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OBJECTIVES To evaluate the efficacy of low-intensity focused ultrasound (LIFU) treatment on rapid relief of delayed-onset muscle soreness (DOMS) triggered by high-intensity exercise. METHODS A total of 16 healthy male college students were randomly divided into two groups: the LIFU group (n = 8) and the Sham group (n = 8). After the exercise protocol, the LIFU group received treatment, which parameters included that the power output was 2.5 W/cm2 , the frequency was 1 MHz, and the treating time was 20 minutes. The Sham group was treated with LIFU without energy output. Visual analog scale was used to evaluate the level of DOMS in every participant. The activities of plasma creatine kinase, lactate dehydrogenase, and the plasma concentration were measured by spectrophotometry. Tumor necrosis factor-α and interleukin-6 of serum were analyzed by enzyme-linked immunosorbent assay. RESULTS The visual analog scale of quadriceps femoris and/or calf muscles in the LIFU group decreased significantly at 24 hours (P

Background Acoustic cavitation plays an important role in the medical treatment using high-intensity focused ultrasound (HIFU), but unnecessarily strong cavitation also could deform the morphology and enlarge the size of lesions. It is known that the increase of ambient hydrostatic pressure (Pstat) can control the acoustic cavitation. But the question of how the decrease of Pstat and dissolved oxygen concentration (DOC) influence the strength of cavitation has not been thoroughly answered. In this study, we aimed to investigate the relationship among the Pstat, DOC and the strength of cavitation. Methods Ex vivo bovine liver tissues were immersed in degassed water with different DOC of 1.0 mg/L, 1.5 mg/L and 2.0 mg/L. Ultrasound (US) of 1 MHz and the spatial and temporal average intensity (Isata) of 6500 W/cm2 was used to expose two groups of in vitro bovine livers for 2 s; one group was under atmospheric pressure (Pstat = 1 bar) and the other was under sub-atmospheric pressure (Pstat = 0.1 bar). Acoustic cavitation was detected by a passive cavitation detector (PCD) during the exposure process. Echo signals at the focal zone of HIFU were monitored by B-mode ultrasound imaging before and after exposure. The difference between two pressure groups was tested using paired sample t-test. The difference among different DOC groups was evaluated by one-way analysis of variance (ANOVA). Results The results demonstrated a significant difference of broadband acoustic emissions from the cavitation bubbles, echo signals on B-mode image, morphology of lesions under various conditions of ambient pressure and DOC. The lesion volume in tissue was increased with the increase of ambient pressure and DOC. Conclusion Cavitation could be suppressed through sub-atmospheric pressure and low DOC level in liver tissue, which could provide a method of controlling cavitation in HIFU treatment to avoid unpredictable lesions.

In this study, novel ZnO/ZnWO4 nanocatalysts were synthesized for the removal of organic compounds under ultraviolet (UV) and visible-light irradiation. ZnO was prepared by a homogenous precipitation process followed by an impregnation technique for the formation of ZnO/ZnWO4 photocatalysts with different percentages of tungsten. The resulting photocatalysts formed a mesoporous network of ZnO nanoparticles, with a size of 18 nm, and modified by tungsten, according to X-ray diffraction and N2 sorption analyses. Their morphology and composition were studied by transmission electron microscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. According to optical studies, the absorption edge of the ZnO nanomaterials revealed that the red-shift with augmented tungsten concentration resulted in a decrease in the forbidden energy gap (Eg) from 3.25 eV to 2.95 eV. Therefore, the ZnO/ZnWO4 compound absorbed light in the visible-light region, which probably indicates that the developed photocatalysts may be active in this region. The presence of surface hydroxyl groups was confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, and these hydroxyl groups play a significant role in the photocatalytic activity of the compounds by catching the formed holes in the valence band under irradiation to create the hydroxyl radical, thus improving the photocatalytic property. Zn–ZnW0.2 showed the best photodegradation of rhodamine B (RhB), with a rate constant Kapp = 0.095 min−1 (98.5% degradation) and Kapp = 0.04 min−1 (91% degradation) after 30 and 60 min of irradiation under UV and visible light, respectively. This improvement was rationalized by the effective separation of photogenerated electron–hole (e−/h+) pairs due to the formation of a heterojunction structure between ZnWO4 (ECB = +0.165 eV; EVB = 2.885 eV) and ZnO (ECB = −0.365 eV; EVB = 3.115 eV). In addition, results confirmed that holes (h+) and ˙OH radicals are the major reactive species involved in the photodegradation of RhB dye. A possible reaction mechanism was proposed for explaining the photodegradation of RhB over the ZnO/ZnWO4 photocatalyst. The Zn–ZnW0.2 photocatalyst retained its high photodegradation rate and good photostability over four consecutive cycles with no changes in its morphology.

BackgroundHigh-intensity focused ultrasound (HIFU) has shown considerable promise in treating solid tumors, but its ultrasonic energy is easily attenuated, resulting in insufficient energy accumulation in the target area. Moreover, HIFU ablation alone may inevitably lead to the presence of residual tumors, which may cause tumor recurrence and metastasis. Here, we describe a synergistic regimen combining HIFU facilitation with immunomodulation based on a novel oxygen-carrying biomimetic perfluorocarbon nanoparticle (M@P-SOP) to stimulate immunogenic cell death in tumor cells while alleviating immune suppression tumor microenvironment.MethodsM@P-SOP was prepared by double emulsion and film extrusion method. The anticancer and antimetastatic effects of M@P-SOP were evaluated on a preclinical transplanted 4T1 tumor model by combining HIFU and immunotherapy. Flow cytometry and immunofluorescence were used to clarify the potential mechanism of HIFU+M@P-SOP and their role in anti-programmed death ligand-1 (PD-L1) therapy.ResultsGuided by photoacoustic/MR/ultrasound (US) multimodal imaging, M@P-SOP was abundantly enriched in tumor, which greatly enhanced HIFU’s killing of tumor tissue in situ, induced stronger tumor immunogenic cell death, stimulated dendritic cell maturation and activated CD8+T cells. At the same time, M@P-SOP released oxygen to alleviate the tumor hypoxic environment, repolarizing the protumor M2-type macrophages into antitumor M1-type. With concurrent anti-PD-L1 treatment, the antitumor immune response was further amplified to the whole body, and the growth of mimic distant tumor was effectively suppressed.ConclusionsOur findings offer a highly promising HIFU synergist for effectively ameliorating acoustic and hypoxia environment, eventually inhibiting tumor growth and metastasis by stimulating host’s antitumor immunity under HIFU ablation, especially in synergizing with PD-L1 antibody immunotherapy.

The introduction of thermal relaxation makes non-Fourier heat transfer more effective than Pennes equation to reflect rapid bio-heat transferring during HIFU, however, the contribution of thermal relaxation in specific tissues needs to be further clarified. In this study, we first measured the thermal relaxation times of porcine muscle and porcine fat. Combining with experimental measurements, the effects of thermal relaxation on temperature elevation in the tissues were investigated by using Pennes equation, thermal wave model of bio-heat transfer (TWMBT) and dual phase-lag (DPL) bio-heat transfer. Results showed that: a) The thermal relaxation times of porcine muscle and porcine fat are experimentally determined as 5.71± 0.11 s and 5.02± 0.06 s, respectively. b) In the absence of cavitation, DPL bio-heat transfer is more accurate to predict the temperature elevation at the focus and 2 mm from the focus than Pennes equation and TWMBT. Particularly, comparing with the reported of bologna (16 s) used in most of the theoretical analysis, the utilization of the measured thermal relaxation time for a specific tissue in DPL bio-heat transfer is more effective in predicting the temperature elevation during HIFU. c) Acoustic cavitation and nonlinear propagation is easier to happen in fat, under which all bio-heat transfer models are failed to forecast the temperature elevation induced by HIFU. The results demonstrate that different tissues have different thermal relaxation, DPL bio-heat transfer with the measured thermal relaxation times of specific tissues can accurately predict the temperature elevation during HIFU without cavitation.

Catalytic hydrogenation provides an important pathway for converting environmentally toxic phenol into less oxygenated and more stable useful chemical feedstock for the production of nylon and multicomponent diesel fuel. In this study, an innovative microwave–SiC-assisted heating technology was adopted to induce the vapor-phase catalytic hydrogenation of phenol over a Pd catalyst supported on Zr/Ce oxide. The H2 flow rate, catalyst support, and reaction temperature influenced the phenol conversion as well as product yield and selectivity. At a modest reaction temperature of 200 °C, the hydrogenation of phenol produced a mixture of cyclohexanol (COL) and cyclohexanone (CONE), and the COL/CONE molar ratio was influenced by the catalyst supports in the following order: Pd/CeO2 > Pd/ZrCeO2 > Pd/ZrO2. Under identical experimental conditions, the microwave–SiC-assisted hydrogenation exhibited superior performance over conventional hydrogenation in terms of both the phenol conversion and product yield. Particula...

Stimulus-responsive drug delivery nanosystems (DDSs) are of great significance in improving cancer therapy for intelligent control over drug release. However, among them, many DDSs are unable to realize rapid and sufficient drug release because most internal stimulants might be consumed during the release process. To address the plight, an abundant supply of stimulants is highly desirable. Herein, a core crosslinked pullulan-di-(4,1-hydroxybenzylene)diselenide nanosystem, which could generate abundant exogenous-stimulant reactive oxygen species (ROS) via tumor-specific NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, was constructed by the encapsulation of β-lapachone. The enzyme-catalytic-generated ROS induced self-triggered cascade amplification release of loaded doxorubicin (DOX) in the tumor cells, thus achieving efficient delivery of DOX to the nuclei of tumor cells by breaking the diselenide bond of the nanosystem. As a result, the antitumor effect of this nanosystem was significantly improved in the HepG2 xenograft model. In general, this study offers a new paradigm for utilizing the interaction between the loaded agent and carrier in the tumor cells to obtain self-triggered drug release in the design of DDSs for enhanced cancer therapy.

Objective Although HIFU has been successfully applied in various clinical applications in the past two decades for the ablation of many types of tumors, one bottleneck in its wider applications is the lack of a reliable and affordable strategy to guide the therapy. This study aims at estimating the therapeutic beam path at the pre-treatment stage to guide the therapeutic procedure. Methods An incident beam mapping technique using passive beamforming was proposed based on a clinical HIFU system and an ultrasound imaging research system. An optimization model was created to map the cross-like beam pattern by maximizing the total energy within the mapped area. This beam mapping technique was validated by comparing the estimated focal region with the HIFU-induced actual focal region (damaged region) through simulation, in-vitro, ex-vivo and in-vivo experiments. Results The results of this study showed that the proposed technique was, to a large extent, tolerant of sound speed inhomogeneities, being able to estimate the focal location with errors of 0.15 mm and 0.93 mm under in-vitro and ex-vivo situations respectively, and slightly over 1 mm under the in-vivo situation. It should be noted that the corresponding errors were 6.8 mm, 3.2 mm, and 9.9 mm respectively when the conventional geometrical method was used. Conclusion This beam mapping technique can be very helpful in guiding the HIFU therapy and can be easily applied in clinical environments with an ultrasound-guided HIFU system. Significance The technique is non-invasive and can potentially be adapted to other ultrasound-related beam manipulating applications.

Objective The objective of this study was to explore the correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of excised uterine fibroids with different signal intensities as visualized on T2-weighted magnetic resonance imaging (MRI). Methods We collected 47 specimens of uterine fibroids after surgical resection and classified them into four groups according to preoperative T2-weighted MRI hypo-intense, isointense, heterogeneous intense and homogeneous hyper-intense. Then, specimens in each group were irradiated by HIFU with the same parameters and the necrotic tissue volume was calculated. The smooth muscle cell (SMC) count and collagen fiber content were quantitatively measured and compared between different groups. We analyzed the correlation between the necrotic tissue volume and SMC count and the collagen fiber content. Results Necrotic tissue volume gradually decreased from the hypo-intense group to the homogeneous hyper-intense group (p = .008). The SMC count from the hypo-intense group to the homogeneous hyper-intense group was 215.6 ± 59.3, 237.0(89.5), 232.3 ± 72.5 and 330.5 ± 30.9, respectively; collagen fiber content was 0.65 ± 0.07, 0.64 ± 0.10, 0.53 ± 0.11 and 0.41 ± 0.06, respectively. Comparison among the four groups showed that SMC count progressively increased (p = .001) but collagen fiber content progressively decreased (p = .000) from the hypo-intense group to the homogeneous hyper-intense group. Correlation analysis showed that necrotic tissue volume was negatively correlated with SMC count (R = -0.488, p=.013) but positively correlated with collagen fiber content (R = 0.534, p = .005). Conclusions Differences in histopathological characteristics may be one of the reasons for different therapeutic effects of HIFU ablation on uterine fibroids with different signal intensities on T2-weighted MRI.

International audience; Accurate segmentation of uterus, uterine fibroids, and spine from MR images is crucial for high intensity fo-cused ultrasound (HIFU) therapy but remains still difficult to achieve because of 1) the large shape and size variations among individuals, 2) the low contrast between adjacent organs and tissues, and 3) the unknown number of uterine fibroids. To tackle this problem, in this paper, we propose a large kernel Encoder-Decoder Network based on a 2D segmentation model. The use of this large kernel can capture multi-scale contexts by enlarging the valid receptive field. In addition, a deep multiple atrous convolution block is also employed to enlarge the receptive field and extract denser feature maps. Our approach is compared to both conventional and other deep learning methods and the experimental results conducted on a large dataset show its effectiveness.

It is well-known that acoustic cavitation associated with the high intensity focused ultrasound (HIFU) treatment often would change the morphology and size of lesions in its treatment. In most studies reported in literature, high ambient hydrostatic pressure was used to suppress the cavitation completely. Investigation of the effects by varying the ambient hydrostatic pressure (Pstat) is still lacking. In this paper, the effects of HIFU on lesions in ex vivo bovine liver specimens under various Pstat are systematically investigated. A 1MHz HIFU transducer, with an aperture diameter of 70mm and a focal length of 55mm, was used to generate two groups US exposure of different acoustic intensities and exposure time (6095W/cm2×8s and 9752W/cm2×5s), while keeping the same acoustic energies per unit area (48760J/cm2). The peak acoustic negative pressures (p-) of the two groups were p1-=9.58MPa and p2-=10.82MPa, respectively, with the difference pd-=p2--p1-=1.24MPa. A passive cavitation detection (PCD) was used to monitor the ultrasonic cavitation signal during exposure of the two groups. The US exposures were done under the following ambient hydrostatic pressures, Pstat: atmospheric pressure, 0.5MPa, 1.0MPa, 1.5MPa, 2.0MPa, 2.5MPa and3.0MPa, respectively. The result of PCD showed that there was a statistically significant increase above background noise level in broadband emissions at dose of 9752W/cm2×5s, but not at dose of 6095W/cm2×8s under atmospheric pressure; i.e., the acoustic cavitation took place for p2- but not for p1- when under atmospheric pressure. The results also showed that there was no statistically difference of the morphology and size of lesions for 6095W/cm2×8s exposure under the aforementioned different ambient hydrostatic pressures. But the lesions generated at 9752W/cm2×5s exposure under Pstat=atmospheric pressure, 0.5MPa, 1.0MPa (all of them are less than pd-), were larger than those under 1.5MPa, 2.0MPa, 2.5MPa and 3.0MPa (all of them are over than pd-) which were consistence with 6095W/cm2×8s group. It was concluded that when Pstat>pd-, the acoustic cavitation was suppressed and prompted that there was no need to elevate Pstat higher than p- to suppress the acoustic cavitation in tissue, just need Pstat higher than pd-.

The near-solid wall multi-bubble cavitation is an extremely complex phenomenon, and cavitation has strong erosiveness. The melting point (about 3410 °C) of tungsten is highest among all pure metals, and its hardness is also very high (its yield strength is greater than 1 GPa). What would happen to pure tungsten wire under extreme conditions caused by collapsing cavitation bubbles at high hydrostatic pressure? In this paper, we have studied the fracture process of pure tungsten wire with diameter of 0.2 mm mounted at the focus of a standing acoustic wave produced by a spherical cavity transducer with two open ends placed in a near spherical pressure container, and also studied the macro and micro morphological characteristics of the fracture and the surface damage at different fracture stages of tungsten wire under various hydrostatic pressures and driving electric powers. The results have shown that the fracture time of tungsten wire is inversely proportional to avitation intensity with hydrostatic pressure and driving electric power, the higher the acoustic pressure caused by higher electric power, the shorter the fracture time. The possible fracture mechanisms of tungsten wire in this situation we found mainly contributed to asymmetrically bubbles collapse near the surface of tungsten wire, leading to tearing the surface apart; consequently cracks along the radial and axial directions of a tungsten wire extend simultaneously, classified as trans-granular fracture and inter-granular fracture, respectively. With the increase of cavitation intensity, the cracks tend to extend more radially and the axial crack propagation path becomes shorter, that is, mainly for trans-granular fracture; with the decrease of cavitation intensity, intergranular fracture becomes more obvious. When the hydrostatic pressure was 10 MPa and the driving electric power was 2 kW, the fibers became softener due to the fracture of the tungsten wire. The fracture caused by acoustic cavitation was different from conventional mechanical fracture, such as tensile, shear, fatigue fracture, on macro and micro morphology.

High intensity focused ultrasound (HIFU) is an early stage medical technology that is in various stages of development worldwide to treat a range of disorders including skin superficial diseases. Optical coherence tomography (OCT) is a rapid development imaging technique in recent ten years, which is a good way to monitor skin because of the millimeter-level detection depth. In this study, OCT system is used to monitor the skin after HIFU treatment. A new high frequency transducer has been fabricated in this study, focal length of the transducer is super small which is suitable for the superficial diseases.

HIFU is a noninvasive, acoustic therapeutic technique that utilizes high intensity acoustic field in the ultrasound focus to kill the targeted tissue for disease treatment purpose. The feasibility of monitoring and guiding HIFU treatment using the optical property change in the superficial area of biological tissue is explored. Ex-vivo bovine liver tissue was treated using different HIFU doses (same energy level for Os, 1s, 5s, 9s) in this research. The 3D structure volume and elastogram were acquired in the lesion area after HIFU treatment. The OCT structure images clearly show the boundary of HIFU lesion area and surrounding normal tissue, even for 1s treatment time, which agree well with the elastography results. The average OCT signal intensity and OCT signal attenuation ratio in the lesion area grows as the treatment time increases. Combined with OCT needle probe, the proposed method has a large potential not only to be used for superficial diseases treatment monitoring, but also to be used for high-precision-demanded diseases treatment monitoring, e.g. nervous disease treatment monitoring.

Aim: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. Materials & methods: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. Results: The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm2. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. Conclusion: DOX-ATRA-NDs demonstrate great potential in clinical applications.

The degradation and transformation of p-nitrophenol (PNP) was evaluated with as-prepared iron oxides (γ-FeOOH, Fe3O4, and α-Fe2O3) as catalyst. Results showed that α-Fe2O3 exhibited higher catalytic activity than the other two samples for reduction transformation and oxidative degradation of PNP. α-Fe2O3 showed higher surface-bound Fe(II) contents in the presence of oxalic acid and stronger affinity to PNP, leading to an increase in PNP reductive transformation. And α-Fe2O3 could effectively adsorb visible light and hinder the recombination of charge carriers, resulting in higher oxidative degradation activity. p-Aminophenol (PAP), as the main reduction transformation product of PNP, could be removed further by oxidative degradation in the reaction system itself. A possible mechanism was suggested for the comprehensive effect of PNP degradation during the reaction process.

The aim of the present study was to evaluate the safety and efficiency of an intravenously delivered nano-hydroxyapatite (Nano-HA) solution into a rabbit model (Oryctolagus cuniculus) to determine the potential enhance- ment of high-intensity focused ultrasound (HIFU) for the ablation of hepatocellular carcinoma (HCC) in liver tissue. The present study clearly indicated that the intravenous delivery of large quantities of Nano-HA into the body of the rabbit model over relatively short periods of time may be absorbed by the hepatic reticuloendothelial system. Subsequent HIFU treat- ment for HCC, as well as intravenous Nano-HA, produced a rapid increase in temperature and an enlargement of the coag- ulated necrotic area during ablation in the in vivo and ex vivo environments. In addition, it was found that the therapeutic doses of Nano-HA produced mild and transient abnormalities in the normal renal function and hepatic enzymes during the first 24 h following administration. The results of the current study indicated that the combination of Nano-HA and HIFU may provide a safe and effective alternative to conventional surgical procedures.

The time–intensity curve (TIC) from contrast-enhanced ultrasound (CEUS) image sequence of uterine fibroids provides important parameter information for qualitative and quantitative evaluation of efficacy of treatment such as high-intensity focused ultrasound surgery. However, respiration and other physiological movements inevitably affect the process of CEUS imaging, and this reduces the accuracy of TIC calculation. In this study, a method of TIC calculation for vascular perfusion of uterine fibroids based on subtraction imaging with motion correction is proposed. First, the fibroid CEUS recording video was decoded into frame images based on the record frame rate. Next, the Brox optical flow algorithm was used to estimate the displacement field and correct the motion between two frames based on warp technique. Then, subtraction imaging was performed to extract the positional distribution of vascular perfusion (PDOVP). Finally, the average gray of all pixels in the PDOVP from each image was determined, and this was considered the TIC of CEUS image sequence. Both the correlation coefficient and mutual information of the results with proposed method were larger than those determined using the original method. PDOVP extraction results have been improved significantly after motion correction. The variance reduction rates were all positive, indicating that the fluctuations of TIC had become less pronounced, and the calculation accuracy has been improved after motion correction. This proposed method can effectively overcome the influence of motion mainly caused by respiration and allows precise calculation of TIC.

A novel multifunctional nanotheranostic agent with targeting, redox-responsive ultrasound imaging and ultrasound imaging-guided high-intensity focused ultrasound (HIFU) therapy (MSNC-PEG-HA(SS)-PFH, abbreviated as MPH(SS)-PFH) capabilities is developed. The redox-responsive guest molecule release and ultrasound imaging functions can be both integrated in such a "smart" theranostic agent, which is accomplished by the redox-triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol-disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor-bearing nude mice can be thoroughly and spatial-accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH(SS)-PFH in the tumors. This novel multifunctional nano-platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound-guidance.

Multifunctional organic/inorganic hybrid nanovesicles, fabricated by a facile self-assembly/sol-gel approach, display a unique morphology (figure) and satisfactory stability under physiological conditions. By co-encapsulation of superparamagnetic magnetite nanoparticles and a liquid perfluorocarbon, the nanovesicles can be used not only as a dual-modality ultrasound/magnetic resonance contrast agent for accurate cancer diagnosis and monitoring, but also as a therapeutic enhancement agent for effective high-intensity focused ultrasound (HIFU) ablation.

Echinococcus granulosus, the etiologic agent of cystic echinococcosis in humans and other animal hosts, is distributed worldwide. Echinococcosis is an increasing public health and socioeconomic concern. The present work evaluated whether or not a superabsorbent polymer (SAP) could enhance the damage efficacy of high-intensity focused ultrasound (HIFU) on the viability of E. granulosus protoscolices in vitro. HIFU of 100 W acoustic power and 0.01 g superabsorbent polymer were used to treat 5,000 protoscolices in 2-ml protoscolices suspension. After different HIFU exposure time (5, 10, 20, 30, 40, 50, and 60 s, respectively), the temperature of protoscolices suspension was taken, and the treated protoscolices were stained by trypan-blue exclusion assay, and their structures were observed by light microscopy. To better understand the biological mechanisms responsible for the deaths of protoscolices, the activity of succinate dehydrogenase (SDH) of the protoscolices treated with HIFU was examined. The temperature of protoscolices suspension treated with HIFU rose slowly, and the death rate of protoscolices was 73.7 % in the group of HIFU treatment time of 40 s; however, with the same HIFU treatment time of 40 s, the temperature of protoscolices suspension in the group of HIFU combined with SAP rose quickly, and the death rate of protoscolices was 100 %. The same protoscolicidal effect (100 %) of HIFU of 100 W acoustic power combined with SAP was also observed in the groups of HIFU treatment time of 50 and 60 s, respectively. The dead protoscolices were stained to blue, shrunken and black calcareous corpuscles, and disordered and decreasing hooks though of intact membrane, as well as some protoscolices lost hooks and tore open on membrane were observed. In the group of HIFU combined with SAP, it was found that the superabsorbent polymer was surrounded by the spoiled, and the destruction of protoscolices was much stronger than in the group of HIFU. The dead protoscolices exhibited the reduction or absence of SDH staining intensity in the parenchymal cell and calcareous corpuscles after HIFU irradiation, where a large number of necrotic cells were evident. These results suggested that HIFU could induce the damage and loss of viability of protoscolices; SAP could enhance the HIFU energy focused and cause more severe destruction efficacy on protoscolices; and mitochondrial energetic function is involved in the regulation of cell-death pathways of protoscolices.

An inorganic enhancement agent (EA) for high-intensity focused ultrasound (HIFU) imaging based on mesoporous silica nanocapsules is presented. The pronounced coagulative necrosis effects demonstrate, both in vitro and in vivo, that the EA can be developed as a highly promising theranostic agent for effective HIFU imaging and therapy owing to its high stability, efficient perfluorohexane loading and release, enhanced tumor ablation capability, and easy uptake by target tissues. Copyright

// Huan Li 1, * , Shi-mei Yuan 1, * , Min Yang 1 , He Zha 1 , Xue-ru Li 1 , Hui Sun 1 , Liang Duan 1 , Yue Gu 1 , Ai-fang Li 1 , Ya-guang Weng 1 , Jin-yong Luo 1 , Tong-chuan He 1, 3 , Yan Wang 2 , Chong-yan Li 2 , Fa-qi Li 2 , Zhi-biao Wang 2 , Lan Zhou 1 1 Key Laboratory of Clinical Diagnosis of Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China 2 State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and The Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China 3 Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA * These authors have contributed equally to this work Correspondence to: Lan Zhou, email: zhoulan0111@foxmail.com Keywords: High intensity focused ultrasound (HIFU), melanoma, metastasis, microRNA-21, PTEN Received: December 23, 2015 Accepted: May 28, 2016 Published: July 6, 2016 ABSTRACT High intensity focused ultrasound (HIFU) technology is becoming a potential noninvasive treatment for solid tumor. To explore whether HIFU can be applied to treat melanoma and its metastasis, we investigated the effect of HIFU on murine melanoma model. While there was little influence on cell survival, viability or apoptosis, HIFU exposure suppressed melanoma cell migration in vitro and metastasis in vivo . The expression of microRNA-21(miR-21) was down-regulated and PTEN expression was up-regulated in response to HIFU exposure, which was in concomitant with the reduction of AKT activity. Furthermore, ectopic miR-21 expression suppressed this effect of HIFU. These results demonstrate that HIFU exposure can inhibit AKT-mediated melanoma metastasis via miR-21 inhibition to restore PTEN expression. Therefore, targeting the miR-21/PTEN/AKT pathway might be a novel strategy of HIFU in treatment of melanoma.

Purpose: In this work, the authors propose a modeling approach to compute the nonlinear acoustic field generated by a flat piston transmitter with an attached aluminum lens. Methods: In this approach, the geometrical parameters (radius and focal length) of a virtual source are initially determined by Snell’s refraction law and then adjusted based on the Rayleigh integral result in the linear case. Then, this virtual source is used with the nonlinear spheroidal beam equation (SBE) model to predict the nonlinear acoustic field in the focal region. Results: To examine the validity of this approach, the calculated nonlinear result is compared with those from the Westervelt and (Khokhlov-Zabolotskaya-Kuznetsov) KZK equations for a focal intensity of 7 kW/cm2. Results indicate that this approach could accurately describe the nonlinear acoustic field in the focal region with less computation time. Conclusions: The proposed modeling approach is shown to accurately describe the nonlinear acoustic field in the focal region. Compared with the Westervelt equation, the computation time of this approach is significantly reduced. It might also be applicable for the widely used concave focused transmitter with a large aperture angle.

Due to its micrometer scale and similar membrane structure as the cell membrane, the giant liposome becomes an important lipid structure and is widely used in many research fields as a cell or cell membrane model, microreactor, carrier, and so on. Electroformation is an important preparing method for giant liposomes. However, it’s a complex process and may be influenced by numerous factors, so its efficiency, size homogeneity and repeatability are still required to be improved. In this work, all main steps of the giant liposome electroformation were analyzed. For several different kinds of lipid molecules, the lipid concentration, lipid film formation style, and the electrical signals were discussed for higher efficiency and repeatability. Furthermore, a collection method was proposed, in which the formed giant liposomes could be sorted and collected. Finally, a microchip integrated the electroformation and collection parts was developed, in which the preparation and collection of conforming to the requirements giant liposomes can be done simply and efficiently.

The life span of model organisms can be modulated by environmental conditions that influence cellular metabolism, oxidation, or DNA integrity. The yeast nicotinamidase gene pnc1 was identified as a key transcriptional target and mediator of calorie restriction and stress-induced life span extension. PNC1 is thought to exert its effect on yeast life span by modulating cellular nicotinamide and NAD levels, resulting in increased activity of Sir2 family class III histone deacetylases. In Caenorhabditis elegans, knockdown of a pnc1 homolog was shown recently to shorten the worm life span, whereas its overexpression increased survival under conditions of oxidative stress. The function and regulation of nicotinamidases in higher organisms has not been determined. Here, we report the identification and biochemical characterization of the Drosophila nicotinamidase, D-NAAM, and demonstrate that its overexpression significantly increases median and maximal fly life span. The life span extension was reversed in Sir2 mutant flies, suggesting Sir2 dependence. Testing for physiological effectors of D-NAAM in Drosophila S2 cells, we identified oxidative stress as a primary regulator, both at the transcription level and protein activity. In contrast to the yeast model, stress factors such as high osmolarity and heat shock, calorie restriction, or inhibitors of TOR and phosphatidylinositol 3-kinase pathways do not appear to regulate D-NAAM in S2 cells. Interestingly, the expression of D-NAAM in human neuronal cells conferred protection from oxidative stress-induced cell death in a sirtuin-dependent manner. Together, our findings establish a life span extending the ability of nicotinamidase in flies and offer a role for nicotinamide-modulating genes in oxidative stress regulated pathways influencing longevity and neuronal cell survival.

Given that erythropoietin (EPO) is no longer believed to have exclusive biological activity in the hematopoietic system, EPO is now considered to have applicability in a variety of nervous system disorders that can overlap with vascular disease, metabolic impairments, and immune system function. As a result, EPO may offer efficacy for a broad number of disorders that involve Alzheimer’s disease, cardiac insufficiency, stroke, trauma, and diabetic complications. During a number of clinical conditions, EPO is robust and can prevent metabolic compromise, neuronal and vascular degeneration, and inflammatory cell activation. Yet, use of EPO is not without its considerations especially in light of frequent concerns that may compromise clinical care. Recent work has elucidated a number of novel cellular pathways governed by EPO that can open new avenues to avert deleterious effects of this agent and offer previously unrecognized perspectives for therapeutic strategies. Obtaining greater insight into the role of EPO in the nervous system and elucidating its unique cellular pathways may provide greater cellular viability not only in the nervous system but also throughout the body.

No longer considered to be exclusive to cellular developmental pathways, the Wnt family of secreted cysteine-rich glycosylated proteins has emerged as versatile targets for a variety of conditions that involve cardiovascular disease, aging, cancer, diabetes, neurodegeneration, and inflammation. In particular, modulation of Wnt signaling may fill a critical void for the treatment of disorders that impact upon both cellular survival and cellular longevity. Yet, in some scenarios, Wnt signaling can become the catalyst for disease development or promote cell senescence that can compromise clinical utility. This double edge sword in regards to the role of Wnt and its signaling pathways highlights the critical need to further elucidate the cellular mechanisms governed by Wnt in conjunction with the development of robust pharmacological ligands that may open new avenues for disease treatment. Here we discuss the influence of the Wnt pathway during cell survival, metabolism, and aging in order for one to gain a greater insight for the novel role of Wnt signaling as well as exemplify its unique cellular pathways that influence both normal physiology and disease.