article
    背景:严重骨质流失的髋臼重建方案仍然有限,迄今为止发表的比较研究很少。这项研究的目的是比较使用多孔金属补片对杯笼和三法兰假体进行翻修全髋关节置换术(THA)治疗严重骨质流失的结果。
    方法:我们回顾了连续的180例患者,这些患者患有Poprosky3A或3B髋臼缺损并接受了THA翻修。将接受多孔增强剂治疗的患者(n=141)与接受杯笼或三法兰结构的患者(n=39)进行比较。髋臼结构的失败被定义为接受髋臼翻修手术或放射学证据的松动。
    结果:接受多孔补片或笼形或三法兰假体翻修THA的患者髋臼组件生存率无差异(92.2对87.2%,P=0.470),平均随访6.6±3.4年。两组之间无任何翻修手术的总生存率相当(78.7对79.5%,P=0.720)。位错也没有差异(5.7对10.3%,P=0.309)或假体周围感染率(7.8对10.3%,P=0.623)。在对骨盆不连续性患者的亚组分析中(n=47),两组之间无任何翻修手术的生存率相当(79.5对72.2%,P=0.543)。
    结论:在严重髋臼骨丢失的情况下,多孔金属增强剂在中期(平均6.6年)随访时表现出优异的生存率,即使在骨盆不连续的情况下,具有与杯笼和三法兰相当的结果。不稳定和感染仍然是该患者人群失败的主要原因。需要长期随访。
    BACKGROUND: Acetabular reconstruction options in the setting of severe bone loss remain limited, with few comparative studies published to date. The purpose of this study was to compare the outcomes of revision total hip arthroplasty (THA) for severe bone loss using porous metal augments to cup cage and triflange prostheses.
    METHODS: We reviewed a consecutive series of 180 patients who had Paprosky 3A or 3B acetabular defects and underwent revision THA. Patients treated with porous augments (n = 141) were compared with those who received cup cages or triflange constructs (n = 39). Failure of the acetabular construct was defined as undergoing acetabular revision surgery or radiographic evidence of loosening.
    RESULTS: There was no difference in acetabular component survivorship in patients undergoing revision THA with porous augments or a cage or triflange prosthesis (92.2 versus 87.2%, P = .470) at a mean follow-up of 6.6 ± 3.4 years. Overall, survivorship free from any revision surgery was comparable between the 2 groups (78.7 versus 79.5%, P = .720). There was also no difference in dislocation (5.7 versus 10.3%, P = .309) or periprosthetic joint infection rates (7.8 versus 10.3%, P = .623). In a subgroup analysis of patients who had pelvic discontinuity (n = 47), survivorship free from any revision surgery was comparable between the 2 groups (79.5 versus 72.2%, P = .543).
    CONCLUSIONS: Porous metal augments in the setting of severe acetabular bone loss demonstrated excellent survivorship at intermediate-term (mean 6.6 years follow-up, even in cases of pelvic discontinuity, with comparable outcomes to cup cages and triflanges. Instability and infection remain major causes of failure in this patient population, and long-term follow-up is needed.
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  • 文章类型: Journal Article
    虽然金属介导的自组装是构建离散纳米物体的流行技术,高度对称的结构,一次由一种配体构建,占主导地位的报告系统。一组不同配体的定制整合需要复杂的方法来避免自恋分离或形成统计混合物。这里,我们演示了三种结构导向效应(金属模板大环化,基于Co(III)salphen金属节点的其他桥接配体和形状互补性)允许合理且高产地合成结构络合物,灯笼形笼与多达四个可区分的桥梁。以一锅反应方法合成了三个新的基于双核Co(III)salphen大环的异配配位笼,并对其进行了充分的表征,包括单晶X射线分析。一个笼组两个相同的配体,围绕对称Co2-bis-salphen环的另外两种不同的配体。在最复杂的结构中,这个环是不对称的,使两个金属中心之间的所有四个连接都可区分。虽然围绕Pd(II)节点的异质组装已被证明是动态的,有利于笼子到笼子的转换,装配级联和自适应系统,本文引入的基于动力学上更惰性的Co(III)salphen的笼将有利于在需要增强的结构和化学稳定性的类酶催化和分子机器中的应用。
    While metal-mediated self-assembly is a popular technique to construct discrete nanosized objects, highly symmetric structures, built from one type of ligand at a time, are dominating reported systems. The tailored integration of a set of different ligands requires sophisticated approaches to avoid narcissistic separation or formation of statistical mixtures. Here, we demonstrate how the combination of three structure-guiding effects (metal-templated macrocyclization, additional bridging ligands and shape-complementarity) based on Co(III)salphen metal nodes allows for a rational and high-yielding synthesis of structurally complex, lantern-shaped cages with up to four differentiable bridges. Three new heteroleptic coordination cages based on dinuclear Co(III)salphen macrocycles were synthesized in a one-pot reaction approach and fully characterized, including single crystal X-ray analyses. One cage groups two of the same ligands, another two different ligands around a symmetric Co2-bis-salphen ring. In the most complex structure, this ring is unsymmetric, rendering all four connections between the two metal centers distinguishable. While heteroleptic assembly around Pd(II) nodes has been shown to be dynamic, beneficial for cage-to-cage transformations, assembly cascades and adaptive systems, the herein introduced cages based on kinetically more inert Co(III)salphen will be advantageous for applications in enzyme-like catalysis and molecular machinery that require enhanced structural and chemical stability.
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  • 文章类型: Journal Article
    背景:机械生物学可以通过提供对骨愈合和融合所需的机械环境的见解来帮助优化脊柱融合。这包括了解最佳加载条件,植入材料的机械性能,以及机械刺激对参与骨形成的细胞的影响。本文回顾了脊柱融合器的表面技术和植入物修饰在增强脊柱融合方面的证据。
    方法:使用的数据库包括Embase,MEDLINE,Springer,科克伦图书馆使用特定的关键字和搜索字段识别相关文章。只有系统的审查,荟萃分析,评论文章,包括英文的原始研究文章。两名研究人员独立进行搜索和选择过程。文章提供了搜索策略和研究选择方法的流程图。
    结果:研究表明,表面修饰可以通过促进细胞粘附来显着增强骨整合和椎体间融合,扩散,分化,和矿化。各种表面改性技术,如涂层,蚀刻,纳米形貌,和功能化实现了这一点。同样,种植体材料改性可以提高种植体的稳定性,生物相容性,和生物活性,导致更好的融合结果。机械生物学通过影响细胞对机械线索的反应和促进骨形成在这一过程中起着至关重要的作用。
    结论:综述的研究表明,表面技术和植入材料改性是提高脊柱融合成功率的有希望的方法。机械生物学通过影响细胞对机械信号的反应并促进骨骼生长而在此过程中至关重要。
    BACKGROUND: Mechanobiology can help optimize spinal fusion by providing insights into the mechanical environment required for bone healing and fusion. This includes understanding the optimal loading conditions, the mechanical properties of implanted materials, and the effects of mechanical stimuli on the cells involved in bone formation. The present article reviews the evidence for surface technologies and implant modification of spinal cages in enhancing spinal fusion.
    METHODS: Databases used included Embase, MEDLINE, Springer, and Cochrane Library. Relevant articles were identified using specific keywords and search fields. Only systematic reviews, meta-analyses, review articles, and original research articles in English were included. Two researchers independently performed the search and selection process. A flowchart of the search strategy and study selection method is provided in the article.
    RESULTS: The studies indicate that surface modification can significantly enhance osseointegration and interbody fusion by promoting cellular adhesion, proliferation, differentiation, and mineralization. Various surface modification techniques such as coating, etching, nanotopography, and functionalization achieve this. Similarly, implant material modification can improve implant stability, biocompatibility, and bioactivity, leading to better fusion outcomes. Mechanobiology plays a vital role in this process by influencing the cellular response to mechanical cues and promoting bone formation.
    CONCLUSIONS: The studies reviewed indicate that surface technologies and implant material modification are promising approaches for improving the success of spinal cage fusion. Mechanobiology is critical in this process by influencing the cellular response to mechanical signals and promoting bone growth.
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  • 文章类型: Journal Article
    向Buckminster富勒烯C60中添加两种不对称的丙二酸酯可导致22种光谱上可区分的异构产物,因此代表了强大的合成挑战。在这项工作中,我们实现了87%的选择性,形成一个单一的(在,通过三种方法结合使用外反式-3)异构体:(I)我们使用起始材料,其中两个丙二酸酯共价连接(系链方法);(ii)我们形成了具有形状持久性[10]CPP大环的C60强超分子复合物(模板方法)和(iii)我们将该复合物进一步嵌入自组装纳米胶囊中(荫罩方法)。间隔链的变化揭示了该方法的局限性,并在具有原子分辨率的硅片中研究了异常[2]连环烷烃中的环动力学。这项工作显着扩大了包含环对亚苯基(CPP)的机械互锁结构的范围。
    The addition of two unsymmetric malonate esters to the Buckminster fullerene C60 can lead to 22 spectroscopically distinguishable isomeric products and therefore represents a formidable synthesis challenge. In this work, we achieve 87 % selectivity for the formation of a single (in,out-trans-3) isomer by combining three approaches: (i) we use a starting material, in which the two malonates are covalently connected (tether approach); (ii) we form the strong supramolecular complex of C60 with the shape-persistent [10]CPP macrocycle (template approach) and (iii) we embed this complex further within a self-assembled nanocapsule (shadow mask approach). Variation of the spacer chain shed light on the limitations of the approach and the ring dynamics in the unusual [2]catenanes were studied in silico with atomistic resolution. This work significantly widens the scope of mechanically interlocked architectures comprising cycloparaphenylenes (CPP).
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  • 文章类型: Journal Article
    碳水化合物的识别在许多生物过程中起着关键作用。因此,人工受体已经被合成来模拟这些生物系统。迄今为止,据报道,大多数碳水化合物络合的受体都存在高度对称的空腔,可能是因为他们的合成需要较少的合成努力,更容易实现和控制。然而,碳水化合物显示复杂,不对称结构表明具有低对称性的宿主可能更适合识别这些客人。这里,我们描述了用于将碳水化合物与呈现低对称性的大环和笼复合的策略,以及这种方法的潜力。首先描述了自组装的笼子,然后给出了共价大环和笼,对于每个示例,将低对称性系统的结合特性与高对称性系统的结合特性进行了比较。
    The recognition of carbohydrate plays a key role in numerous biological processes. Thus, artificial receptors have been synthesized to mimic these biological systems. To date, most of the receptors reported for carbohydrate complexation present highly symmetrical cavities, probably because their syntheses require less synthetic efforts and are easier to achieve and control. However, carbohydrates display complex, asymmetrical structures suggesting that hosts with low symmetry might be more adapted to recognize these guests. Here, we described the strategies that have been used to complex carbohydrates with macrocycles and cages presenting low symmetry and the potential of this approach. Self-assembled cages are first described, then covalent macrocycles and cages are presented and for each example the binding properties of low-symmetry systems are compared to those of their higher-symmetry counterparts.
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  • 文章类型: News
    涉及动物的研究仍然是增加我们对人类和动物身体如何工作的理解的重要工具;疾病如何影响它们以及化学品的安全性评估,比如杀虫剂,它们对人类健康或环境的可能影响;以及如何通过开发和测试人类或动物的药物和疫苗来预防或治疗疾病。以发展中国家的动物操作和实验为基础,实现高质量的科学,实验动物的适当福利需要成为所有相关人员的必要条件。ACURET.ORG在促进发展中国家的人道动物护理和科学用途方面处于最前沿,专注于非洲,寻求帮助和促进机构实验室动物计划的方面,除了其培训和教育计划,在过去的11年中,自8年前成立和成立以来。ACURET已着手进行标记为“ACURETCage财团项目”的项目,为小鼠和大鼠提供可重复使用的“开放式”笼子,以代替在非洲许多设施中用于容纳此类动物的多种人造住房材料。ACURET正在寻找旧的但功能性的笼子和配件,仍然“适合目的”;其他畜牧业和研究设备,作为机构和行业的捐赠,分发给非洲的机构,这些机构需要他们改善实验室动物福利计划。在实验动物有限公司的分阶段资助下,ACURET将负责从各个地点收集捐赠物品,重新包装它们,以便海运到拉各斯的NIMR,从那里它们将被分发到成功应用机构动物设施,在\'先到,首先服务的基础。ACURET笼联盟项目的核心是使非洲的研究人员能够在他们所照顾和使用的实验动物的福利得到确认后,参与其研究的实质。最终,我们预计,该项目将支持提高对在发展中国家从事人道动物护理和用于科学目的的非洲人的标准。
    Research involving animals remains an essential tool to increase our understanding of how human and animal bodies work; how diseases affect them and the safety assessment of chemicals, such as pesticides, for their possible effects on human health or the environment; and how diseases can be prevented or treated via developing and testing medicines and vaccines for humans or animals. To achieve high quality science based on animal manipulations and experimentations from developing countries, adequate welfare of the lab animals needs to become sine qua non for all concerned.ACURET.ORG is in the forefront of promoting humane animal care and use for scientific purposes in developing countries, with focus on Africa, seeking to aid and facilitate aspects of Institutional Lab Animal programmes in addition to its training and education programmes in the last 11 years since its inception and incorporation eight years ago. ACURET has embarked upon a project tagged \'ACURET Cage Consortium Project\', the provision of re-usable \'open-top\' cages for mice and rats in place of the many varied artificial housing materials being used to hold such animals in many facilities in Africa. ACURET is seeking old but functional cages and accessories, still \'fit for purpose\'; other animal husbandry and research equipment, as donations from institutions and industry for distribution to institutions in Africa who require them to improve their lab animal welfare programme.With a phased funding support from Laboratory Animal Ltd., ACURET will be responsible for the collection of donated items from locations, re-package them for sea-shipping to NIMR in Lagos, from where they will be distributed to successful applying institutional animal facilities, on a \'first come, first served\' basis.At the heart of the ACURET Cage Consortium Project is the enablement of researchers in Africa to engage in the essence of their research when the welfare of the laboratory animals they care for and use has been affirmed. Ultimately, we anticipate that the project will support raising the bar on Africans skilled in humane animal care and use for scientific purposes in developing countries.
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