Cyril Besnard*, Ali Marie, Sisini Sasidharan, Shashidhara Marathe, Kaz Wanelik, Robert A. Harper, Christoph Rau, Richard M. Shelton, Gabriel Landini and Alexander M. Korsunsky*,
{"title":"Advanced Time-Stepping Interpretation of Fly-Scan Continuous Rotation Synchrotron Tomography of Dental Enamel Demineralization","authors":"Cyril Besnard*, Ali Marie, Sisini Sasidharan, Shashidhara Marathe, Kaz Wanelik, Robert A. Harper, Christoph Rau, Richard M. Shelton, Gabriel Landini and Alexander M. Korsunsky*, ","doi":"10.1021/cbmi.3c00121","DOIUrl":"10.1021/cbmi.3c00121","url":null,"abstract":"<p >High-resolution spatial and temporal analysis and 3D visualization of time-dependent processes, such as human dental enamel acid demineralization, often present a challenging task. Overcoming this challenge often requires the development of special methods. Dental caries remains one of the most important oral diseases that involves the demineralization of hard dental tissues as a consequence of acid production by oral bacteria. Enamel has a hierarchically organized architecture that extends down to the nanostructural level and requires high resolution to study its evolution in detail. Enamel demineralization is a dynamic process that is best investigated with the help of <i>in situ</i> experiments. In previous studies, synchrotron tomography was applied to study the 3D enamel structure at certain time points (time-lapse tomography). Here, another distinct approach to time-evolving tomography studies is presented, whereby the sample image is reconstructed as it undergoes continuous rotation over a virtually unlimited angular range. The resulting (single) data set contains the data for multiple (potentially overlapping) intermediate tomograms that can be extracted and analyzed as desired using time-stepping selection of data subsets from the continuous fly-scan recording. One of the advantages of this approach is that it reduces the amount of time required to collect an equivalent number of single tomograms. Another advantage is that the nominal time step between successive reconstructions can be significantly reduced. We applied this approach to the study of acidic enamel demineralization and observed the progression of demineralization over time steps significantly smaller than the total acquisition time of a single tomogram, with a voxel size smaller than 0.5 μm. It is expected that the approach presented in this paper can be useful for high-resolution studies of other dynamic processes and for assessing small structural modifications in evolving hierarchical materials.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 3","pages":"213–221"},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139853102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ankyrons: There Might Be a “Gold Mine” for Students, Scientists, and Clinicians","authors":"Yingbo Li*, and , Junfeng Wang*, ","doi":"10.1021/cbmi.4c00004","DOIUrl":"10.1021/cbmi.4c00004","url":null,"abstract":"","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 3","pages":"165–167"},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139871792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Activity-Independent Enzyme-Powered Amplification for Improving Signal Stability and Fidelity in Biosensing","authors":"Yibo Zhou*, Shan Hu, Hong-Wen Liu, Xinyue Xiao, Weiju Chen, Sheng Yang, Huiqiu Shi, Zhengxuan Gu, Junbin Li, Ronghua Yang* and Zhihe Qing*, ","doi":"10.1021/cbmi.3c00127","DOIUrl":"10.1021/cbmi.3c00127","url":null,"abstract":"<p >Enzymes are an important tool used for signal amplification in biosensing. However, traditional amplification methods based on enzymes are always dependent on their catalytic activities, so their signals fluctuate with the change of microenvironment (e.g., pH and temperature). In this work, we communicate an activity-independent enzyme-powered (AIEP) amplification strategy for biosensing to improve signal stability and fidelity. To verify this hypothesis, the monitoring of oxidative stress during drug-induced liver injury was carried out. Carboxylesterase (CEs), highly expressed in hepatic tissue, was selected as the amplification tool. A CEs configuration-matching fluorophore (CMF) was designed and screened, and a nanobeacon was fabricated by loading CMF within an O<sub>2</sub><sup>•–</sup>-responsive polymeric micelle. Since the degradation of the nanobeacon was triggered by O<sub>2</sub><sup>•–</sup>, CMF was released to bind with CEs, and the fluorescence was lit by CEs-CMF configuration matching but not catalytic reaction. Results demonstrated that the oxidative stress during drug-induced liver injury could be successfully monitored, and the hepatoprotective effects of repair drugs could be evaluated by cell and in vivo imaging. This strategy is flexible for bioactive molecules by altering the responsive unit and generally accessible for pharmacological evaluation.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 4","pages":"304–312"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140472139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenchen Bian, Miaomiao Liu, Jiayi Cheng, Lei Yang*, Zhanxian Li* and Mingming Yu*,
{"title":"Dual-Functional Fluorescent Probe in the Diagnosis of Liver Injury and the Evaluation of Drug Therapy with Double Signal Amplification","authors":"Chenchen Bian, Miaomiao Liu, Jiayi Cheng, Lei Yang*, Zhanxian Li* and Mingming Yu*, ","doi":"10.1021/cbmi.3c00128","DOIUrl":"10.1021/cbmi.3c00128","url":null,"abstract":"<p >Viscosity and polarity are crucial microenvironmental parameters within cells, intimately linked to the physiological activities of organisms. We constructed and synthesized an innovative dual-functional fluorescent probe, DHBP. In the green channel, the fluorescence signal notably intensifies with decreasing environmental polarity, while in the red channel, fluorescence signal amplification occurs due to the collaborative effects of viscosity and polarity, resulting in more pronounced changes. Additionally, DHBP demonstrates high sensitivity in detecting changes in polarity and viscosity induced by drug-induced inflammation in cells and mice. Importantly, DHBP has been effectively utilized to monitor alterations in viscosity and polarity in the liver injury induced by diabetes in vivo in mice and further employed to assess the therapeutic efficacy of drugs. Therefore, DHBP holds promise for advancing research on viscosity and polarity in future studies of physiological and pathological processes.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 2","pages":"156–164"},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139594254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zachary T. Piontkowski*, Dulce C. Hayes, Anthony McDonald, Kalista Pattison, Kimberly S. Butler and Jerilyn A. Timlin*,
{"title":"Label-Free, Noninvasive Bone Cell Classification by Hyperspectral Confocal Raman Microscopy","authors":"Zachary T. Piontkowski*, Dulce C. Hayes, Anthony McDonald, Kalista Pattison, Kimberly S. Butler and Jerilyn A. Timlin*, ","doi":"10.1021/cbmi.3c00106","DOIUrl":"10.1021/cbmi.3c00106","url":null,"abstract":"<p >Characterizing and identifying cells in multicellular <i>in vitro</i> models remain a substantial challenge. Here, we utilize hyperspectral confocal Raman microscopy and principal component analysis coupled with linear discriminant analysis to form a label-free, noninvasive approach for classifying bone cells and osteosarcoma cells. Through the development of a library of hyperspectral Raman images of the K7M2-wt osteosarcoma cell lines, 7F2 osteoblast cell lines, RAW 264.7 macrophage cell line, and osteoclasts induced from RAW 264.7 macrophages, we built a linear discriminant model capable of correctly identifying each of these cell types. The model was cross-validated using a k-fold cross validation scheme. The results show a minimum of 72% accuracy in predicting cell type. We also utilize the model to reconstruct the spectra of K7M2 and 7F2 to determine whether osteosarcoma cancer cells and normal osteoblasts have any prominent differences that can be captured by Raman. We find that the main differences between these two cell types are the prominence of the β-sheet protein secondary structure in K7M2 versus the α-helix protein secondary structure in 7F2. Additionally, differences in the CH<sub>2</sub> deformation Raman feature highlight that the membrane lipid structure is different between these cells, which may affect the overall signaling and functional contrasts. Overall, we show that hyperspectral confocal Raman microscopy can serve as an effective tool for label-free, nondestructive cellular classification and that the spectral reconstructions can be used to gain deeper insight into the differences that drive different functional outcomes of different cells.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 2","pages":"147–155"},"PeriodicalIF":0.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139600531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Small Molecule Chemiluminophore with near 600 nm Emission for In Vivo Imaging of Myeloperoxidase and Inflammatory Diseases","authors":"Tianjiao Meng, Xueru Zhang, Wei Tang, Chenghui Liu* and Xinrui Duan*, ","doi":"10.1021/cbmi.3c00105","DOIUrl":"10.1021/cbmi.3c00105","url":null,"abstract":"<p >Chemiluminescence has emerged as a vital tool for bioimaging in vivo. The red shift emission of chemiluminophores is extremely useful for in vivo bioimaging. In this work, the conjugation system of the luminol was extended to achieve a red-shifted emission (591 nm) along with excellent water solubility. The probe (HM-ASPH-PF) has a molecular weight of only 396.42, which contains a benzothiazole and a cyclic phthalhydrazide structure. The probe has been used for in vivo luminescence imaging of neutrophil-mediated acute liver injury, including alcoholic liver injury (ALI) and acute liver failure (ALF) in mice, by exploiting myeloperoxidase (MPO) as a biomarker. The activated neutrophils were specifically imaged by HM-ASPH-PF. HM-ASPH-PF was also successfully applied to monitor the neutrophils in livers in mouse models of ALI and ALF. Consequently, HM-ASPH-PF, as an effective luminescent small molecule that possesses a red-shift emission near 600 nm, has been applied for the detection of MPO in living cells and neutrophil-mediated acute liver injury. This work also demonstrates the applied potential of the luminescent probe for the diagnosis of other neutrophil-associated liver diseases.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 3","pages":"205–212"},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139606421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Talia Bergaglio, Olena Synhaivska and Peter Niraj Nirmalraj*,
{"title":"3D Holo-tomographic Mapping of COVID-19 Microclots in Blood to Assess Disease Severity","authors":"Talia Bergaglio, Olena Synhaivska and Peter Niraj Nirmalraj*, ","doi":"10.1021/cbmi.3c00126","DOIUrl":"10.1021/cbmi.3c00126","url":null,"abstract":"<p >The coronavirus disease 2019 (COVID-19) has impacted health globally. Cumulative evidence points to long-term effects of COVID-19 such as cardiovascular and cognitive disorders, diagnosed in patients even after the recovery period. In particular, micrometer-sized blood clots and hyperactivated platelets have been identified as potential indicators of long COVID. Here, we resolve microclot structures in the plasma of patients with different subphenotypes of COVID-19 in a label-free manner, using 3D digital holo-tomographic microscopy (DHTM). Based on 3D refractive index (RI) tomograms, the size, dry mass, and prevalence of microclot composites were quantified and then parametrically differentiated from fibrin-rich microclots and platelet aggregates in the plasma of COVID-19 patients. Importantly, fewer microclots and platelet aggregates were detected in the plasma of healthy controls compared to COVID-19 patients. Our imaging and analysis workflow is built around a commercially available DHT microscope capable of operation in clinical settings with a 2 h time period from sample preparation and data acquisition to results.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 3","pages":"194–204"},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139443192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Excited-State Conjugation/De-Conjugation Driven Nonradiative Thermal Deactivation for Developing Fluorogenic Probes to Diagnose Cancers","authors":"Hongxing Zhang, Guanlin Lao, Mengxing Liu, Zhihui Jia, Jing Liu* and Wei Guo*, ","doi":"10.1021/cbmi.3c00107","DOIUrl":"10.1021/cbmi.3c00107","url":null,"abstract":"<p >Fluorogenic probes have shown great potential in imaging biological species as well as in diagnosing diseases, especially cancers. However, the fluorogenic mechanisms are largely limited to a few photophysical processes to date, typically including photoinduced electron transfer (PeT), fluorescence resonant energy transfer (FRET), and intramolecular charge transfer (ICT). Herein, by calculations and experiments, we set forth that the inhibition of the excited-state π-conjugation in <i>meso</i>-ester Si-rhodamine <b>SiR-COOM</b> or the de-π-conjugation in <i>meso</i>-ester cyanine 5 <b>Cy5-COOM</b> via the “<i>ester-to-carboxylate</i>” conversion can operate as a general fluorogenic mechanism to fabricate fluorogenic probes. Based on the mechanism and considering the higher chemical stability of <b>Cy5-COOM</b> than that of <b>SiR-COOM</b>, we developed, as a proof-of-concept, three fluorogenic probes <b>Cy5-APN</b>, <b>Cy5-GGT</b>, and <b>Cy5-NTR</b> on the basis of the <b>Cy5-COOM</b> platform for sensing cancer biomarkers aminopeptidase N (APN), γ-glutamyltranspeptidase (GGT), and nitroreductase (NTR), respectively, and demonstrated their outstanding performances in distinguishing between cancerous and normal tissues with the high tumor-to-normal tissue ratios in the range of 9–14.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 6","pages":"432–441"},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinlan Luo, Changyong Song, Yunling Chen and Keyin Liu*,
{"title":"Near-Infrared Fluorescent Probe with pH- and Viscosity-Switchable Performance for the Detection of Thrombi in Live Animals and Organs","authors":"Jinlan Luo, Changyong Song, Yunling Chen and Keyin Liu*, ","doi":"10.1021/cbmi.3c00110","DOIUrl":"10.1021/cbmi.3c00110","url":null,"abstract":"<p >Blood viscosity changes and blood clots are high-impact diseases, but the pathogenic mechanisms and detection methods are still limited. Due to the complexity of the cellular microenvironment, viscosity is a key factor in regulating the behavior of mitochondria and lysosomes in cells. Conventional fluorescence probes are highly restrictive for complex viscosity detection in live animals. Therefore, we developed two near-infrared fluorescence probes, <b>QL1</b> and <b>QL2</b>, with dual responses to the pH and viscosity. Notably, <b>QL2</b> has two maximum fluorescence emissions at 680 and 750 nm, when excitation by 580 and 700 nm, respectively. <b>QL2</b> exhibited both a pH and viscosity switchable fluorescence response. The two emission peaks exhibited a reverse change trend: the fluorescence at 680 nm decreased by 90%, and the fluorescence at 750 nm increased by about 5-fold with pH from 2 to 10. Meanwhile, both emission peaks show remarkable fluorescence enhancement toward viscosity change, with 185 and 32 times enhancement, respectively. The sensing mechanism and spectral changes are confirmed by DFT calculations. <b>QL2</b> was further used for viscosity imaging in live cells, zebrafish, and live animals. Most importantly, <b>QL2</b> is able to successfully track changes in blood clots in live mice and organs, thus enabling the study of blood clots in cerebral strokes and the underlying pathological mechanisms.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 6","pages":"422–431"},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139387474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yang, Xiaoyang Liu, Xiaofeng Wu* and Gaolin Liang*,
{"title":"Enzyme-Instructed CBT-Cys-like Click Cyclization Reactions for Bioimaging","authors":"Yang Yang, Xiaoyang Liu, Xiaofeng Wu* and Gaolin Liang*, ","doi":"10.1021/cbmi.3c00117","DOIUrl":"10.1021/cbmi.3c00117","url":null,"abstract":"<p >With high efficiency, mild conditions, and rapid reaction rate, click reactions have garnered much attention in the field of bioimaging since proposed by Sharpless et al. in 2001 ( <cite><i>Angew. Chem., Int. Ed.</i></cite> <span>2001</span>, <em>40</em>, 2004−2021). Inspired by the regenerative pathway of <span>d</span>-luciferin in fireflies, Liang et al. ( <cite><i>Nat. Chem.</i></cite> <span>2010</span>, <em>2</em>, 54−60) raised a 2-cyanobenzothiazole (CBT)-cysteine (Cys) click condensation reaction in 2010, which exhibits a higher second-order reaction rate (9.19 M<sup>–1</sup> s<sup>–1</sup>) and superior biocompatibility. As it has been developed in the past decade, remarkable progress has been made in the construction of enzyme-instructed CBT-Cys-based bioimaging probes. This review introduces the concept of the CBT-Cys click reaction, elucidates the mechanism of the CBT-Cys click reaction, and concerns the development progress of CBT-Cys reaction and its derived reactions [i.e., 2-cyano-6-hydroxyquinoline (CHQ)-Cys reaction and 2-pyrimidinecarbonitrile (PMN)-Cys reaction]. Furthermore, we give a comprehensive and up-to-date review of enzyme-instructed CBT-Cys-like click reaction-based probes with significantly enhanced imaging signal and contrast for various bioimaging modes, including fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and positron emission tomography. In the end, we discuss the possible challenges and opportunities that may arise in the future.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 2","pages":"98–116"},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.3c00117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139130978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}