Ultrasound-assisted water oxidation: unveiling the role of piezoelectric metal-oxide sonocatalysts for cancer treatment.

Ultrasound radiation has been widely used in biomedical application for both diagnosis and therapy. Metal oxides nanoparticles (NPs), like ZnO or TiO2 NPs, have been widely demonstrated to act as excellent sonocatalysts and significantly enhance cavitation at their surface, making them optimal for sonodynamic cancer therapy. These NPs often possess semiconductive and piezoelectric properties that contribute to the complex phenomena occurring at the water-oxide interface during sonostimulation. Despite the great potential in applied sonocatalysis and water splitting, the complex mechanism that governs the phenomenon is still a research subject. This work investigates the role of piezoelectric ZnO micro- and nano-particles in ultrasound-assisted water oxidation. Three metal oxides presenting fundamental electronic and mechanical differences are evaluated in terms of ultrasound-triggered reactive oxygen species generation in aqueous media: electromechanically inert SiO2 NPs, semiconducting TiO2 NPs, piezoelectric and semiconducting ZnO micro- and nanoparticles with different surface areas and sizes. The presence of silver ions in the aqueous solution was further considered to impart a potential electron scavenging effects and better evaluate the oxygen generation performances of the different structures. Following sonoirradiation, the particles are optically and chemically analyzed to study the effect of sonostimulation at their surface. The production of gaseous molecular oxygen is measured, revealing the potential of piezoelectric particles to generate oxygen under hypoxic conditions typical of some cancer environments. Finally, the best candidates, i.e. ZnO nano and micro particles, were tested on osteosarcoma and glioblastoma cell lines to demonstrate their potential for cancer treatment.

Development and external validation of a machine learning model for the prediction of persistent acute kidney injury stage 3 in multi-centric, multi-national intensive care cohorts.

BACKGROUND: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. RESULTS: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92-0.95) in the US external validation cohort and 0.85 (95% CI 0.83-0.88) in the Italian external validation cohort. CONCLUSIONS: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice.

Sampling from Extracorporeal Circuit: A Step Forward for Dose Monitoring in Continuous Renal Replacement Therapy.

INTRODUCTION: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate. METHODS: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute. RESULTS: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction. DISCUSSION/CONCLUSIONS: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician.

Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community.

A comparative analysis of low intensity ultrasound effects on living cells: from simulation to experiments.

Ultrasounds are already broadly exploited in clinical diagnostics and are now becoming a powerful and not harmful tool in antitumoral therapies, as they are able to produce damages towards cancer cells, thank to inertial cavitation and temperature increase. The use of US alone or combined to molecular compounds, microbubbles or solid-state nanoparticles is the focus of current research and clinical trials, like thermoablation, drug sonoporation or sonodynamic therapies. In the present work, we discuss on the non-thermal effects of ultrasound and the conditions which enable oxygen radical production and which role they can have in provoking the death of different cancer cell lines. In this perspective, we set a mathematical model to predict the pressure spatial distribution in a defined water sample volume and thus obtain a map of acoustic pressures and acoustic intensities of the applied ultrasound at different input powers. We then validate and verify these numerical results with direct acoustic measurements and by detecting the production of reactive oxygen species (ROS) by means of sonochemiluminescence (SCL) and electron paramagnetic resonance (EPR) spectroscopy, applied to the same water sample volume and using the same US input parameters adopted in the simulation. Finally, the various US conditions are applied to two different set of cancer cell lines, a cervical adenocarcinoma and a hematological cancer, Burkitt's lymphoma. We hypothesize how the ROS generation can influence the recorded cell death. In a second set of experiments, the role of semiconductor metal oxide nanocrystals, i.e. zinc oxide, is also evaluated by adding them to the water and biological systems. In particular, the role of ZnO in enhancing the ROS production is verified. Furthermore, the interplay among US and ZnO nanocrystals is evaluated in provoking cancer cell death at specific conditions. This study demonstrates a useful correlation between numerical simulation and experimental acoustic validation as well as with ROS measurement at both qualitative and quantitative levels during US irradiation of simple water solution. It further tries to translate the obtained results to justify one of the possible mechanisms responsible of cancer cell death. It thus aims to pave the way for the use of US in cancer therapy and a better understanding on the non-thermal effect that a specific set of US parameters can have on cancer cells cultured in vitro.

Artificial and Naturally Derived Phospholipidic Bilayers as Smart Coatings of Solid-State Nanoparticles: Current Works and Perspectives in Cancer Therapy.

Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and possible applications. However, possible drawbacks arising from the use of nanoparticles in nanomedicine, such as the nonspecific uptake of these materials in healthy organs, their aggregation in biological environments and their possible immunogenicity, must be taken into account. Considering these limitations and the intrinsic capability of phospholipidic bilayers to act as a biocompatible shield, their exploitation for effectively encasing solid-state nanoparticles seems a promising strategy to broaden the frontiers of cancer nanomedicine, also providing the possibility to engineer the lipid bilayers to further enhance the therapeutic potential of such nanotools. This work aims to give a comprehensive overview of the latest developments in the use of artificial liposomes and naturally derived extracellular vesicles for the coating of solid-state nanoparticles for cancer treatment, starting from in vitro works until the up-to-date advances and current limitations of these nanopharmaceutics in clinical applications, passing through in vivo and 3D cultures studies.

Enhancing the preservation of liposomes: The role of cryoprotectants, lipid formulations and freezing approaches.

In the last decades, liposomes acquired a striking success in the biomedical field thanks to their biocompatibility and drug delivery ability. Many liposomal drug formulations have been already approved by the Food and Drug Administration (FDA) and used for the treatment of a wide range of pathologies with or without further engineering. Their clinical application requires strict compliance with high standard quality rules, and it is crucial to employ storage methods that do not affect the integrity of the vesicles and preventing the leakage of their cargo. In this work, the design of a suitable formulation for freeze-drying had been investigated for two different liposomes, DOPC-DOTAP and the PEGylated counterpart, DOPC-DOTAP-DSPE-PEG. The role of various cryoprotectants was evaluated paying attention to their ability to preserve the structural integrity of liposomes. At first, the study was focused on freezing and two methodologies were investigated, quenching in liquid nitrogen and shelf-ramped freezing. This analysis showed that the disaccharides (cellobiose, glucose, lactose, sucrose, and trehalose) and the polyol (mannitol) protected successfully the integrity of liposomes, while during the process, in the presence of a surfactant, liposomes were strongly damaged and fragmented by the ice crystals. Furthermore, the choice of the rate of freezing depended on the different compositions of the lipid bilayer. Finally, the effects of lyophilization on liposomes with and without additives were studied; cellobiose, lactose and trehalose showed encouraging results for the maintenance of the morpho-functional parameters of liposomes during the entire freeze-drying process.

COVID-19 and Its Global Economic Impact.

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.

The urgent need for integrated science to fight COVID-19 pandemic and beyond.

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.

EVs and Bioengineering: From Cellular Products to Engineered Nanomachines.

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications.

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer.

At present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical-chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.

Functionalized ZnO nanowires for microcantilever biosensors with enhanced binding capability.

An efficient way to increase the binding capability of microcantilever biosensors is here demonstrated by growing zinc oxide nanowires (ZnO NWs) on their active surface. A comprehensive evaluation of the chemical compatibility of ZnO NWs brought to the definition of an innovative functionalization method able to guarantee the proper immobilization of biomolecules on the nanostructured surface. A noteworthy higher amount of grafted molecules was evidenced with colorimetric assays on ZnO NWs-coated devices, in comparison with functionalized and activated silicon flat samples. ZnO NWs grown on silicon microcantilever arrays and activated with the proposed immobilization strategy enhanced the sensor binding capability (and thus the dynamic range) of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices. Graphical Abstract An efficient way to increase the binding capability of microcantilever biosensors is represented by growing zinc oxide nanowires (ZnO NWs) on their active surface. ZnO NWs grown on silicon microcantilever arrays and activated with an innovative immobilization strategy enhanced the sensor binding capability of nearly 1 order of magnitude, with respect to the commonly employed flat functionalized silicon devices.

Comparison of photocatalytic and transport properties of TiO2 and ZnO nanostructures for solar-driven water splitting.

Titanium dioxide (TiO2) and zinc oxide (ZnO) nanostructures have been widely used as photo-catalysts due to their low-cost, high surface area, robustness, abundance and non-toxicity. In this work, four TiO2 and ZnO-based nanostructures, i.e. TiO2 nanoparticles (TiO2 NPs), TiO2 nanotubes (TiO2 NTs), ZnO nanowires (ZnO NWs) and ZnO@TiO2 core-shell structures, specifically prepared with a fixed thickness of about 1.5 µm, are compared for the solar-driven water splitting reaction, under AM1.5G simulated sunlight. Complete characterization of these photo-electrodes in their structural and photo-electrochemical properties was carried out. Both TiO2 NPs and NTs showed photo-current saturation reaching 0.02 and 0.12 mA cm(-2), respectively, for potential values of about 0.3 and 0.6 V vs. RHE. In contrast, the ZnO NWs and the ZnO@TiO2 core-shell samples evidence a linear increase of the photocurrent with the applied potential, reaching 0.45 and 0.63 mA cm(-2) at 1.7 V vs. RHE, respectively. However, under concentrated light conditions, the TiO2 NTs demonstrate a higher increase of the performance with respect to the ZnO@TiO2 core-shells. Such material-dependent behaviours are discussed in relation with the different charge transport mechanisms and interfacial reaction kinetics, which were investigated through electrochemical impedance spectroscopy. The role of key parameters such as electronic properties, specific surface area and photo-catalytic activity in the performance of these materials is discussed. Moreover, proper optimization strategies are analysed in view of increasing the efficiency of the best performing TiO2 and ZnO-based nanostructures, toward their practical application in a solar water splitting device.

Electrophoretic deposition of mesoporous bioactive glass on glass-ceramic foam scaffolds for bone tissue engineering.

In this work, the coating of 3-D foam-like glass-ceramic scaffolds with a bioactive mesoporous glass (MBG) was investigated. The starting scaffolds, based on a non-commercial silicate glass, were fabricated by the polymer sponge replica technique followed by sintering; then, electrophoretic deposition (EPD) was applied to deposit a MBG layer on the scaffold struts. EPD was also compared with other techniques (dipping and direct in situ gelation) and it was shown to lead to the most promising results. The scaffold pore structure was maintained after the MBG coating by EPD, as assessed by SEM and micro-CT. In vitro bioactivity of the scaffolds was assessed by immersion in simulated body fluid and subsequent evaluation of hydroxyapatite (HA) formation. The deposition of a MBG coating can be a smart strategy to impart bioactive properties to the scaffold, allowing the formation of nano-structured HA agglomerates within 48 h from immersion, which does not occur on uncoated scaffold surfaces. The mechanical properties of the scaffold do not vary after the EPD (compressive strength ~19 MPa, fracture energy ~1.2 × 10(6) J m(-3)) and suggest the suitability of the prepared highly bioactive constructs as bone tissue engineering implants for load-bearing applications.

Flexible tactile sensing based on piezoresistive composites: a review.

The large expansion of the robotic field in the last decades has created a growing interest in the research and development of tactile sensing solutions for robot hand and body integration. Piezoresistive composites are one of the most widely employed materials for this purpose, combining simple and low cost preparation with high flexibility and conformability to surfaces, low power consumption, and the use of simple read-out electronics. This work provides a review on the different type of composite materials, classified according to the conduction mechanism and analyzing the physics behind it. In particular piezoresistors, strain gauges, percolative and quantum tunnelling devices are reviewed here, with a perspective overview on the most used filler types and polymeric matrices. A description of the state-of-the-art of the tactile sensor solutions from the point of view of the architecture, the design and the performance is also reviewed, with a perspective outlook on the main promising applications.

Ultra-fast photocatalytic degradation of Rhodamine B exploiting oleate-stabilized zinc oxide nanoparticles.

Rhodamine B (RhB) is a harmful dye released by industrial wastewaters, thus necessitating its urgent removal. Advanced oxidation processes constitute promising strategies to purify polluted water. Among others, photocatalysis relies on reactive oxygen species (ROS) produced by photocatalytic particles, typically semiconductors like titania or zinc oxide (ZnO), excited by solar or UV-Vis light. However, their wide band gap limits their catalytic capabilities within the absorption of the UV spectrum and causes fast electron-hole recombination. This study presents novel strategies to overcome these limitations: (i) doping semiconductors to increase photocatalytic efficiency; (ii) sensitization-mediated photocatalysis for visible light activation using chemical moieties to trap dye molecules; (iii) nanosizing the photocatalysts to enhance the surface area. ZnO nanoparticles, doped with iron or gadolinium and capped with oleic acid are here synthesized and tested in RhB dye solutions. Remarkably, the results demonstrate an ultra-fast RhB degradation, driven by oleic acid having crucial role in dye adsorption. The degradation mechanisms, including ROS-induced N-deethylation and xanthene group cleavage, are also unraveled. These findings underscore the efficacy of the proposed semiconductor photocatalyst design, highlighting a significant advancement with extensive potential applications in wastewater remediation. This innovative approach paves the way for more efficient and practical solutions to combat industrial dye pollution.

Anti-CD38 targeted nanotrojan horses stimulated by acoustic waves as therapeutic nanotools selectively against Burkitt's lymphoma cells.

The horizon of nanomedicine research is moving toward the design of therapeutic tools able to be completely safe per se, and simultaneously be capable of becoming toxic when externally activated by stimuli of different nature. Among all the stimuli, ultrasounds come to the fore as an innovative approach to produce cytotoxicity on demand in presence of NPs, without invasiveness, with high biosafety and low cost. In this context, zinc oxide nanoparticles (NPs) are among the most promising metal oxide materials for theranostic application due to their optical and semi-conductor properties, high surface reactivity, and their response to ultrasound irradiation. Here, ZnO nanocrystals constitute the stimuli-responsive core with a customized biomimicking lipidic shielding, resembling the composition of natural extracellular vesicles. This core-shell hybrid structure provides high bio- and hemocompatibility towards healthy cells and is here proofed for the treatment of Burkitt's Lymphoma. This is a very common haematological tumor, typically found in children, for which consolidated therapies are so far the combination of chemo-therapy drugs and targeted immunotherapy. In this work, the proposed safe-by-design antiCD38-targeted hybrid nanosystem exhibits an efficient selectivity toward cancerous cells, and an on-demand activation, leading to a significant killing efficacy due to the synergistic interaction between US and targeted hybrid NPs. Interestingly, this innovative treatment does not significantly affect healthy B lymphocytes nor a negative control cancer cell line, a CD38- acute myeloid leukemia, being thus highly specific and targeted. Different characterization and analyses confirmed indeed the effective formation of targeted hybrid ZnO NPs, their cellular internalization and the damages produced in Burkitt's Lymphoma cells only with respect to the other cell lines. The presented work holds promises for future clinical applications, as well as translation to other tumor types.

Spallation and particles infusion into the extracorporeal circuit during CRRT: a preventable phenomenon.

Patients in intensive care are exposed to the risk of microparticle infusion via extracorporeal lines and the resulting complications. A possible source of microparticle release could be the extracorporeal circuit used in blood purification techniques, such as continuous renal replacement therapy (CRRT). Disposable components of CRRT circuits, such as replacement bags and circuit tubing, might release microparticles such as salt crystals produced by precipitation in replacement bags and plastic microparticles produced by spallation. In-line filtration has proven effective in retaining microparticles both in in-vitro and in-vivo studies. In our study, we performed an in-vitro model of CRRT-treatment with the aim of detecting the microparticles produced and released into the circuit by means of a qualitative and quantitative analysis, after sampling the replacement and patient lines straddling a series of in-line filters. Working pressures and flows were monitored during the experiment. This study showed that microparticles are indeed produced and released into the CRRT circuit. The inclusion of in-line filters in the replacement lines allows to reduce the burden of microparticles infused into the bloodstream during extracorporeal treatments, reducing the concentration of microparticles from 14 mg/mL pre in-line filter to 11 mg/mL post in-line filter. Particle infusion and related damage must be counted among the pathophysiological mechanisms supporting iatrogenic damage due to artificial cross-talk between organs during CRRT applied to critically ill patients. This damage can be reduced by using in-line filters in the extracorporeal circuit.

A crystal engineering approach for rational design of curcumin crystals for Pickering stabilization of emulsions.

Emulsions stabilized via Pickering particles are becoming more and more popular due to their high stability and biocompatibility. Hence, developing new ways to produce effective Pickering particles is essential. In this work, we present a crystal engineering approach to obtain precise control over particle properties such as size, shape, and crystal structure, which may affect wettability and surface chemistry. A highly reproducible synthesis method via anti-solvent crystallization was developed to produce sub-micron sized curcumin crystals of the metastable form III, to be used as Pickering stabilizers. The produced crystals presented a clear hydrophobic nature, which was demonstrated by their preference to stabilize water-in-oil (W/O) emulsions. A comprehensive experimental and computational characterization of curcumin crystals was performed to rationalize their hydrophobic nature. Analytical techniques including Raman spectroscopy, powder X-ray diffraction (PXRD), Solid-State Nuclear Magnetic Resonance (SSNMR), scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC), confocal fluorescence microscopy and contact angle measurements were used to characterize curcumin particles in terms of shape, size and interfacial activity. The attachment energy model was instead applied to study relevant surface features of curcumin crystals, such as topology and facet-specific surface chemistry. This work contributes to the understanding of the effect of crystal properties on the mechanism of Pickering stabilization, and paves the way for the formulation of innovative products in fields ranging from pharmaceuticals to food science.