High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.
Mn–Co–O
catalysts with different Mn/Co molar ratios
were synthesized by means of a facile inverse coprecipitation strategy
and applied for the oxidation of propane (C3H8). The XRD pattern of Co2Mn1Oδ (molar ratio of Mn:Co = 1:2) indicates a Co3O4 phase, and most Mn incorporates into Co3O4 lattice to form a solid solution. Minor distributed Mn species occur
structure reforming, totally converting to a stable Co–Mn solid
solution during oxidation process. Meanwhile, Co2Mn1Oδ features a porous core–shell morphology,
the core and shell of which are made up of Co–Mn solid solution,
giving rise to a high surface area. The optimized synergistic effect
of manganese and cobalt improves low temperature reducibility and
produces rich surface active Co3+ species and surface-absorbed
oxygen over Co2Mn1Oδ. As a
result, it exhibits a prominent excellent catalytic activity, and
delivers good thermal stability in the presence of 5 vol % H2O and 5 vol % CO2. In situ DRIFTs analysis displays the
reaction path of C3H8 over Co2Mn1Oδ, where dominate intermediate species formate
are easily decomposed into CO2. The synthesized porous
core–shell Mn–Co–O can be a promising candidate
replacing non-noble catalysts toward C3H8 oxidation
at low temperature.
Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50µg, ICV) treatment. The depressionlike behavior of rats was evaluated by sucrose preference test and open-eld test. The protein expression of Rac1, Glur1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as Glur1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The speci c mechanism of Sketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity.
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