太赫兹技术在生物医学中的应用

在人类可持续发展的道路上,生物医学研究始终处于核心地位。太赫兹(THz)技术依靠其自身的优势,在生物医学领域得到了广泛的应用。本文着重介绍了太赫兹表征技术以及太赫兹生物效应在生物医学方面的应用。太赫兹表征技术应用领域的介绍主要分为5个部分:氨基酸和多肽、DNA、蛋白质、癌症的检测和龋齿诊断等其他领域的应用。太赫兹生物效应的研究则集中于THz对机体组织和细胞的作用上。此外,本文简单介绍了化学计量学方法以及其与THz技术结合在生物医学方面的应用。最后总结了THz技术在生物医学领域的不足,并对进一步研究的方向进行了讨论。本文主要对太赫兹技术在生物医学方面的应用进行综述,为相关研究奠定了基础。     

太赫兹(THz)光谱在生物大分子研究中的应用

太赫兹(THz)辐射是一种新型的远红外相干辐射源,近年来,在生物大分子研究中得到了广泛的应用,特别是在生物分子的结构和动力学特性等方面有着巨大的应用潜力.结合THz光谱的特点,介绍了利用THz光谱对蛋白质、糖类及DNA等生物大分子的探索研究,以及THz技术在测定水环境与生物分子相互作用等方面的应用.探讨了该技术在生物学领域应用中有待解决的问题及发展前景.     

盐酸胍诱导CP43和CP47变性的太赫兹时域光谱技术研究

太赫兹时域光谱技术(THz-TDS)是近年来新兴的一种研究分子构型状态的技术. 把这项技术运用到两种光合膜蛋白CP43和CP47的研究上, 研究结果表明, 运用太赫兹时域光谱技术能有效地把具有相似结构的蛋白质区分开来, 这项技术也是监测蛋白质变性的一种有力工具. 在盐酸胍(GuHCl)作用下, CP47和游离叶绿素a(Chl a)的太赫兹(THz)振幅谱中都出现一个明显的位于1.8 THz处的峰. 我们认为这个峰来自于叶绿素a和盐酸胍的相互作用. 和CP43相比, CP47中的叶绿素a更易于和盐酸胍发生作用.     

褪黑素的太赫兹时域光谱

太赫兹时域光谱技术是一种新兴的无损探测技术。利用太赫兹波的低能性以及大部分生物分子的振动跃迁和旋转在该频段表现出的强色散和吸收作用等特点,可以对生物分子及生命体的活动进行无损探测和研究。本文分别采用透射式和反射式太赫兹时域光谱系统,对不同质量比的褪黑素压片进行测试,分析它在太赫兹波段的光学性质,发现它在0.29、0.50、0.70、0.91、1.20、2.17和2.55 THz处存在特征吸收峰;频域谱的强度随样品浓度的变化呈线性关系。利用Gaussian 09及Gaussian VIEW软件进行模拟分析,得到褪黑素在0.46、0.91、1.15、2.01、2.23和2.61 THz处存在特征吸收峰,为实验结果提供了有力地支持。这些工作为褪黑素等生化样品的检测和鉴定提供了依据和参考。     

基于不同光源的无标记显微成像技术

目的:随着对微观世界探索的不断深入,人们对显微成像系统的性能,如成像效率、成像质量以及三维成像等均提出了越来越高的要求。方法:近年来,在显微成像领域涌现出一批代表性的技术如定量相位成像技术、太赫兹成像技术以及结构光超分辨成像技术等,此类技术凭借无损伤、无侵入、无电离辐射、可实时、可定量等优势,在医学诊断、无损检测和安全检查等方面有着广泛应用。结论:本文根据光源的不同对显微成像技术进行了分类,首先对高相干激光、低相干光、太赫兹波以及结构光作为光源的四类无标记成像技术进行了简要介绍,并阐明了成像的基本原理,然后对这几类技术进行了特征分析。最后探讨了显微成像技术的发展趋势。     

蛙胚的微波辐射及其对泽蛙胚胎发育的影响

引言近年来,微波生物学已发展成为一门相当热门的边缘学科,其研究对象主要是微波对生物体辐射时,微波场在机体内的传输、反射、功率分布以及伴随产生的生物、化学和物理的各种变化及机理。目前,人们对微波辐射下的生物效应,一般认为有两种,即热效应和非热效应。热效应较直观,看法较一致,实验证据也较多,但非热效应则不然,看法尚不一致,目前实验证据也较少。本文以实验初步证明了非热     

太赫兹刺激听神经的测试平台搭建

目的 近年来，用于脑功能调控的神经调控技术蓬勃发展，很多方法已在临床上被推广应用，主要包括电极深部脑刺激、经颅磁刺激、光遗传技术、超声深脑刺激等。但是这些调控技术存在刺激靶点改变灵活性差、空间分辨率不足、需要注射病毒转染等问题。与这些技术相比，太赫兹波调控则能以较高的时空分辨率、无需引入外源基因的方式对神经活动进行干预。激光神经刺激是一种具有较明确靶向性的刺激方法，可以通过调整不同激光参数（激光波长、脉冲能量等）控制引起神经兴奋或者抑制。但是由于该研究方向的实验手段和实验平台的缺乏，相关研究开展较少。方法 针对这个问题，从听觉神经入手，在分子、细胞和在体不同层面为相关领域的研究搭建了不同的测试平台。结果 实验结果表明，这些系统在时间和空间上具有良好的耦合性和靶向性，测得的信号受噪音干扰小。结论 这些系统可以有效测试神经系统对太赫兹刺激的响应并精确控制刺激时间和位置。     

单哺乳动物细胞封装技术研究进展

细胞封装技术是指将细胞包裹在半透膜或者水凝胶组成的封装层内,该封装层能够有效阻挡外界大尺寸物质与封装细胞的直接接触,从而避免免疫细胞、抗体、酶等物质的攻击;同时保证氧气、营养物质、代谢物等一些小尺寸物质的自由交换,从而维持细胞各项生物学活动和正常功能.细胞封装技术在生物材料、生物医学以及生命科学等领域具有重要应用前景.单细胞封装技术,即将单个活细胞包裹在半透性的封装层内,是细胞封装向高封装效率、低封装层尺寸、高稳定性封装发展的必然趋势.单细胞封装系统在提高氧气、营养物质、代谢物等交换效率,维持细胞活性和各项生物学功能,以及单细胞水平上的细胞生物组学研究等方面具有显著优势.本文就基于哺乳动物细胞的单细胞封装技术进行了系统阐述,重点介绍了单细胞微胶囊封装系统和单细胞纳米封装系统两大单细胞封装制备技术的研究进展,对单细胞封装系统在细胞治疗、组织工程与再生医学、单细胞生物学分析以及全细胞传感器领域的应用现状进行了分析和归纳.最后,对单细胞封装技术所面临的问题和发展前景进行了总结和展望.     

植物单细胞转录组测序研究进展

单细胞转录组测序是一种在单细胞水平上研究基因表达的技术.多孔板法和液滴法是目前应用于植物研究的两类主要的单细胞转录组技术.首先概述了植物单细胞转录组测序的技术原理和数据分析流程,然后介绍了植物单细胞转录组的研究进展,重点阐述了单细胞转录组测序技术在鉴定植物细胞类型、揭示细胞演化轨迹和构建细胞间调控网络中的应用.单细胞转...     

美国《Science》杂志评出2011年十大科学突破——清除衰老细胞可以延缓衰老性疾病的发生

美国《Science》杂志评出2011年十大科学突破,本刊连续给予了介绍。本刊前两期(中国细胞生物学学报2012;34(2):195-6.中国细胞生物学学报2012;34(3):295-7.)分别介绍了在阻断艾滋病传播和光合作用研究领域所取得的突破性研究成果,本期重点介绍科学家们在抗衰老领域所取得的研究成果。     

Intrinsic radiation sensitivity: cellular signaling is the key

The concept that the balance between DNA damage and repair determines intrinsic radiation sensitivity has dominated radiobiology for several decades. There is undeniably a cause- effect relationship between radiation-induced molecular alterations in the genomic DNA and cellular consequences. In the last decade, however, it has become obvious that the chromatin context affects the fate of damaged DNA and that cellular signaling is an important factor in defining intrinsic radiation sensitivity. Damaged DNA is the site of signal generation; however, alternative signaling at the plasma membrane is triggered: Reactive oxygen species (ROS) inactivate phosphatases and consequently cause activation of kinases localized at the plasma membrane; this includes ligand-independent activation of receptor kinases. Cells with an apparently functional DNA repair system may show increased radiation sensitivity due to deficiencies in specific kinases essential for repair activation and checkpoint control. Other signals that determine intrinsic radiosensitivity may affect proneness to apoptosis, the balance between DNA damage fixation and repair, and the translocation of proteins participating in the response to ionizing radiation. Interplay between the various signals decides the extent to which the repair of radiation-inflicted damage is supported or limited; in some cell types, this includes DNA-damage-independent processes guided by plasma membrane-generated signaling. Cellular signaling in the context of specific subcellular structures is the key to understanding how the molecular effects of radiation are expressed as biological consequences in various cell types. A systems approach should bring us closer to this end.     

Cellular responses to reactive oxygen species-induced DNA damage and aging

Oxidative stress in cells and tissues can occur during pathophysiological developments, e.g., during inflammatory and allergic diseases or during ischemic or toxic and hyperglycemic conditions via the generation of reactive oxygen species (ROS). Moreover, ROS can be generated by radiation (UV, X-rays) and pharmacologically, e.g., by anthracyclins as chemotherapeutic compounds for treatment of a variety of tumors to induce 'stress or aberrant signaling-inducing senescence' (STASIS). Although STASIS is distinguished from intracellular replicative senescence, a variety of cellular mechanisms appear similar in both aging pathways. It is generally accepted that oxidative stress and ROS eventually cause DNA damage, whereby insufficient cellular repair mechanisms may contribute to premature aging and apoptosis. Conversely, ROS-induced imbalances of the signaling pathways for metabolic protein turnover may also result in opposite effects to recruit malfunctioning aberrant proteins and compounds that trigger tumorigenic processes. Consequently, DNA damage plays a role in the development of carcinogenesis, but is also associated with an aging process in cells and organisms.     

Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation

Ionizing radiation is classified as a potent carcinogen, and its injury to living cells is, to a large extent, due to oxidative stress. The molecule most often reported to be damaged by ionizing radiation is DNA. Hydroxyl radicals (*OH), considered the most damaging of all free radicals generated in organisms, are often responsible for DNA damage caused by ionizing radiation. Melatonin, N-acetyl-5-methoxytryptamine, is a well-known antioxidant that protects DNA, lipids, and proteins from free-radical damage. The indoleamine manifests its antioxidative properties by stimulating the activities of antioxidant enzymes and scavenging free radicals directly or indirectly. Among known antioxidants, melatonin is a highly effective scavenger of *OH. Melatonin is distributed ubiquitously in organisms and, as far as is known, in all cellular compartments, and it quickly passes through all biological membranes. The protective effects of melatonin against oxidative stress caused by ionizing radiation have been documented in in vitro and in vivo studies in different species and in in vitro experiments that used human tissues, as well as when melatonin was given to humans and then tissues collected and subjected to ionizing radiation. The radioprotective effects of melatonin against cellular damage caused by oxidative stress and its low toxicity make this molecule a potential supplement in the treatment or co-treatment in situations where the effects of ionizing radiation are to be minimized.     

Review of the specific effects of microwave radiation on bacterial cells

The aim of the present review was to evaluate the literature suggesting that consideration be given to the existence of specific microwave (MW) effects on prokaryotic microorganisms; that is, effects on organisms that cannot be explained by virtue of temperature increases alone. This review considered a range of the reported effects on cellular components; including membranes, proteins, enzyme activity as well as cell death. It is concluded that the attribution of such effects to non-thermal mechanisms is not justified due to poor control protocols and because of the possibility that an unmeasurable thermal force, relating to instantaneous temperature (T (i)) that occurs during MW processing, has not been taken into account. However, due to this lack of control over T (i), it also follows that it cannot be concluded that these effects are not 'non-thermal'. Due to this ambiguity, it is proposed that internal 'micro'-thermal effects may occur that are specific to MW radiation, given its inherent unusual energy deposition patterning.     

Reconciling the chemistry and biology of reactive oxygen species

There is a vast literature on the generation and effects of reactive oxygen species in biological systems, both in relation to damage they cause and their involvement in cell regulatory and signaling pathways. The biological chemistry of different oxidants is becoming well understood, but it is often unclear how this translates into cellular mechanisms where redox changes have been demonstrated. This review addresses this gap. It examines how target selectivity and antioxidant effectiveness vary for different oxidants. Kinetic considerations of reactivity are used to assess likely targets in cells and how reactions might be influenced by restricted diffusion and compartmentalization. It also highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.     

Production of hydrogen peroxide and redox cycling can explain how sanguinarine and chelerythrine induce rapid apoptosis

Sanguinarine and chelerythrine are naturally occurring benzophenanthridines with multiple biological activities. Sanguinarine is believed to be a potential anticancer agent but its mechanism of action has not been fully elucidated. We previously found that it causes oxidative DNA damage and very rapid apoptosis that is not mediated by p53-dependent DNA damage signaling. Here we show that sanguinarine and chelerythrine cause the production of large amounts of reactive oxygen species (ROS), in particular hydrogen peroxide, which may deplete cellular antioxidants and provide a signal for rapid execution of apoptosis. Several oxidoreductases contribute to cell death induced by sanguinarine and chelerythrine which appear to be reduced upon entering the cell. We propose a model in which the generation of lethal amounts of hydrogen peroxide is explained by enzyme-catalyzed redox cycling between the reduced and oxidized forms of the phenanthridines and discuss the implications of such a mechanism for potential pharmaceutical applications.     

Design,Fabrication, and Experimental Characterization of Plasmonic Photoconductive Terahertz Emitters

In this video article we present a detailed demonstration of a highly efficient method for generating terahertz waves. Our technique is based on photoconduction, which has been one of the most commonly used techniques for terahertz generation ^1-8. Terahertz generation in a photoconductive emitter is achieved by pumping an ultrafast photoconductor with a pulsed or heterodyned laser illumination. The induced photocurrent, which follows the envelope of the pump laser, is routed to a terahertz radiating antenna connected to the photoconductor contact electrodes to generate terahertz radiation. Although the quantum efficiency of a photoconductive emitter can theoretically reach 100%, the relatively long transport path lengths of photo-generated carriers to the contact electrodes of conventional photoconductors have severely limited their quantum efficiency. Additionally, the carrier screening effect and thermal breakdown strictly limit the maximum output power of conventional photoconductive terahertz sources. To address the quantum efficiency limitations of conventional photoconductive terahertz emitters, we have developed a new photoconductive emitter concept which incorporates a plasmonic contact electrode configuration to offer high quantum-efficiency and ultrafast operation simultaneously. By using nano-scale plasmonic contact electrodes, we significantly reduce the average photo-generated carrier transport path to photoconductor contact electrodes compared to conventional photoconductors ⁹. Our method also allows increasing photoconductor active area without a considerable increase in the capacitive loading to the antenna, boosting the maximum terahertz radiation power by preventing the carrier screening effect and thermal breakdown at high optical pump powers. By incorporating plasmonic contact electrodes, we demonstrate enhancing the optical-to-terahertz power conversion efficiency of a conventional photoconductive terahertz emitter by a factor of 50 ¹⁰.     

Modeling radioprotective mechanisms in the dose effect relation at low doses and low dose rates of ionizing radiation

A new model (Random Coincidence Model--Radiation Adapted (RCM-RA)) is proposed which explains a possible pseudo threshold for stochastic radiation effects. It describes the formation of cancer in the case of multistep fixation of lesions in the critical regions of tumor associated genes such as proto-oncogenes or tumor-suppressor genes. The RCM-RA contains two different possibilities of DNA damage to complementary nucleotides. The damage may be caused either by radiation or by natural processes such as cellular radicals or thermal damage or by chemical cytotoxins. The model is based on the premise that radiation initially is bionegative, damaging organisms at their different levels of organization. The radiation, however, also induces various cellular radioprotective mechanisms which decrease the damage by natural processes. Considering both effects together, the theory explains apparent thresholds in the dose-response relation for radiation carcinogenesis without contradiction to the classical assumption that radiation is predominantly bionegative at doses typically found in occupational exposures.     

Bio-soliton model that predicts non-thermal electromagnetic frequency bands,that either stabilize or destabilize living cells

Solitons, as self-reinforcing solitary waves, interact with complex biological phenomena such as cellular self-organization. A soliton model is able to describe a spectrum of electromagnetism modalities that can be applied to understand the physical principles of biological effects in living cells, as caused by endogenous and exogenous electromagnetic fields and is compatible with quantum coherence. A bio-soliton model is proposed, that enables to predict which eigen-frequencies of non-thermal electromagnetic waves are life-sustaining and which are, in contrast, detrimental for living cells. The particular effects are exerted by a range of electromagnetic wave eigen-frequencies of one-tenth of a Hertz till Peta Hertz that show a pattern of 12 bands, and can be positioned on an acoustic reference frequency scale. The model was substantiated by a meta-analysis of 240 published articles of biological electromagnetic experiments, in which a spectrum of non-thermal electromagnetic waves were exposed to living cells and intact organisms. These data support the concept of coherent quantized electromagnetic states in living organisms and the theories of Fröhlich, Davydov and Pang. It is envisioned that a rational control of shape by soliton-waves and related to a morphogenetic field and parametric resonance provides positional information and cues to regulate organism-wide systems properties like anatomy, control of reproduction and repair.     

The time course of long-distance signaling in radiation-induced bystander effect in vivo in Arabidopsis thaliana demonstrated using root micro-grafting

The radiation-induced bystander effect has been demonstrated in whole organisms as well as in multicellular tissues in vitro and single-cell culture systems in vitro. However, the time course of bystander signaling, especially in whole organisms, is not clear. Long-distance bystander/abscopal effects in vivo in plants have been demonstrated by our group. Plant grafting is a useful experimental tool for studying the root-shoot signaling of plants. In the present study, we developed a root micro-grafting technique with young seedlings of Arabidopsis thaliana in which the bystander signaling communication of root-to-shoot could easily be stopped or started at specific times after root irradiation. Using this methodology, we demonstrated the time course of long-distance signaling in radiation-induced bystander effects at the level of the organism using the expression level of the AtRAD54 gene as a biological end point. Briefly, an 8-h accumulation of damage signals in bystander parts after irradiation was essential for eliciting a bystander response. The protraction of signal accumulation was not related to the transmission speed of signaling molecules in plants and did not result from the delayed initiation of bystander signals in targeted root cells. It was suggested that the bystander effect might be induced jointly by multiple bystander signals initiated at different stages after irradiation. Moreover, reactive oxygen species (ROS) were shown to be implicated in the response process of bystander cells to radiation damage signals rather than in the generation of bystander signals in targeted cells.