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Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive moleculesin live cells and in vivo

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 4-33 doi: 10.1007/s11705-021-2041-2

摘要： The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases, such as cancer and neurodegenerative and cardiovascular diseases. Therefore, the simultaneous, accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases. Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and due to its excellent performances, including high sensitivity and selectivity, noninvasive properties, real-time and high spatial temporal resolution. Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems. Hence, in this review, we focus on summarizing the design strategies, classifications, and bioimaging applications of dual-response fluorescent probes over the past decade. Furthermore, future research directions in this field are proposed.

关键词： bioactive molecules fluorescent probes in living cells and in vivo review

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Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF

Dan Wu, Gonzalo Durán-Sampedro, Donal F. O’Shea

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 97-104 doi: 10.1007/s11705-019-1828-x

摘要： Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

关键词： NIR-fluorophores live cell imaging NIR-AZA

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In vivo imaging of hematopoietic stem cell development in the zebrafish

Panpan Zhang, Feng Liu

《医学前沿（英文）》 2011年第5卷第3期页码 239-247 doi: 10.1007/s11684-011-0123-0

摘要： imaging is crucial for developmental biology and can further help to follow cell development/differentiation in normal and pathological conditions. Recent advances in optical imaging techniques has facilitated tracing of the developmental dynamics of a specific organ, tissue, or even a single cell. The zebrafish is an excellent model for imaging of hematopoiesis due to its transparent embryo at early stage; moreover, different zebrafish hematopoietic stem cells (HSCs) transgenic lines have been demonstrated as very useful tools for illustrating the details of the HSC developmental process. In this review, we summarize recent studies related to the non-invasive imaging of HSC transgenics, to show that zebrafish transgenic lines are powerful tools for developmental biology and disease. At the end of the review, the perspective and some open questions in this field will be discussed.

关键词： hematopoietic stem cell hematopoiesis in vivo imaging transgenics zebrafish

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Fluorescent probes and functional materials for biomedical applications

《化学科学与工程前沿（英文）》 2022年第16卷第10期页码 1425-1437 doi: 10.1007/s11705-022-2163-1

摘要： Due to their simplicity in preparation, sensitivity and selectivity, fluorescent probes have become the analytical tool of choice in a wide range of research and industrial fields, facilitating the rapid detection of chemical substances of interest as well as the study of important physiological and pathological processes at the cellular level. In addition, many long-wavelength fluorescent probes developed have also proven applicable for in vivo biomedical applications including fluorescence-guided disease diagnosis and theranostics (e.g., fluorogenic prodrugs). Impressive progresses have been made in the development of sensing agents and materials for the detection of ions, organic small molecules, and biomacromolecules including enzymes, DNAs/RNAs, lipids, and carbohydrates that play crucial roles in biological and disease-relevant events. Here, we highlight examples of fluorescent probes and functional materials for biological applications selected from the special issues “Fluorescent Probes” and “Molecular Sensors and Logic Gates” recently published in this journal, offering insights into the future development of powerful fluorescence-based chemical tools for basic biological studies and clinical translation.

关键词： fluorescent probes imaging cell biomedicine biomolecules

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高压纳米X射线成像技术的应用 Article

毛立文, 林昱, 刘宜晋, 刘锦

《工程（英文）》 2019年第5卷第3期页码 479-489 doi: 10.1016/j.eng.2019.01.006

摘要： "font-family:宋体">纳米级透射X射线显微镜（nanoscale transmission X-ray microscopy, nanoTXM）与金刚石对顶砧（diamond anvil cell

关键词： X射线成像高压金刚石对顶砧

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evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

《医学前沿（英文）》 2014年第8卷第4期页码 471-476 doi: 10.1007/s11684-014-0365-8

摘要：

This work aims to estimate the value of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in detecting early-stage kidney injury in type 2 diabetic patients with normoalbuminuria (NAU) versus microalbuminuria (MAU) prospectively. A total of 30 T2DM patients with normal kidney function were recruited and assigned to the NAU group (n = 14) or MAU group (n= 16) according to 8 h overnight urinary albuminuria excretion rate (AER) results. A contemporary cohort of health check-up recipients were included as controls (n = 12). DWI and DTI scans were performed on bilateral kidney using SE single-shot EPI, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the renal parenchyma was determined from ADC and FA maps of the three groups. ADC and FA values were compared among the three groups. According to DWI with a b value of 400 s/mm², the MAU and NAU groups showed significantly lowered mean ADC values compared with the healthy controls (P<0.01). The mean ADC in the MAU group [(2.22±0.07)×10^–3 mm²/s] was slightly lower than that of the NAU group [(2.31±0.22)×10^–3 mm²/s], but this difference was not statistically significant (P>0.05). The FA value in the MAU group was higher than that in the control group (0.45±0.07 vs. 0.39±0.03, P = 0.004) but did not differ from that in the NAU group (0.42±0.03) (P>0.05). ADC and FA values may be more sensitive than urine AER in reflecting early-stage kidney injury and, hence, may facilitate earlier detection and quantitative evaluation of kidney injury in T2DM patients. Combined evaluation of ADC and FA values may provide a better quantitative approach for identifying diabetic nephropathy at early disease stages.

关键词： type 2 diabetes mellitus microalbuminuria diffusion weighted imaging diffusion tensor imaging early-stage kidney injury

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activated rapid addition and mitochondrial targeting ratiometric fluorescent probes for in vivo cellH₂S imaging

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 64-71 doi: 10.1007/s11705-021-2048-8

摘要： Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity. They play an important role in the design of new structural entities for medical applications. Similarly, indoles and their derivatives are found widely in nature. Amino acids, alkaloids and auxin are all derivatives of indoles, as are dyes, and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents. In this work, we combine these two groups organically to construct a rapid response site (within 30 s) for H S, and at the same time, a ratiometric fluorescence response is presented throughout the process of H S detection. As such, the lower detection limit can reach 55.7 nmol/L for H S. In addition, cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H S. Finally, this probe application was verified by imaging H S in nude mice.

关键词： heterocyclic compound hydrogen sulfide ratiometric mitochondrial targeted

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全球首例猪心脏移植人体手术

Sarah C. P. Williams

《工程（英文）》 2022年第16卷第9期页码 6-8 doi: 10.1016/j.eng.2022.07.006

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Carbon dots-based fluorescence sensor for two-photon imaging of pH in diabetic mice

《化学科学与工程前沿（英文）》 2023年第17卷第3期页码 298-306 doi: 10.1007/s11705-022-2212-9

摘要： Herein, a reversible pH fluorescent sensor was developed using caffeic acid as the precursor by one-step solvothermal synthesis method. The carbon dots-based sensor (CA-CDs) exhibited pH-dependent increase in fluorescence intensity and showed linear relationship in the range of pH 6.60 and 8.00. Notably, the fluorescence sensor has a reversible response to pH change. Finally, the CA-CDs has been successfully applied for two-photon imaging of the pH in liver and kidney of diabetic mice. Imaging results showed that the pH value in kidney of diabetic mice was lower than that of the normal mice, while the pH value in liver of diabetic mice was almost the same as that of the normal mice. The present study provides a simple analytical method for pH detection suitable for in vivo.

关键词： carbon dots two-photon imaging pH diabetic mice

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全氟化碳乳剂¹⁹F磁共振成像的最新进展 Review

Anne H. Schmieder,Shelton D. Caruthers,Jochen Keupp,Samuel A. Wickline,Gregory M. Lanza

《工程（英文）》 2015年第1卷第4期页码 475-489 doi: 10.15302/J-ENG-2015103

摘要：

¹⁹F磁共振成像(MRI) 的研究可追溯到30多年前。在这30多年间，氢原子核(¹H)成像技术迅速发展，并在全球得到广泛应用，使得磁共振成像成为生物医学诊断成像技术中不可缺少的支柱。多年来，由于各种原因，对¹⁹F成像技术的研究进展缓慢。但是在过去的十年间，尤其是最近几年，¹⁹F成像的研究和临床相关性呈爆发式发展。部分原因归结为MRI仪器、¹⁹F/¹H线圈设计以及临床前和临床核磁共振仪的超高速脉冲序列的发展。这些成就再加上对解剖生理学分子成像技术的兴趣以及一批创新造影剂的出现使¹⁹F的概念进入了早期的临床评估中。本篇综述重点探讨以液态全氟化碳化合物为基础的造影剂，并试图呈现这段丰富的研究和发展历史。

关键词：氟磁共振成像(MRI) 双调线圈全氟化碳血管生成术细胞标记

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Anefficient quadrature demodulator for medical ultrasound imaging

Hao ZHOU,Yin-fei ZHENG

《信息与电子工程前沿（英文）》 2015年第16卷第4期页码 301-310 doi: 10.1631/FITEE.1400205

摘要： Quadrature demodulation is used in medical ultrasound imaging to derive the envelope and instantaneous phase of the received radio-frequency (RF) signal. In quadrature demodulation, RF signal is multiplied with the sine and cosine wave reference signal and then low-pass filtered to produce the base-band complex signal, which has high computational complexity. In this paper, we propose an efficient quadrature demodulation method for B-mode and color flow imaging, in which the RF signal is demodulated by a pair of finite impulse response filters without mixing with the reference signal, to reduce the computational complexity. The proposed method was evaluated with simulation and in vivo experiments. From the simulation results, the proposed quadrature demodulation method produced similar normalized residual sum of squares (NRSS) and velocity profile compared with the conventional quadrature demodulation method. In the in vivo color flow imaging experiments, the time of the demodulation process was 5.66 ms and 3.36 ms, for the conventional method and the proposed method, respectively. These results indicated that the proposed method can maintain the performance of quadrature demodulation while reducing computational complexity.

关键词： B-mode ultrasound imaging Color flow imaging Quadrature demodulation Finite impulse response filter

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光场成像技术：模型、标定、重建及应用 Review

Hao ZHU, Qing WANG, Jingyi YU

《信息与电子工程前沿（英文）》 2017年第18卷第9期页码 1236-1249 doi: 10.1631/FITEE.1601727

摘要：光场成像是计算摄像学领域一项新兴技术。基于对成像模型和光路的创新设计，光场相机不仅记录了三维物体的空间强度，而且捕获了物理世界中的角度信息。这为解决三维重建、显著区域检测、目标识别等计算机视觉问题提供了新途径。本文首先回顾了光场相机的三个关键问题，包括成像模型、标定理论以及重建方法。然后，系统介绍了光场成像技术在信息学、物理学、医学和生物学等领域的应用现状。最后，讨论了光场成像目前存在的问题，并展望了光场成像技术的应用前景。

关键词：光场成像；全光函数；成像模型；标定；重建

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Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging

Liangqian Tong, Ming Zhao, Shu Zhu, Jing Chen

《医学前沿（英文）》 2011年第5卷第4期页码 379-387 doi: 10.1007/s11684-011-0162-6

摘要： Superparamagnetic iron oxide (SPIO) nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility. A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles, such as surface-coated, targeted ligand-conjugated, and/or drug-loaded SPIO nanoparticles, as powerful tools for targeted imaging and therapy. Moreover, the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment. In the present review, we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis, targeted therapy, and cancer imaging.

关键词： nanoparticles superparamagnetic iron oxide targeted therapy molecular imaging cancer

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A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 103-111 doi: 10.1007/s11705-021-2064-8

摘要： Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are enzymes involved in the biotransformation of important endogenous compounds such as steroids, bile acids, and hormones as well as exogenous substances including drugs, environmental toxicants, and carcinogens. Here, a novel fluorescent probe BDMP was developed based on boron-dipyrromethene (BODIPY) with high sensitivity for the detection of UGT1A8. The glucuronidation of BDMP not only exhibited a red-emission wavelength (λ_ex/λ_em = 500/580 nm), but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration. Based on this perfect biocompatibility and cell permeability, BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines (LoVo and HCT15) in real time. In addition, BDMP could also be used to visualize UGT1A8 in tumor tissues. These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.

关键词： UDP-glucuronosyltransferase 1A8 fluorescent probe subtype selectivity fluorescence imaging

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of the mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging

《医学前沿（英文）》页码 993-1005 doi: 10.1007/s11684-023-0989-7

摘要： Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients’ metabolites/proteins may precede that of the brain.

关键词： acupuncture migraine fMRI metabolome proteome