Efficient sonochemical catalytic degradation of tetracycline using TiO2 fractured nanoshells.

Overexposure to antibiotics originating in wastewater has profound environmental and health implications. Conventional treatment methods are not fully effective in removing certain antibiotics, such as the commonly used antibiotic, tetracycline, leading to its accumulation in water catchments. Alternative antibiotic removal strategies are garnering attention, including sonocatalytic oxidative processes. In this work, we investigated the degradation of tetracycline using a combination of TiO2 fractured nanoshells (TFNs) and an advanced sonochemical reactor design. The study encompassed an examination of multiple process parameters to understand their effects on the degradation of tetracycline. These included tetracycline adsorption on TFNs, reaction time, initial tetracycline concentration, solvent pH, acoustic pressure amplitude, number of acoustic cycles, catalyst dosage, TFNs' reusability, and the impact of adjuvants such as light and H2O2. Though TFNs adsorbed tetracycline, the addition of ultrasound was able to degrade tetracycline completely (with 100% degradation) within six minutes. Under the optimal operating conditions, the proposed sonocatalytic system consumed 80% less energy compared to the values reported in recently published sonocatalytic research. It also had the lowest CO2 footprint when compared to the other sono-/photo-based technologies. This study suggests that optimizing the reaction system and operating the reaction under low power and at a lower duty cycle are effective in achieving efficient cavitation for sonocatalytic reactions.

Enhancement of sonochemical production of hydroxyl radicals from pulsed cylindrically converging ultrasound waves.

Sonochemistry is the use of ultrasound to generate highly reactive radical species through the inertial collapse of a gas/vapour cavity and is a green alternative for hydrogen production, wastewater treatment, and chemical synthesis and modifications. Yet, current sonochemical reactors often are limited by their design, resulting in low efficacy and yields with slow reaction kinetics. Here, we constructed a novel sonochemical reactor design that creates cylindrically converging ultrasound waves to create an intense localised region of high acoustic pressure amplitudes (15 MPaPKPK) capable of spontaneously nucleating cavitation. Using a novel dosimetry technique, we determined the effect of acoustic parameters on the yield of hydroxyl radicals (HO), HO production rate, and ultimately the sonochemical efficiency (SE) of our reactor. Our reactor design had a significantly higher HO production rate and SE compared to other conventional reactors and across literature.

A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption.

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.

Development of a morphologically realistic mouse phantom for pre-clinical photoacoustic imaging.

BACKGROUND: Characterizations based on anatomically realistic phantoms are highly effective to perform accurate technical validation of imaging systems. Specifically for photoacoustic imaging (PAI), although a variety of phantom models with simplified geometries are reported, an unmet need still exists to establish morphologically realistic heterogeneous pre-clinical phantoms. So the development of a mouse-mimicking phantom can reduce the use of animals for the validation and standardization studies of pre-clinical PAI systems and thus eventually translate the PAI technology to clinical research. PURPOSE: Here we designed, developed, and fabricated a stable phantom that mimics the detailed morphology of a mouse, to be used as a realistic tool for PAI. METHODS: The mouse phantom, has been designed by using a combination of image modeling and 3D-printing techniques. As a tissue-mimicking material, we have used copolymer-in-oil-based material that was recently proposed by the International Photoacoustic Standardization Consortium (IPASC). In particular, the anatomically realistic phantom has been modeled by using the real atlas of a mouse as a reference. The mouse phantom includes a 3D-printed skeleton and the main abdominal organs such as the liver, spleen, and kidneys obtained by using doped copolymer-in-oil material with 3D-printed molds. In addition, the acoustic and optical properties of the tissue-mimicking material and the long-term stability have been broadly characterized. RESULTS: Furthermore, our studies showed that the phantom is durable and stable for more than 200 days, under normal storage and repeated use. Fabrication protocol is easy to reproduce. As a result, the proposed morphologically realistic mouse phantom offers durability, material compatibility, and an unprecedented realistic resemblance to the actual rodents' anatomy in PAI. CONCLUSION: This durable morphologically realistic mouse phantom would minimize the animal experiments in compliance with the 3R principle of Replacement, Reduction, and Refinement. To our knowledge, this is the first time an anatomically realistic heterogeneous mouse phantom has been proposed for PAI in pre-clinical animal imaging and tested its durability over 200 days.

Compressibility of Lithium Hexafluorophosphate Solutions in Two Carbonate Solvents.

Speed-of-sound measurements are performed to establish how the isentropic bulk modulus K s of the electrolyte system comprising lithium hexafluorophospate (LiPF6) in blends of propylene carbonate (PC) and ethyl methyl carbonate (EMC) varies with salt molality m, mass fraction of PC in the PC:EMC cosolvent f, and temperature T. Bulk moduli are calculated by combining acoustic time-of-flight data between parallel walls of a liquid-filled cuvette with densitometric data for a sequence of binary and ternary salt solutions. Correlations are presented to yield K s (m, f, T) accurately for nine compositions spanning the range m = 0-2 mol kg-1 and f = 0-1, at temperatures T ranging from 283.15 to 313.15 K. Electrolyte compressibility varies most with solvent ratio, followed by salt content and temperature, with K s ranging from 1 to 3 GPa. Composition-dependent acoustical properties elucidate the nature of speciation and solvation states in bulk electrolytes, and could be useful to identify the features of individual phases within solution-permeated porous electrodes.

Fluorescence-based chemical tools for monitoring ultrasound-induced hydroxyl radical production in aqueous solution and in cells.

We report the synthesis of hydroxyl-radical (˙OH) responsive fluorescent probes that utilise the 3,5-dihydroxybenzyl (DHB) functionality. 4-Methylumbeliferone-DHB (Umb-DHB) and resorufin-DHB (Res-DHB) in the presence of ˙OH radicals resulted in significant increases in their respective fluorescent emission intensities at 460 nm and 585 nm. The incubation of Res-DHB in HeLa cells followed by therapeutic ultrasound (1 MHz) resulted in a significant increase in fluorescence emission intensity thus permitting the ability to monitor ultrasound-induced ˙OH production in live cells.

Aortic Stenosis: Haemodynamic Benchmark and Metric Reliability Study.

Aortic stenosis is a condition which is fatal if left untreated. Novel quantitative imaging techniques which better characterise transvalvular pressure drops are being developed but require refinement and validation. A customisable and cost-effective workbench valve phantom circuit capable of replicating valve mechanics and pathology was created. The reproducibility and relationship of differing haemodynamic metrics were assessed from ground truth pressure data alongside imaging compatibility. The phantom met the requirements to capture ground truth pressure data alongside ultrasound and magnetic resonance image compatibility. The reproducibility was successfully tested. The robustness of three different pressure drop metrics was assessed: whilst the peak and net pressure drops provide a robust assessment of the stenotic burden in our phantom, the peak-to-peak pressure drop is a metric that is confounded by non-valvular factors such as wave reflection. The peak-to-peak pressure drop is a metric that should be reconsidered in clinical practice. The left panel shows manufacture of low cost, functional valves. The central section demonstrates circuit layout, representative MRI and US images alongside gross valve morphologies. The right panel shows the different pressure drop metrics that were assessed for reproducibility.

Genetic engineering biofilms in situ using ultrasound-mediated DNA delivery.

The ability to directly modify native and established biofilms has enormous potential in understanding microbial ecology and application of biofilm in 'real-world' systems. However, efficient genetic transformation of established biofilms at any scale remains challenging. In this study, we applied an ultrasound-mediated DNA delivery (UDD) technique to introduce plasmid to established non-competent biofilms in situ. Two different plasmids containing genes coding for superfolder green fluorescent protein (sfGFP) and the flavin synthesis pathway were introduced into established bacterial biofilms in microfluidic flow (transformation efficiency of 3.9 ± 0.3 × 10-7 cells in biofilm) and microbial fuel cells (MFCs), respectively, both employing UDD. Gene expression and functional effects of genetically modified bacterial biofilms were observed, where some cells in UDD-treated Pseudomonas putida UWC1 biofilms expressed sfGFP in flow cells and UDD-treated Shewanella oneidensis MR-1 biofilms generated significantly (P < 0.05) greater (61%) bioelectricity production (21.9 ± 1.2 µA cm-2 ) in MFC than a wild-type control group (~ 13.6 ± 1.6 µA cm-2 ). The effects of UDD were amplified in subsequent growth under selection pressure due to antibiotic resistance and metabolism enhancement. UDD-induced gene transfer on biofilms grown in both microbial flow cells and MFC systems was successfully demonstrated, with working volumes of 0.16 cm3 and 300 cm3 , respectively, demonstrating a significant scale-up in operating volume. This is the first study to report on a potentially scalable direct genetic engineering method for established non-competent biofilms, which can be exploited in enhancing their capability towards environmental, industrial and medical applications.

Quantification of mycophenolic acid in human plasma by liquid chromatography with time-of-flight mass spectrometry for therapeutic drug monitoring.

This study presents, for the first time, the development and validation of a liquid chromatography and time-of-flight mass-spectrometry (LC-TOF-MS) based assay to quantify mycophenolic acid (MPA) in patient samples as part of a routine therapeutic drug monitoring service. MPA was extracted from 50 µl human plasma by protein precipitation, using sulindac as internal standard (IS). Separation was obtained on a Luna™ Omega polar C18 column kept at 40°C. The mobile phase consisted of a mixture of acetonitrile-deionized water (50:50, v/v) with 0.1% formic acid at a flow rate of 350 µl/min. Analyte and IS were monitored on a TOF-MS using a Jet-Stream™ (electrospray) interface running in positive mode. Assay performance was evaluated by analysing patient plasma (N = 69) and external quality assessment (N = 6) samples. The retention times were 2.66 and 2.18 min for MPA and IS, respectively. The lower limit of quantification of MPA was 0.1 µg/ml. The within- and between-assay reproducibility results ranged from 1.81 to 10.72%. Patient and external quality assessment sample results were comparable with those obtained previously by an in-house validated LC-MS/MS method. This method showed satisfactory analytical performance for the determination of MPA in plasma over the calibration range of 0.1-15.0 µg/ml.

The influence of droplet concentration on phase change and inertial cavitation thresholds associated with acoustic droplet vaporization.

Acoustic droplet vaporization (ADV) is an important process that enables the theragnostic application of acoustically activated droplets, where the nucleation of inertial cavitation (IC) activity must be precisely controlled. This Letter describes threshold pressure measurements for ADV and acoustic emissions consistent with IC activity of lipid-shelled non-superheated perfluoropentane nanodroplets over a range of physiologically relevant concentrations at 1.1-MHz. Under the frequency investigated, results show that the thresholds were relatively independent of concentration for intermediate concentrations (105, 106, and 107 droplets/ml), thus indicating an optimal range of droplet concentrations for conducting threshold studies. For the highest concentration, the difference between the threshold for IC and the threshold for ADV was greatly reduced, suggesting that it might prove difficult to induce ADV without concomitant IC in applications that employ higher concentrations.

Optimal Control of SonoVue Microbubbles to Estimate Hydrostatic Pressure.

The measurement of cardiac and aortic pressures enables diagnostic insight into cardiac contractility and stiffness. However, these pressures are currently assessed invasively using pressure catheters. It may be possible to estimate these pressures less invasively by applying microbubble ultrasound contrast agents as pressure sensors. The aim of this study was to investigate the subharmonic response of the microbubble ultrasound contrast agent SonoVue (Bracco Spa, Milan, Italy) at physiological pressures using a static pressure phantom. A commercially available cell culture cassette with Luer connections was used as a static pressure chamber. SonoVue was added to the phantom, and radio frequency data were recorded on the ULtrasound Advanced Open Platform (ULA-OP). The mean subharmonic amplitude over a 40% bandwidth was extracted at 0-200-mmHg hydrostatic pressures, across 1.7-7.0-MHz transmit frequencies and 3.5%-100% maximum scanner acoustic output. The Rayleigh-Plesset equation for single-bubble oscillations and additional hysteresis experiments were used to provide insight into the mechanisms underlying the subharmonic pressure response of SonoVue. The subharmonic amplitude of SonoVue increased with hydrostatic pressure up to 50 mmHg across all transmit frequencies and decreased thereafter. A decreasing microbubble surface tension may drive the initial increase in the subharmonic amplitude of SonoVue with hydrostatic pressure, while shell buckling and microbubble destruction may contribute to the subsequent decrease above 125-mmHg pressure. In conclusion, a practical operating regime that may be applied to estimate cardiac and aortic blood pressures from the subharmonic signal of SonoVue has been identified.

Universal scaling across biochemical networks on Earth.

The application of network science to biology has advanced our understanding of the metabolism of individual organisms and the organization of ecosystems but has scarcely been applied to life at a planetary scale. To characterize planetary-scale biochemistry, we constructed biochemical networks using a global database of 28,146 annotated genomes and metagenomes and 8658 cataloged biochemical reactions. We uncover scaling laws governing biochemical diversity and network structure shared across levels of organization from individuals to ecosystems, to the biosphere as a whole. Comparing real biochemical reaction networks to random reaction networks reveals that the observed biological scaling is not a product of chemistry alone but instead emerges due to the particular structure of selected reactions commonly participating in living processes. We show that the topology of biochemical networks for the three domains of life is quantitatively distinguishable, with >80% accuracy in predicting evolutionary domain based on biochemical network size and average topology. Together, our results point to a deeper level of organization in biochemical networks than what has been understood so far.

Photo- and Sono-Dynamic Therapy: A Review of Mechanisms and Considerations for Pharmacological Agents Used in Therapy Incorporating Light and Sound.

As irreplaceable energy sources of minimally invasive treatment, light and sound have, separately, laid solid foundations in their clinic applications. Constrained by the relatively shallow penetration depth of light, photodynamic therapy (PDT) typically involves involves superficial targets such as shallow seated skin conditions, head and neck cancers, eye disorders, early-stage cancer of esophagus, etc. For ultrasound-driven sonodynamic therapy (SDT), however, to various organs is facilitated by the superior... transmission and focusing ability of ultrasound in biological tissues, enabling multiple therapeutic applications including treating glioma, breast cancer, hematologic tumor and opening blood-brain-barrier (BBB). Considering the emergence of theranostics and precision therapy, these two classic energy sources and corresponding sensitizers are worth reevaluating. In this review, three typical therapies using light and sound as a trigger, PDT, SDT, and combined PDT and SDT are introduced. The therapeutic dynamics and current designs of pharmacological sensitizers involved in these therapies are presented. By introducing both the history of the field and the most up-to-date design strategies, this review provides a systemic summary on the development of PDT and SDT and fosters inspiration for researchers working on 'multi-modal' therapies involving light and sound.

HIFU-induced changes in optical scattering and absorption of tissue over nine orders of thermal dose.

The optical properties of tissue change during thermal ablation. Multi-modal methods such as acousto-optic (AO) and photo-acoustic (PA) imaging may provide a real-time, direct measure of lesion formation. Baseline changes in optical properties have been previously measured over limited ranges of thermal dose for tissues exposed to a temperature-controlled water bath, however, there is scant data for optical properties of lesions created by HIFU. In this work, the optical scattering and absorption coefficients from 400-1300 nm of excised chicken breast exposed to HIFU were measured using an integrating sphere spectrophotometric technique. HIFU-induced spatiotemporal temperature elevations were measured using an infrared camera and used to calculate the thermal dose delivered to a localized region of tissue. Results obtained over a range of thermal dose spanning 9 orders of magnitude show that the reduced scattering coefficient increases for HIFU exposures exceeding a threshold thermal dose of CEM43 = 600 ± 81 cumulative equivalent minutes. HIFU-induced thermal damage results in changes in scattering over all optical wavelengths, with a 2.5-fold increase for thermal lesions exceeding 70 °C. The tissue absorption coefficient was also found to increase for thermally lesioned tissue, however, the magnitude was strongly dependent on the optical wavelength and there was substantial sample-to-sample variability, such that the existence of a threshold thermal dose could not be determined. Therapeutic windows, where the optical penetration depth is expected to be greatest, were identified in the near infrared regime centered near 900 nm and 1100 nm. These data motivate further research to improve the real-time AO and PA sensing of lesion formation during HIFU therapy as an alternative to thermometry.

Effect of Temperature on the Size Distribution, Shell Properties, and Stability of Definity®.

Physical characterization of an ultrasound contrast agent (UCA) aids in its safe and effective use in diagnostic and therapeutic applications. The goal of this study was to investigate the impact of temperature on the size distribution, shell properties, and stability of Definity®, a U.S. Food and Drug Administration-approved UCA used for left ventricular opacification. A Coulter counter was modified to enable particle size measurements at physiologic temperatures. The broadband acoustic attenuation spectrum and size distribution of Definity® were measured at room temperature (25 °C) and physiologic temperature (37 °C) and were used to estimate the viscoelastic shell properties of the agent at both temperatures. Attenuation and size distribution was measured over time to assess the effect of temperature on the temporal stability of Definity®. The attenuation coefficient of Definity® at 37 °C was as much as 5 dB higher than the attenuation coefficient measured at 25 °C. However, the size distributions of Definity® at 25 °C and 37 °C were similar. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10-6 ± 0.07 × 10-6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10-6 ± 0.04 × 10-6 kg/s at 37 °C, respectively. Size-dependent differences in dissolution rates were observed within the UCA population at both 25 °C and 37 °C. Additionally, cooling the diluted UCA suspension from 37 °C to 25 °C accelerated the dissolution rate. These results indicate that although temperature affects the shell properties of Definity® and can influence the stability of Definity®, the size distribution of this agent is not affected by a temperature increase from 25 °C to 37 °C.

Using cluster edge counting to aggregate iterations of centroid-linkage clustering results and avoid large distance matrices.

Sequence clustering is a fundamental tool of molecular biology that is being challenged by increasing dataset sizes from high-throughput sequencing. The agglomerative algorithms that have been relied upon for their accuracy require the construction of computationally costly distance matrices which can overwhelm basic research personal computers. Alternative algorithms exist, such as centroid-linkage, to circumvent large memory requirements but their results are often input-order dependent. We present a method for bootstrapping the results of many centroid-linkage clustering iterations into an aggregate set of clusters, increasing cluster accuracy without a distance matrix. This method ranks cluster edges by conservation across iterations and reconstructs aggregate clusters from the resulting ranked edge list, pruning out low-frequency cluster edges that may have been a result of a specific sequence input order. Aggregating centroid-linkage clustering iterations can help researchers using basic research personal computers acquire more reliable clustering results without increasing memory resources.

Loss of gas from echogenic liposomes exposed to pulsed ultrasound.

The destruction of echogenic liposomes (ELIP) in response to pulsed ultrasound excitations has been studied acoustically previously. However, the mechanism underlying the loss of echogenicity due to cavitation nucleated by ELIP has not been fully clarified. In this study, an ultra-high speed imaging approach was employed to observe the destruction phenomena of single ELIP exposed to ultrasound bursts at a center frequency of 6 MHz. We observed a rapid size reduction during the ultrasound excitation in 139 out of 397 (35%) ultra- high-speed recordings. The shell dilation rate, which is defined as the microbubble wall velocity divided by the instantaneous radius, [Formula: see text] /R, was extracted from the radius versus time response of each ELIP, and was found to be correlated with the deflation. Fragmentation and surface mode vibrations were also observed and are shown to depend on the applied acoustic pressure and initial radius. Results from this study can be utilized to optimize the theranostic application of ELIP, e.g. by tuning the size distribution or the excitation frequency.

Using Dendritic Heat Maps to Simultaneously Display Genotype Divergence with Phenotype Divergence.

The advancement of techniques to visualize and analyze large-scale sequencing datasets is an area of active research and is rooted in traditional techniques such as heat maps and dendrograms. We introduce dendritic heat maps that display heat map results over aligned DNA sequence clusters for a range of clustering cutoffs. Dendritic heat maps aid in visualizing the effects of group differences on clustering hierarchy and relative abundance of sampled sequences. Here, we artificially generate two separate datasets with simplified mutation and population growth procedures with GC content group separation to use as example phenotypes. In this work, we use the term phenotype to represent any feature by which groups can be separated. These sequences were clustered in a fractional identity range of 0.75 to 1.0 using agglomerative minimum-, maximum-, and average-linkage algorithms, as well as a divisive centroid-based algorithm. We demonstrate that dendritic heat maps give freedom to scrutinize specific clustering levels across a range of cutoffs, track changes in phenotype inequity across multiple levels of sequence clustering specificity, and easily visualize how deeply rooted changes in phenotype inequity are in a dataset. As genotypes diverge in sample populations, clusters are shown to break apart into smaller clusters at higher identity cutoff levels, similar to a dendrogram. Phenotype divergence, which is shown as a heat map of relative abundance bin response, may or may not follow genotype divergences. This joined view highlights the relationship between genotype and phenotype divergence for treatment groups. We discuss the minimum-, maximum-, average-, and centroid-linkage algorithm approaches to building dendritic heat maps and make a case for the divisive "top-down" centroid-based clustering methodology as being the best option visualize the effects of changing factors on clustering hierarchy and relative abundance.

Effect of Frequency-Dependent Attenuation on Predicted Histotripsy Waveforms in Tissue-Mimicking Phantoms.

Tissue-mimicking phantoms are employed for the assessment of shocked histotripsy pulses in vitro. These broadband shock waves are critical for tissue ablation and are influenced by the frequency-dependent attenuation of the medium. The density, sound speed and attenuation spectra (2-25 MHz) were measured for phantoms that mimic key histotripsy targets. The influence of non-linear propagation relative to the attenuation was described in terms of Gol'dberg number. An expression was derived to estimate the bandwidth of shocked histotripsy pulses for power law-dependent attenuation. The expression is independent of the fundamental frequency of the histotripsy pulse for linear frequency-dependent attenuation.