chromophore

发色团
  • 文章类型: Journal Article
    高性能电光材料的制备是决定5G通信等光电通信技术应用的关键因素之一,雷达探测,太赫兹,和电光调制器。有机电光材料具有高电光系数(〜1000pm/V)的优点,可以利用光子器件进行电子学和光子学的芯片级集成,与无机电光材料相比。然而,有机非线性光学材料在商用电光调制器等领域的应用也面临着技术瓶颈。获得具有大电光系数(r33值)的有机电光发色团,热稳定性,而长期稳定仍是行业的难点。这篇简要综述总结了最近的重大进展以及获得具有高电光系数和/或强长期稳定性的高性能OEO材料的策略。D-π-A结构的构型,材料的种类,详细总结了分子工程对发色团电光系数和玻璃化转变温度的影响。还讨论了有机电光材料在实际应用中的难点和未来的发展趋势。
    The preparation of high-performance electro-optical materials is one of the key factors determining the application of optoelectronic communication technology such as 5G communication, radar detection, terahertz, and electro-optic modulators. Organic electro-optic materials have the advantage of a high electro-optic coefficient (~1000 pm/V) and could allow the utilization of photonic devices for the chip-scale integration of electronics and photonics, as compared to inorganic electro-optic materials. However, the application of organic nonlinear optical materials to commercial electro-optic modulators and other fields is also facing technical bottlenecks. Obtaining an organic electro-optic chromophore with a large electro-optic coefficient (r33 value), thermal stability, and long-term stability is still a difficulty in the industry. This brief review summarizes recent great progress and the strategies to obtain high-performance OEO materials with a high electro-optic coefficient and/or strong long-term stability. The configuration of D-π-A structure, the types of materials, and the effects of molecular engineering on the electro-optical coefficient and glass transition temperature of chromophores were summarized in detail. The difficulties and future development trends in the practical application of organic electro-optic materials was also discussed.
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  • 文章类型: Journal Article
    皮肤疾病(如特应性皮炎,痤疮,牛皮癣,脱发和慢性伤口)是第四大最常见的人类疾病,影响了世界近三分之一的人口。皮肤病在全球范围内导致严重的非致命残疾,影响个人,合作伙伴,和整个社会。最近的证据表明,在我们的皮肤及其附属物中定居的特定微生物通常在疾病中占主导地位。因此,以非侵入性和安全的方式操纵微生物组的相互作用为皮肤和毛囊状况的管理提供了有吸引力的方法。由于其已证明的抗微生物和抗炎作用,蓝光(380-495nm)作为管理皮肤生态失调的可能的“魔术子弹”受到了相当大的关注。作为人类,我们在阳光照射的影响下进化,其中包含了很大一部分蓝光。越来越多的证据表明,我们的常驻皮肤微生物组具有通过发色团的表达来检测和响应蓝光的能力。这可以调节生理反应,从细胞毒性到增殖。在这篇综述中,我们首先提出了皮肤微生物组成员表达的不同蓝光敏感发色团的证据。随后,我们讨论了在皮肤和毛囊普遍的情况下,蓝光如何影响宿主与其皮肤微生物组之间的对话。最后,我们研究了这种非侵入性治疗策略的局限性,并概述了进一步研究的前瞻性途径.总的来说,这些发现提供了关于蓝光作为治疗普遍皮肤状况的修复工具的潜在效用的全面证据。此外,他们强调了对理解蓝光对宿主和微生物行为的影响的整个系统方法的关键未满足需求。
    Cutaneous diseases (such as atopic dermatitis, acne, psoriasis, alopecia and chronic wounds) rank as the fourth most prevalent human disease, affecting nearly one-third of the world\'s population. Skin diseases contribute to significant non-fatal disability globally, impacting individuals, partners, and society at large. Recent evidence suggests that specific microbes colonising our skin and its appendages are often overrepresented in disease. Therefore, manipulating interactions of the microbiome in a non-invasive and safe way presents an attractive approach for management of skin and hair follicle conditions. Due to its proven anti-microbial and anti-inflammatory effects, blue light (380 - 495nm) has received considerable attention as a possible \'magic bullet\' for management of skin dysbiosis. As humans, we have evolved under the influence of sun exposure, which comprise a significant portion of blue light. A growing body of evidence indicates that our resident skin microbiome possesses the ability to detect and respond to blue light through expression of chromophores. This can modulate physiological responses, ranging from cytotoxicity to proliferation. In this review we first present evidence of the diverse blue light-sensitive chromophores expressed by members of the skin microbiome. Subsequently, we discuss how blue light may impact the dialog between the host and its skin microbiome in prevalent skin and hair follicle conditions. Finally, we examine the constraints of this non-invasive treatment strategy and outline prospective avenues for further research. Collectively, these findings present a comprehensive body of evidence regarding the potential utility of blue light as a restorative tool for managing prevalent skin conditions. Furthermore, they underscore the critical unmet need for a whole systems approach to comprehend the ramifications of blue light on both host and microbial behaviour.
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  • 文章类型: Journal Article
    吞咽口服固体剂型对于那些有药物吞咽困难的人来说是具有挑战性的。包括吞咽困难的患者。一种选择是将药物(全部或压碎的)与厚载体(药物润滑剂)混合。以前的体外研究一致表明,厚载体可能会影响固体剂型的溶出度,可能影响他们的治疗效果,但不考虑口腔处理和吞咽过程中发生的变化。这项研究旨在研究药物润滑剂对药物释放的潜在影响,并检查口服处理的效果。在有和没有口服处理的情况下,测试了与五种市售药物润滑剂(两种IDDSI2级,两种IDDSI3级和一种IDDSI4级)混合的完整和压碎的扑热息痛片剂的体外溶出;将含/不含扑热息痛的药物润滑剂放入口中(五名健康志愿者),准备吞咽,然后吐出并评估身体特征和药物释放。药物润滑剂,单独和与扑热息痛片混合,口服处理后粘度显着降低。没有口腔处理,IDDSI3级和4级润滑剂显著延迟扑热息痛片剂的溶解。经口处理后,特别是压碎的药片,溶出度大幅增加。这些发现表明溶出度测试高估了药物润滑剂对药物溶出度的影响。因此,不鼓励使用体外溶出试验来预测与浓载体混合的药物的溶出速率。必须考虑将口腔环境和口腔处理的影响纳入用于口服药物给药的厚载体的方法。
    Swallowing oral solid dosage forms is challenging for those who have medication swallowing difficulties, including patients with dysphagia. One option is to mix the drug (whole or crushed) with a thick vehicle (medication lubricant). Previous in vitro studies consistently suggest that thick vehicles could impact the dissolution of solid dosage forms, potentially influencing their therapeutic effectiveness, but do not account for changes that happen during oral processing and swallowing. This study aims to investigate the potential impact of medication lubricants on drug release and examine the effect of oral processing. In vitro dissolution of whole and crushed paracetamol tablets mixed with five commercially available medication lubricants (two IDDSI level 2, two IDDSI level 3, and one IDDSI level 4) were tested with and without oral processing; a medication lubricant with/without paracetamol was placed in the mouth (five healthy volunteers), prepared for swallowing, but then expectorated and assessed for physical characteristics and drug release. Medication lubricants, both alone and mixed with crushed paracetamol tablets, showed a significant decrease in viscosity after oral processing. Without oral processing, IDDSI level 3 and 4 lubricants significantly delayed the dissolution of paracetamol tablets. After oral processing, particularly with crushed tablets, there was a substantial increase in the dissolution rate. These findings suggest that dissolution testing overestimates the impact of medication lubricants on drug dissolution. Therefore, using in vitro dissolution tests to predict the dissolution rate of medications mixed with thick vehicles is discouraged. It is essential to consider ways to incorporate the effects of the oral environment and oral processing on thick vehicles used for oral medication administration.
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  • 文章类型: Journal Article
    氟原子具有许多固有性质,当掺入到小分子中时,这些性质是有益的。这些属性包括原子的大小,电负性,和阻断代谢氧化位点的能力。以氟和含氟基团为特征的取代基目前在降低胆固醇的药物中普遍存在,缓解哮喘,治疗焦虑症,以及改善各种药物和显像剂的化学性质。染料支架(荧光素/罗丹明,香豆素,BODIPY,碳青,和squaraine染料)报告将解决支架中氟原子的掺入及其对其作为成像剂的应用的贡献。在疾病的早期检测中识别用于PET成像的放射性标记的氟原子也是重要的。这篇综述将讨论将氟原子掺入小分子的许多好处,并给出制药工业和成像技术中使用的氟化分子的例子。
    The fluorine atom possesses many intrinsic properties that can be beneficial when incorporated into small molecules. These properties include the atom\'s size, electronegativity, and ability to block metabolic oxidation sites. Substituents that feature fluorine and fluorine-containing groups are currently prevalent in drugs that lower cholesterol, relieve asthma, and treat anxiety disorders, as well as improve the chemical properties of various medications and imaging agents. The dye scaffolds (fluorescein/rhodamine, coumarin, BODIPY, carbocyanine, and squaraine dyes) reported will address the incorporation of the fluorine atom in the scaffold and the contribution it provides to its application as an imaging agent. It is also important to recognize radiolabeled fluorine atoms used for PET imaging in the early detection of diseases. This review will discuss the many benefits of incorporating fluorine atoms into small molecules and give examples of fluorinated molecules used in the pharmaceutical industry and imaging techniques.
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  • 文章类型: Journal Article
    视紫红质(Rho)和视锥视蛋白对于检测光至关重要。它们通过光异构化反应,将它们的席夫碱加成的11-顺式-视黄基发色团转化为全反式构型,引发构象变化以激活视蛋白信号。随后的希夫碱水解释放全反式视网膜,启动保持连续视力的两个重要周期-Rho光循环和视觉周期通路。希夫碱水解已使用光活化视紫红质进行了彻底研究,但未使用视锥细胞。使用既定的方法,我们直接测量了视网膜发色团与哺乳动物视觉和非视觉视蛋白之间席夫碱的形成。接下来,我们确定了光诱导发色团水解的速率。我们发现,光活化视锥视蛋白的视网膜水解明显快于光活化视紫红质。牛视网膜G蛋白偶联受体RGR(bRGR)显示其11-顺式-视黄叉光产物的快速水解,以快速提供11-顺式-视黄醛,重新结合全反式视网膜。天然视网膜色素上皮(RPE)微粒体膜中bRGR内的水解比洗涤剂胶束中纯化的bRGR快6倍。N-末端靶向抗体显著减缓bRGR水解,而C端抗体没有影响。我们的研究强调了锥形视蛋白相对于Rho的光循环要快得多,以及RGR在白天发色团回收中的关键作用。相比之下,在我们的实验条件下,牛过视蛋白(bRRH)在全反式视网膜的存在下不形成色素,也没有任何单顺式视网膜异构体,不确定这种视蛋白作为光传感器的作用。
    Rhodopsin (Rho) and cone opsins are essential for detection of light. They respond via photoisomerization, converting their Schiff-base-adducted 11-cis-retinylidene chromophores to the all-trans configuration, eliciting conformational changes to activate opsin signaling. Subsequent Schiff-base hydrolysis releases all-trans-retinal, initiating two important cycles that maintain continuous vision-the Rho photocycle and visual cycle pathway. Schiff-base hydrolysis has been thoroughly studied with photoactivated Rho but not with cone opsins. Using established methodology, we directly measured the formation of Schiff-base between retinal chromophores with mammalian visual and nonvisual opsins of the eye. Next, we determined the rate of light-induced chromophore hydrolysis. We found that retinal hydrolysis from photoactivated cone opsins was markedly faster than from photoactivated Rho. Bovine retinal G protein-coupled receptor (bRGR) displayed rapid hydrolysis of its 11-cis-retinylidene photoproduct to quickly supply 11-cis-retinal and re-bind all-trans-retinal. Hydrolysis within bRGR in native retinal pigment epithelium microsomal membranes was >6-times faster than that of bRGR purified in detergent micelles. N-terminal-targeted antibodies significantly slowed bRGR hydrolysis, while C-terminal antibodies had no effect. Our study highlights the much faster photocycle of cone opsins relative to Rho and the crucial role of RGR in chromophore recycling in daylight. By contrast, in our experimental conditions, bovine peropsin did not form pigment in the presence of all-trans-retinal nor with any mono-cis retinal isomers, leaving uncertain the role of this opsin as a light sensor.
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  • 文章类型: Journal Article
    在这项工作中,我们合成了一种绿色荧光染料衍生物,1,3,5,7-四甲基-BODIPY,在8位具有庚基取代基。所获得的高度疏水性化合物能够快速且不可逆地结合真核细胞。将细胞与染料一起孵育不同的时间或以不同的浓度使我们能够控制细胞标记的程度和荧光水平。这使得可以调节不同真核细胞培养物的荧光水平,然后在细胞计数实验中通过绿色通道中的荧光信号水平来区分它们。可以在相同条件下使用染料不发荧光的通道在同一试管中组合并进一步分析标记的细胞。这种方法已经在许多在其表面上含有HER2受体的肿瘤细胞培养物上进行了测试。使用基于杂合蛋白DARPin9_29-mCherry的HER2特异性配体,在一次运行中在一个试管中分析了这些细胞中受体的代表,在光谱的红色区域发出荧光。
    In this work, we synthesized a green fluorescent dye derivative, 1,3,5,7-tetramethyl-BODIPY, with a heptyl substituent at the 8-position. The obtained highly hydrophobic compound was able to rapidly and irreversibly bind to eukaryotic cells. Incubation of cells with the dye over different periods of time or at different concentrations allowed us to control the degree of cell labeling and the level of fluorescence. This made it possible to modulate the fluorescence level of different eukaryotic cell cultures and then distinguish them by their level of fluorescence signal in the green channel in cytometric experiments. The labeled cells can be combined and further analyzed in the same test tube under identical conditions using the channels in which the dye does not fluoresce. This approach has been tested on a number of tumor cell cultures containing the HER2 receptor on their surface. The representation of the receptor in these cells was analyzed in one test tube in one run using a HER2-specific ligand based on the hybrid protein DARPin9_29-mCherry, which fluoresces in the red region of the spectrum.
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  • 文章类型: Journal Article
    在白天,对视觉发色团(11-顺式视网膜)的需求超过了经典视觉周期的供应。这种不足得到了补偿,在某种程度上,视网膜G蛋白偶联受体(RGR)光异构酶,在视网膜色素上皮(RPE)和Müller细胞中表达。RGR的这两个细胞池对维持感光体光响应的相对贡献是未知的。这里,我们使用细胞特异性基因再激活方法来阐明光照后RGR介导的光感受器反应恢复的动力学。在RGR表达仅限于任一细胞类型的小鼠中进行的视网膜电图测量表明,RPE和Müller神经胶质的专门子集对暗视和明视功能都有贡献。我们证明了通过光异构化形成的11-顺式视网膜是快速水解的,与它在快速视觉色素再生过程中的作用一致。我们的研究表明,RGR为在持续光照条件下释放的全反式视网膜提供了全视网膜槽,并通过光视觉周期支持快速生色团再生。
    In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.
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  • 文章类型: Journal Article
    过氧化氢是在终止气相化学和在冷凝相中的硫酸盐形成方面重要的主要大气氧化剂。实验室实验表明,过氧化氢在晶界产生了意想不到的氧化加速作用。虽然晶界在天然冰雪中很常见,并且已知含有杂质,目前尚不清楚过氧化氢如何以及在多大程度上进入该水库。我们提供了第一个实验证据,证明过氧化氢直接从气相扩散到晶界中。我们已经加工了一种新颖的流动反应器系统,该系统具有钻孔的冰流管,使我们能够辨别冰粒边界含量对吸收的影响。Further,在235至258K的温度下,对冰表面的吸附进行了量化。解开这两种吸收过程的贡献表明,在与极地环境相关的温度下,过氧化氢从大气到雪的转移比以前认为的要明显得多。Further,扩散吸收到晶界似乎是非酸性痕量气体填充雪晶界中高反应性杂质储层的一种新机制。
    Hydrogen peroxide is a primary atmospheric oxidant significant in terminating gas-phase chemistry and sulfate formation in the condensed phase. Laboratory experiments have shown an unexpected oxidation acceleration by hydrogen peroxide in grain boundaries. While grain boundaries are frequent in natural snow and ice and are known to host impurities, it remains unclear how and to which extent hydrogen peroxide enters this reservoir. We present the first experimental evidence for the diffusive uptake of hydrogen peroxide into grain boundaries directly from the gas phase. We have machined a novel flow reactor system featuring a drilled ice flow tube that allows us to discern the effect of the ice grain boundary content on the uptake. Further, adsorption to the ice surface for temperatures from 235 to 258 K was quantified. Disentangling the contribution of these two uptake processes shows that the transfer of hydrogen peroxide from the atmosphere to snow at temperatures relevant to polar environments is considerably more pronounced than previously thought. Further, diffusive uptake to grain boundaries appears to be a novel mechanism for non-acidic trace gases to fill the highly reactive impurity reservoirs in snow\'s grain boundaries.
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  • 文章类型: Journal Article
    视觉视蛋白的光循环对于维持视网膜的光敏感性至关重要。Böll和Kühne在1870年代对视紫红质光循环的早期物理观察启发了一个多世纪以来对视紫红质生物化学的研究。单光子异构化视紫红质的希夫碱连接的11-顺式-视黄基发色团,将其转换为全反式激动剂,以通过光活化视紫红质(Rho*)引起光转导。该激动剂的希夫碱水解是光循环中的关键步骤,不仅减少正在进行的光转导,而且还允许新鲜的11-顺式发色团进入和结合,以再生视紫红质色素并保持光敏性。在测量这种水解速率时遇到了许多挑战,但是最近的进展促进了对视紫红质天然膜环境中水解的研究。这些技术现在可以应用于研究介导光转导或发色团周转的其他视蛋白中激动剂的水解。在这次审查中,我们讨论了在表征视紫红质光循环方面取得的进展,以及表征其全反式-视黄叉基激动剂水解的过程。
    The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century\'s worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff-base linked 11-cis-retinylidene chromophore of rhodopsin, converting it to the all-trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11-cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all-trans-retinylidene agonist.
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  • 文章类型: Journal Article
    为了持续的视力,光活化视紫质(Rho*)必须经历水解和释放的全反式视网膜,产生视觉周期的底物和可用于11-顺式视网膜再生的apo-视蛋白。对于视紫红质在其天然膜环境中的这种水解的动力学尚待描述。我们开发了一种由异丙醇/硼氢化物同时变性和生色团捕获组成的方法,接着是详尽的蛋白质消化,完全提取,和液相色谱-质谱联用。使用我们的方法,我们追踪了Rho*水解,随后与释放的全反式视网膜形成N-视黄亚甲基-磷脂酰乙醇胺(N-ret-PE)加合物,并将全反式视黄醛还原为全反式视黄醇。我们发现,与通常用于研究膜蛋白的洗涤剂胶束相比,天然膜中的水解发生得更快。天然膜中水解的活化能测定为17.7±2.4kcal/mol。我们的数据支持的解释,视紫红质的信号状态,是经历水解和释放其全反式视网膜的主要物种。在没有NADPH的情况下,游离的全反式视黄醛与磷脂酰乙醇胺(PE)反应,形成大量的N-ret-PE(在生理pH值下约占全部全反式视网膜的40%),比Rho*水解快一个数量级的速率。然而,通过NADPH依赖性地将全反式视黄醛还原为全反式视黄醇,N-ret-PE形成被高度减弱。N-ret-PE形成和全反式-视网膜还原均不影响Rho*的水解速率。我们的研究提供了Rho*的水解和全反式视网膜的释放及其重新进入视觉周期的全面图片,改变可导致严重视网膜病变的过程。
    For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all-trans-retinal, producing substrate for the visual cycle and apo-opsin available for regeneration with 11-cis-retinal. The kinetics of this hydrolysis has yet to be described for rhodopsin in its native membrane environment. We developed a method consisting of simultaneous denaturation and chromophore trapping by isopropanol/borohydride, followed by exhaustive protein digestion, complete extraction, and liquid chromatography-mass spectrometry. Using our method, we tracked Rho* hydrolysis, the subsequent formation of N-retinylidene-phosphatidylethanolamine (N-ret-PE) adducts with the released all-trans-retinal, and the reduction of all-trans-retinal to all-trans-retinol. We found that hydrolysis occurred faster in native membranes than in detergent micelles typically used to study membrane proteins. The activation energy of the hydrolysis in native membranes was determined to be 17.7 ± 2.4 kcal/mol. Our data support the interpretation that metarhodopsin II, the signaling state of rhodopsin, is the primary species undergoing hydrolysis and release of its all-trans-retinal. In the absence of NADPH, free all-trans-retinal reacts with phosphatidylethanolamine (PE), forming a substantial amount of N-ret-PE (∼40% of total all-trans-retinal at physiological pH), at a rate that is an order of magnitude faster than Rho* hydrolysis. However, N-ret-PE formation was highly attenuated by NADPH-dependent reduction of all-trans-retinal to all-trans-retinol. Neither N-ret-PE formation nor all-trans-retinal reduction affected the rate of hydrolysis of Rho*. Our study provides a comprehensive picture of the hydrolysis of Rho* and the release of all-trans-retinal and its reentry into the visual cycle, a process in which alteration can lead to severe retinopathies.
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