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Molecular Imaging Probes for Early Detection and Staging of Liver Fibrosis. 分子成像探针用于肝纤维化的早期发现和分期。
IF 5.7 Pub Date : 2025-07-10 eCollection Date: 2025-11-24 DOI: 10.1021/cbmi.5c00055
Xiuqi Hu, Mengdan Xu, Xiao Xiao, Ning Wang, Qianqian Zhang, Jianxian Ge, Jianfeng Zeng

Liver fibrosis, a progressive condition marked by excessive extracellular matrix deposition and activation of hepatic stellate cells, often develops asymptomatically in its early stages, leading to delayed clinical intervention. Conventional imaging techniques typically fail to detect mild fibrosis, resulting in diagnosis only at advanced stages such as cirrhosis, when therapeutic efficacy is significantly compromised. Recent advances in molecular imaging have facilitated the development of targeted contrast agents that enhance diagnostic sensitivity by selectively binding to fibrosis-specific biomarkers or responding to pathological microenvironmental changes. These include both nonresponsive probes that accumulate in fibrotic tissue and activatable probes sensitive to enzymes, small molecules, and other fibrosis-associated signals. This review systematically summarizes these emerging strategies and evaluates their potential for improving early diagnosis, staging accuracy, and therapeutic monitoring, thereby guiding future development and applications in hepatic fibrosis management.

肝纤维化是一种以细胞外基质过度沉积和肝星状细胞活化为特征的进行性疾病,通常在早期无症状发展,导致临床干预延迟。传统的成像技术通常无法检测到轻度纤维化,导致只有在晚期(如肝硬化)才能诊断出来,此时治疗效果明显受损。分子成像的最新进展促进了靶向造影剂的发展,通过选择性地结合纤维化特异性生物标志物或响应病理微环境变化来提高诊断敏感性。这包括在纤维化组织中积累的无反应探针和对酶、小分子和其他纤维化相关信号敏感的可激活探针。本文系统地总结了这些新兴策略,并评估了它们在提高早期诊断、分期准确性和治疗监测方面的潜力,从而指导了肝纤维化治疗的未来发展和应用。
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引用次数: 0
Revealing Prostate Calcification Heterogeneity through Their Elemental Distribution. 通过元素分布揭示前列腺钙化的异质性。
IF 5.7 Pub Date : 2025-07-07 eCollection Date: 2025-12-22 DOI: 10.1021/cbmi.5c00050
Sarah B Gosling, Emily L Arnold, Lois Adams, Paul Cool, Kalotina Geraki, Mark O Kitchen, Iain D Lyburn, Keith D Rogers, Tim Snow, Nick Stone, Charlene E Greenwood

Calcifications across the body offer snapshots of the surrounding ionic environment at the time of their formation. Links between prostate calcification chemistry and cancer are becoming of increasing interest, particularly in identifying biomarkers for disease. This study utilizes X-ray fluorescence mapping of 72 human prostate calcifications, measured at the I18 beamline at the Diamond Light Source, to determine the links between calcifications and their environment. This paper offers the first investigation of the elemental heterogeneity of prostate calcifications, demonstrating lower relative levels of minor elements at the calcification center compared to the edge but higher levels of zinc. Importantly, this study uniquely presents links between average Fe, Cr, Mn, Cu, and Ni ratios and grade Group (a classification system for urological tumors, specifically for prostate cancer), highlighting a potential avenue of exploration for biomarkers in prostate calcifications.

全身的钙化提供了它们形成时周围离子环境的快照。前列腺钙化化学与癌症之间的联系越来越引起人们的兴趣,特别是在确定疾病的生物标志物方面。这项研究利用x射线荧光测绘72人前列腺钙化,测量在钻石光源的I18光束线,以确定钙化和他们的环境之间的联系。本文首次对前列腺钙化的元素异质性进行了研究,表明钙化中心的微量元素相对于边缘的含量较低,但锌的含量较高。重要的是,这项研究独特地展示了平均Fe, Cr, Mn, Cu和Ni比率与grade Group(泌尿系统肿瘤,特别是前列腺癌的分类系统)之间的联系,突出了探索前列腺钙化生物标志物的潜在途径。
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引用次数: 0
Unveiling the Invisible: Multiscale Molecular Insights through Raman Imaging 揭示不可见:通过拉曼成像的多尺度分子洞察
IF 5.7 Pub Date : 2025-07-04 DOI: 10.1021/cbmi.5c00083
Sanjun Fan*,  and , Liang Luo*, 
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引用次数: 0
USSGAN: Unsupervised Spectral and Spatial Attention-Based Generative Adversarial Network for Cholangiocarcinoma Detection. USSGAN:用于胆管癌检测的无监督频谱和空间注意力生成对抗网络。
IF 5.7 Pub Date : 2025-07-01 eCollection Date: 2025-12-22 DOI: 10.1021/cbmi.5c00054
Sikhakolli Sravan Kumar, Anuj Deshpande, Pooja A Nair, Suresh Aala, Sunil Chinnadurai, Vineela Chandra Dodda, Inbarasan Muniraj, Md Abdul Latif Sarker, Hala Mostafa

Cholangiocarcinoma, a form of liver bile duct cancer, is challenging to detect due to its critically low 5-year survival rate. Conventional imaging modalities, such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), are widely used, but recent advancements in Hyperspectral Imaging (HSI) offer a promising, non-invasive alternative for cancer diagnosis. However, supervised learning methods often require large annotated datasets that can be difficult to obtain. To alleviate this limitation, we propose an unsupervised learning strategy using Generative Adversarial Networks (GANs) for cholangiocarcinoma detection. This approach, named Unsupervised Spectral and Spatial Attention-based GAN (USSGAN), employs an unsupervised Spectral-Spatial attention-based GAN to classify and segment cancerous regions without relying on labeled training data. The integration of an adaptive step size into Tasmanian Devil Optimization (TDO) enhances the convergence speed and effectively captures diverse cancerous features. Enhanced Tasmanian Devil Optimization (ETDO) further improves segmentation performance, making the framework robust and computationally efficient. The proposed method was tested on a publicly available multidimensional choledochal cholangiocarcinoma dataset, achieving superior performance compared with existing techniques in the literature. USSGAN demonstrated high accuracy across key metrics such as overall accuracy (OA), average accuracy (AA), and Cohen's Kappa. Ablation studies confirmed the critical contributions of the proposed enhancements to the overall performance. With an overall accuracy of 98.03%, the USSGAN closely aligns with the assessments of experienced pathologists while maintaining minimal computational requirements. Its lightweight nature ensures real-time deployment, providing results within a minute, making it a practical and effective solution for clinical applications.

胆管癌是肝胆管癌的一种,由于其5年生存率极低,很难被发现。传统的成像方式,如计算机断层扫描(CT)和磁共振成像(MRI),被广泛使用,但最近在高光谱成像(HSI)的进展提供了一个有前途的,非侵入性的替代癌症诊断。然而,监督学习方法通常需要难以获得的大型带注释的数据集。为了减轻这一限制,我们提出了一种使用生成对抗网络(GANs)进行胆管癌检测的无监督学习策略。这种方法被称为基于无监督光谱和空间注意力的GAN (USSGAN),它采用基于无监督光谱和空间注意力的GAN来对癌变区域进行分类和分割,而不依赖于标记的训练数据。将自适应步长集成到塔斯马尼亚魔鬼优化(TDO)中,提高了收敛速度,有效地捕获了各种癌症特征。增强的塔斯马尼亚魔鬼优化(ETDO)进一步提高了分割性能,使框架鲁棒性和计算效率。该方法在一个公开的多维胆总管胆管癌数据集上进行了测试,与文献中现有的技术相比,取得了更好的性能。USSGAN在总体精度(OA)、平均精度(AA)和Cohen’s Kappa等关键指标上都表现出了很高的准确性。消融研究证实了所提出的增强对整体性能的关键贡献。总体精度为98.03%,USSGAN与经验丰富的病理学家的评估密切一致,同时保持最低的计算要求。它的轻量特性确保了实时部署,在一分钟内提供结果,使其成为临床应用的实用有效的解决方案。
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引用次数: 0
Direct Optical Visualization of In Situ Photodegradation Dynamics in Metal-Organic Frameworks. 金属-有机框架中原位光降解动力学的直接光学可视化。
IF 5.7 Pub Date : 2025-07-01 eCollection Date: 2025-11-24 DOI: 10.1021/cbmi.5c00047
Jinn-Kye Lee, Shuyang Wu, Mingyu Ma, Jia Xin Chan, Pei Chong Lim, Zhengyang Zhang

Metal-organic frameworks (MOFs), such as HKUST-1, have been used in many applications such as catalysis, gas capture, and more. However, one major limitation hindering their application is inherent chemical instability, and conducting in situ studies on their degradation with sufficient spatial-temporal resolution remains a challenge. In this work, we employ optical microscopy to quantitatively monitor the degradation of HKUST-1 under alkaline and acidic reducing environments with video-rate temporal resolution. By color-mapping the degradation progress over different time intervals with alkaline hole (h+) scavengers (sodium ascorbate, NaAs), we observe a sigmoidal time-dependent degradation trend. The results reveal the presence of confined regions with faster degradation. It is discovered that degradation begins with the chemical reduction of HKUST-1 into Cu2O nanoparticles, followed by self-photoreduction into Cu2O/Cu. Furthermore, it is observed that there is a h+ scavenger concentration and laser-wavelength-dependent degradation. At higher concentrations and irradiation energy, there is faster degradation in the HKUST-1 framework. Under acidic reducing conditions with lactic acid (LA), the degradation rate constant is 22% higher than that under alkaline conditions, while the valence state of Cu remains unchanged. This can be attributed to distinct degradation mechanisms at different pH levels, in which acidolysis and metal-ligand disruption dominate in the presence of LA, while HKUST-1 degradation is primarily redox-driven in NaAs solution. These findings offer mechanistic insight into the degradation behavior of HKUST-1 and provide valuable guidance for optimizing MOF stability in practical applications.

金属有机框架(MOFs),如HKUST-1,已在催化,气体捕获等许多应用中得到应用。然而,阻碍其应用的一个主要限制是其固有的化学不稳定性,并且以足够的时空分辨率对其降解进行原位研究仍然是一个挑战。在这项工作中,我们使用光学显微镜以视频速率时间分辨率定量监测HKUST-1在碱性和酸性还原环境下的降解。通过对碱孔(h+)清除剂(抗坏血酸钠,NaAs)在不同时间间隔内的降解过程进行彩色映射,我们观察到一个s型的时间依赖性降解趋势。结果表明存在降解较快的受限区域。研究发现,降解始于HKUST-1的化学还原成Cu2O纳米颗粒,然后自光还原成Cu2O/Cu。此外,还观察到存在h+清除剂浓度和激光波长相关的降解。在较高的浓度和辐照能量下,HKUST-1框架内的降解速度更快。在乳酸(LA)酸性还原条件下,Cu的降解速率常数比碱性条件下高22%,而Cu的价态保持不变。这可归因于不同pH水平下不同的降解机制,其中酸解和金属配体破坏在LA存在下占主导地位,而HKUST-1降解主要是在NaAs溶液中氧化还原驱动。这些发现为深入了解HKUST-1的降解行为提供了机制,并为在实际应用中优化MOF稳定性提供了有价值的指导。
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引用次数: 0
Bridged-Bicyclic Fluorophores Push Photophysical Boundaries for Live-Cell Imaging. 桥-双环荧光团推动了活细胞成像的光物理界限。
IF 5.7 Pub Date : 2025-06-27 eCollection Date: 2025-10-27 DOI: 10.1021/cbmi.5c00078
Dongjuan Si, Lu Wang
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引用次数: 0
Gamma Correction and Color Space Transformations for Quantitative Analysis of Electrochemiluminescence Images Using Smartphone Cameras. 使用智能手机相机的电化学发光图像定量分析的伽玛校正和色彩空间变换。
IF 5.7 Pub Date : 2025-06-26 eCollection Date: 2025-11-24 DOI: 10.1021/cbmi.5c00056
Stephania Rodríguez Muiña, Rajendra Kumar Reddy Gajjala, Eduardo Fernández Martín, Francisco Javier Del Campo

Quantitative imaging of luminescent signals, ranging from electrochemiluminescence (ECL) and chemiluminescence to colorimetric assays, is increasingly performed using consumer-grade digital cameras and smartphones. However, device-dependent variability, nonlinear signal encoding, and the absence of standardized workflows hinder reproducibility and quantification accuracy. This work presents a generalized methodology for robust signal quantification in luminescent systems using digital imaging, with ECL as a model case. By combining synchronized electrochemical control, manual optimization of imaging parameters, gamma correction, and color space transformations, accurate device-independent analysis is enabled. Using Ru-(bpy)3 2+/TPrA as a test system, we evaluate RGB, CIEXYZ, and CIELAB color spaces, identifying optimal channels for sensitivity and dynamic range. Our performance assessment underscores the importance of transfer function selection and supports both linear and nonlinear quantification models. Results show that linearized r and X color channels offer broad dynamic ranges with moderate sensitivity, while encoded R and a* channels provide higher sensitivity at low concentrations, requiring nonlinear modeling to extend their quantification range. This scalable approach enables standardized, high-throughput optical analysis using low-cost camera platforms, with broad applications in diagnostics, biosensing, and analytical chemistry.

发光信号的定量成像,从电化学发光(ECL)和化学发光到比色分析,越来越多地使用消费级数码相机和智能手机进行。然而,设备相关的可变性、非线性信号编码以及标准化工作流程的缺乏阻碍了再现性和量化准确性。这项工作提出了一个广义的方法,鲁棒信号量化在发光系统中使用数字成像,与ECL作为一个模型的情况下。通过结合同步电化学控制、手动优化成像参数、伽玛校正和色彩空间转换,可以实现与设备无关的精确分析。使用Ru-(bpy) 32 +/TPrA作为测试系统,我们评估了RGB, CIEXYZ和CIELAB色彩空间,确定了灵敏度和动态范围的最佳通道。我们的性能评估强调了传递函数选择的重要性,并支持线性和非线性量化模型。结果表明,线性化的r和X颜色通道具有较宽的动态范围和中等的灵敏度,而编码的r和a*通道在低浓度下具有较高的灵敏度,需要非线性建模来扩展其量化范围。这种可扩展的方法可以使用低成本的相机平台进行标准化,高通量的光学分析,在诊断,生物传感和分析化学中具有广泛的应用。
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引用次数: 0
Imaging Copper Levels during Life in the Brain and beyond Using a Fluorescent Copper Sensor with Multimodal Capacity. 使用具有多模态容量的荧光铜传感器成像大脑生命期间及以后的铜水平。
IF 5.7 Pub Date : 2025-06-24 eCollection Date: 2025-10-27 DOI: 10.1021/cbmi.5c00024
Liam D Adair, Benjamin G Trist, Marcus E Graziotto, Tom J Hawtrey, Benjamin D Rowlands, Sarah A Rosolen, Veronica Cottam, Michael Kuligowski, Jessica L Chitty, Ellie T Y Mok, Thomas R Cox, Michael P Gotsbacher, Kay L Double, Elizabeth J New

Copper is an essential trace element for normal development and function throughout the body, including the central nervous system (CNS). Alterations to cellular copper levels result in severe neurological consequences and are linked to a range of CNS disorders, positioning treatments that restore copper balance as promising therapies for these disorders. However, despite the clear relationship between copper balance and CNS health, there are limited tools to measure copper levels in vivo in humans. This constitutes a significant challenge for both diagnosing disorders of copper imbalance and monitoring the efficacy of copper-altering treatments for these disorders. Here we report the synthesis and characterization of Fluorine-labeled Naphthalimide Copper sensor 1 (F-NpCu1), a fluorescent sensor for copper that contains a fluorine atom for future radiolabeling for clinical application. We demonstrate that the probe exhibits good stability and is highly selective for copper above other transition metals present in biological tissues. Copper binding promotes covalent bond formation between the sensor and proximal cellular proteins. F-NpCu1 is nontoxic and can be measured using fluorescence microscopy in living cells and fixed tissue sections from both mouse brain and pancreas. Furthermore, F-NpCu1 exhibits good blood-brain-barrier permeability and can report differences in brain copper levels induced by copper modulating therapies in living mice using intravital fluorescence microscopy. This study represents a promising advance toward the development of the first clinical tool for measuring copper in living humans, including in the CNS, with radiolabeling studies underway to develop 18F-NpCu1 for PET imaging of copper in vivo.

铜是人体包括中枢神经系统(CNS)的正常发育和功能所必需的微量元素。细胞铜水平的改变会导致严重的神经系统后果,并与一系列中枢神经系统疾病有关,因此恢复铜平衡的治疗方法是治疗这些疾病的有希望的治疗方法。然而,尽管铜平衡与中枢神经系统健康之间存在明确的关系,但测量人体体内铜水平的工具有限。这对诊断铜失衡疾病和监测改变铜治疗这些疾病的疗效构成了重大挑战。在这里,我们报道了氟标记的萘酰亚胺铜传感器1 (F-NpCu1)的合成和表征,这是一种含有氟原子的铜荧光传感器,用于未来临床应用的放射性标记。我们证明探针具有良好的稳定性,并且对铜的选择性高于生物组织中存在的其他过渡金属。铜结合促进传感器和近端细胞蛋白之间形成共价键。F-NpCu1是无毒的,可以使用荧光显微镜在小鼠脑和胰腺的活细胞和固定组织切片中测量。此外,F-NpCu1表现出良好的血脑屏障通透性,可以通过活体荧光显微镜报道铜调节疗法诱导的活小鼠脑铜水平的差异。这项研究代表了一个有希望的进展,即开发第一个用于测量活人(包括中枢神经系统)铜的临床工具,同时正在进行放射性标记研究,以开发用于体内铜的PET成像的18F-NpCu1。
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引用次数: 0
Spatially Resolving and Regulating Heterogeneity of Electronic Coupling at the Single Silver Nanoentity Level. 单银纳米实体水平上电子耦合的空间分辨与调控异质性。
IF 5.7 Pub Date : 2025-06-24 eCollection Date: 2025-09-22 DOI: 10.1021/cbmi.5c00035
Zhihui Wang, Yu-Ling Zou, Bo Jiang, Wei Wang, Hui Wang

Interfacial electron transfer governs electrochemical heterogeneity at the single-entity level. Herein, we investigated the electronic coupling event during electrodissolution processes of single silver nanoentities on a Au electrode through a synchronized electrochemical-optical tracking platform. By implementing strategic control of interfacial gap distances and electrolyte composition, a marked differentiation of single-particle reaction dynamics can be achieved. The integration of superlocalization methodology reveals position-correlated optical centroid shifts during electrodissolution processes, demonstrating heterogeneous oxidation dynamics arising from spatially nonuniform surface oxide formation. Crucially, SAM-mediated gap regulation enables the precise regulation of interfacial electric field enhancement. Our methodology resolves electronic coupling heterogeneity at subnanowire scale while proving molecular interlayer-dependent modulation of coupling lifetimes. This electrochemical-optical imaging strategy establishes nanoscale spatial mapping of electrochemical dynamics, quantitative correlation between interfacial structure and coupling efficiency, and real-time tracking of transient electronic states. These findings demonstrate the capability of advanced optical imaging methodologies in elucidating structure-activity relationships at nanoscale interfaces, providing mechanistic insights for single-entity electrochemistry and nanoscale energy conversion systems.

界面电子转移控制着单实体水平的电化学非均质性。在此,我们通过同步电化学-光学跟踪平台研究了单个银纳米实体在金电极上电溶解过程中的电子耦合事件。通过对界面间隙距离和电解质组成的策略控制,可以实现单粒子反应动力学的显著分化。集成超局域化方法揭示了电溶解过程中位置相关的光学质心位移,证明了由空间不均匀表面氧化物形成引起的非均质氧化动力学。至关重要的是,sam介导的间隙调节能够精确调节界面电场增强。我们的方法解决了亚纳米线尺度上的电子耦合异质性,同时证明了耦合寿命的分子层间依赖调制。这种电化学-光学成像策略建立了电化学动力学的纳米尺度空间映射,界面结构与耦合效率之间的定量关联,以及瞬态电子状态的实时跟踪。这些发现证明了先进的光学成像方法在阐明纳米级界面结构-活性关系方面的能力,为单实体电化学和纳米级能量转换系统提供了机制见解。
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引用次数: 0
Pub Date : 2025-06-23
Yong Tian, Weigeng Huang, Zhijia Sheng, Dingyuan Yan*, Dong Wang* and Ben Zhong Tang*, 
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引用次数: 0
期刊
Chemical & Biomedical Imaging
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