13 results on '"Chao Zhao"'
Search Results
2. iSegMSI: An Interactive Strategy to Improve Spatial Segmentation of Mass Spectrometry Imaging Data
- Author
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Lei Guo, Xingxing Liu, Chao Zhao, Zhenxing Hu, Xiangnan Xu, Kian-Kai Cheng, Peng Zhou, Yu Xiao, Mudassir Shah, Jingjing Xu, Jiyang Dong, and Zongwei Cai
- Subjects
Diagnostic Imaging ,Mice ,Fetus ,Image Processing, Computer-Assisted ,Animals ,Humans ,Mass Spectrometry ,Analytical Chemistry - Abstract
Spatial segmentation is a critical procedure in mass spectrometry imaging (MSI)-based biochemical analysis. However, the commonly used unsupervised MSI segmentation methods may lead to inappropriate segmentation results as the MSI data is characterized by high dimensionality and low signal-to-noise ratio. This process can be improved by the incorporation of precise prior knowledge, which is hard to obtain in most cases. In this study, we show that the incorporation of partial or coarse prior knowledge from different sources such as reference images or biological knowledge may also help to improve MSI segmentation results. Here, we propose a novel interactive segmentation strategy for MSI data called iSegMSI, which incorporates prior information in the form of scribble-regularization of the unsupervised model to fine-tune the segmentation results. By using two typical MSI data sets (including a whole-body mouse fetus and human thyroid cancer), the present results demonstrate the effectiveness of the iSegMSI strategy in improving the MSI segmentations. Specifically, the method can be used to subdivide a region into several subregions specified by the user-defined scribbles or to merge several subregions into a single region. Additionally, these fine-tuned results are highly tolerant to the imprecision of the scribbles. Our results suggest that the proposed iSegMSI method may be an effective preprocessing strategy to facilitate the analysis of MSI data.
- Published
- 2022
3. A System-Wide Spatiotemporal Characterization of ErbB Receptor Complexes by Subcellular Fractionation Integrated Quantitative Mass Spectrometry
- Author
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Mansheng Li, Shujuan Wang, Chao Zhao, Yong Zheng, and Cunjie Zhang
- Subjects
Proteomics ,Receptor complex ,Chemistry ,010401 analytical chemistry ,Protein complex assembly ,Cell Fractionation ,010402 general chemistry ,01 natural sciences ,Mass Spectrometry ,0104 chemical sciences ,Analytical Chemistry ,Cell biology ,ErbB Receptors ,Mice ,Targeted mass spectrometry ,ErbB ,Organelle ,Animals ,Cell fractionation ,Subcellular Fractions - Abstract
Precise spatiotemporal regulation of protein complex assembly is essential for cells to achieve a meaningful rely of information flow via intracellular signaling networks in response to extracellular cues, whose disruption would lead to disease. Although various attempts have been made for spatial and/or temporal analysis of protein complexes, it is still a challenge to track cell-wide dynamics of a particular protein complex under physiological conditions. Here we describe a workflow that combines endogenous expression of tagged proteins, organelle marker distribution-directed subcellular fractionation, scaffold protein-mediated receptor complex purification, and targeted proteomics for spatiotemporal quantification of protein complexes in whole cell scale. We applied our method to investigate the assembly kinetics of EGF-dependent ErbB receptor complexes. After fractionation using the density gradient centrifugation and organelle assignment based on organelle markers, endogenous ErbB complex in different subcellular fractionation was efficiently enriched. By using targeted mass spectrometry, ErbB complex components that expressed medium to low level was precisely quantified with in-depth coverage, simultaneously in time and subcellular spaces. Our results revealed a sophisticated scheme of complex behaviors characterized by multiple subcomplexes with distinct molecular composition formed across subcellular fractions enriched with cytosol, plasma membrane, endosome, or mitochondria, implying organelle-specific ErbB functions. Remarkably, our results demonstrated for the first time that activated ErbB receptors might increase their signaling range through promoting a cytosolic, receptor-free subcomplex, consisting of Shc1, Grb2, Arhgef5, Garem1, and Lrrk1. These findings emphasize the potential of our strategy as a powerful tool to study spatiotemporal dynamics of protein complexes.
- Published
- 2021
4. Data Filtering and Its Prioritization in Pipelines for Spatial Segmentation of Mass Spectrometry Imaging
- Author
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Jiyang Dong, Xiangnan Xu, Zhenxing Hu, Zongwei Cai, Shujuan Wang, Chao Zhao, Jingjing Xu, and Lei Guo
- Subjects
Diagnostic Imaging ,Pixel ,business.industry ,Chemistry ,010401 analytical chemistry ,Pattern recognition ,Filter (signal processing) ,010402 general chemistry ,01 natural sciences ,Pipeline (software) ,Mass Spectrometry ,Mass spectrometry imaging ,0104 chemical sciences ,Analytical Chemistry ,Pipeline transport ,Mice ,Software ,Robustness (computer science) ,Animals ,Segmentation ,Artificial intelligence ,business ,Algorithms - Abstract
Mass spectrometry imaging (MSI) could provide vast amounts of data at the temporal-spatial scale in heterogeneous biological specimens, which challenges us to segment accurately suborgans/microregions from complex MSI data. Several pipelines had been proposed for MSI spatial segmentation in the past decade. More importantly, data filtering was found to be an efficient procedure to improve the outcomes of MSI segmentation pipelines. It is not clear, however, how the filtering procedure affects the MSI segmentation. An improved pipeline was established by elaborating the filtering prioritization and filtering algorithm. Lipidomic-characteristic-based MSI data of a whole-body mouse fetus was used to evaluate the established pipeline on localization of the physiological position of suborgans by comparing with three commonly used pipelines and commercial SCiLS Lab software. Two structural measurements were used to quantify the performances of the pipelines including the percentage of abnormal edge pixel (PAEP) and CHAOS. Our results demonstrated that the established pipeline outperformed the other pipelines in visual inspection, spatial consistence, time-cost, and robustness analysis. For example, the dorsal pallium (isocortex) and hippocampal formation (Hpf) regions, midbrain, cerebellum, and brainstem on the mouse brain were annotated and located by the established pipeline. As a generic pipeline, the established pipeline could help with the accurate assessment and screening of drug/chemical-induced targeted organs and exploration of the progression and molecular mechanisms of diseases. The filter-based strategy is expected to become a critical component in the standard operating procedure of MSI data sets.
- Published
- 2021
5. Preparation of Frozen Sections of Multicellular Tumor Spheroids Coated with Ice for Mass Spectrometry Imaging
- Author
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Peisi Xie, Wei Huang, Chao Zhao, Zongwei Cai, Yanyan Chen, and Xiaoping Liang
- Subjects
Frozen section procedure ,food.ingredient ,Chemistry ,Ice ,010401 analytical chemistry ,Tumor spheroid ,010402 general chemistry ,Drug penetration ,01 natural sciences ,Gelatin ,Mass Spectrometry ,Mass spectrometry imaging ,Specimen Handling ,0104 chemical sciences ,Analytical Chemistry ,Optimal cutting temperature compound ,Drug biotransformation ,food ,Neoplasms ,Spheroids, Cellular ,Tumor Cells, Cultured ,Frozen Sections ,Humans ,Sample preparation ,Biomedical engineering - Abstract
Increasing studies have utilized mass spectrometry imaging (MSI) that is a label-free tool to investigate drug penetration and drug biotransformation in multicellular tumor spheroids (MCTS). Currently, the gelatin-assisted sectioning method is widely used to prepare frozen sections of MCTS for MSI. However, owing to the limited transparency of frozen gelatin, MCTS with diameters less than 500 μm that closely mimic solid tumors are difficult to be detected when cryosectioning. In order to identify the presence of MCTS, hematoxylin and eosin staining for frozen sections and dye pretreatment for MCTS were employed in previous works, which either increased the analytical time and cost in sample preparation or caused signal suppression in sample analysis. Herein, a new sectioning method was developed to prepare MCTS frozen sections. MCTS was coated with ice to ensure good visibility for small-size MCTS. The optimal cutting temperature compound was added around the ice block to assist the formation of frozen sections. A precast frozen mold was prepared to allow the acquisition of complete MCTS frozen sections. The developed method was applied to investigate lipid distribution in MCTS by using matrix-assisted laser desorption/ionization MSI. Compared to the gelatin-assisted sectioning method, our method did not cause signal suppression and analyte delocalization. Thus, this method provides an easy, universal, and innovative strategy to prepare MCTS frozen sections for further MSI analysis. Besides, we applied our method to investigate the penetration of bisphenol A in MCTS.
- Published
- 2020
6. Water Splitting-Assisted Electrocatalytic Oxidation of Glucose with a Metal-Organic Framework for Wearable Nonenzymatic Perspiration Sensing
- Author
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Shuai Yuan, Ju Yinhui, Xiaofei Zhu, Jun Yang, Hong Liu, and Chao Zhao
- Subjects
Wearable computer ,Nanotechnology ,Biosensing Techniques ,010402 general chemistry ,Electrocatalyst ,01 natural sciences ,Catalysis ,Analytical Chemistry ,medicine ,Glucose test ,Humans ,Perspiration ,Electrodes ,Metal-Organic Frameworks ,medicine.diagnostic_test ,Chemistry ,Glucose meter ,010401 analytical chemistry ,Water ,Electrochemical Techniques ,0104 chemical sciences ,Electrochemical gas sensor ,Glucose ,Water splitting ,medicine.symptom ,Oxidation-Reduction ,Zeolitic imidazolate framework - Abstract
In this work, a nonenzymatic electrochemical sensor based on electrochemical water splitting-assisted electrocatalysis is developed for wearable perspiration glucose analysis. Pd nanoparticles (Pd NPs) encapsulated in a Co-based zeolitic imidazolate framework (ZIF-67) is prepared and used as the electrocatalyst. In comparison to previously reported nonenzymatic glucose sensors which detect glucose in alkaline buffers, the proposed sensor analyzes glucose under physiological pH with no additional reagents, which enables wearable, maintenance-free perspiration glucose monitoring for a long time. The nonenzymatic sensor and a flexible printed circuit board (FPCB) is integrated into a sweatband for real-time analysis of perspiration glucose. The test results of perspiration glucose using our sensor are correlated to those of blood glucose tests by a commercial glucose meter. The sensitivity of the sensor remains stable within 2 months when it is stored unpacked under ambient conditions. Therefore, we believe it is promising for wearable nonenzymatic glucose monitoring for noninvasive clinical analysis and sport applications.
- Published
- 2019
7. MALDI-MS Imaging Reveals Asymmetric Spatial Distribution of Lipid Metabolites from Bisphenol S-Induced Nephrotoxicity
- Author
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Hailin Wang, Ting Yong, Peisi Xie, Zongwei Cai, Chao Zhao, and Arthur C.K. Chung
- Subjects
0301 basic medicine ,Renal cortex ,010501 environmental sciences ,urologic and male genital diseases ,Mass spectrometry ,01 natural sciences ,Analytical Chemistry ,Nephrotoxicity ,03 medical and health sciences ,chemistry.chemical_compound ,Membrane Lipids ,Phenols ,Lipidomics ,Renal medulla ,medicine ,Animals ,Humans ,Metabolomics ,Tissue Distribution ,Sulfones ,0105 earth and related environmental sciences ,Kidney ,Mice, Inbred BALB C ,Metabolic pathway ,030104 developmental biology ,medicine.anatomical_structure ,Biochemistry ,Bisphenol S ,chemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Female ,Kidney Diseases - Abstract
With the continuous exposure of environmental pollutants in organisms, determination of abundance variation and spatial distribution of lipids might expand our understanding of toxicological mechanisms occurring in the kidney. Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 μg bisphenol S (BPS)/kg body weight/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways. We elucidated the lipids spatial heterogeneity by using morphological analysis, probabilistic latent semantic analysis, and coregistered multimodal three-dimensional (3D)-MSI. In morphological analysis, both 10 and 100 μg BPS induced significant nephrotoxicity to mice, including glomerular necrosis in renal cortex, cloudy swelling in renal medulla, and interstitial collapsing in renal pelvis. Significant differential signaling lipids such as sphingomyelin (SM) (d22:0/20:4), ceramide (Cer) (d18:2/24:1), and sphingosine (d18:0) related to inflammation were found to be up-regulated and colocalized in the renal cortex, medulla, and pelvis, respectively. Also, seven significant differential lipids, which are considered to be involved in membrane homeostasis and cellular function, were found to be colocalized in the renal cortex. The observed significant variations of morphology, lipid accumulation, and metabolism in the renal cortex implicated that lipids in the renal cortex were more sensitive to BPS exposure than those in the renal medulla and pelvis. Moreover, we reconstructed a 3D-MSI model of kidney and identified two heterogeneous-related substructures in the renal cortex and pelvis upon 100 μg BPS exposure. It might be used in novel specificity evaluation and early diagnosis for environmental pollutant-induced kidney diseases.
- Published
- 2018
8. Capillary Monolithic Bioreactor of Immobilized Snake Venom Phosphodiesterase for Mass Spectrometry Based Oligodeoxynucleotide Sequencing
- Author
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Junfa Yin, Hailin Wang, Ruichuan Yin, Chao Zhao, and Dapeng Zhang
- Subjects
geography ,Chromatography ,geography.geographical_feature_category ,Chemistry ,Oligonucleotide ,DNA damage ,Mutagenesis ,Oligonucleotides ,Electrophoresis, Capillary ,Sequence Analysis, DNA ,DNA Solutions ,Enzymes, Immobilized ,Mass spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Bioreactors ,Phosphodiesterase I ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Bioreactor ,Monolith ,DNA ,Snake Venoms - Abstract
A capillary monolithic bioreactor of snake venom phosphodiesterase (SVP) was constructed to generate different single-nucleotide mass ladders of oligodeoxynucleotides for mass spectrometry (MS)-based sequencing by immobilization. The immobilization of SVP in the porous silica monolith significantly enhances its stability for prolonged and repeated applications. The constructed capillary bioreactor has the advantages of handling (sub)microliter DNA samples and having good permeability. Benefiting from its good permeability, DNA solutions can be directly injected into the sequential digestion bioreactor simply by hand pushing or a low-pressure microinjection pump. Moreover, the immobilization of SVP facilitates the elimination or repression of the metal adducts of oligodeoxynucleotides, improving the analytical performance of MS sequencing. By the application of capillary bioreactor of immobilized SVP, the sequence-specific modification of single-stranded oligodeoxynucleotide induced by a ubiquitous pollutant acrolein (Acr) was identified, demonstrating its promising applications in identification of sequence-specific damage, which may further our understanding of DNA damage caused mutagenesis.
- Published
- 2011
9. An ammonium bicarbonate-enhanced stable isotope dilution UHPLC-MS/MS method for sensitive and accurate quantification of acrolein-DNA adducts in human leukocytes
- Author
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Hailin Wang, Chao Zhao, Meiling Lu, Moon-shong Tang, Shengquan Liu, and Ruichuan Yin
- Subjects
Male ,Radioisotope Dilution Technique ,Chromatography ,Formic acid ,Electrospray ionization ,Mass spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Ammonia ,Bicarbonates ,DNA Adducts ,Ammonium bicarbonate ,chemistry ,Tandem Mass Spectrometry ,Cell Line, Tumor ,Ammonium formate ,Leukocytes ,Humans ,Ammonium ,Female ,Acrolein ,Ammonium acetate ,Chromatography, High Pressure Liquid - Abstract
Acrolein (Acr), a ubiquitous environmental pollutant, can react directly with genomic DNA to form mutagenic adducts without undergoing metabolic activation. To sensitively and accurately quantify Acr-DNA adducts (including structural isomers and stereoisomers) in human leukocytes, we developed an enhanced stable isotope dilution ultrahigh performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS/MS) method using ammonium bicarbonate (NH4HCO3), which is thermally unstable and degrades readily to carbon dioxide and ammonia in heated gas phase. Interestingly, ammonium bicarbonate (as an additive to the mobile phase) not only improves the protonation of AcrdG adducts but also suppresses the formation of MS signal-deteriorating metal-AcrdG complexes during electrospray ionization, leading to the enhancement of their MS detection by 2.3-8.7 times. In contrast, routinely used ammonium salts (ammonium acetate and ammonium formate) and formic acid do not show similar enhancement. The developed method is potentially useful for enhancing ESI-MS detection of other modified 2'-deoxyribonucleosides that have difficulty in protonation and may form excess metal complexes during electrospray ionization. The limits of detection (LODs, S/N = 3) are estimated to be about 40-80 amol. By the use of the developed method, we found that the Acr adducts of three nucleotides (dG, dA, and dC) can be detected in human leukocytes. In addition to the known γ-AcrdG, α-AcrdA is also identified as an Acr-adduct of high abundance (2.5-20 adducts per10(8) nts).
- Published
- 2013
10. MALDI-MS Imaging Reveals Asymmetric Spatial Distribution of Lipid Metabolites from Bisphenol S-Induced Nephrotoxicity.
- Author
-
Chao Zhao, Peisi Xie, Ting Yong, Hailin Wang, Chung, Arthur Chi Kong, and Zongwei Cai
- Subjects
- *
NEPHROTOXICOLOGY , *MASS spectrometry , *DESORPTION , *KIDNEY cortex , *KIDNEY pelvis , *HOMEOSTASIS - Abstract
With the continuous exposure of environmental pollutants in organisms, determination of abundance variation and spatial distribution of lipids might expand our understanding of toxicological mechanisms occurring in the kidney. Herein, an integrated method involving mass spectrometry (MS)-based lipidomics and matrix-assisted laser desorption/ionization-MS imaging (MALDI-MSI) was developed for the study of nephrotoxicity in mice exposed to 10 and 100 μg bisphenol S (BPS)/kg body weight/day. The BPS exposure remarkable perturbed abundances of 91 potential markers that mainly involved in five metabolic pathways. We elucidated the lipids spatial heterogeneity by using morphological analysis, probabilistic latent semantic analysis, and coregistered multimodal three-dimensional (3D)-MSI. In morphological analysis, both 10 and 100 μg BPS induced significant nephrotoxicity to mice, including glomerular necrosis in renal cortex, cloudy swelling in renal medulla, and interstitial collapsing in renal pelvis. Significant differential signaling lipids such as sphingomyelin (SM) (d22:0/20:4), ceramide (Cer) (d18:2/24:1), and sphingosine (d18:0) related to inflammation were found to be up-regulated and colocalized in the renal cortex, medulla, and pelvis, respectively. Also, seven significant differential lipids, which are considered to be involved in membrane homeostasis and cellular function, were found to be colocalized in the renal cortex. The observed significant variations of morphology, lipid accumulation, and metabolism in the renal cortex implicated that lipids in the renal cortex were more sensitive to BPS exposure than those in the renal medulla and pelvis. Moreover, we reconstructed a 3D-MSI model of kidney and identified two heterogeneous-related substructures in the renal cortex and pelvis upon 100 μg BPS exposure. It might be used in novel specificity evaluation and early diagnosis for environmental pollutant-induced kidney diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
11. An Ammonium Bicarbonate-Enhanced Stable Isotope Dilution UHPLC-MS/MS Method for Sensitive and Accurate Quantification of Acrolein - DNA Adducts in Human Leukocytes.
- Author
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Ruichuan Yin, Shengquan Liu, Chao Zhao, Meiling Lu, Moon-shong Tang, and Hailin Wang
- Published
- 2013
- Full Text
- View/download PDF
12. Cyclopentane-Peptide Nucleic Acids for Qualitative, Quantitative, and Repetitive Detection of Nucleic Acids.
- Author
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Micklitsch, Christopher M., Oquare, Bereket Yemane, Chao Zhao, and Appella, Daniel H.
- Published
- 2013
- Full Text
- View/download PDF
13. Capillary Monolithic Bioreactor of Immobilized Snake Venom Phosphodiesterase for Mass Spectrometry Based Oligodeoxynucleotide Sequencing.
- Author
-
Chao Zhao, Ruichuan Yin, Junfa Yin, Dapeng Zhang, and Hailin Wang
- Subjects
- *
MONOLITHIC reactors , *SNAKE venom , *MASS spectrometry , *PHOSPHODIESTERASES , *NUCLEOTIDE sequence , *ACROLEIN , *BIOREACTORS , *POROUS silica - Abstract
A capillary monolithic bioreactor of snake venom phosphodiesterase (SVP) was constructed to generate different single-nucleotide mass ladders of oligodeoxynucleotides for mass spectrometry (MS)-based sequencing by immobilization. The immobilization of SVP in the porous silica monolith significantly enhances its stability for prolonged and repeated applications. The constructed capillary bioreactor has the advantages of handling (sub)microliter DNA samples and having good permeability. Benefiting from its good permeability, DNA solutions can be directly injected into the sequential digestion bioreactor simply by hand pushing or a low-pressure microinjection pump. Moreover, the immobilization of SVP facilitates the elimination or repression of the metal adducts of oligodeoxynucleotides, improving the analytical performance of MS sequencing. By the application of capillary bioreactor of immobilized SVP, the sequence-specific modification of single-stranded oligodeoxynucleotide induced by a ubiquitous pollutant acrolein (Acr) was identified, demonstrating its promising applications in identification of sequence-specific damage, which may further our understanding of DNA damage caused mutagenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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