Search Results (40)

Background/Objectives: Anti-vascular therapy presents a potential strategy for activating anti-tumor immunity. Disrupted vascular debris provides effective antigens that activate dendritic cells, leading to subsequent immune responses. However, the resulting tumor hypoxia following vascular disruption may contribute to immune suppression, thereby hindering effective immune activation. Ultrasound-stimulated microbubble cavitation can locally disrupt tumor vessels through mechanical effects to achieve physical anti-vascular therapy. Therefore, this study designed oxygen-loaded nanobubbles (ONBs) to combine anti-vascular effects with local oxygen release under ultrasound stimulation. The feasibility of enhancing anti-tumor immune activation by alleviating tumor hypoxia was evaluated. Methods: A murine pancreatic subcutaneous solid tumor model was used to evaluate the efficacy of anti-vascular therapy-associated immunotherapy. Results: After ONB treatment, tumor perfusion was reduced to 52 ± 5%, which resulted in a subsequent 57 ± 11% necrosis and a 29 ± 4% reduction in hypoxia, demonstrating the anti-vascular effect and reoxygenation, respectively. However, subsequent immune responses exhibited no significant activation in intratumoral cytokine expression or splenic immune cell composition. Primary tumors exhibited a 15.7 ± 5.0% increase in necrosis following ONB treatment, but distant tumor growth was not significantly inhibited. Conclusions: These results highlighted a crucial issue regarding the complex correlations between vessel disruption, antigen production, oxygen delivery, hypoxia, and immunity when combining anti-vascular therapy with immunotherapy. Full article

The thermal development in heavy oil reservoirs with edge and bottom water is poor, while gas huff-n-puff development shows a high recovery and strong adaptability. The formation of foamy oil during gas huff-n-puff is one of the reasons for the high recovery. In order to determine the factors affecting the foamy oil flow during gas huff-n-puff, experiments using a one-dimensional sandpack were conducted. The influences of drawdown pressure and cycle number were analyzed. The formation conditions of foamy oil were preliminarily clarified, and the enhanced oil recovery (EOR) mechanism of foamy oil was revealed. The experimental results show that the drawdown pressure and cycle number are two important factors affecting the formation of foamy oil. Foamy oil flow is prone to forming under a moderate drawdown pressure of 0.5–0.75 MPa, and being too small or too large is unfavorable. Foamy oil is more likely to form in the first two cycles, and it becomes increasingly challenging with the increase in the cycle number. These two factors reflect two necessary conditions for the formation of foamy oil during gas huff-n-puff: one is allowing the oil and gas to flow adequately to provide the shear and mixing for the generation of micro-bubbles, and the other is that the oil content should not be too small to avoid the inability to disperse and stabilize bubbles. The formation of foamy oil, on the one hand, increases the volume of the oil phase, and on the other hand, it reduces the mobility of the gas phase and slows down the pressure decline rate in the core, thereby enhancing the driving force for oil displacement. So, under the influence of the foamy oil, the gas production volume in a cycle declined by about 26%, and the average oil recovery increased by 4.5–6.9%. Full article

Microbubbles, acting as cavitation nuclei, undergo cycles of expansion, contraction, and collapse. This collapse generates shockwaves, alters local shear forces, and increases local temperature. Cavitation causes severe changes in pressure and temperature, resulting in surface erosion. Shockwaves strip material from surfaces, forming pits and cracks. Prolonged cavitation reduces the mechanical strength and fatigue life of materials, potentially leading to failure. Controlling bubble size and generating monodispersed bubbles is crucial for accurately modeling cavitation phenomena. In this work, we generate monodispersed microbubbles with controllable size using a novel and low-cost microfluidic method. We created an innovative T-junction structure that controls the two-phase flow for tiny, monodispersed bubble generation. Monodisperse microbubbles with diameters below one-fifth of the channel width (W = 100 µm) are produced due to the controlled pressure gradient. This microstructure, fabricated by a CNC milling technique, produces 20 μm bubbles without requiring high-resolution equipment and cleanroom environments. Bubble size is controlled with gas and liquid pressure ratio and microgeometry. This microbubble generation method provides a controllable and reproducible way for cavitation research. Full article

In practical applications, polyurethane (PU) foam must be rigid to meet the demands of various industries and provide comfort and protection in everyday life. PU foam components are extensively used in structural foam, thermal insulation, decorative panels, packaging, imitation wood, and floral foam, as well as in models and prototypes. Conventional technology for producing PU foam parts often leads to defects such as deformation, short shots, entrapped air, warpage, flash, micro-bubbles, weld lines, and voids. Therefore, the development of rigid PU foam parts has become a crucial research focus in the industry. This study proposes an innovative manufacturing process for producing rigid PU foam parts using silicone rubber molds (SRMs). The deformation of the silicone rubber mold can be predicted based on its wall thickness, following a trend equation with a correlation coefficient of 0.9951. The volume of the PU foam part can also be predicted by the weight of the PU foaming agent, as indicated by a trend equation with a correlation coefficient of 0.9824. The optimal weight ratio of the foaming agent to water, yielding the highest surface hardness, was found to be 5:1. The surface hardness of the PU foam part can also be predicted based on the weight of the water used, according to a proposed prediction equation with a correlation coefficient of 0.7517. The average surface hardness of the fabricated PU foam part has a Shore O hardness value of approximately 75. Foam parts made with 1.5 g of water added to 15 g of a foaming agent have the fewest internal pores, resulting in the densest interior. PU foam parts exhibit excellent mechanical properties when 3 g of water is added to the PU foaming agent, as evidenced by their surface hardness and compressive strength. Using rigid PU foam parts as a backing material in the proposed method can reduce rapid tool production costs by about 62%. Finally, an innovative manufacturing process for creating large SRMs using rigid PU foam parts as backing material is demonstrated. Full article

This work reports a simple bubble generator for the high-speed generation of microbubbles with constant cumulative production. To achieve this, a gas–liquid co-flowing microfluidic device with a tiny capillary orifice as small as 5 μm is fabricated to produce monodisperse microbubbles. The diameter of the microbubbles can be adjusted precisely by tuning the input gas pressure and flow rate of the continuous liquid phase. The co-flowing structure ensures the uniformity of the generated microbubbles, and the surfactant in the liquid phase prevents coalescence of the collected microbubbles. The diameter coefficient of variation (CV) of the generated microbubbles can reach a minimum of 1.3%. Additionally, the relationship between microbubble diameter and the gas channel orifice is studied using the low Capillary number (Ca) and Weber number (We) of the liquid phase. Moreover, by maintaining a consistent gas input pressure, the CV of the cumulative microbubble volume can reach 3.6% regardless of the flow rate of the liquid phase. This method not only facilitates the generation of microbubbles with morphologic stability under variable flow conditions, but also ensures that the cumulative microbubble production over a certain period of time remains constant, which is important for the volume-dominated application of chromatographic analysis and the component analysis of natural gas. Full article

Therapeutic microbubbles (thMBs) contain drug-filled liposomes linked to microbubbles and targeted to vascular proteins. Upon the application of a destructive ultrasound trigger, drug uptake to tumour is improved. However, the structure of thMBs currently uses powerful non-covalent bonding of biotin with avidin-based proteins to link both the liposome to the microbubble (MB) and to bind the targeting antibody to the liposome–MB complex. This linkage is not currently FDA-approved, and therefore, an alternative, maleimide–thiol linkage, that is currently used in antibody–drug conjugates was examined. In a systematic manner, vascular endothelial growth factor receptor 2 (VEGFR2)-targeted MBs and thMBs using both types of linkages were examined for their ability to specifically bind to VEGFR2 in vitro and for their ultrasound imaging properties in vivo. Both showed equivalence in the production of the thMB structure, in vitro specificity of binding and safety profiles. In vivo imaging showed subtle differences for thMBs where biotin thMBs had a faster wash-in rate than thiol thMBs, but thiol thMBs were longer-lived. The drug delivery to tumours was also equivalent, but interestingly, thiol thMBs altered the biodistribution of delivery away from the lungs and towards the liver compared to biotin thMBs, which is an improvement in biosafety. Full article

There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and green approach to synthesizing reduced graphene oxide with ellagic acid (rGO-EA). To investigate the application of a graphene derivative in ultrasound contrast agents, rGO-EA was dispersed in saline solution and mixed with SonoVue (SV) to fabricate SV@rGO-EA microbubbles. To determine the properties of the product, analyses were performed, including ultraviolet–visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectrum (XPS), X-ray diffraction analysis (XRD) and zeta potential analysis. Additionally, cell viability measurements and a hemolysis assay were conducted for a biosafety evaluation. SV@rGO-EA microbubbles were scanned at various mechanical index values to obtain the B-mode and contrast-enhanced ultrasound (CEUS) mode images in vitro. SV@rGO-EA microbubbles were administered to SD rats, and their livers and kidneys were imaged in CEUS and B-mode. The absorption of rGO-EA resulted in an enhanced echo intensity and mechanical index tolerance of SV@rGO-EA, surpassing the performance of SV microbubbles both in vitro and in vivo. This work exhibited the application potential of graphene derivatives in the field of ultrasound precision medicine. Full article

Conventional methods for producing porous metals involve the use of chemicals such as thickeners and foaming agents under high temperatures and pressures. However, these methods are costly and pose a risk of dust explosion. Thus, the objective of this research is to achieve the cost-effective and safe production of porous metals by introducing microbubbles generated by ultrasonic oscillation into the molten metal. One end of an ultrasonic horn was inserted into three different molten metals—white metal, Pb-free solder, and zinc—and microbubbles were generated at the horn end by the strong ultrasonic oscillation in the molten metals. The microbubbles that contained molten metal changed phase to porous metal through solidification, and the diameter, porosity, and stress–strain curve of the generated porous metals were measured. The results indicate that the porosity of white metal, Pb-free solder, and zinc foams reached 54%, 76%, and 48%, respectively, and these porous metals had many micropores less than 1 mm in diameter. It was also observed that the higher the melting point, the larger the pore diameter and the lower the porosity. Furthermore, in the case of white metal, a plateau region of large deformation at constant stress was observed in the stress–strain curve. Full article

Pentacyclic triterpenoids (TTs) represent a unique family of phytochemicals with interesting properties and pharmacological effects, with some representatives, such as betulinic acid (BA) and betulin (B), being mainly investigated as potential anticancer molecules. Considering the recent scientific and preclinical investigations, a review of their anticancer mechanisms, structure-related activity, and efficiency improved by their insertion in nanolipid vehicles for targeted delivery is presented. A systematic literature study about their effects on tumor cells in vitro and in vivo, as free molecules or encapsulated in liposomes or nanolipids, is discussed. A special approach is given to liposome-TTs and nanolipid-TTs complexes to be linked to microbubbles, known as contrast agents in ultrasonography. The production of such supramolecular conjugates to deliver the drugs to target cells via sonoporation represents a new scientific and applicative direction to improve TT efficiency, considering that they have limited availability as lipophilic molecules. Relevant and recent examples of in vitro and in vivo studies, as well as the challenges for the next steps towards the application of these complex delivery systems to tumor cells, are discussed, as are the challenges for the next steps towards the application of targeted delivery to tumor cells, opening new directions for innovative nanotechnological solutions. Full article

The froth flotation technique can be considered one of the most efficient methods for the separation of minerals. Prior to utilizing any physicochemical separation method, the size of the mined ore must be decreased to facilitate the release of the valuable materials. This practice, along with the increased exploitation of ores that carry fine mineral particles caused the production of fine and ultrafine particles which are difficult to recover with classical enrichment methods, due to their different characteristics compared to coarser particles. It is established that fine and ultrafine particles are difficult to float, leading to losses of valuable minerals, mainly due to their low collision efficiency with bubbles. Moreover, fine particles require higher reagent consumption due to the fact that have a higher specific area, and finally, their flotation is limited by low kinetic energy. Flotation of fines can be enhanced by either decreasing bubble diameter or increasing their apparent size, or moreover, by enhancing the collector’s adsorption (their hydrophobic behavior) using alternative reagents (non-ionic co-collectors). In the present research, flotation experiments on a hybrid electrolytic flotation column that can produce microbubbles (−50 μm), were carried out for recovering fine magnesite (−25 μm) particles. In addition, the synergistic effect of anionic/non-ionic collectors were studied for the enhancement of fines recovery. Experimental flotation results so far designate the enhancement of fine magnesite particle recovery by approximately 8% with the addition of microbubbles. Finally, the synergistic effect of anionic/non-anionic collectors led to the improvement of flotation recovery by almost 12%. Full article

The presence of multi-drug resistant biofilms in chronic, persistent infections is a major barrier to successful clinical outcomes of therapy. The production of an extracellular matrix is a characteristic of the biofilm phenotype, intrinsically linked to antimicrobial tolerance. The heterogeneity of the extracellular matrix makes it highly dynamic, with substantial differences in composition between biofilms, even in the same species. This variability poses a major challenge in targeting drug delivery systems to biofilms, as there are few elements both suitably conserved and widely expressed across multiple species. However, the presence of extracellular DNA within the extracellular matrix is ubiquitous across species, which alongside bacterial cell components, gives the biofilm its net negative charge. This research aims to develop a means of targeting biofilms to enhance drug delivery by developing a cationic gas-filled microbubble that non-selectively targets the negatively charged biofilm. Cationic and uncharged microbubbles loaded with different gases were formulated and tested to determine their stability, ability to bind to negatively charged artificial substrates, binding strength, and, subsequently, their ability to adhere to biofilms. It was shown that compared to their uncharged counterparts, cationic microbubbles facilitated a significant increase in the number of microbubbles that could both bind and sustain their interaction with biofilms. This work is the first to demonstrate the utility of charged microbubbles for the non-selective targeting of bacterial biofilms, which could be used to significantly enhance stimuli-mediated drug delivery to the bacterial biofilm. Full article

Membrane filtration is a key technology in dairy processing for the separation of dairy liquids to clarify, concentrate, and fractionate a variety of dairy products. Ultrafiltration (UF) is widely applied for whey separation, protein concentration and standardization, and lactose-free milk production, though its performance can be hindered by membrane fouling. As an automated cleaning process commonly used in the food and beverage industries, cleaning in place (CIP) uses large amounts of water, chemicals, and energy, resulting in significant environmental impacts. This study introduced micron-scale air-filled bubbles (microbubbles; MBs) with mean diameters smaller than 5 μm into cleaning liquids to clean a pilot-scale UF system. During the UF of model milk for concentration, cake formation was identified as the dominant membrane fouling mechanism. The MB-assisted CIP process was conducted at two bubble number densities (2021 and 10,569 bubbles per mL of cleaning liquid) and two flow rates (130 and 190 L/min). For all the cleaning conditions tested, MB addition largely increased the membrane flux recovery by 31–72%; however, the effects of bubble density and flow rate were insignificant. Alkaline wash was found to be the main step in removing proteinaceous foulant from the UF membrane, though MBs did not show a significant effect on the removal due to the operational uncertainty of the pilot-scale system. The environmental benefits of MB incorporation were quantified by a comparative life cycle assessment and the results indicated that MB-assisted CIP had up to 37% lower environmental impact than control CIP. This is the first study incorporating MBs into a full CIP cycle at the pilot scale and proving their effectiveness in enhancing membrane cleaning. This novel CIP process can help reduce water and energy use in dairy processing and improve the environmental sustainability of the dairy industry. Full article

Galectin-3 (Gal-3) participates in myocardial fibrosis (MF) in a variety of ways. Inhibiting the expression of Gal-3 can effectively interfere with MF. This study aimed to explore the value of Gal-3 short hairpin RNA (shRNA) transfection mediated by ultrasound-targeted microbubble destruction (UTMD) in anti-myocardial fibrosis and its mechanism. A rat model of myocardial infarction (MI) was established and randomly divided into control and Gal-3 shRNA/cationic microbubbles + ultrasound (Gal-3 shRNA/CMBs + US) groups. Echocardiography measured the left ventricular ejection fraction (LVEF) weekly, and the heart was harvested to analyze fibrosis, Gal-3, and collagen expression. LVEF in the Gal-3 shRNA/CMB + US group was improved compared with the control group. On day 21, the myocardial Gal-3 expression decreased in the Gal-3 shRNA/CMBs + US group. Furthermore, the proportion of the myocardial fibrosis area in the Gal-3 shRNA/CMBs + US group was 6.9 ± 0.41% lower than in the control group. After inhibition of Gal-3, there was a downregulation in collagen production (collagen I and III), and the ratio of Col I/Col III decreased. In conclusion, UTMD-mediated Gal-3 shRNA transfection can effectively silence the expression of Gal-3 in myocardial tissue, reduce myocardial fibrosis, and protect the cardiac ejection function. Full article

A recent development in the production of lightweight concrete is the use of bubble or hollow aggregates. Due to its exceptional energy absorption and ductility properties, engineered cementitious composite (ECC) is increasingly recommended and used for structural applications, particularly in earthquake-prone regions. As a result, researchers have started looking into the benefits of lightweight ECC for such applications. However, the strength is considerably compromised due to the use of lightweight fillers such as perlite, cenospheres, glass microbubbles, and crumb rubber (CR). This study evaluates an origami-shaped bubble aggregate (OBA) novel application in rubberized ECC (RECC) to achieve density reduction at a relatively lower strength loss. The experiment is designed using response surface methodology (RSM) with the spacing of the OBA at 10, 15, and 20 mm and its quantity at 9, 15, and 21 as the input factors (independent variables). The dependent variables (responses) assessed are density, compressive strength, modulus of elasticity, and Poisson’s ratio. The results showed that adding the OBA lowered the density of the RECC by 20%. It was revealed that using up to 15 OBAs with spacings between 15 and 20 mm, a lightweight OBA-RECC with substantial strength could be produced. Similarly, utilizing 15 and 21 OBAs at 20 mm spacing, a lightweight OBA-RECC with a comparable modulus of elasticity as the control could be developed. Models for predicting the responses were developed and validated using analysis of variance (ANOVA) with high R² values. The spacing and quantity of the OBA’s optimal input levels were determined using the RSM multi-objective optimization to be 20 and 9, respectively. These levels produced optimal responses of 1899 kg/m³, 45.3 MPa, 16.1 GPa, and 0.22 for the density, compressive strength, modulus of elasticity, and Poisson ratio, respectively. Full article

Hydrogen and carbon dioxide fermentation to methane, called bio-methanation, is a promising way to provide renewable and easy-to-store energy. The main challenge of bio-methanation is the low gas-to-liquid transfer of hydrogen. Gas injection through a porous membrane can be used to obtain microbubbles and high gas-to-liquid transfer. However, the understanding of bubble formation using a membrane in the fermentation broth is still missing. This study focused on the impact of liquid pressure and flow rate in the membrane, gas flow rate, membrane hydrophobicity, surface, and pore size on the overall gas-to-liquid mass transfer coefficient (K_La) for hydrogen with gas injection through a porous membrane in real fermentation conditions. It has been shown that K_La increased by 13% with an increase in liquid pressure from 0.5 bar to 1.5 bar. The use of a hydrophilic membrane increased the K_La by 17% compared to the hydrophobic membrane. The membrane with a pore size of 0.1 µm produced a higher K_La value compared to 50 and 300 kDa. The liquid crossflow velocity did not impact the K_La in the studied range. Full article