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Biomimetic Metal-Organic Framework Nanoparticles for Cooperatively Combination of Antiangiogenesis and Photodynamic Therapy for Enhanced Efficacy
摘要： Photodynamic therapy (PDT) is a promising anticancer treatment and is clinically approved for different types of tumors. However, current PDT suffers several obstacles, including its neutralization by excess glutathione (GSH) in the tumor tissue and its strongly proangiogenic tumor response. In this work, a biomimic, multifunctional nanoparticle-based PDT agent, combining a tumor-targeted photosensitizer with GSH scavenging and antiangiogenesis therapy, is developed. A porphyrinic Zr–metal–organic framework nanoparticle is used simultaneously as the photosensitizer and the delivery vehicle of vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib. The core nanoparticles are wrapped in MnO2 to consume the intratumoral GSH and then decorated with a tumor cell membrane camouflage. After intravenous administration, the nanoparticles selectively accumulate in tumor through homotypic targeting mediated by the biomimic decoration, and the combination of enhanced PDT and antiangiogenic drug significantly improves their tumor inhibition efficiency. This study provides an integrated solution for mechanism-based enhancement of PDT and demonstrates the encouraging potential for multifunctional nanosystem applicable for tumor therapy.
关键词： glutathione metabolism,photodynamic therapy,MOF,angiogenesis inhibition,biomimetic nanoparticle
更新于2025-11-21 11:08:12
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Comparative assessment of linear least-squares, nonlinear least-squares, and Patlak graphical method for regional and local quantitative tracer kinetic modelling in cerebral dynamic <sup>18</sup> F-FDG PET
摘要： Purpose: Dynamic 18F-FDG PET allows quantitative estimation of cerebral glucose metabolism both at the regional and local (voxel) level. Although sensitive to noise and highly computationally expensive, nonlinear least-squares (NLS) optimization stands as the reference approach for the estimation of the kinetic model parameters. Nevertheless, faster techniques, including linear least-squares (LLS) and Patlak graphical method, have been proposed to deal with high resolution noisy data, representing a more adaptable solution for routine clinical implementation. Former research investigating the relative performance of the available algorithms lack precise evaluation of kinetic parameter estimates under realistic acquisition conditions. Methods: The present study aims at the systematic comparison of the feasibility and pertinence of kinetic modelling of dynamic cerebral 18F-FDG PET using NLS, LLS, and Patlak method, based on numerical simulations and patient data. Numerical simulations were used to study and parameters estimation bias and variance under representative noise levels. Patient data allowed to assess the concordance between the three methods at the regional and voxel scale, and to evaluate the robustness of the estimations with respect to patient head motion. Results and Conclusions: Our findings indicate that at the regional level NLS and LLS provide kinetic parameter estimates ( and ) with similar bias and variance characteristics ( bias ± rel. std dev. 0.0±5.1% and 0.1%±4.9% for NLS and LLS respectively, bias ± rel. std dev. 0.1%±4.5% and -0.7%±4.4% for NLS and LLS respectively), NLS estimates being however slightly less sensitive to patient motion. At the voxel level, provided that patient motion is negligible or corrected, LLS offers an appealing alternative solution for local mapping, with high correlation with NLS values (Pearson’s r = 0.95 on actual data) in computations times less than two orders of magnitude lower. Last, Patlak method appears as the most robust and accurate technique for the estimation of values at the regional and voxel scale, with or without head motion. It provides low bias / low variance quantification (bias ± rel. std dev. -1.5±9.5% and -4.1±19.7% for Patlak and NLS respectively) as well as smooth parametric images suitable for visual assessment.
关键词： kinetic analysis,18F-FDG PET,cerebral glucose metabolism,quantification
更新于2025-09-23 15:23:52
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Feasibility of simultaneous 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction
摘要： Background. Simultaneous dual-tracer imaging using isotopes with close photo-peaks may benefit from improved properties of cadmium-zinc-telluride (CZT)-based scanners. Methods. Thirty patients having undergone primary percutaneous coronary intervention for acute myocardial infarction underwent single-(99mTc-tetrofosmin (TF) or 123I-BMIPP first) followed by simultaneous 99mTc-TF /123I-BMIPP dual-tracer imaging using a Discovery NM/CT 670 CZT. The values for the quantitative gated-SPECT (QGS) and the quantitative perfusion SPECT (QPS) were assessed. Results. The intra-class correlation (ICC) coefficients between the single- and dual-tracer imaging were high in all the QGS and QPS data (Summed motion score: 0.95, summed thickening score: 0.94, ejection fraction: 0.98, SRS for 99mTc-TF: 0.97/ for 123I-BMIPP: 0.95). Wall motion, wall thickening and rest scores per coronary-territory-based regions were also comparable between the single- and dual imaging (ICC coefficient > 0.91). The interrater concordance in the visual analysis for the infarction and perfusion-metabolism mismatch was significant for the global and regional left ventricle (P < 0.001). Conclusion. The quantitative/semi-quantitative values for global and regional left-ventricular function, perfusion, and fatty acid metabolism were closely comparable between the dual-tracer imaging and the single-tracer mode. These data suggests the feasibility of the novel CZT-based scanner for the simultaneous 99mTc-TF /123I-BMIPP dual-tracer acquisitions in clinical settings.
关键词： acute myocardial infarction,dual imaging,CZT camera,Perfusion-metabolism mismatch
更新于2025-09-23 15:23:52
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In vivo multiphoton microscopy detects longitudinal metabolic changes associated with delayed skin wound healing
摘要： Chronic wounds are difficult to diagnose and characterize due to a lack of quantitative biomarkers. Label-free multiphoton microscopy has emerged as a useful imaging modality capable of quantifying changes in cellular metabolism using an optical redox ratio of FAD/(NADH+FAD) autofluorescence. However, the utility of an optical redox ratio for long-term in vivo monitoring of tissue metabolism has not been robustly evaluated. In this study, we demonstrate how multiphoton microscopy can be used to monitor changes in the metabolism of individual full-thickness skin wounds in vivo. 3D optical redox ratio maps and NADH fluorescence lifetime images identify differences between diabetic and control mice during the re-epithelialization of wounds. These metabolic changes are associated with a transient increase in keratinocyte proliferation at the wound edge. Our study demonstrates that high-resolution, non-invasive autofluorescence imaging can be performed in vivo and that optical redox ratios can serve as quantitative optical biomarkers of impaired wound healing.
关键词： metabolism,optical redox ratio,autofluorescence,multiphoton microscopy,in vivo imaging,diabetes,FAD,NADH,wound healing
更新于2025-09-23 15:23:52
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Inner Retinal Oxygen Delivery and Metabolism in Streptozotocin Diabetic Rats
摘要： PURPOSE. The purpose of the study is to report global measurements of inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in streptozotocin (STZ) diabetic rats. METHODS. Phosphorescence lifetime and blood flow imaging were performed in rats 4 (STZ/4wk; n = 10) and 6 (STZ/6wk; n = 10) weeks following injection of STZ to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). DO2_IR and MO2_IR were calculated from measurements of F and O2A and of F and the arteriovenous oxygen content difference, respectively. Data in STZ rats were compared to those in healthy control rats (n = 10). RESULTS. Measurements of O2A and O2V were not significantly different among STZ/4wk, STZ/6wk, and control rats (P ≥ 0.28). Likewise, F was similar among all groups of rats (P = 0.81). DO2_IR measurements were 941 ± 231, 956 ± 232, and 973 ± 243 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.95). MO2_IR measurements were 516 ± 175, 444 ± 103, and 496 ± 84 nL O2/min in control, STZ/4wk, and STZ/6wk rats, respectively (P = 0.37). CONCLUSIONS. Global inner retinal oxygen delivery and metabolism were not significantly impaired in STZ rats in early diabetes.
关键词： delivery,retina,rat,oxygen,metabolism,diabetes
更新于2025-09-23 15:22:29
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A novel bioreactor for combined magnetic resonance spectroscopy and optical imaging of metabolism in 3D cell cultures
摘要： Purpose: Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized 13C‐pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures. Methods: The model fitting for FLIM data analysis and the theory behind a model for the diffusion of pyruvate into a collagen gel are detailed. The device is MRI‐compatible, including an optical window, a temperature control system and an injection port for the introduction of contrast agents. Three‐dimensional printing, computer numerical control machining and laser cutting were used to fabricate custom parts. Results: Performance of the bioreactor is demonstrated for 4 T1 murine breast cancer cells under glucose deprivation. Mean nicotinamide adenine dinucleotide (NADH) fluorescence lifetimes were 10% longer and hyperpolarized 13C lactate:pyruvate (Lac:Pyr) ratios were 60% lower for glucose‐deprived 4 T1 cells compared to 4 T1 cells in normal medium. Looking at the individual components of the NADH fluorescent lifetime, τ1 (free NADH) showed no significant change, while τ2 (bound NADH) showed a significant increase, suggesting that the increase in mean lifetime was due to a change in bound NADH. Conclusion: A novel bioreactor that is compatible with, and can exploit the benefits of, both FLIM and 13C MRS in 3D cell cultures for studies of cell metabolism has been designed and applied.
关键词： multimodal,optical imaging,bioreactor,magnetic resonance spectroscopy (MRS),nicotinamide adenine dinucleotide (NADH),metabolism,fluorescence lifetime imaging (FLIM),lactate production
更新于2025-09-23 15:22:29
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Extreme-Learning-Machine-Based Noniterative and Iterative Nonlinearity Mitigation for LED Communication Systems
摘要： Oxidation of substrates to generate ATP in mitochondria is mediated by redox reactions of NADH and FADH2. Cardiac ischemia and reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation. We hypothesize that IR alters the metabolic heterogeneity of mitochondrial redox state of the heart that is only evident in the 3-D optical cryoimaging of the perfused heart before, during, and after IR. The study involved four groups of hearts: time control (TC: heart perfusion without IR), global ischemia (Isch), global ischemia followed by reperfusion (IR) and TC with PCP (a mitochondrial uncoupler) perfusion. Mitochondrial NADH and FAD autofluorescence signals were recorded spectrofluorometrically online in guinea pig ex vivo-perfused hearts in the Langendorff mode. At the end of each specified protocol, hearts were rapidly removed and snap frozen in liquid N2 for later 3-D optical cryoimaging of the mitochondrial NADH, FAD, and NADH/FAD redox ratio (RR). The TC hearts revealed a heterogeneous spatial distribution of NADH, FAD, and RR. Ischemia and IR altered the spatial distribution and caused an overall increase and decrease in the RR by 55% and 64%, respectively. Uncoupling with PCP resulted in the lowest level of the RR (73% oxidation) compared with TC. The 3-D optical cryoimaging of the heart provides novel insights into the heterogeneous distribution of mitochondrial NADH, FAD, RR, and metabolism from the base to the apex during ischemia and IR. This 3-D information of the mitochondrial redox state in the normal and ischemic heart was not apparent in the dynamic spectrofluorometric data.
关键词： Optical cryoimaging,redox state,metabolism,ischemia and reperfusion,mitochondria
更新于2025-09-23 15:21:01
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Protein Corona Formation of Human Serum Albumin with Carbon Quantum Dots from Roasted Salmon
摘要： As the food-borne nanoparticles enter the biological system, they will contact with various proteins to form protein coronas, which can affect their physicochemical properties and biological identity. In this study, the protein corona formation of carbon quantum dots (CQDs) from roast salmon with human serum albumin (HSA), as well as biological identity involving cell apoptosis, energy, glucose and lipid metabolism and acute toxicity in mice, were investigated. The HSA-CQD coronas formed between HSA and CQDs via static binding mechanism, and the binding site of CQDs on HSA located both in Sudlow’s site I and site II. The HSA-CQD coronas entered the cytoplasm and present in lysosomes or autolysosomes. Importantly, the HSA coronas mitigated the cytotoxicity of CQDs from 18.65% to 9.26%, and the energy metabolism was rectified from glycolytic to aerobic metabolism. The glucose and lipid metabolite profile of the HSA-CQD coronas differed from that of the CQDs, indicating that HSA-CQD coronas rectified disturbance in metabolism. Histopathological and blood biochemical analysis revealed no statistically significant difference between the testing and control mice after a single CQDs dose of 2000 mg/kg body weight. Overall, the results confirmed the formation of protein corona between HSA and food-borne fluorescent CQDs, and could be helpful for evaluating the safety of fluorescent CQDs from roast food items.
关键词： cytotoxicity,acute toxicity,protein coronas,human serum albumin,carbon quantum dots,metabolism,food-borne nanoparticles
更新于2025-09-23 15:21:01
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Exploring Triple-isotopic Signatures of Water in Human Exhaled Breath, Gastric Fluid and Drinking Water Using Integrated Cavity Output Spectroscopy
摘要： Water, the major body fluid in humans, has four main naturally occurring isotopologues, H2 16O, H2 17O, H2 18O and H2H16O (i.e. HD16O) with different masses. The underlying mechanisms of the isotope-specific water-metabolism in human gastrointestinal (GI) tract and respiratory system are largely unknown and remained illusive for several decades. Here, a new strategy has been demonstrated that provides the direct quantitative experimental evidences of triple-isotopic signatures of water-metabolism in human body in response to the individual’s water intake habit. The distribution of water isotopes have been monitored in drinking water (DW) (δD =-36.59±10.64‰ (SD), δ18O= -5.41±1.47‰ (SD) and δ17O= -2.92±0.79‰ (SD)), GI fluid (GF) (δD =-35.91±7.30‰ (SD), δ18O= -3.98±1.29‰ (SD) and δ17O= -2.37±0.57‰ (SD)) and human exhaled breath (EB) (δD =-119.63±7.27‰ (SD), δ18O= -13.69±1.23‰ (SD) and δ17O= -8.77±0.98‰ (SD)) using the laser-based off-axis integrated cavity output spectroscopy (OA-ICOS) technique. This study explored a new analytical method to disentangle the competing effects of isotopic fractionations of water during respiration in humans. In addition, our findings revealed that deuterium-enriched exhaled semi-heavy water, i.e. HD16O is a new marker of the non-invasive assessment of the ulcer-causing H. pylori gastric pathogen. We also clearly showed that the water-metabolism-derived triple-isotopic compositions due to impaired water absorption in GI tract can be used as unique tracers to track the onset of various GI dysfunctions. These findings are thus bringing a new analytical methodology for better understanding the isotope-selective water-metabolism that will have enormous applications in clinical testing purpose.
关键词： triple-isotopic signatures,human exhaled breath,integrated cavity output spectroscopy,drinking water,water-metabolism,gastric fluid
更新于2025-09-23 15:21:01
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[American Society of Agricultural and Biological Engineers 2018 Detroit, Michigan July 29 - August 1, 2018 - ()] 2018 Detroit, Michigan July 29 - August 1, 2018 - <i>The dose-effect relationships between green light and metabolism rate in chick embryos</i>
摘要： Green light during artificial incubation can affect the development of chick embryos. However, there has been relatively little work systematically assessing dose-effect relationships between green light and metabolism rate in chick embryos. Eggs (n=800) were incubated under photoperiods of either 0 h of light and 24 h of darkness (0L:24D), 6 h of light and 18 h of darkness (6L:18D), 12 h of light and 12 h of darkness (12L:12D), or 18 h of light and 6 h of darkness (18L:6D). In accordance with dose-effect on embryonic development, the response of carbon dioxide production rate to variations in illuminance was consistent with lipid reserve in yolk residue and hepatic glycogen in chick embryos. This sensitivity to green light indicates that the variation in illuminance within certain range of green light can have a significant impact on embryonic development and metabolic rate in chick embryos during artificial incubation. The results of this study indicate that providing 18 h of green light during incubation can have significantly improved the development and metabolism of the chick embryos.
关键词： chick embryos,metabolism rate,artificial incubation,green light
更新于2025-09-23 15:21:01