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We study microbubbles (MBs) in aqueous electrolyte solutions and show that increasing the salt concentration slows down the kinetics of MB dissolution. We modified the Epstein–Plesset theory and experimented with NaCl aqueous solutions to estimate the MB effective surface charge and to compare it with predictions from the modified Poisson–Boltzmann theory. Our results reveal a mechanism responsible for the change in the dissolution of MBs in aqueous electrolyte solutions, with implications for emerging fields ranging from physics of solutions to soft and biological matter. [ABSTRACT FROM AUTHOR]

Coated microbubbles are widely used in medical applications, particularly in enhanced drug and gene delivery. One of the mechanisms underlying these applications involves the shear stress exerted on the cell membrane by acoustic microstreaming generated through cavitation bubbles. In this study, we develop a novel simulation approach that combines the smooth dissipative particle dynamics (SDPD) simulation method with numerical modeling of the Rayleigh–Plesset-like equation in an ad hoc manner to simulate stable cavitation of microbubbles at microsecond and micrometer scales. Specifically, the SDPD method is utilized to model fluid dynamics, while the Rayleigh–Plesset-like equation is employed to describe bubble dynamics. Adopting a 1.5 μm coated microbubble driven by ultrasound with a frequency of 2 MHz and a pressure of 500 kPa as a representative example, we observe a high-velocity microstreaming pattern emerging around the bubble on a very small scale of a few micrometers after only a few microseconds. These spatiotemporal scales may pose challenges for experimental observation. The formation of this microstreaming arises from the opposing motion of the fluid layer next to the bubble and the fluid layers further away. Furthermore, our simulations reveal high shear stress levels of thousands of Pascals exerted on a wall located a few micrometers from the bubble. This contrasts with the shear stress values of a few Pascals calculated from theoretical models in the literature, which do not incorporate radial streaming into their theories. The implications of our results for bubble cavitation-induced pore formation on the cell membrane are discussed in some details. [ABSTRACT FROM AUTHOR]

In this study, the round-trip motion of air-rich bubbles exhaled from a water vapor-rich bubble was investigated. The local heating of non-degassed water produced a vapor-rich bubble with a maximum diameter of 9 μ m, which intermittently exhaled air-rich bubbles with a radius of less than 1 μ m. The exhaled air-rich bubbles initially moved away from the heat source; however, as the air-rich bubbles fused and grew larger, they returned to the heat source and fused with the vapor-rich bubble. This round-trip motion of the air-rich bubbles is explained by the balance between the Marangoni and quasi-steady drag forces induced on the bubbles. As the quasi-steady drag force is approximately proportional to the bubble radius and the Marangoni force is proportional to the square of the bubble radius, a larger bubble correlates with a greater effect of the Marangoni force. To produce a quasi-steady drag force that can balance the increased Marangoni force, air-rich bubbles were attracted to the heat source against the flow created by the vapor-rich bubble. These results provide insight into the stabilization of water-vapor-rich microbubbles in non-degassed water, which can generate strong flows on the order of 1 m/s. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated that the local heating of degassed water can generate water vapor microbubbles and induce a rapid flow around the bubble. Although flow generation involves the self-excited oscillation of bubbles at a local heating point, the conditions under which the bubbles oscillate are not fully understood. In this study, the dependence of microbubble size and oscillation frequency on the concentration of non-condensable gases in water was investigated. A continuous-wave laser beam was focused on a β -FeSi 2 thin film, and water was locally heated using the photothermal conversion properties of the film. The results showed that the lower the concentration of non-condensable gases dissolved in water, the smaller the bubble size and the higher the oscillation frequency. Furthermore, it was found that the bubbles oscillate when the amount of non-condensable gas absorbed by the bubbles, i.e., the bubble size, falls below a specific level. This study can provide a new understanding of the bubble oscillation mechanism and lead to the development of fluid control technology using bubbles. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations in the microcanonical ensemble are performed to study the collapse of a bubble in liquid water using the single-site mW and the four-site TIP4P/2005 water models. To study system size effects, simulations for pure water systems are performed using periodically replicated simulation boxes with linear dimensions, L, ranging from 32 to 512 nm with the largest systems containing 8.7 × 106 and 4.5 × 109 molecules for the TIP4P/2005 and mW water models, respectively. The computationally more efficient mW water model allows us to reach converging behavior when the bubble dynamics results are plotted in reduced units, and the limiting behavior can be obtained through linear extrapolation in L−1. Qualitative differences are observed between simulations with the mW and TIP4P/2005 water models, but they can be explained by the models' differences in predicted viscosity and surface tension. Although bubble collapse occurs on time scales of only hundreds of picoseconds, the system sizes used here are sufficiently large to obtain bubble dynamics consistent with the Rayleigh–Plesset equation when using the models' thermophysical properties as input. For the conditions explored here, extreme heating of the interfacial water molecules near the time of collapse is observed for the larger mW water systems (but the model underpredicts the viscosity), whereas heating is less pronounced for the TIP4P/2005 water systems because its larger viscosity contribution slows the collapse dynamics. The presence of nitrogen within the bubble only starts to affect bubble dynamics near the very end of the initial collapse, leading to an incomplete collapse and strong rebound for the mW water model. Although nitrogen is non-condensable at 300 K, it becomes highly compressed and reaches a liquid-like density near the collapse point. We find that the dissolution of nitrogen is much slower than the movement of the collapsing water front, and the re-expansion of the dense nitrogen droplet gives rise to bubble rebound. The incompatibility of the collapse and dissolution time scales should be considered for continuum-scale modeling of bubble dynamics. We also confirm that the diffusion coefficient for dissolved nitrogen is insensitive to pressure as the liquid transitions from a compressed to a stretched state. [ABSTRACT FROM AUTHOR]

Microbubble-enhanced ultrasound provides a noninvasive physical method to locally overcome major obstacles to the accumulation of blood-borne therapeutics in the brain, posed by the blood-brain barrier (BBB). However, due to the highly nonlinear and coupled behavior of microbubble dynamics in brain vessels, the impact of microbubble resonant effects on BBB signaling and function remains undefined. Here, combined theoretical and prospective experimental investigations reveal that microbubble resonant effects in brain capillaries can control the enrichment of inflammatory pathways that are sensitive to wall shear stress and promote differential expression of a range of transcripts in the BBB, supporting the notion that microbubble dynamics exerted mechanical stress can be used to establish molecular, in addition to spatial, therapeutic windows to target brain diseases. Consistent with these findings, a robust increase in cytotoxic T-cell accumulation in brain tumors was observed, demonstrating the functional relevance and potential clinical significance of the observed immuno-mechano-biological responses.

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (sham). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p

Antibubbles are liquid droplets encapsulated by a gas film that have recently been explored for on-demand ultrasound-triggered drug release. However, their ultrasound imaging capabilities are limited by their stiff shells stabilized with silica nanoparticles. Here, we develop polymeric antibubbles that generate greater ultrasound contrast than silica-based antibubbles, while showing better stability than conventional polymeric microbubbles. [ABSTRACT FROM AUTHOR]

Microbubbles have emerged as versatile carriers used both for cancer diagnosis and therapy. Microbubbles in the presence of ultrasound waves undergo cavitation, generating bioeffects near the cell's vicinity. Studies have shown ultrasound-stimulated microbubbles (USMB) to cause mechanical perturbation of endothelial cells, resulting in acid sphingomyelinase (ASMase)-induced ceramide production. Disruption of endothelial cells further causes vascular deterioration, leading to secondary tumor cell death. These effects are known to be synergistically higher when USMB is combined with radiation. This paper provides insight into the use of USMB as a potential radioenhancer. The possible underlying mechanism and therapeutic effects of combining USMB and radiation therapy are also presented. [ABSTRACT FROM AUTHOR]

Breath-hold diving is a challenging activity that can lead to serious and dangerous complications, such as the "Taravana" syndrome. This syndrome is characterized by the onset of neurological symptoms after deep or repeated dives. The main clinical manifestations are cerebral, including stroke and cognitive impairment. The pathophysiology of Taravana syndrome is still widely debated, but the most accepted theory is that it is a specific form of decompression sickness. We have reviewed the main theories explaining the onset of Taravana syndrome and, through the description of a particularly illustrative case of a freediver using an underwater scooter, we have formulated a hypothesis according to which micro-bubbles formed directly in cerebral structures would be at the origin of this syndrome. MRI showed diffuse encephalopathy with vasogenic edema. Analysis of the radiological sequences did not suggest an ischemic or embolic mechanism. This finding is likely to be associated with the diagnosis of posterior reversible encephalopathy syndrome. The rapid ascent speeds associated with underwater scooter use could potentially result in the formation of nitrogen micro-bubbles in the capillaries of brain tissue. The emergence of scooters in freediving can be a hazard because of their ability to facilitate very rapid ascents. It is therefore essential to take preventive measures to ensure the safety of users of these devices. [ABSTRACT FROM AUTHOR]

Microfluidics has achieved a paradigm-shifting advancement in life sciences, automation, thermal management, and various other engineering streams. In recent years, a considerable amount of research has been conducted on the use of microfluidics in designing novel systems and fabricating next-generation smart materials that are capable of outperforming historical barriers and achieving unprecedented qualities. One such innovative development is the integration of fluidics into building artificially structured smart materials called acoustic metamaterials to achieve active tunability for a real-time controllable manipulation of acoustic waves. Leveraging the capability of microfluidics to automate the manipulation of liquid droplets, fluid streams, or bubbles in a required arrangement has revolutionised the development of actively tunable fluidics-integrated acoustic metamaterials for widescale applications. This review first discusses the prominent microfluidic actuation mechanisms used in the literature to develop fluidics-integrated smart acoustic metamaterials, and then it details integrated metamaterial design and extraordinary applications such as active acoustic wave manipulation or building tunable acoustic holograms etc. The following review concludes by providing the importance and future perspective of integrating microfluidic techniques with novel metamaterial designs, paving the way for innovative futuristic applications. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) is an advanced ultrasound (US) technique utilizing ultrasound contrast agents (UCAs) to provide detailed visualization of anatomic and vascular architecture, including the depiction of microcirculation. CEUS has been well-established in echocardiography and imaging of focal hepatic lesions and recent studies have also shown the utility of CEUS in non-hepatic applications like the urinary system. The updated guidelines by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from 2018 describe the use of CEUS for non-hepatic applications. CEUS' excellent safety profile and spatial resolution make it a superior modality to conventional US and is often comparable and even superior to CECT in some instances. In comparison to other cross-sectional imaging modalities such as CECT or MRI, CEUS offers a safe (by virtue of non-nephrotoxic US contrast agents), accurate, cost-efficient, readily available, and a quick means of evaluation of multiple pathologies of the urinary system. CEUS also has the potential to reduce the overall economic burden on patients requiring long-term follow-up due to its low cost as compared to CT or MRI techniques. This comprehensive review focuses on the applications of CEUS in evaluating the urinary system from the kidneys to the urinary bladder. CEUS can be utilized in the kidney to evaluate complex cystic lesions, indeterminate lesions, pseudotumors (vs solid renal tumors), renal infections, and renal ischemic disorders. Additionally, CEUS has also been utilized in evaluating renal transplants. In the urinary bladder, CEUS is extremely useful in differentiating a bladder hematoma and bladder cancer when conventional US techniques show equivocal results. Quantitative parameters of time-intensity curves (TICs) of CEUS examinations have also been studied to stage and grade bladder cancers. Although promising, further research is needed to definitively stage bladder cancers and classify them as muscle-invasive or non-muscle invasive using quantitative CEUS to guide appropriate intervention. CEUS has been very effective in the classification of cystic renal lesions, however, further research is needed in differentiating benign from malignant renal masses. [ABSTRACT FROM AUTHOR]

Gas bubbling can be an effective means to float out alumina inclusions from liquid steel in a ladle. However, large spherical cap bubbles are formed when using porous plugs, as the liquid steel is nonwetting to the porous refractory. These bubbles rise rapidly through the liquid steel, forming a fast‐moving bubble plume, restricting contact times. Sized microbubbles, by contrast, have now been generated in liquid metals by shearing methods, involving linear crossflows to an entering flow of gas, or alternatively by rotational shearing. Combined with these convective shearing forces, local kinetic energy of turbulence can also play an important part in determining final microbubble size distributions. As microbubbles have much smaller rise velocities and present a far greater inclusion capture surface area than those of a single large bubble of the same gross volume, this will allow us to remove sub‐50 μm inclusions from liquid steel. It is expected that this goal will require a redesign of current ladle shrouds. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions. Methods: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied. Results: CEUS analysis showed that the time-averaged estimated contrast was significantly higher (p = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM (p = 0.001 for CH cases and p < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher (p = 0.032) for CH (m = 0.61) than for CM (m = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher (p = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM. Conclusions: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions. [ABSTRACT FROM AUTHOR]

Sonoporation-based delivery has great promise for noninvasive drug and gene therapy. After short-term membrane resealing, the long-term function recovery of sonoporated cells affects the efficiency and biosafety of sonoporation-based delivery. It is necessary to identify the key early biological signals that influence cell fate and to develop strategies for manipulating the long-term fates of sonoporated cells. Here, we used a customized experimental platform with a single cavitating microbubble induced by a single ultrasound pulse (frequency: 1.5 MHz, pulse length:13.33 μs, peak negative pressure: ∼0.40 MPa) to elicit single-site reversible sonoporation on a single HeLa cell model. We used a living-cell microscopic imaging system to trace the long-term fates of sonoporated HeLa cells in real-time for 48 h. Fluorescence from intracellular propidium iodide and Fluo-4 was used to evaluate the degree of sonoporation and intracellular calcium fluctuation (ICF), respectively. Changes in cell morphology were used to assess the long-term cell fates (i.e., proliferation, arrest, or death). We found that heterogeneously sonoporated cells had different long-term fates. With increasing degree of sonoporation, the probability of normal (proliferation) and abnormal fates (arrest and death) in sonoporated cells decreased and increased, respectively. We identified ICF as an important early event for triggering different long-term fates. Reversibly sonoporated cells exhibited stronger proliferation and restoration at lower extents of ICF. We then regulated ICF dynamics in sonoporated cells using 2-APB or BAPTA treatment to reduce calcium release from intracellular organelles and enhance intracellular calcium clearance, respectively. This significantly enhanced the proliferation and restoration of sonoporated cells and reduced the occurrence of cell-cycle arrest and death. Finally, we found that the long-term fates of sonoporated cells at multiple sites and neighboring cells were also dependent on the extent of ICF, and that 2-APB significantly enhanced their viability and reduced death. Thus, using a single HeLa cell model, we demonstrated that regulating intracellular calcium can effectively enhance the proliferation and restoration capabilities of sonoporated cells, therefore rescuing the long-term viability of sonoporated cells. These findings add to our understanding of the biophysical process of sonoporation and help design new strategies for improving the efficiency and biosafety of sonoporation-based delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

Cell-based therapies have shown significant promise for treating many diseases, including cancer. Current cell therapy manufacturing processes primarily utilize viral transduction to insert genomic material into cells, which has limitations, including variable transduction efficiency and extended processing times. Non-viral transfection techniques are also limited by high variability or reduced molecular delivery efficiency. Novel 3D-printed acoustofluidic devices are in development to address these challenges by delivering biomolecules into cells within seconds via sonoporation. In this study, we assessed biological parameters that influence the ultrasound-mediated delivery of fluorescent molecules (i.e. , calcein and 150 kDa FITC-Dextran) to human T cells using flow cytometry and confocal imaging. Low cell plating densities (100,000 cells/mL) enhanced molecular delivery compared to higher cell plating densities (p < 0.001), even though cells were resuspended at equal concentrations for acoustofluidic processing. Additionally, cells in the S phase of the cell cycle had enhanced intracellular delivery compared to cells in the G2/M phase (p < 0.001) and G0/G1 phase (p < 0.01), while also maintaining higher viability compared to G0/G1 phase (p < 0.001). Furthermore, the calcium chelator (EGTA) decreased overall molecular delivery levels. Confocal imaging indicated that the actin cytoskeleton had important implications on plasma membrane recovery dynamics after sonoporation. In addition, confocal imaging indicates that acoustofluidic treatment can permeabilize the nuclear membrane, which could enable rapid intranuclear delivery of nucleic acids. The results of this study demonstrate that a 3D-printed acoustofluidic device can enhance molecular delivery to human T cells, which may enable improved techniques for non-viral processing of cell therapies. [ABSTRACT FROM AUTHOR]

Purpose: Brain tumors, particularly glioblastoma multiforme (GBM), present significant prognostic challenges despite multimodal therapies, including surgical resection, chemotherapy, and radiotherapy. One major obstacle is the limited drug delivery across the blood–brain barrier (BBB). Focused ultrasound (FUS) combined with systemically administered microbubbles has emerged as a non-invasive, targeted, and reversible approach to transiently open the BBB, thus enhancing drug delivery. This review examines clinical trials employing BBB opening techniques to optimise pharmacotherapy for brain tumors, evaluates current challenges, and proposes directions for further research. Methods: A systematic literature search was conducted in PubMed and ClinicalTrials.gov up to November 2023, searching for "ultrasound" AND "brain tumor". The search yielded 1446 results. After screening by title and abstract, followed by full-text screening (n = 48), 35 studies were included in the analysis. Results: Our analysis includes data from 11 published studies and 24 ongoing trials. The predominant focus of these studies is on glioma, including GMB and astrocytoma. One paper investigated brain metastasis from breast cancer. Evidence indicates that FUS facilitates BBB opening and enhances drug uptake following sonication. Exploration of FUS in the pediatric population is limited, with no published studies and only three ongoing trials dedicated to this demographic. Conclusion: FUS is a promising strategy to safely disrupt the BBB, enabling precise and non-invasive lesion targeting, and enhance drug delivery. However, pharmacokinetic studies are required to quantitatively assess improvements in drug uptake. Most studies are phase I clinical trials, and long-term follow-up investigating patient outcomes is essential to evaluate the clinical benefit of this treatment approach. Further studies involving diverse populations and pathologies will be beneficial. [ABSTRACT FROM AUTHOR]

Soil contamination by heavy metals poses serious risks to human health due to their high toxicity and resistance to biodegradation, especially when they accumulate through the food chain. Soil drenching technology is one of the most promising methods for soil pollution remediation. In this research, microbubbles were introduced into the disodium ethylenediamine tetraacetate(EDTA-2Na) solution during soil drenching, combined with Polysorbate 80(TW-80) to remove heavy metals(Cu, Cd) from the soil. The microbubbles contributed to concentrating heavy metals, thus lowering their levels in the solution. The efficiency of heavy metal removal was found to be positively correlated with both time and detergent concentration, and negatively correlated with pH levels. Under conditions where the washing time was 120 minutes, EDTA-2Na concentration was 1 g/L, TW-80 concentration was 2 g/L, the solid-liquid ratio was 1:30, the gas-liquid ratio was 1:3, and the pH was maintained at 3, the removal rates for Cu and Cd were 86.67% and 85.52%, respectively. The Community Bureau of Reference (BCR) sequential extraction procedure revealed that intensive was Ahile et al., 2021 hing with microbubbles effectively eliminated acid-soluble (F1) and reducible (F2) heavy metals from the soil, thereby mitigating their detrimental effects on soil ecosystems. These insights offer a theoretical and practical foundation for employing microbubble technology in the remediation of heavy metal ion pollution in soils. [ABSTRACT FROM AUTHOR]

Quasi‐3D plasmonic nanostructures are in high demand for their ability to manipulate and enhance light‐matter interactions at subwavelength scales, making them promising building blocks for diverse nanophotonic devices. Despite their potential, the integration of these nanostructures with optical sensors and imaging systems on a large scale poses challenges. Here, a robust technique for the rapid, scalable, and seamless replication of quasi‐3D plasmonic nanostructures is presented straight from their production wafers using a microbubble process. This approach not only simplifies the integration of quasi‐3D plasmonic nanostructures into a wide range of standard and custom optical imaging devices and sensors but also significantly enhances their imaging and sensing performance beyond the limits of conventional methods. This study encompasses experimental, computational, and theoretical investigations, and it fully elucidates the operational mechanism. Additionally, it explores a versatile set of options for outfitting nanophotonic devices with custom‐designed plasmonic nanostructures, thereby fulfilling specific operational criteria. [ABSTRACT FROM AUTHOR]

Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US‐enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer‐mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA‐based MB products, facilitating the potential translation of next‐generation PBCA MB. [ABSTRACT FROM AUTHOR]

Bubble printing is a patterning method in which particles are accumulated by the convection of bubbles generated by laser focusing. It is attracting attention as a method that enables the high-speed, high-precision patterning of various micro/nanoparticles. Although the bubble printing method is used for metallic particles and organic particles, most reports have focused on the patterning of solid particles and not on the patterning of liquid particles. In this study, liquid metal wiring patterns were fabricated using a bubble printing method in which eutectic gallium‒indium alloy (EGaIn) colloidal particles (≈diameter 0.7 µm) were fixed on a glass substrate by generating microbubbles through heat generation by focusing a femtosecond laser beam on the EGaIn colloidal particles. The wiring was then made conductive by replacing gallium oxide, which served as a resistance layer on the surface of the EGaIn colloidal particles, with silver via galvanic replacement. Fine continuous lines of liquid metal colloids with a line width of 3.4 µm were drawn by reducing the laser power. Liquid metal wiring with a conductivity of ≈1.5 × 105 S/m was formed on a glass substrate. It was confirmed that the conductivity remained consistent even when the glass substrate was bent to a curvature of 0.02 m−1. [ABSTRACT FROM AUTHOR]

Nanodroplets have demonstrated potential for the range detection of hadron radiotherapies. Our formulation uses superheated perfluorobutane (C4F10) stabilized by a poly(vinyl-alcohol) shell. High-LET (linear energy transfer) particles vaporize the nanodroplets into echogenic microbubbles. Tailored ultrasound imaging translates the generated echo-contrast into a dose distribution map, enabling beam range retrieval. This work evaluates the response of size-sorted nanodroplets to carbon-ion radiation. We studied how thesize of nanodroplets affects their sensitivity at various beam-doses and energies, as a function of concentration and shell cross-linking. First, we show the physicochemical characterization of size-isolated nanodroplets by differential centrifugation. Then, we report on the irradiations of the nanodroplet samples in tissue-mimicking phantoms. We compared the response of large (≈900 nm) and small (≈400 nm) nanodroplets to different carbon-ions energies and evaluated their dose linearity and concentration detection thresholds by ultrasound imaging. Additionally, we verified the beam range detection accuracy for the nanodroplets samples. All nanodroplets exhibited sensitivity to carbon-ions with high range verification precision. However, smaller nanodroplets required a higher concentration sensitivity threshold. The vaporization yield depends on the carbon-ions energy and dose, which are both related to particle count/spot. These findings confirm the potential of nanodroplets for range detection, with performance depending on nanodroplets' properties and beam parameters. [ABSTRACT FROM AUTHOR]

Introduction: Coaxial 3D bioprinting has advanced the formation of tissue constructs that recapitulate key architectures and biophysical parameters for in-vitro disease modeling and tissue-engineered therapies. Controlling gene expression within these structures is critical for modulating cell signaling and probing cell behavior. However, current transfection strategies are limited in spatiotemporal control because dense 3D scaffolds hinder diffusion of traditional vectors. To address this, we developed a coaxial extrusion 3D bioprinting technique using ultrasound-responsive gene delivery bioinks. These bioink materials incorporate echogenic microbubble gene delivery particles that upon ultrasound exposure can sonoporate cells within the construct, facilitating controllable transfection. Methods: Phospholipid-coated gas-core microbubbles were electrostatically coupled to reporter transgene plasmid payloads and incorporated into cell-laden alginate bioinks at varying particle concentrations. These bioinks were loaded into the coaxial nozzle core for extrusion bioprinting with CaCl2 crosslinker in the outer sheath. Resulting bioprints were exposed to 2.25 MHz focused ultrasound and evaluated for microbubble activation and subsequent DNA delivery and transgene expression. Results: Coaxial printing parameters were established that preserved the stability of ultrasound-responsive gene delivery particles for at least 48 h in bioprinted alginate filaments while maintaining high cell viability. Successful sonoporation of embedded cells resulted in DNA delivery and robust ultrasound-controlled transgene expression. The number of transfected cells was modulated by varying the number of focused ultrasound pulses applied. The size region over which DNA was delivered was modulated by varying the concentration of microbubbles in the printed filaments. Conclusions: Our results present a successful coaxial 3D bioprinting technique designed to facilitate ultrasound-controlled gene delivery. This platform enables remote, spatiotemporally-defined genetic manipulation in coaxially bioprinted tissue constructs with important applications for disease modeling and regenerative medicine. [ABSTRACT FROM AUTHOR]

Continuous-wave lasers generated bubbles in microfluidic channels are proposed for applications such as needle-free jet injection due to their small size and affordable price of these lasers. However, water is transparent in the visible and near-IR regime, where the affordable diode lasers operate. Therefore, a dye is required for absorption, which is often unwanted in thermocavitation applications, such as vaccines or cosmetics. In this work, we explore a different mechanism of the absorption of optical energy. The microfluidic channel wall is partially covered with a thin gold layer, which absorbs light from a blue laser diode. This surface absorption is compared with the conventional volumetric absorption by a red dye. The results show that this surface absorption can be used to generate bubbles without the requirement of a dye. However, the generated bubbles are smaller and grow slower when compared to the dye-generated bubbles. Furthermore, heat dissipation in the glass channel walls affects the overall efficiency. Finally, degradation of the gold layer over time reduces the reproducibility and limits its lifetime. Further experiments and simulations are proposed to potentially solve these problems and optimize the bubble formation. Our findings can inform the design and operation of microfluidic devices used in phase transition experiments and other cavitation phenomena, such as jet injectors or liquid dispensing for bio-engineering. [ABSTRACT FROM AUTHOR]

Previous atomic force microscopy studies have suggested that surface micro- and nanobubbles exhibit a flat shape. In this study, we directly observed surface microbubbles formed in an NH3BH3 solution using an optical microscope. No flat microbubbles were observed. Instead, on an SiO2/Si substrate, we discovered a relationship where the sum of the contact angle of a microbubble and the contact angle of a droplet equaled ∼180°. This relationship allowed us to control the shape of surface microbubbles by manipulating the wettability of the surface and the surface tension of the liquid, similar to droplet control. We were able to produce almost perfectly spherical microbubbles. Conversely, on a Cu foil, this relationship did not hold, although we still observed the formation of nearly spherical microbubbles. In this scenario, the shape of microbubbles appeared to be influenced by contact line pinning. [ABSTRACT FROM AUTHOR]

Acoustic trap, using ultrasound interference to ensnare bioparticles, has emerged as a versatile tool for life sciences due to its non-invasive nature. Bolstered by magnetic resonance imaging's advances in sensing acoustic interference and tracking drug carriers (e.g., microbubble), acoustic trap holds promise for increasing MRI-guided microbubbles (MBs) accumulation in target microvessels, improving drug carrier concentration. However, accurate trap generation remains challenging due to complex ultrasound propagation in tissues. Moreover, the MBs' short lifetime demands high computation efficiency for trap position adjustments based on real-time MRI-guided carrier monitoring. To this end, we propose a machine learning-based model to modulate the transducer array. Our model delivers accurate prediction of both time-of-flight (ToF) and pressure amplitude, achieving low average prediction errors for ToF (−0.45 µs to 0.67 µs, with only a few isolated outliers) and amplitude (−0.34% to 1.75%). Compared with the existing methods, our model enables rapid prediction (<10 ms), achieving a four-order of magnitude improvement in computational efficiency. Validation results based on different transducer sizes and penetration depths support the model's adaptability and potential for future ultrasound treatments. [ABSTRACT FROM AUTHOR]

When illuminated by a resonant laser, noble metal nanoparticles immersed in liquids can efficiently produce a huge amount of heat and rapidly vaporize surrounding liquid, leading to the nucleation of plasmonic bubbles. Plasmonic bubbles are gaining increasing attention and emerged in numerous applications due to their unique properties and excellent controllability, such as microfabrication, micromanipulation, robot propulsion, molecule enrichment, and clinical therapies. In this review paper, the research progress of plasmonic bubbles in the past decade is summarized, including the plasmonic effect‐induced heat generation, experimental methods of plasmonic bubble observation, growth dynamics of plasmonic bubbles, approaches of optomechanical energy conversion via plasmonic bubbles, as well as their applications. This work provides a comprehensive understanding of the state of the art in the field and inspires researchers to explore more promising applications of plasmonic bubbles in different fields, like biology, microfluidics, and micromanufacturing. [ABSTRACT FROM AUTHOR]

[Display omitted] The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans. Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB–saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner. All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments. Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE. [ABSTRACT FROM AUTHOR]

To enhance the anesthetic efficacy and reduce toxic side effects, a strategy is proposed involving the utilization of general anesthetics of Propofol (Pro) and Etomidate (Eto) to synergistic inhibition GABA receptors simultaneously. Four‐in‐one molecular aggregates were prepared to implement this strategy, which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate (GMO) and surfactant F127 through intermolecular forces. The blood‐brain barrier (BBB) targeted lactoferrin (LF) is affixed to their surface, obtaining the final molecular aggregates. By employing lactoferrin enrich aggregates to the BBB, followed by ultrasound combine microbubbles to open the BBB, a remarkable 4.5‐fold enhancement in brain drug delivery was achieved. The molecular aggregates group maintained stable parameters of heart rate, diastolic blood pressure, and systolic blood pressure. A notable increase of more than twice therapeutic index (TI) value was observed, implying their higher anesthesia efficiency and reduced toxicity. Electroencephalogram (EEG) experiments demonstrate a significant elevation in the proportion of δ waves from 28% to 80% for aggregates, accompanied by a nearly fivefold reduction in the proportion of θ waves, meaning a significant improvement in synergistic anesthesia effectiveness (interaction index 0.289) with lower drug dosage. Furthermore, mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously, resulting in synergistic inhibition of GABA receptors. [ABSTRACT FROM AUTHOR]

Sonazoid, an ultrasound contrast agent, has been covered by insurance in Japan since January 2007 for the diagnosis of hepatic mass lesions and is widely used for diagnosing not only primary liver cancer but also liver metastases such as those from breast cancer and colorectal cancer. Contrast-enhanced ultrasound for breast mass lesions has been covered by insurance since August 2012 after phase II and phase III clinical trials showed that the diagnostic performance was significantly superior to that of B-mode and contrast-enhanced magnetic resonance imaging. This paper describes the principles of imaging techniques in contrast-enhanced ultrasonography including the filter, pulse inversion, amplitude modulation, and amplitude-modulated pulse inversion methods. The pulse inversion method, which visualizes the second-harmonic component using the nonlinear scattering characteristics of the contrast agent, is widely used regardless of the contrast agent and target organ because of its high resolution. Sonazoid has a stiffer shell and requires a higher acoustic amplitude than Sonovue to generate nonlinear vibrations. The higher transmitted sound pressure generates more tissue harmonic components. Since pulse inversion allows visualization of the tissue harmonic components, amplitude modulation and amplitude-modulated pulse inversion, which include few tissue harmonic components, are primarily used. Amplitude modulation methods detect nonlinear signals from the contrast agent in the fundamental band. The mechanism of the amplitude modulation is considered to be changes in the echo signal's phase depending on the sound pressure. Since the tissue-derived component is minor in amplitude modulation methods, good contrast sensitivity can be obtained. [ABSTRACT FROM AUTHOR]

Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy to promote drug delivery across the BBB is sonopermeation, which relies on the combined use of ultrasound (US) and microbubbles (MB) to induce temporally and spatially controlled opening of the BBB. We developed an advanced in vitro BBB model to study the impact of sonopermeation on the delivery of the prototypic polymeric drug carrier pHPMA as a larger molecule and the small molecule antiviral drug ribavirin. This was done under standard and under inflammatory conditions, employing both untargeted and RGD peptide-coated MB. The BBB model is based on human cerebral capillary endothelial cells and human placental pericytes, which are co-cultivated in transwell inserts and which present with proper transendothelial electrical resistance (TEER). Sonopermeation induced a significant decrease in TEER values and facilitated the trans-BBB delivery of fluorescently labeled pHPMA (Atto488-pHPMA). To study drug delivery under inflamed endothelial conditions, which are typical for e.g. tumors, neurodegenerative diseases and CNS infections, tumor necrosis factor (TNF) was employed to induce inflammation in the BBB model. RGD-coated MB bound to and permeabilized the inflamed endothelium-pericyte co-culture model, and potently improved Atto488-pHPMA and ribavirin delivery. Taken together, our work combines in vitro BBB bioengineering with MB-mediated drug delivery enhancement, thereby providing a framework for future studies on optimization of US-mediated drug delivery to the brain. [ABSTRACT FROM AUTHOR]

Ultrasound is a mechanical wave that can non-invasively penetrate the skull to deep brain regions to activate neurons. Transcranial focused ultrasound neuromodulation is a promising approach, with the advantages of noninvasiveness, high-resolution, and deep penetration, which developed rapidly over the past years. However, conventional transcranial ultrasound's spatial resolution is lowprecision which hinders its use in precision neuromodulation. Here we focus on methods that could increase the spatial resolution, gain modulation efficiency at the focal spot, and potential mechanisms of ultrasound neuromodulation. In this paper, we summarize strategies to enhance the precision of ultrasound stimulation, which could potentially improve the ultrasound neuromodulation technic. [ABSTRACT FROM AUTHOR]

Simple Summary: Submicron bubbles, known as nanobubbles, are demonstrated to overcome the limitations of microbubbles. The small size of the bubbles allows it to penetrate the vascular endothelial wall, enabling it to move freely through tumor tissues. Studies suggest that ultrasound-stimulated nanobubbles (USNBs) enhance the effect of existing cancer therapies (chemotherapy, immunotherapy, and/ or radiation therapy). This review overviews recent research on nanobubbles and their combinatory biological effects with existing cancer therapies. In recent years, ultrasound-stimulated microbubbles (USMBs) have gained great attention because of their wide theranostic applications. However, due to their micro-size, reaching the targeted site remains a challenge. At present, ultrasound-stimulated nanobubbles (USNBs) have attracted particular interest, and their small size allows them to extravasate easily in the blood vessels penetrating deeper into the tumor vasculature. Incorporating USNBs with existing cancer therapies such as chemotherapy, immunotherapy, and/or radiation therapy in several preclinical models has been demonstrated to have a profound effect on solid tumors. In this review, we provide an understanding of the composition and formation of nanobubbles (NBs), followed by the recent progress of the therapeutic combinatory effect of USNBs and other cancer therapies in cancer treatment. [ABSTRACT FROM AUTHOR]

Ozone-based advanced oxidation processes (AOPs) have emerged a promising avenue for water treatment, offering effective removal of micropollutants. Recent research underscores the potential of ozone microbubbles to enhance ozone mass transfer during water treatment, particularly when combined with pre-treatment steps. This study aimed to evaluate the efficacy of three different combined processes (chlorine/KMnO4/PAC pre-treatment followed by ozonation) in removing atrazine, a common micropollutant from natural source water. Results revealed that all combined processes achieved higher atrazine removal rates compared to individual pre-treatment or ozonation methods. Notably, the highest atrazine removal rates were observed under alkaline pH conditions, with treatment outcomes influenced by oxidant dose and pH levels. Among the combined processes, chlorine pre-treatment followed by ozonation emerged as the most effective approach, achieving a removal rate of 59.7% that exceeded the sum of individual treatments. However, this treatment efficacy was affected by water quality parameters, particularly the presence of organic matter and elevated ammonia nitrogen concentration (> 0.5 mg/L). This study highlights the potential for utilizing ozone micro/nanobubbles to enhance ozone mass transfer and offers valuable insights for optimizing the combined application of pre-treatment and ozonation strategies for efficient atrazine removal from natural water sources. [ABSTRACT FROM AUTHOR]

Introduction: Primarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be 'burst' to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound‐stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action. Methods: Primary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action. Results: Overall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action. Conclusions: USMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to target all three phases of radiation action. [ABSTRACT FROM AUTHOR]

Bulk nanobubbles, nanoscopic gaseous domains in aqueous solutions, exhibit surprising long-term stability and unique properties under varying environmental conditions. This study investigates the effects of external pressure on nanobubble stability and behavior through three experimental setups: pressurization at room temperature, pressurization at elevated temperatures, and constant pressure loading. Our findings reveal that increasing external pressure reduces nanobubble concentration and reshapes the bubble size distribution. Larger nanobubbles either disappeared or transformed into microbubbles, while smaller ones expanded, significantly narrowing the size distribution. These changes were found to be irreversible. Additionally, nanobubble stability is influenced by both the magnitude and duration of the applied pressure. Elevated temperatures further narrowed the size distribution at atmospheric pressure, and subsequent pressurization caused these nanobubbles to shrink, showing different response characteristics compared to room temperature. This research highlights the complex interplay between pressure, temperature, and nanobubble stability, offering valuable insight for practical applications in fields such as drug delivery, water treatment, and nanomaterial synthesis. [ABSTRACT FROM AUTHOR]

Molecular ultrasound imaging with actively targeted microbubbles (MB) proved promising in preclinical studies but its clinical translation is limited. To achieve this, it is essential that the actively targeted MB can be produced with high batch-to-batch reproducibility with a controllable and defined number of binding ligands on the surface. In this regard, poly (n-butyl cyanoacrylate) (PBCA)-based polymeric MB have been used for US molecular imaging, however, ligand coupling was mostly done via hydrolysis and carbodiimide chemistry, which is a multi-step procedure with poor reproducibility and low MB yield. Herein, we developed a single-step coupling procedure resulting in high MB yields with minimal batch-to-batch variation. Actively targeted PBCA-MB were generated using an aminolysis protocol, wherein amine-containing cRGD was added to the MB using lithium methoxide as a catalyst. We confirmed the successful conjugation of cRGD on the MB surface, while preserving their structure and acoustic signal. Compared to the conventional hydrolysis protocol, aminolysis resulted in higher MB yields and better reproducibility of coupling efficiency. Optical imaging revealed that under flow conditions, cRGD- and rhodamine-labelled MB, generated by aminolysis, specifically bind to tumor necrosis factor-alpha (TNF-α) activated endothelial cells in vitro. Furthermore, US molecular imaging demonstrated a markedly higher binding of the cRGD-MB than of control MB in TNF-α activated mouse aortas and 4T1 tumors in mice. Thus, using the aminolysis based conjugation approach, important refinements on the production of cRGD-MB could be achieved that will facilitate the production of clinical-scale formulations with excellent binding and ultrasound imaging performance. [ABSTRACT FROM AUTHOR]

Dynamic Ultrasound Localization Microscopy (DULM) has first been developed for non-invasive Pulsatility measurements in the rodent brain. DULM relies on the localization and tracking of microbubbles (MBs) injected into the bloodstream, to obtain highly resolved velocity and density cine-loops. Previous DULM techniques required ECG-gating, limiting its application to specific datasets, and increasing acquisition time. The objective of this study is to eliminate the need for ECG-gating in DULM experiments by introducing a motion-matching method for time registration. We developed a motion-matching algorithm based on tissue Doppler that leverages the cyclic tissue motion within the brain. Tissue Doppler was estimated for each group of frames in the acquisitions, at multiple locations identified as local maxima in the skin above the skull. Subsequently, each group of frames was time-registered to a reference group by delaying it based on the maximum correlation value between their respective tissue Doppler signals. This synchronization ensured that each group of frames aligned with the brain tissue motion of the reference group, and consequently, with its cardiac cycle. As a result, velocities of MBs could be averaged to retrieve flow velocity variations over time. Initially validated in ECG-gated acquisitions in a rat model (n = 1), the proposed method was successfully applied in a mice model in 2D (n = 3) and in a feline model in 3D (n = 1). Performing time-registration with the proposed motion-matching method or by using ECG-gating leads to similar results. For the first time, dynamic velocity and density cine-loops were extracted without the need for any information on the animal ECG, and complex dynamic markers such as the Pulsatility index were estimated. Results suggest that DULM can be performed without external gating, enabling the use of DULM on any ULM dataset where enough MBs are detectable. Time registration by motion-matching represents a significant advancement in DULM techniques, making DULM more accessible by simplifying its experimental complexity. [ABSTRACT FROM AUTHOR]

Both microbubble ultrasound contrast agents and acoustic phase change droplets (APCD) have been explored in hepatocellular carcinoma (HCC). This work aimed to evaluate changes to the HCC microenvironment following either microbubble or APCD destruction in a syngeneic pre-clinical model. Mouse RIL-175 HCC tumors were grown in the right flank of 64 immunocompetent mice. Pre-treatment, photoacoustic volumetric tumor oxygenation, and power Doppler measurements were obtained using a Vevo 3100 system (VisualSonics, Toronto, Canada). The experimental groups received a 0.1 mL bolus injection of either Definity ultrasound contrast agent (Lantheus Medical Imaging) or APCD fabricated by condensing Definity. Following injection, ultrasound destruction was performed using flash-replenishment sequences on a Sequoia with a 10L4 probe (Siemens) for the duration of enhancement. Tumor oxygenation and power Doppler measurements were then repeated immediately post-ultrasound treatment. Twenty-four hours post-treatment, animals were euthanized, and tumors were harvested and stained for CD31, Cleaved Caspase 3 and CD45. Imaging biomarkers demonstrated a significant reduction in percent vascularity following either microbubble or APCD destruction in the tumor microenvironment (p < 0.022) but no significant changes in tumor oxygenation (p = 0.12). Similarly, immunohistochemistry data demonstrated a significant decrease in CD31 expression (p < 0.042) and an increase in apoptosis (p < 0.014) in tumors treated with destroyed microbubbles or APCD relative to controls. Finally, a significant increase in CD45 expression was observed in tumors treated with APCD (p = 0.046), indicating an increase in tumor immune response. Ultrasound-triggered destruction of both microbubbles and APCD reduces vascularity, increases apoptosis, and may also increase immune response in this HCC model. [ABSTRACT FROM AUTHOR]

Oxygen plays an important role in aquaculture by serving as an essential component for oxidizing food substances to produce energy, thereby influencing metabolic rates often quantified by oxygen consumption per unit of time. Particularly in intensive aquaculture systems characterized by high stocking densities and maximal feeding rates, oxygen content assumes paramount importance. This study aimed to evaluate the growth performance of tambaqui (Colossoma macropomum) treated with increased oxygen in two different systems. The study was conducted on a laboratory scale by applying Ttest data analysis. The difference in treatment level applied when comparing aeration and microbubble consists of two treatments and three replications. This research used commercial floating pellets PF0 with 25% protein content, the feeding rate was 5% of the biomass. The feed was given daily during the culture for two times a day. Data from the study were analyzed using a T-test on the Statistical Product and Service Solutions (SPSS) software Version 17.0. Results of the study showed that aeration system using microbubble resulted in dissolved oxygen (DO) of 6.5 ± 0.17, 100% pomfret fish survival rate (SR), Survival Growth Rate (SGR) of 1.83 ± 0.24, Feed Conversion Ratio (FCR) of 1.37 ± 0.17, Protein Efficiency Ratio (PER) of 2.79 ± 0.37, Feed Utilization Efficiency (FUE) of 0.67 ± 0.09, Absolute Weight Growth of 52.02 ± 1.60; it was better than using aeration. This study has developed a model of tambaqui aquaculture to provide growth value. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study, three dogs and three cats were selected from the database of the Chonnam National University Teaching Hospital from February 2017 to June 2019. The inclusion criteria for the selection of patients were as follows: (1) clinical data including age, sex, breed, clinical signs, histology, fine-needle aspiration, or fluid centesis were available and (2) intraluminal CEUS was performed; CEUS findings helped confirm the diagnosis. Each patient underwent physical examination, blood tests, radiography, and conventional ultrasonography. Intraluminal CEUS was performed using contrast agents, including SonoVue, agitated saline, saline, or a combination for GI hydrosonography in two patients and sono-cystourethrography in four patients. GI hydrosonography could assess the anatomic relationship between the mass and gastric lumen after administration of a mixture of 0.1 mL SonoVue and 30 mL/kg water in case 1 and could dilate the colonic lumen to detect the thickened wall using saline infusion in case 2. Upon sono-cystourethrography, communication between the urinary tract and prostatic cyst was clearly visualized in case 3, and narrowing of the urethral lumen secondary to prostatomegaly could be ruled out in case 4 with pyogranulomatous prostitis using agitated saline. The saline or agitated saline is appropriate for filling the lumen and improving the acoustic window for GI hydrosonography. Intraluminal CEUS examinations helped to assess the patency of the lumen, evaluate the extent of luminal dilation, rule out luminal narrowing, determine the presence of a mass within the lumen, and identify rupture sites. Administering intraluminal fluid can improve the acoustic window for the visualization of the lumen and wall layers in the cavitary organs. Microbubbles in ultrasound contrast agents can also be used for intracavitary applications to enhance visualization of the lesion in human patients. However, there was no literature extending the clinical application of intraluminal contrast-enhanced ultrasonography (CEUS) to patients with naturally occurring diseases in veterinary medicine. This case series aims to describe the detailed application and diagnostic value of intraluminal CEUS in six clinical cases with naturally occurring gastrointestinal (GI) and urinary tract diseases. [ABSTRACT FROM AUTHOR]

Abstract To investigate the effects of low-intensity pulsed ultrasound combined with microbubble (LIPUS-MB) mediated JNK/c-Jun pathway reversal on multidrug resistance in triple-negative breast cancer and the underlying mechanisms. An orthogonal experiment was designed to screen for the optimal parameters of LIPUS-MB in MDA-MB-231/DOX cells. The CCK-8 assay was used to determine the drug resistance of the cells and to measure their proliferation activity and resistance reversal efficiency at the optimal parameters. Hoechst 33,342 staining and Annexin V-FITC/PI staining were employed to detect cell morphological changes and apoptosis, respectively. The MDA-MB-231/DOX models of transplanted tumor were established in BALB/c. The impact of LIPUS-MB on allograft tumor growth was observed in vivo. Immunohistochemistry was employed to investigate the expression of P-gp, ABCG2, and Ki-67 in tumor tissues, while western blot was utilized to assess the protein expression of P-gp, ABCG2, JNK, p-JNK, c-Jun, p-c-Jun, Bcl-2 and Bax in both MDA-MB-231/DOX cells and allograft tumor tissues. The optimal LIPUS-MB parameters for MDA-MB-231/DOX cells are the microbubble concentration of 20%, ultrasound intensity of 1.0 W/cm2, and irradiation time of 60 s. The drug resistance index of MDA-MB-231/DOX cells is 19.17. Following the optimal parameter application, the IC50 value of the cells decreases by 5.71-fold, with a reversal efficiency of 87.03%, and a simultaneous decrease in cell proliferation activity. Compared with other groups, the DOX + LIPUS-MB group displayed the highest incidence of apoptotic nuclear morphology, and the greatest quantity of cellular apoptosis and the most pronounced decrease in the expression levels of P-gp, ABCG2, p-JNK, p-c-Jun, and Bcl-2 proteins within the cells. Conversely, the expression levels of Bax proteins reach the highest levels (all P

Іndustrial synthesis of gas hydrates is a promising area for storage, transportation and utilisation of natural gas. The aim of this work is to evaluate the factors that affect the efficiency of gas hydrate synthesis, in particular, the influence of gas microbubble generation. To achieve the goal, the following tasks were solved: the experimental unit was developed and assembled; the experimental research methodology was proposed; experimental data were obtained and their statistical analysis was performed; a mathematical model of hydrodynamic and heat and mass-exchange processes in the nozzle was developed; оn the basis of the mathematical model, a calculation program was created which allows analyzing the nozzle operation in different thermobaric conditions under different hydrodynamic regimes. The most important are the results of experiments, which allowed us to determine the factors that have the greatest influence on the intensification of propane hydrate synthesis: the presence of gas microbubbles, liquid temperature, gas temperature, gas pressure in the reactor and others. The influence of individual factors and the presence of gas mixture microbubbles on the intensity of mass transfer processes of hydrate formation in the reactor was determined. The influence of nozzle design features on the efficiency of hydrate formation was analyzed. The significance of the obtained results is to expand knowledge about the influence of various factors on the intensification of gas hydrate synthesis. The research results can be used for designing industrial plants for gas hydrate synthesis.

Purpose: This study aims to investigate the radiation enhancement effects of ultrasound-stimulated microbubbles (USMB) with X-rays and nanoparticles on pancreatic cancer cells in vitro. Methods: Sonazoid™ microbubbles were used for USMB treatment with a commercially available ultrasound unit. The characterization of the microbubbles before and after ultrasound exposure with different mechanical parameters was evaluated microscopically. Two pancreatic cancer cell lines, MIAPaCa-2 and PANC-1, were treated with different concentrations of microbubbles in combination with 150 kVp X-rays and hydrogen peroxide-modified titanium dioxide nanoparticles. Cell viability was evaluated using a water-soluble tetrazolium dye and a colony formation assay. In addition, intracellular reactive oxygen species (ROS) induced by the combined treatment were assessed. Results: The number of burst microbubbles increased with ultrasound’s higher mechanical index and the exposure time. A significant radiation enhancement effect with a significant increase in ROS levels was observed in MIAPaCa-2 cells treated with USMB and 6 Gy X-rays, whereas it was not significant in PANC-1 cells treated with the same. When a higher concentration of USMB was applied with X-rays, no radiation enhancement effects were observed in either cell line. Moreover, there was no radiation enhancement effect by USMB between cells treated with and without nanoparticles. Conclusions: The results indicate that USMB treatment can additively enhance the therapeutic efficacy of radiation therapy on pancreatic cancer cells, while the synergistic enhancement effects are likely to be cell type and microbubble concentration dependent. In addition, USMB did not improve the efficacy of nanoparticle-induced radiosensitization in the current setting.

Ultrasound in combination with microbubbles can enhance accumulation and improve the distribution of various therapeutic agents in tumor tissue, leading to improved efficacy. Understanding the impact of treatment on the tumor microenvironment, concurrently with how microenvironment attributes affect treatment outcome, will be important for selecting appropriate patient cohorts in future clinical trials. The main aim of this work was to investigate the influence of ultrasound and microbubbles on the functional vasculature of cancer tissue. Four different tumor models in mice (bone, pancreatic, breast and colon cancer) were characterized with respect to vascular parameters using contrast-enhanced ultrasound imaging. The effect of treatment with microbubbles and ultrasound was then investigated using immunohistochemistry and confocal microscopy, quantifying the total amount of vasculature and fraction of functional vessels. Two different microbubbles were used, the clinical contrast agent SonoVue and the large bubbles generated by Acoustic Cluster Therapy (ACT), tailored for therapeutic purposes. The colon cancer model displayed slower flow but a higher vascular volume than the other models. The pancreatic model showed the fastest flow but also the lowest vascular volume. Ultrasound and SonoVue transiently reduced the amount of functional vasculature in breast and colon tumors immediately after treatment. No reduction was observed for ACT, likely due to shorter ultrasound pulses and lower pressures applied. Variation between tumor models due to tissue characteristics emphasizes the importance of evaluating treatment suitability in the specific tissue of interest, as altered perfusion could have a large impact on drug delivery and therapeutic outcome. [ABSTRACT FROM AUTHOR]

To explore the efficacy and mechanisms of stimulating the nucleus accumbens (NAc) in heroin-addicted mice using focused ultrasound and microbubbles (MBs). The conditioned place preference (CPP) method was employed to establish a heroin-addicted mice model. Mice were randomized into control (C), heroin (H), heroin + ultrasound (H + U) and H + U + MBs. Ultrasound (2 MHz fundamental frequency, 1.34 MPa peak-negative pressure, 1 MHz pulse repetition frequency, 5% duty cycle, 15 min/d, over 2 d) was applied to stimulate the NAc in the latter 2 groups. Whereas H + U + MBs received an injection of sulfur hexafluoride MBs during the stimulation. Subsequently, CPP scores, open-field test (OFT), and elevated plus-maze test (EPMT) were conducted to assess behavioral changes in addiction memory, anxiety and exercise status. HE staining was performed to detect pathological structures. Neurotransmitters such as dopamine (DA), serotonin (5-HT) and glutamate (Glu) were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy (TEM) was used to observe ultrastructural changes of synapses in NAc. Immunohistochemistry (IHC) was utilized to detect Cleaved Caspase-3 in the NAc region. Western blotting (WB) was used to detect the protein expression of Cleaved Caspase-3, Bax and Bcl-2 in NAc. HE staining showed small patches of erythrocyte exudation were observed in the NAc and adjacent areas in H + U + MBs. The CPP scores of H + U + MBs were lower (p < 0.05) than H. After ultrasound treatment, all indices of the OFT and EPMT in H + U + MBs were significantly higher than H (p < 0.05). UPLC-MS/MS revealed that the levels of DA, 5-HT and Glu in H + U + MBs were lower than H (p < 0.01). TEM showed decrease the number of synapses (p < 0.05), and noticeable swelling of mitochondria, membrane damage, as well as damage to the cristae. Further detection by IHC and WB showed that the pro-apoptotic proteins Cleaved Caspase-3 and Bax increased and Bcl-2 decreased as anti-apoptotic proteins after ultrasound combined with MBs (p < 0.05). Focused ultrasound combined with MBs stimulate the NAc can weaken the addictive memory and improve anxiety of heroin-related mice. The mechanical effect of ultrasound combined with the cavitation effect may be a potential treatment for addiction. [ABSTRACT FROM AUTHOR]

The global scarcity of drinking water is an emerging problem associated with increasing pollution with many chemicals from industry and rapid microbial growth in aquatic systems. Despite the wide availability of conventional water and wastewater treatment methods, many limitations and challenges exist to overcome. Applying technology based on microbubbles (MBs) and nano-bubbles (NBs) offers ecological, fast, and cost-effective water treatment. All due to the high stability and long lifetime of the bubbles in the water, high gas transfer efficiency, free radical generation capacity, and large specific surface areas with interface potential of generated bubbles. MBs and NBs-based technology are attractive solutions in various application areas to improve existing water and wastewater treatment processes including industrial processes. In this paper, recent progress in NBs and MBs technology in water purification and wastewater treatment along with fundamentals, application, challenges, and future research were comperhensively discussed. [ABSTRACT FROM AUTHOR]

Microbubbles are widely used for biomedical applications, ranging from imagery to therapy. In these applications, microbubbles can be functionalized to allow targeted drug delivery or imaging of the human body. However, functionalization of the microbubbles is quite difficult, due to the unstable nature of the gas/liquid interface. In this paper, we describe a simple protocol for rapid functionalization of microbubbles and show how to use them inside a microfluidic chip to develop a novel type of biosensor. The microbubbles are functionalized with biochemical ligand directly at their generation inside the microfluidic chip using a DSPE-PEG-Biotin phospholipid. The microbubbles are then organized inside a chamber before injecting the fluid with the bioanalyte of interest through the static bubbles network. In this proof-of-concept demonstration, we use streptavidin as the bioanalyte of interest. Both functionalization and capture are assessed using fluorescent microscopy thanks to fluorescent labeled chemicals. The main advantages of the proposed technique compared to classical ligand based biosensor using solid surface is its ability to rapidly regenerate the functionalized surface, with the complete functionalization/capture/measurement cycle taking less than 10 min. [ABSTRACT FROM AUTHOR]