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OBJECTIVE: To investigate the impact of different tracer modifications on the imaging of cancer metabolism, focusing on the comparison of fluorescent glucose-analog tracers (2-NBDG and 2-DG-750) and the radiolabeled tracer 18F-FDG in both in-vitro and in-vivo settings. METHODS: We conducted an in-vitro comparative study using four cancer cell lines, each with unique glucose uptake characteristics. The study involved direct comparison of three tracers: 2-NBDG, 2-DG-750 and 18F-FDG, examining their internalization behaviors, metabolic functionality and localization effects in cancer metabolism imaging. RESULTS: The study revealed that each tracer exhibits distinct internalization behaviors correlated with imaging label size and type. 18F-FDG showed the highest uptake efficiency. Fluorescent molecules were found to accumulate in tumors primarily due to hydrophobic interactions and possible aggregation, indicating inefficiency in metabolism and suitability for imaging metabolic phenomena when compared to radiolabeled biomolecules. CONCLUSION: Our findings demonstrate that despite certain impracticalities, nuclear imaging, particularly using radiolabeled biomolecules like 18F-FDG, offers significant potential for accurately capturing biological phenomena. This is crucial for future advancements in both clinical and research settings. The study emphasizes the limitations of fluorescent molecules in imaging metabolic activities due to their inefficient metabolism and aggregation tendencies.

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This study aims to extract the energy feature distributions in the form of marginal frequency (MF) and Hilbert spectrum (HS) in the intrinsic mode functions (IMF) domain for actual movement (AM)-based and motor imagery (MI)-based electroencephalogram (EEG) signals using the Hilbert-Huang transformation (HHT) time frequency (TF) analysis method. Accordingly, F5 and F6 EEG signal TF energy feature distributions in delta (0.5-4 Hz) rhythm are explored. We propose IMF-based and residue function (RF)-based MF and HS feature information extraction methods with IMFRFERDD (IMFRF energy refereed distribution density), IMFRFMFERDD (IMFRF MF energy refereed distribution density), and IMFRFHSERDD (IMFRF HS energy refereed distribution density) parameters using HHT with application to AM, MI EEG F5, and F6 signals in delta rhythm. The AM and MI tasks involve simultaneously opening fists and feet, as well as simultaneously closing fists and feet. Eight samples (32 in total) with a time duration of 1000 ms are extracted for analyzing F5AM, F5MI, F6AM, and F6MI EEG signals, which are decomposed into five IMFs and one RF. The maximum average IMFRFERDD values of IMF4 are 3.70, 3.43, 3.65, and 3.69 for F5AM, F5MI, F6 AM, and F6MI, respectively. The maximum average IMFRFMFERDD values of IMF4 in the delta rhythm are 21.50, 20.15, 21.02, and 17.30, for F5AM, F5MI, F6AM, and F6MI, respectively. Additionally, the maximum average IMFRFHSERDD values of IMF4 in delta rhythm are 39,21, 39.14, 36.29, and 33.06 with time intervals of 500-600, 800-900, 800-900, and 500-600 ms, for F5AM, F5MI, F6AM, and F6MI, respectively. The results of this study, advance our understanding of meaningful feature information of F5MM, F5MI, F6MM, and F6MI, enabling the design of MI-based brain-computer interface assistive devices for disabled persons.

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@#[摘 要] 目的： 探讨circ_0001821通过靶向miR-203调控皮肤鳞状细胞癌（cutaneous squamous cell carcinoma，CSCC）A431细胞增殖、凋亡、迁移及侵袭的分子机制。方法：选取2018年2月至2019年8月海南医学院第二附属医院收治的39例CSCC患者的癌及配对癌旁组织，以及人CSCC细胞系A431，用qPCR法检测CSCC癌和癌旁组织中circ_0001821的表达水平。利用脂质体转染技术，分别将si-circ_0001821、si-NC、miR-203 mimic、miR-NC、si-circ_0001821与anti-miR-NC、si-circ_0001821与anti-miR-203转染至A431细胞，用qPCR法检测转染细胞中circ_0001821和miR-203的表达水平，MTT法、流式细胞术和Transwell实验分别检测A431细胞的增殖、凋亡、迁移及侵袭能力，WB法检测细胞中增殖、凋亡、迁移及侵袭相关蛋白的表达水平。通过Circinteractome数据库预测circ_0001821与miR-203存在结合位点，双荧光素酶报告基因实验验证circ_0001821与miR-203的靶向关系。结果：CSCC组织中circ_0001821的表达水平显著高于癌旁组织（P<0.01）。转染si-circ_0001821可显著降低细胞中circ_0001821的表达水平（P<0.01），降低细胞增殖、迁移和侵袭能力（均P<0.01），提高细胞凋亡率（P<0.01）。双荧光素酶报告基因实验证实，circ_0001821可靶向结合miR-203。转染miR-203 mimic可显著降低A431细胞的增殖、迁移和侵袭能力（均P<0.01），提高细胞凋亡率（P<0.01）。共转染si-circ_0001821与anti-miR-203可明显逆转下调circ_0001821表达对A431细胞增殖、迁移、侵袭及凋亡的调控作用。结论：circ_0001821通过靶向miR-203调控CSCC细胞A431的增殖、迁移、侵袭能力及细胞凋亡。

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Molecular dynamics simulations of the biphalin molecule, (Tyr-D-Ala-Gly-Phe-NH)(2), and the active tetrapeptide hydrazide, Tyr-D-Ala-Gly-Phe-NH-NH(2) were performed to investigate the cause of the increased µ and δ receptor binding affinities of the former over the latter. The simulation results demonstrate that the acylation of the two equal tetrapeptide fragments of biphalin produces the constrained hydrazide bridges [Formula: see text] and [Formula: see text], which in turn increase the opportunity of conformations for binding to µ or δ receptors. Meanwhile, the connection of the two active tetrapeptide fragments of biphalin also results in the constrained side chain torsion angle χ(2) at one of the two residues Phe. This constrained side chain torsion angle not only significantly increases the δ receptor binding affinity but also makes most of the δ receptor binding conformations of biphalin bind to the δ receptor through the fragment containing the mentioned residue Phe.

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The conformational stability of the extended antiparallel dimer structure of Met-enkephalin in water was analyzed by examining the hydration structure of enkephalin using molecular dynamics simulations. The result shows that, despite of the hydrophicility of the terminal atoms in the pentapeptide, the main contributor for the stability of the dimer in water is the four intermolecular hydrogen bonds between the Gly(2) and Phe(4) groups. The three-dimensional model of the delta-opioid pharmacophore for this dimer structure was also established. Such a model was demonstrated to match the delta-opioid pharmacophore query derived from the non-peptides SIOM, TAN-67, and OMI perfectly. This result thus strongly supports the assumption that the dimer structure of Met-enkephalin is a possible delta-receptor binding conformation.

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