The inability to intraoperatively diagnose and eliminate microscopic residual tumors represents a significant challenge in cancer surgery. These residual microtumors cause lethal recurrence and metastasis. Herein, we show a crucial example of Raman imaging with gap-enhanced Raman tags (GERTs) to serve as a robust platform for intraoperative detection and eradication of residual microscopic foci, which exist in surgical margins, tumor invasion, and multifocal tumor spread. The GERTs feature gap-enhanced gold core-shell nanostructures, with Raman reporters embedding inside the interior gap junction. This nanostructure elicits highly sensitive and photostable Raman signals for microtumor detection by applying a 785 nm, low-energy laser and produces hyperthermia effects for microtumor ablation upon switching a 808 nm, high-power laser. In the orthotopic prostate metastasis tumor model, systematic delivery of GERTs enabled precise imaging and real-time ablation of macroscopic malignant lesions around the surgical bed without damaging normal tissues. Consequently, the GERTs-based surgery prevented local recurrence and delivered 100% tumor-free survival. These results suggest the efficiency of theranostic GERTs for precise detection and removal of residual miroctumors, broadening the avenues to apply Raman-based imaging for theranostic precision medicine.
The approach and coalescence behavior of gold nanoparticles on a silicon surface were investigated by experiments and molecular dynamics simulations. By analyzing the behavior of the atoms in the nanoparticles in the simulations, it was found that the atoms in a single isolated nanoparticle randomly fluctuated and that the surface atoms showed greater fluctuation. The fluctuation increased as the temperature increased. When there were two or more neighboring nanoparticles, the fluctuating surface atoms of the nanoparticles "flowed" toward the neighboring nanoparticle because of atomic interaction forces between the nanoparticles. With the surface atoms "flowing", the gold nanoparticles approached and finally coalesced. The simulation results were in good agreement with the experimental results. It can be concluded that surface thermodynamic fluctuations and atomic interaction forces are the causes of the approach and coalescence behavior of the gold nanoparticles.
Platelet-activating factor (PAF, 1-
O
-alkyl-2-acetyl-
sn
-glycero-3-phosphocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine if PAF synthesis is elevated in damaged coronary arteries after a sustained period of cyclic flow variation (CFV), a phenomenon caused by alternating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anterior descending coronary arteries (LADs) of 10 dogs. After 8 hours of CFV, the section of damaged LAD containing the thrombus and control sections of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purified by silica column chromatography and high-performance liquid chromatography and assayed by both a rabbit platelet bioassay and a PAF radioimmunoassay. With the platelet bioassay, PAF levels of 8.9±4.0 (range, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF receptor antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3±12.9 (range, 4.5 to 41.8) pg/mg wet wt were observed in the LADs. Overall, these PAF levels were 3- to 64-fold higher than in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PAF in blood samples taken from the LAD and the aorta (control) failed to demonstrate any site-specific increase of PAF in the blood. In related experiments, PAF was also measured in 23 endarterectomy samples taken from the coronary arteries of 16 patients with severe atherosclerosis. The PAF levels in these samples were highly variable (2.9±2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissue mass, suggesting that PAF is affected by factors other than the simple presence of atherosclerotic tissue in the vessel. These findings provide direct evidence that PAF is synthesized locally at the site of endothelial injury during thrombosis and that PAF accumulates in the atherosclerotic plaque of some patients with advanced coronary artery disease.
Five major reactive oxygen species (ROS) are generated in diseases including HO, OH, O, ROO, and O. Simultaneous detection of the five ROS with a single probe is crucial for a comprehensive understanding of the development and progression of many diseases, such as cancer and inflammatory diseases. However, currently reported detection systems are limited by targeting one ROS with one probe. This one-to-one detection mode may fail to sufficiently unveil the diseased state. In this study, we achieved simultaneous detection of all the five ROS with one probe (i.e., one-to-all detection), by designing a novel para-aminothiophenol (PATP) and hemin-decorated gold (Au/PATP/Hemin) nanoprobe. The design is principled by our discovery that PATP can react with OH, O, ROO, and O by a radical oxidative coupling mechanism to form 4,4'-dimercaptoazobenzene (DMAB). The DMAB then elicited strong characteristic surface-enhanced Raman scattering (SERS) peaks at 1142, 1386, and 1432 cm; which in turn enables direct detection of OH, O, ROO, and O and indirect detection of HO by hemin-catalyzed fenton reaction to convert HO into OH. In two representative ROS-elevated mice models of tumors and allergic dermatitis, the Au/PATP/Hemin nanoprobe demonstrated its robust performance of monitoring tumor development and inflammation progression in a highly sensitive and quantitative manner.
Scaled-charge force
fields (FFs) are widely employed in the simulation of neat ionic liquids
(ILs), where the charges on the ions are empirically scaled to approximately
account for electronic polarization and/or charge transfer. Such charge
scaling has been found to yield significant improvement in liquid-state
thermodynamic and dynamic properties (when compared to experiment).
However, the mean field approximation inherent in charge scaling becomes
suspect when applied to IL mixtures or solutions. In this work, we
simulate solutions of IL with various nonpolar and polar gas solutes
and compare results of charge-scaled and polarizable FFs to experiment.
Our results demonstrate that scaling of the Coulomb interaction inherent
in scaled-charge FFs leads to an underestimation of the solute–solvent
electrostatic interaction and thus also the enthalpy and free energy
of solvation; this effect is particularly pronounced for polar solutes.
In some cases, we find that this artificial reduction in the solute–solvent
interaction can also alter the apparent phase behavior of the resulting
solution. Overall, the totality of our results suggests that explicit
polarization (rather than charge scaling) is likely necessary to provide
high transferability to both neat IL and IL mixtures and solutions.
Background Platelets play an important role in the pathophysiology of acute coronary syndromes. The interaction between the platelet glycoprotein lb receptor and von Willebrand factor is a critical event allowing platelet adhesion and aggregation and subsequent thrombus formation in vessels with high shear rates and damaged endothelium. Therefore, we tested the hypotheses that VCL, an antagonist of von Willebrand-glycoprotein lb binding domain, (1) attenuates/ abolishes cyclic flow variations in stenosed, endotheliuminjured coronary arteries in nonhuman primates and (2) reduces botrocetin-induced platelet aggregation in vitro after intravenous in vivo administration.Methods and Results Cyclic flow variations were established in anesthetized, open-chest baboons (n= 18). The baboons were divided into three groups. One group (n=8) received a bolus of VCL (4 mg/kg IV) followed by an infusion (6 mg * kg-1* h-') for 90 minutes (schedule A). Another group (n=6) received a 2-mg/kg bolus followed by an infusion of 3 mg* kg`1 h-1 for 90 minutes (schedule B). The third group received a placebo infusion of normal saline. Under dosing schedule A, cyclic flow variations were abolished in 7 of 8 baboons after 33 ± 18 minutes and markedly attenuated in 1. The frequency of cyclic flow variations fell from 18±9.4 per hour during the control period to 1±2.5 per hour after VCL infusion, P<.002. After cessation of infusion, cyclic flow variations remained abolished in 5 of 7
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