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Pursuing theranostics: a multimodal architecture approach. 追求治疗学:多模式架构方法。
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-24 DOI: 10.1039/d4sd00221k
Aidan A Bender, Connor K Holiski, Mary Embree, Heather M Hennkens, John R Klaehn, Ellie Lundgreen, Andrew G Roberts, Peter R Zalupski, Tara Mastren

Theranostics is a field of nuclear medicine which uses the same targeting vector and chelating system for both a diagnostic and therapeutic radionuclide, allowing for uniformity in imaging and treatment. This growing field requires the development of more flexible chelate systems that permit novel targeting strategies. Toward this end, a multimodal architecture has been realized, making use of a phosphazene-based core and click chemistry to achieve a flexible and customizable scaffold. The six arm phosphazene-based core can scaffold six DTPA chelating motifs or a mixed set of 3 : 3 DTPA : DFO chelates resulting in two multimodal compounds, pDbDt and pDbDtDf, respectively. Terbium complexes displayed strong luminescence, supporting that the structures act as an organic antenna for luminescence. Metal displacement titration studies confirmed the desired structures as well as the capability for heterometallic labeling of the structures. These structures were found to have high thermal and biological stability in vitro. Radiolabeling of each compound resulted in high molar activity labeling of each compound: 169 MBq nmol-1: [161Tb]Tb-pDbDt, 170 MBq nmol-1: [89Zr]Zr-pDbDtDf, and the mixed radiolabeling illustrated chelation of both radionuclides in a 1 : 1 ratio. This multimodal architecture is promising as a heterometallic structure for coupling of both a diagnostic and a therapeutic radionuclide with a highly customizable core structure.

Theranostics 是核医学的一个领域,它将相同的靶向载体和螯合系统用于诊断和治疗放射性核素,从而实现成像和治疗的一致性。这一不断发展的领域需要开发更灵活的螯合剂系统,以实现新颖的靶向策略。为此,我们实现了一种多模态结构,利用基于磷烯的核心和点击化学实现了一种灵活的、可定制的支架。六臂膦基核心可以构建六个 DTPA 螯合基团,也可以构建一组 3 :3 DTPA :DFO 螯合剂,从而分别形成两种多模式化合物 pDbDt 和 pDbDtDf。铽复合物显示出很强的发光性能,证明这种结构可以作为发光的有机天线。金属置换滴定研究证实了所需的结构以及这些结构的异金属标记能力。研究发现,这些结构在体外具有很高的热稳定性和生物稳定性。对每种化合物进行放射性标记后,发现每种化合物的摩尔活度都很高:169 MBq nmol-1:[161Tb]Tb-pDbDt;170 MBq nmol-1:[89Zr]Zr-pDbDtDf;混合放射性标记显示两种放射性核素以 1 :1 的比例螯合。这种多模式结构是一种很有前途的异金属结构,可将诊断性和治疗性放射性核素与高度可定制的核心结构耦合在一起。
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引用次数: 0
A review on Ti3C2Tx based nanocomposites for the electrochemical sensing of clinically relevant biomarkers 基于 Ti3C2Tx 的纳米复合材料用于临床相关生物标记物电化学传感的综述
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-11 DOI: 10.1039/D4SD00171K
Anjali Sugunan, Anusree V. Rethnakumaran and Mini Mol Menamparambath

Reckoning the significance of next-generation biosensors and point-of-care sensors, scientists are interested in developing superior nanomaterials with advantageous characteristics that can serve as electrode modifiers in the development of functional devices. MXenes are a broad class of two-dimensional metal carbides and nitrides characterized by their exceptional hydrophilicity, high specific surface area, and high conductivity. MXenes and their derived nanocomposites are presently gaining importance as electrode materials for the electrochemical detection of various biomarkers. This review assesses and summarises current notable accomplishments in the concepts, fabrication, and diverse applications of MXene-based nanocomposites for electrochemical monitoring of a variety of clinically relevant biomarkers. Furthermore, an outline of the existing impediments linked to technological advancement is included, accompanied by proposals for further investigation into the issues.

考虑到下一代生物传感器和护理点传感器的重要性,科学家们对开发具有优势特性的优质纳米材料很感兴趣,这些材料可在开发功能器件时用作电极改性剂。MXenes 是一类广泛的二维金属碳化物和氮化物,具有优异的亲水性、高比表面积和高导电性。目前,MXenes 及其衍生纳米复合材料作为电化学检测各种生物标记物的电极材料正变得越来越重要。本综述评估并总结了目前在基于 MXene 的纳米复合材料用于电化学监测各种临床相关生物标记物的概念、制造和各种应用方面取得的显著成就。此外,还概述了与技术进步相关的现有障碍,并提出了进一步研究这些问题的建议。
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引用次数: 0
Introduction to Supramolecular Sensors: From Molecules to Materials 超分子传感器简介:从分子到材料
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-10-02 DOI: 10.1039/D4SD90034K
Sankarasekaran Shanmugaraju, Robert B. P. Elmes and Valeria Amendola

A graphical abstract is available for this content

本内容有图解摘要
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引用次数: 0
A comprehensive FTIR micro-spectroscopic analysis and classification of precancerous human oral tissue aided by machine learning† 机器学习辅助下的人类口腔癌前组织傅立叶变换红外微光谱综合分析与分类†。
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-27 DOI: 10.1039/D4SD00122B
Pranab Jyoti Talukdar, Kartikeya Bharti, Sumita Banerjee, Sautami Basu, Sanjeet Kumar Das, Ranjan Rashmi Paul, Mousumi Pal, Mahendra Prasad Mishra, Saikat Mukherjee, Pooja Lahiri and Basudev Lahiri

We present an analysis of the molecular vibrational assessments of different grades of oral precancerous tissue sections, aiming to an early, alternative method other than histopathology to definitively distinguish their grades and remove the interobserver variability related to histopathological grading. Assessment of the prognosis of oral potentially malignant disorders (OPMDs) is dependent only on clinical features, and no defined criteria are still proposed to analyze the treatment outcome. Chair-side analysis of the lymph node metastasis and staging of oral squamous cell carcinoma (OSCC) is also dependent on palpatory findings followed by magnetic resonance imaging (MRI). Among these, Fourier-transform infrared (FTIR) micro-spectroscopy emerges as a highly promising and versatile approach for analyzing oral cancer and precancer specimens, enabling the identification of chemical and molecular changes in tissue samples. In this work, an adequate number of tissue sections affected by different grades of precancer (mild dysplasia, moderate dysplasia, and severe dysplasia) were investigated for biochemical changes in the epithelium and sub-epithelium layers as characterized by their corresponding molecular vibration spectrum. The current study demonstrated distinct alterations based on the spectrum shift of proteins (particularly amide I and amide III) over the progression of precancer. Additionally, using the amide I and amide III regions, a peak fitting method was employed to estimate the secondary structures of proteins. Further, chemometric techniques of principal components analysis–linear discriminant analysis (PCA–LDA) were used to create discrimination models for the precancerous and control groups. Our investigation revealed that the predictive performance of the amide III region was better than that of the amide I region, achieving a 95% accuracy rate. To the best of our knowledge, this is one of the first studies on the application of FTIR micro-spectroscopy for the classification of oral precancers in humans, aided by machine learning.

我们对不同等级的口腔癌前组织切片进行了分子振动评估分析,旨在提供一种组织病理学以外的早期替代方法,以明确区分其等级,并消除与组织病理学分级相关的观察者间差异。口腔潜在恶性疾病(OPMD)的预后评估仅依赖于临床特征,目前仍未提出明确的标准来分析治疗结果。口腔鳞状细胞癌(OSCC)的淋巴结转移和分期也依赖于触诊结果和磁共振成像(MRI)。在这些方法中,傅立叶变换红外(FTIR)显微光谱法是一种极具前景的多功能方法,可用于分析口腔癌和癌前病变标本,从而识别组织样本中的化学和分子变化。在这项工作中,研究人员对受不同等级癌前病变(轻度发育不良、中度发育不良和重度发育不良)影响的大量组织切片进行了调查,以了解上皮层和上皮下层的生化变化,并通过相应的分子振动光谱对其进行表征。本研究根据蛋白质(尤其是酰胺 I 和酰胺 III)在癌前病变进展过程中的频谱移动,证明了其明显的变化。此外,利用酰胺 I 和酰胺 III 区域,采用峰拟合方法估算了蛋白质的二级结构。此外,我们还利用主成分分析-线性判别分析(PCA-LDA)的化学计量学技术为癌前病变组和对照组建立了判别模型。我们的调查显示,酰胺 III 区域的预测性能优于酰胺 I 区域,准确率达到 95%。据我们所知,这是首次应用傅立叶变换红外微光谱在机器学习的辅助下对人类口腔癌前病变进行分类的研究。
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引用次数: 0
Novel thiosemicarbazone based sensors for transition metals† 基于硫代氨基羰基化合物的新型过渡金属传感器†
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-26 DOI: 10.1039/D4SD00266K
Repale Anil Vithal, Ram Kishore, Dongare Suvarna Janardan, N. S. Chundawat, Nitin Srivastava and Girdhar Pal Singh

A novel and efficient thiosemicarbazone based chemosensor for the detection of transition metals through UV-visible fluorescence has been reported in this research. Dibenzyl thiosemicarbazones can bind with the transition metal ions and lead to the enhancement of the fluorescence. The reported dibenzyl thiosemicarbazone can detect Zn2+, Co2+, Ni2+ and Hg2+ appreciably due to inhibition of electron transfer while quenching of fluorescence occurs in Mn2+ and Cu2+ due to photoinduced electron transfer.

本研究报告了一种基于硫代氨基脲的新型高效化学传感器,可通过紫外可见荧光检测过渡金属。二苄基硫代氨基甲酸唑能与过渡金属离子结合,从而增强荧光。所报告的二苄基硫代氨基甲酸唑能明显探测到 Zn2+、Co2+、Ni2+ 和 Hg2+,这是由于电子传递受到抑制,而 Mn2+ 和 Cu2+ 则由于光诱导电子传递而发生荧光淬灭。
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引用次数: 0
Highly sensitive flux-type non-invasive alcohol biosensor based on direct electron transfer of PQQ-dependent alcohol dehydrogenases adsorbed on carbon nanotubes† 基于吸附在碳纳米管上的 PQQ 依赖性醇脱氢酶直接电子传递的高灵敏通量型无创酒精生物传感器†。
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-24 DOI: 10.1039/D4SD00161C
Citra Dewi Rakhmania, Yoshi Izzuddin Azhar, Kenji Shida, Erika Shinchi, Taiki Adachi, Keisei Sowa, Yuki Kitazumi, Osamu Shirai and Masato Tominaga

Ethanol gas excreted by human skin can be used to determine auto-brewery syndrome (drunken disease), blood alcohol levels, and/or a body state of alcoholism. Considering the limitations of continuous non-invasive alcohol gas monitoring based on the electrochemical method, which requires high sensitivity and selectivity, a CNF film sensor was developed. This sensor was developed by utilizing pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) and multiwalled carbon nanotubes (MWCNTs) based on cellulose nanofiber (CNF) film platform. With a compact design, a PQQ-ADH/MWCNTs/CNF film sensor was built in a three-electrode system. This system could continuously detect ethanol gas with ultra-high sensitivity, a wide detection range (24 ppb–25 ppm), and high selectivity for ethanol. Finally, the CNF film sensor was used for ethanol gas monitoring in the human subject, and we were able to detect metabolism abnormalities of the subject by analyzing the declining slope (detoxification rate) of the ethanol gas concentration monitored. The CNF film sensor aims to gain valuable insights and enhance future standard health screening practices through non-invasive wearable daily monitoring sensors.

人体皮肤排出的乙醇气体可用于确定自酿综合征(醉酒病)、血液酒精含量和/或酗酒的身体状态。基于电化学方法的连续无创酒精气体监测需要高灵敏度和高选择性,考虑到这种方法的局限性,我们开发了一种 CNF 薄膜传感器。该传感器是在纤维素纳米纤维(CNF)薄膜平台上利用吡咯喹啉醌依赖性酒精脱氢酶(PQQ-ADH)和多壁碳纳米管(MWCNTs)开发的。PQQ-ADH/MWCNTs/CNF 薄膜传感器设计紧凑,采用三电极系统。该系统可连续检测乙醇气体,具有超高灵敏度、宽检测范围(24 ppb-25 ppm)和对乙醇的高选择性。最后,我们将 CNF 薄膜传感器用于人体乙醇气体监测,并通过分析监测到的乙醇气体浓度的下降斜率(解毒率)来检测人体的代谢异常。CNF 薄膜传感器旨在通过非侵入式可穿戴日常监测传感器获得有价值的见解,并加强未来的标准健康检查实践。
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引用次数: 0
Modulation of the binding sites for an adaptable DNA interactive probe: efficient chromo-fluorogenic recognition of Al3+ and live cell bioimaging† 调节 DNA 交互探针的结合位点:高效的 Al3+ 色荧光精细识别及其活细胞生物成像技术
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-18 DOI: 10.1039/D4SD00242C
Atanu Maji, Debarpan Mitra, Amitav Biswas, Moumita Ghosh, Rahul Naskar, Saswati Gharami Nabendu Murmu and Tapan K. Mondal

Herein, a chromone-based simple reversible fluorescent “turn-on” probe, HMCP [6-(hydroxymethyl)-N′-((6-methyl-4-oxo-4H-chromen-3-yl)methylene)picolinohydrazide], was successfully utilized to detect Al3+ over a group of other coexisting metal cations in MeOH/H2O (9 : 1, v/v) (HEPES buffer, pH = 7.2). The “turn on” emission response along with the effective enhancement of the fluorescence intensity upon addition of Al3+ can be attributed to the inhibition of photo-induced electron transfer (PET) and CN isomerization, as well as the initiation of chelation-enhanced-fluorescence (CHEF). The HMCP sensor binds Al3+ in a 1 : 1 stoichiometry with an excellent binding constant and good detection limit on the orders of 103 M−1 and 10−7 M, respectively. The mode of binding interaction between HMCP with Al3+ was evidenced by 1H NMR titration, HRMS, and Job's plot analyses. Theoretical calculations and molecular logic gate applications were also used to demonstrate the binding mode. A DNA binding study was also executed to elucidate the possible bioactivity of the probe and found that HMCP interacts with DNA more effectively than the other analogues studied. Furthermore, the applicability of the probe in a live cell imaging study indicated that HMCP is highly efficient for the detection of exogenous Al3+ in living cells. In addition, real water sample analysis and a dip-stick experiment demonstrate that the probe can be used in a wide range of practical and convenient applications.

本文成功引入了一种基于铬酮的简单可逆荧光 "开启 "探针 HMCP [6-(Hydroxymethyl)-N'-((6-methyl-4-oxo-4H-chromen-3-yl)methylene)picolinohydrazide] ,用于在 pH 值为 7.2 的甲醇中检测 Al3+,而不是其他共存金属离子。加入 Al3+ 后的 "开启 "发射响应和荧光强度的有效增强可归因于光诱导电子转移(PET)和 C=N 异构化的抑制以及螯合增强荧光(CHEF)的启动。传感器 HMCP 与 Al3+ 的结合比例为 1:1,其结合常数和检测限分别为 103 M-1 和 10-7 M。通过 1H-NMR 滴定、HRMS、约伯图分析、理论计算以及分子逻辑门应用,证明了 HMCP 与 Al3+ 的结合模式。为了阐明可能的生物活性,还进行了 DNA 结合研究,结果发现 HMCP 与 DNA 的相互作用比其他类似物更有效。此外,活细胞成像研究表明,HMCP 能高效检测活细胞中的外源 Al3+。此外,真实样品分析和浸渍棒实验也为探针的实际应用提供了广泛的便利。
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引用次数: 0
A liquid crystal-based biomaterial platform for rapid sensing of heat stress using machine learning 利用机器学习快速感知热应力的液晶生物材料平台
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-18 DOI: 10.1039/D4SD00213J
Prateek Verma, Elizabeth Adeogun, Elizabeth S. Greene, Sami Dridi, Ukash Nakarmi and Karthik Nayani

Novel biomaterials that bridge the knowledge gap in coupling molecular/protein signatures of disease/stress with rapid readouts are a critical need of society. One such scenario is an imbalance between bodily heat production and heat dissipation which leads to heat stress in organisms. In addition to diminished animal well-being, heat stress is detrimental to the poultry industry as poultry entails fast growth and high yields, resulting in greater metabolic activity and higher body heat production. When stressed, cells overexpress heat shock proteins (such as HSP70, a well-established intracellular stress indicator) and may undergo changes in their mechanical properties. Liquid crystals (LCs, fluids with orientational order) are facile sensors as they can readily transduce chemical signals to easily observable optical responses. In this work, we introduce a hybrid LC–cell biomaterial within which the difference in the expression of HSP70 is linked to optical changes in the response pattern via the use of convolutional neural networks (CNNs). The machine-learning (ML) models were trained on hundreds of such LC-response micrographs of chicken red blood cells with and without heat stress. The trained models exhibited remarkable accuracy of up to 99% on detecting the presence of heat stress in unseen microscopy samples. We also show that cross-linking chicken and human RBCs using glutaraldehyde in order to simulate a diseased cell was an efficient strategy for planning, building, training, and evaluating ML models. Overall, our efforts build towards designing biomaterials that can rapidly detect disease in organisms that is accompanied by a distinct change in the mechanical properties of cells. We aim to eventuate CNN-enabled LC-sensors that can rapidly report the presence of disease in scenarios where human judgment could be prohibitively difficult or slow.

新型生物材料通过快速读数弥补了疾病/压力的分子/蛋白质信号耦合方面的知识差距,是社会的迫切需要。其中一种情况是身体产热和散热不平衡,导致生物体产生热应激。除了动物健康受损外,热应激还不利于家禽业,因为家禽需要快速生长和高产,从而导致新陈代谢活动增加,体热产生增加。当受到应激时,细胞会过度表达热休克蛋白(如 HSP70,一种公认的细胞内应激指标),并可能改变其机械特性。液晶(LC,具有定向有序性的流体)是一种简便的感应器,因为它们能轻易地将化学信号转导为易于观察的光学响应。在这项工作中,我们引入了一种混合桥接液晶细胞生物材料,通过使用卷积神经网络(CNN),将 HSP70 表达的差异与响应模式的光学变化联系起来。机器学习(ML)模型是在数百张有热应力和无热应力的鸡红细胞的 LC 反应显微照片上训练出来的。训练后的模型在检测未见显微镜样本中是否存在热应力方面的准确率高达 99%。我们还表明,使用戊二醛交联鸡和人类红细胞以模拟病变细胞是规划、构建、训练和评估 ML 模型的有效策略。总之,我们的努力是为了设计出能快速检测生物体内伴随着细胞机械特性明显变化的疾病的生物材料。我们的目标是使支持 CNN 的液相色谱传感器能够在人类判断过于困难或缓慢的情况下快速报告疾病的存在。
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引用次数: 0
Point-of-care biosensors and devices for diagnostics of chronic kidney disease 用于诊断慢性肾病的床旁生物传感器和设备
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-16 DOI: 10.1039/D4SD00241E
Yuan Liu, Xinping Zhao, Min Liao, Guoliang Ke and Xiao-Bing Zhang

Chronic kidney disease (CKD) is a growing global health concern, necessitating early and accurate diagnostic tools to manage and mitigate its progression. Point-of-care (POC) biosensors and devices offer a promising solution for rapid, cost-effective, and accessible diagnostics. This review explores the latest advancements in POC biosensors and devices specifically designed for CKD diagnostics. In this review, we discuss the biosensors most likely to achieve on-site detection of CKD, focusing on their design and application in real samples, including electrochemical, fluorescent, and colorimetric sensors. Also, the innovative platforms are summarized from lateral flow devices, lab-on-a-chip devices, and microfluidic-based devices. The potential of these technologies for real-time monitoring, early detection, and personalized treatment is underscored. The review concludes by envisioning future perspectives and the transformative impact of POC biosensors in CKD diagnostics, aiming to improve patient outcomes and healthcare efficiency.

慢性肾脏病(CKD)是一个日益严重的全球性健康问题,需要早期准确的诊断工具来控制和缓解病情发展。床旁 (POC) 生物传感器和设备为快速、经济、方便的诊断提供了一种前景广阔的解决方案。本综述探讨了专为慢性肾功能衰竭诊断设计的 POC 生物传感器和设备的最新进展。在这篇综述中,我们讨论了最有可能实现 CKD 现场检测的生物传感器,重点是它们在真实样本中的设计和应用,包括电化学、荧光和比色传感器。此外,还总结了横向流动装置、片上实验室装置和微流控装置等创新平台。这些技术在实时监测、早期检测和个性化治疗方面的潜力得到了强调。综述最后展望了 POC 生物传感器在 CKD 诊断中的未来前景和变革性影响,旨在改善患者预后和提高医疗效率。
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引用次数: 0
Tumor diagnosis based on nucleolus labeling 基于核仁标记的肿瘤诊断
IF 3.5 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2024-09-16 DOI: 10.1039/D4SD00238E
Caiwei Jia, Jiani Gao, Dong Xie and Jin-Ye Wang

The nucleolus is crucial for ribonucleoprotein particle assembly. Vital molecular regulators such as RB (retinoblastoma protein) and p53 (tumor suppressor protein) influence nucleolar function and tumorigenesis. The absence or inactivation of these proteins often leads to nucleolar dysfunction and alteration, which is a key indicator among the primary histopathological features of malignancy. These changes are closely related to the proliferation, differentiation, and survival of tumor cells, such as abnormalities in the number, size, and shape of nucleoli. In recent years, as the relationship between nucleoli and tumorigenesis has been further explored, various nucleolar labeling techniques have been developed for pathological analysis and tumor diagnosis, such as immunohistochemistry (IHC)/immunofluorescence (IF), and fluorescence labeling. These methods complement the traditional use of transmission electron microscopy (TEM) for observing nucleoli. In this review, we explore the relationship between the nucleolus and tumorigenesis and evaluate current methods for diagnosing tumors by examining nucleolar characteristics. We discuss the advantages, disadvantages, and applications of diagnostic techniques such as TEM, IHC/IF, and fluorescence labeling for analyzing the nucleolus.

核仁对于核糖核蛋白颗粒的组装至关重要。RB(视网膜母细胞瘤蛋白)和 p53(肿瘤抑制蛋白)等重要的分子调控因子影响着核小体的功能和肿瘤的发生。这些蛋白的缺失或失活往往会导致核小体功能障碍和改变,这是恶性肿瘤主要组织病理学特征中的一个关键指标。这些变化与肿瘤细胞的增殖、分化和存活密切相关,如核小体的数量、大小和形状异常。近年来,随着人们对核小体与肿瘤发生之间关系的进一步探索,各种用于病理分析和肿瘤诊断的核小体标记技术应运而生,如免疫组织化学(IHC)/免疫荧光(IF)和荧光标记等。这些方法是对传统的透射电子显微镜(TEM)观察核小体的补充。在这篇综述中,我们探讨了核小体与肿瘤发生之间的关系,并评估了目前通过检查核小体特征诊断肿瘤的方法。我们讨论了用于分析核小体的 TEM、IHC/IF 和荧光标记等诊断技术的优缺点和应用。
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引用次数: 0
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