Gold nanoparticles (AuNPs) have been frequently utilized for the construction of diverse colorimetric biosensors. Normally, AuNPs with sharp edges could have better sensitivity. However, the poor monodipersity of AuNPs with sharp edges seriously confines their utility for colorimetric biosensing. Herein, we demonstrate the utility of highly uniform gold nanobipyramids (Au NBPs) for ultrasensitive colorimetric detection of HN virus. The proposed method is based on the fact that alkaline phosphatase (ALP) could catalyze the decomposition of 4-aminophenyl phosphate (4-APP) to generate 4-aminophenol (4-AP), which would then reduce silver nitrate to metal silver and then deposited on Au NBPs. The metal silver shell coated on the Au NBPs changed the refractive index of gold and thus resulted in a blue shift of longitudinal localized surface plasmon resonance (LSPR) and accompanied a vivid color change. This method exhibited a higher sensitivity than that of other Au NPs such as gold nanorods due to the high-index-faceted on the tips of the Au NBPs. This method was used to detect the activity of ALP. It exhibited a linear range of 0.1-5 mU/mL with a limit of detection (LOD) of 0.086 mU/mL. Finally, the proposed method was used in immunoassay to detect HN virus. The results showed that the corresponding linear range for the detection of HN virus antigen was 0.001-2.5 ng/mL, and the LOD was determined to be 1 pg/mL, which is more sensitive than those in most of the colorimetric biosensors reported previously.
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.
Multicellular tumor spheroids (MCTS) have gained increasing attention in cancer research because they may closely mimic some physiological characteristics of solid tumors. MCTS have been considered as a useful three-dimensional cell model for evaluating the effect of exogenous molecules on tumor progression. However, little is known about the metabolic response in MCTS after exposure to exogenous molecules. Herein, we applied metabolomics combined with MALDI-mass spectrometry imaging (MSI) to investigate the proliferation of threedimensional MDA-MB-231 breast cancer cell spheroids treated with bisphenol S (BPS). MSI data revealed that BPS, a common environmental contaminant, penetrated MCTS in 5 min and gradually localized in the core of MCTS within 4 h. Metabolomic data demonstrated that BPS exposure induced significant changes in the levels of 28 metabolites that are involved in several pathways, including purine metabolism and the tricarboxylic acid cycle. The MSI results showed that three upregulated metabolites (ATP, ADP, and AMP) acting major roles in energy supply distributed in the proliferative zone of cell spheroids, further indicating the proliferative response of MDA-MB-231 cell spheroids caused by BPS exposure. One downregulated metabolite (xanthine) associated with reactive oxidative stress was found to localize toward the inner region of cell spheroids. These MSI results demonstrated that the increase of energy supply in the outer layer of cell spheroids might be responsible for BPS-induced proliferative response. Taken together, this integrated method might offer a more accurate and intuitive assessment for the effect of exogenous molecules on cancer progression.
Imaging of lipids of whole-body specimens in two-dimensional (2D) analysis provides a global picture of the lipid changes in lipid-disturbed diseases, enabling a better understanding of lipid functions and lipid-modulation processes in different organs. However, 2D imaging of a single cross section can hardly characterize the whole-body lipid alterations. In this work, a three-dimensional matrix-assisted laser desorption/ionization mass spectrometry imaging (3D MALDI-MSI) approach was developed for analysis of whole-body zebrafish, for the first time, and applied to identify altered lipids and map their spatial distributions by using a zebrafish model of Niemann–Pick disease type C1 (NPC1), a neurovisceral lipid storage disorder causing both neurodegenerative disorder and visceral organ damage. The constructed 3D fish model provided comprehensive information on the 3D distribution of lipids of interest and allowed direct correlations between these lipids and organs of the fish. Obtained results revealed that several sphingolipids and phospholipids showed significant alterations and exhibited different localization patterns in various organs such as the brain, spinal cord, intestines, and liver–spleen region in the npc1 gene mutant fish compared to those of the wild type. The whole-body 3D MALDI-MSI approach revealed unique lipid signatures for different NPC1-affected organs, which might offer insights into the link between the impaired lipid storage and subsequent clinical symptoms, such as neurodegeneration and hepatosplenomegaly.
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