Natural Hydrogels Support Kidney Organoid Generation and Promote in vitro Angiogenesis.

To date strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized extracellular matrix (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features, and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique culture cell platforms for personalized medicine. This article is protected by copyright. All rights reserved.

Boosting the Efficiency of Photoactive Rod-Shaped Nanomotors via Magnetic Field-Induced Charge Separation.

Photocatalytic nanomotors have attracted a lot of attention because of their unique capacity to simultaneously convert light and chemical energy into mechanical motion with a fast photoresponse. Recent discoveries demonstrate that the integration of optical and magnetic components within a single nanomotor platform offers novel advantages for precise motion control and enhanced photocatalytic performance. Despite these advancements, the impact of magnetic fields on energy transfer dynamics in photocatalytic nanomotors remains unexplored. Here, we introduce dual-responsive rod-like nanomotors, made of a TiO2/NiFe heterojunction, able to (i) self-propel upon irradiation, (ii) align with the direction of an external magnetic field, and (iii) exhibit enhanced photocatalytic performance. Consequently, when combining light irradiation with a homogeneous magnetic field, these nanomotors exhibit increased velocities attributed to their improved photoactivity. As a proof-of-concept, we investigated the ability of these nanomotors to generate phenol, a valuable chemical feedstock, from benzene under combined optical and magnetic fields. Remarkably, the application of an external magnetic field led to a 100% increase in the photocatalytic phenol generation in comparison with light activation alone. By using various state-of-the-art techniques such as photoelectrochemistry, electrochemical impedance spectroscopy, photoluminescence, and electron paramagnetic resonance, we characterized the charge transfer between the semiconductor and the alloy component, revealing that the magnetic field significantly improved charge pair separation and enhanced hydroxyl radical generation. Consequently, our work provides valuable insights into the role of magnetic fields in the mechanisms of light-driven photocatalytic nanomotors for designing more effective light-driven nanodevices for selective oxidations.

Synthetic DNA-based Swimmers Driven by Enzyme Catalysis.

Here, we report DNA-based synthetic nanostructures decorated with enzymes (hereafter referred to as DNA-enzyme swimmers) that self-propel by converting the enzymatic substrate to the product in solution. The DNA-enzyme swimmers are obtained from tubular DNA structures that self-assemble spontaneously by the hybridization of DNA tiles. We functionalize these DNA structures with two different enzymes, urease and catalase, and show that they exhibit concentration-dependent movement and enhanced diffusion upon addition of the enzymatic substrate (i.e., urea and H2O2). To demonstrate the programmability of such DNA-based swimmers, we also engineer DNA strands that displace the enzyme from the DNA scaffold, thus acting as molecular "brakes" on the DNA swimmers. These results serve as a first proof of principle for the development of synthetic DNA-based enzyme-powered swimmers that can self-propel in fluids.

Merging BioActuation and BioCapacitive properties: A 3D bioprinted devices to self-stimulate using self-stored energy.

Biofabrication of three-dimensional (3D) cultures through the 3D Bioprinting technique opens new perspectives and applications of cell-laden hydrogels. However, to continue with the progress, new BioInks with specific properties must be carefully designed. In this study, we report the synthesis and 3D Bioprinting of an electroconductive BioInk made of gelatin/fibrinogen hydrogel, C2C12 mouse myoblast and 5% w/w of conductive poly (3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The influence of PEDOT NPs, incorporated in the cell-laden BioInk, not only showed a positive effect in cells viability, differentiation and myotube functionalities, also allowed the printed constructs to behaved as BioCapacitors. Such devices were able to electrochemically store a significant amount of energy (0.5 mF/cm2), enough to self-stimulate as BioActuator, with typical contractions ranging from 27 to 38 µN, during nearly 50 min. The biofabrication of 3D constructs with the proposed electroconductive BioInk could lead to new devices for tissue engineering, biohybrid robotics or bioelectronics.

Psychosocial and vocational impact of an internship program for people diagnosed with severe mental illnesses.

PURPOSE: Unemployment is an obstacle in recovery for people with severe mental illnesses (SMI), both in reducing psychopathological symptoms and in achieving a high quality of life. The aim of this study was to explore the impact of an internship program for people diagnosed with SMI on psychosocial variables using a pre-test and post-test design. METHOD: Four scales were administered to a sample of 127 study participants, all of whom were diagnosed with SMI. The results of standard and sheltered employment outcomes were obtained by comparing the number and type of contracts gained by participants up to one year after program completion. A repeated measures ANOVA analysis was carried out with intervention being an independent intra-subject variable and type of participant diagnosis being a between-subjects variable. RESULTS: A limited increase in social functioning was found, as well as a significant decrease in psychiatric distress for users diagnosed with personality disorders. Participants in the internship program obtained a greater number of employment contracts than their peers who did not participate in the program, albeit with a low effect size. CONCLUSIONS: Though results were positive, extension of internship length and provision of more intensive counselling for participants may be useful.

An internship program for persons with severe mental illnesses yielded modest improvements in social functioning.A decrease in psychiatric distress in participants with personality disorders was found after the internships.Participants in the internship obtained a greater number of employment contracts.An extended internship programme with workplace support is likely to be beneficial.

Urease-powered nanobots for radionuclide bladder cancer therapy.

Bladder cancer treatment via intravesical drug administration achieves reasonable survival rates but suffers from low therapeutic efficacy. To address the latter, self-propelled nanoparticles or nanobots have been proposed, taking advantage of their enhanced diffusion and mixing capabilities in urine when compared with conventional drugs or passive nanoparticles. However, the translational capabilities of nanobots in treating bladder cancer are underexplored. Here, we tested radiolabelled mesoporous silica-based urease-powered nanobots in an orthotopic mouse model of bladder cancer. In vivo and ex vivo results demonstrated enhanced nanobot accumulation at the tumour site, with an eightfold increase revealed by positron emission tomography in vivo. Label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders confirmed tumour penetration by nanobots ex vivo. Treating tumour-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in a tumour size reduction of about 90%, positioning nanobots as efficient delivery nanosystems for bladder cancer therapy.

Enzymatic micro/nanomotors in biomedicine: from single motors to swarms.

Micro/nanomotors (MNMs) have evolved from single self-propelled entities to versatile systems capable of performing one or multiple biomedical tasks. When single MNMs self-assemble into coordinated swarms, either under external control or triggered by chemical reactions, they offer advantages that individual MNMs cannot achieve. These benefits include intelligent multitasking and adaptability to changes in the surrounding environment. Here, we provide our perspective on the evolution of MNMs, beginning with the development of enzymatic MNMs since the first theoretical model was proposed in 2005. These enzymatic MNMs hold immense promise in biomedicine due to their advantages in biocompatibility and fuel availability. Subsequently, we introduce the design and application of single motors in biomedicine, followed by the control of MNM swarms and their biomedical applications. In the end, we propose viable solutions for advancing the development of MNM swarms and anticipate valuable insights into the creation of more intelligent and controllable MNM swarms for biomedical applications.

Swarms of Enzyme-Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media.

Over the past decades, the development of nanoparticles (NPs) to increase the efficiency of clinical treatments has been subject of intense research. Yet, most NPs have been reported to possess low efficacy as their actuation is hindered by biological barriers. For instance, synovial fluid (SF) present in the joints is mainly composed of hyaluronic acid (HA). These viscous media pose a challenge for many applications in nanomedicine, as passive NPs tend to become trapped in complex networks, which reduces their ability to reach the target location. This problem can be addressed by using active NPs (nanomotors, NMs) that are self-propelled by enzymatic reactions, although the development of enzyme-powered NMs, capable of navigating these viscous environments, remains a considerable challenge. Here, the synergistic effects of two NMs troops, namely hyaluronidase NMs (HyaNMs, Troop 1) and urease NMs (UrNMs, Troop 2) are demonstrated. Troop 1 interacts with the SF by reducing its viscosity, thus allowing Troop 2 to swim more easily through the SF. Through their collective motion, Troop 2 increases the diffusion of macromolecules. These results pave the way for more widespread use of enzyme-powered NMs, e.g., for treating joint injuries and improving therapeutic effectiveness compared with traditional methods.

Correction: López-Vilos et al. Clustering-Based Energy-Efficient Self-Healing Strategy for WSNs under Jamming Attacks. Sensors 2023, 23, 6894.

In the published publication [...].

Unveiling protein corona formation around self-propelled enzyme nanomotors by nanoscopy.

The interaction of nanoparticles with biological media is a topic of general interest for drug delivery systems and among those for active nanoparticles, also called nanomotors. Herein, we report the use of super resolution microscopy, in particular, stochastic optical reconstruction microscopy (STORM), to characterize the formation of a protein corona around active enzyme-powered nanomotors. First, we characterized the distribution and number of enzymes on nano-sized particles and characterized their motion capabilities. Then, we incubated the nanomotors with fluorescently labelled serum proteins. Interestingly, we observed a significant decrease of protein corona formation (20%) and different composition, which was studied by proteomic analysis. Moreover, motion was not hindered, as nanomotors displayed enhanced diffusion regardless of the protein corona. Elucidating how active particles interact with biological media and maintain their self-propulsion after protein corona formation will pave the way for the use of these systems in complex biological fluids in biomedicine.

Real-Time Optical Tracking of Protein Corona Formation on Single Nanoparticles in Serum.

The formation of a protein corona, where proteins spontaneously adhere to the surface of nanomaterials in biological environments, leads to changes in their physicochemical properties and subsequently affects their intended biomedical functionalities. Most current methods to study protein corona formation are ensemble-averaging and either require fluorescent labeling, washing steps, or are only applicable to specific types of particles. Here we introduce real-time all-optical nanoparticle analysis by scattering microscopy (RONAS) to track the formation of protein corona in full serum, at the single-particle level, without any labeling. RONAS uses optical scattering microscopy and enables real-time and in situ tracking of protein adsorption on metallic and dielectric nanoparticles with different geometries directly in blood serum. We analyzed the adsorbed protein mass, the affinity, and the kinetics of the protein adsorption at the single particle level. While there is a high degree of heterogeneity from particle to particle, the predominant factor in protein adsorption is surface chemistry rather than the underlying nanoparticle material or size. RONAS offers an in-depth understanding of the mechanisms related to protein coronas and, thus, enables the development of strategies to engineer efficient bionanomaterials.

A Review of Hybrid VLC/RF Networks: Features, Applications, and Future Directions.

The expectation for communication systems beyond 5G/6G is to provide high reliability, high throughput, low latency, and high energy efficiency services. The integration between systems based on radio frequency (RF) and visible light communication (VLC) promises the design of hybrid systems capable of addressing and largely satisfying these requirements. Hybrid network design enables complementary cooperation without interference between the two technologies, thereby increasing the overall system data rate, improving load balancing, and reducing non-coverage areas. VLC/RF hybrid networks can offer reliable and efficient communication solutions for Internet of Things (IoT) applications such as smart lighting, location-based services, home automation, smart healthcare, and industrial IoT. Therefore, hybrid VLC/RF networks are key technologies for next-generation communication systems. In this paper, a comprehensive state-of-the-art study of hybrid VLC/RF networks is carried out, divided into four areas. First, indoor scenarios are studied considering lighting requirements, hybrid channel models, load balancing, resource allocation, and hybrid network topologies. Second, the characteristics and implementation of these hybrid networks in outdoor scenarios with adverse conditions are analyzed. Third, we address the main applications of hybrid VLC/RF networks in technological, economic, and socio-environmental domains. Finally, we outline the main challenges and future research lines of hybrid VLC/RF networks.

A Novel Approach of a Low-Cost Voltage Fault Injection Method for Resource-Constrained IoT Devices: Design and Analysis.

The rapid development of the Internet of Things (IoT) has brought about the processing and storage of sensitive information on resource-constrained devices, which are susceptible to various hardware attacks. Fault injection attacks (FIAs) stand out as one of the most widespread. Particularly, voltage-based FIAs (V-FIAs) have gained popularity due to their non-invasive nature and high effectiveness in inducing faults by pushing the IoT hardware to its operational limits. Improving the security of devices and gaining a comprehensive understanding of their vulnerabilities is of utmost importance. In this study, we present a novel fault injection method and employ it to target an 8-bit AVR microcontroller. We identify the optimal attack parameters by analyzing the detected failures and their trends. A case study is conducted to validate the efficacy of this new method in a more realistic scenario, focusing on a simple authentication method using the determined optimal parameters. This analysis not only demonstrates the feasibility of the V-FIA but also elucidates the primary characteristics of the resulting failures and their propagation in resource-constrained devices. Additionally, we devise a hardware/software countermeasure that can be integrated into any resource-constrained device to thwart such attacks in IoT scenarios.

Clustering-Based Energy-Efficient Self-Healing Strategy for WSNs Under Jamming Attacks.

The Internet of Things (IoT) is a key technology to interconnect the real and digital worlds, enabling the development of smart cities and services. The timely collection of data is essential for IoT services. In scenarios such as agriculture, industry, transportation, public safety, and health, wireless sensor networks (WSNs) play a fundamental role in fulfilling this task. However, WSNs are commonly deployed in sensitive and remote environments, thus facing the challenge of jamming attacks. Therefore, these networks need to have the ability to detect such attacks and adopt countermeasures to guarantee connectivity and operation. In this work, we propose a novel clustering-based self-healing strategy to overcome jamming attacks, in which we denominate fairness cooperation with power allocation (FCPA). The proposed strategy, aware of the presence of the jammer, clusters the network and designates a cluster head that acts as a sink node to collect information from its cluster. Then, the most convenient routes to overcome the jamming are identified and the transmit power is adjusted to the minimum value required to guarantee the reliability of each link. Finally, through the weighted use of the relays, the lifetime of each subnetwork is extended. To show the impact of each capability of FCPA, we compare it with multiple benchmarks that only partially possess these capabilities. In the proposal evaluation, we consider a WSN composed of 64 static nodes distributed in a square area. Meanwhile, to assess the impact of the jamming attack, we consider seven different locations of the attacker. All experiments started with each node's battery full and stopped after one of these batteries was depleted. In these scenarios, FCPA outperforms all other strategies by more than 50% of the information transmitted, due to the efficient use of relay power, through the weighted balance of cooperative routes. On average, FCPA permits 967,961 kb of information transmitted and 63% of residual energy, as energy efficiency, from all the analyzed scenarios. Additionally, the proposed clustering-based self-healing strategy adapts to the change of jammer location, outperforming the rest of the strategies in terms of information transmitted and energy efficiency in all evaluated scenarios.

Light-Triggered Mechanical Disruption of Extracellular Barriers by Swarms of Enzyme-Powered Nanomotors for Enhanced Delivery.

Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nanocarriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.

Respuesta inmunitaria anti-SARS-CoV-2: Infección Naturalvs. Vacunación / Anti-SARS-CoV-2 immune response: natural infection vs vaccination

Este trabajo es una revisión bibliográfica que compara la inmunidad anti-SARS-CoV-2 inducida por la infección natural y la inducida por vacunación, para entenderlas particularidades de la respuesta en cada caso, así como sus ventajas y desventajas. Se escogieron artículos que reportaran la medición de concentración de anticuerpos séricos, determinantes de inmunidad celular y/o evolución clínica de los pacientes. Se encontró que: A) Los pacientes recuperados de una infección por SARS-CoV-2 presentaron una respuesta mayor y más heterogénea de anticuerpos y células B de memoria que los pacientes vacunados, con un mayor número de linfocitos TCD4+, que cooperan con la diferenciación de linfocitos B y con la producción de anticuerpos neutralizantes. B) La vacunación previene la tormenta de citocinas asociada a la infección natural. C) Dos dosis de una vacuna basada en ARN mensajero logran una concentración de anticuerpos de clase IgG prácticamente igual a la de los pacientes severamente enfermos, pero sin el daño a los nódulos linfáticos asociado a la infección natural. D) Se puede aumentar el número de linfocitos B administrando dosis de refuerzo de la vacuna. Si bien, tanto la vacunación como la infección natural generan respuestas anti-SARS-CoV-2 significativas, la vacunación es el método más seguro para proteger a la población, pues evita el riesgo a la inmunopatología y a la mortalidad asociados con la infección natural. Más aún, la inmunidad híbrida (aquella que adquieren los pacientes que superaron la infección natural y fueron después vacunados) induce una producción de anticuerpos capaces de neutralizar por completo al SARS-CoV-2(AU)

This work is a bibliographic review that comparesanti-SARS-CoV-2 inmmune response induced by natural infección with that induced by vaccination, to understand theparticularities of each response, as well as their advantages and disadvantages. Research articles that reported levels of antibodies in serum, determinants of cellular inmmunity and/or clinical evolution of patients were chosen. It was found that: A) Pacients previously infected with SARS-CoV-2 presented a larger and more heterogeneous response of antibodies and memory B cells than vaccined patients, with a larger number of CD4+T cells that cooperate with the differentiation of B cells and production of neutralizing antibodies. B) Vaccination prevents the cytokine storm associated with natural infection. C) Two doses of an mRNA vaccine induced an IgG concentration nearly equal to severe ill patients but without the damage to lymph nodes associated with natural infection. D) B cell levels can be increased by giving booster doses of the vaccine. Althought both vaccination and natural infection generate significant anti-SARS-CoV-2 immune responses, vaccination is the safest method to protect general population, because it avoids the risk of immunopathology and mortality associated with natural infection. Futhermore, hybrid immunity (thatadquired by patients who overcame the natural infection and were later vaccinated), induces production of antibodies capable of completely neutralizing SARS-CoV-2(AU)

Quality of life and psychiatric distress in people with serious mental illness, the role of personal recovery.

OBJECTIVES: When considering the personal recovery of people with serious mental illness (SMI), it is essential to examine their reported psychiatric distress and quality of life (QoL). However, there is no consolidated model in the literature that clearly relates these variables. In this study we first analysed the relationships between QoL, psychiatric distress and recovery, and several sociodemographic variables. Second, we analysed the linear effects of psychiatric distress and recovery on QoL. Third, and most important, we tested two hypotheses that considered personal recovery as a moderator or mediator of the relationship between psychiatric distress and QoL. DESIGN AND METHODS: 234 volunteers with a diagnosis of SMI completed three self-report questionnaires, The Recovery Assessment Scale-24, The World Health Organization QoL and the Clinical Outcomes in Routine Evaluation-Outcome Measure, which showed very good levels of validity and reliability. The PROCESS macro for SPSS developed by Hayes (Introduction to mediation, moderation, and conditional process analysis: A regression-based approach, The Guilford Press, 2022) was applied using the Bootstrap method to verify our moderation and mediation hypotheses. RESULTS: We found a negative linear effect of psychiatric distress on QoL, as well as a positive effect of recovery on said variable. Our results do not confirm the moderating effect of recovery on the relationship between distress and QoL. However, we do confirm the second hypothesis; recovery functioned as a mediating variable between psychiatric distress and QoL. CONCLUSIONS: These findings allow us to reflect on how personal recovery affect the relationship between psychiatric distress and QoL and discuss its theoretical and practical implications as public policies.

Biohybrid robots: recent progress, challenges, and perspectives.

The past ten years have seen the rapid expansion of the field of biohybrid robotics. By combining engineered, synthetic components with living biological materials, new robotics solutions have been developed that harness the adaptability of living muscles, the sensitivity of living sensory cells, and even the computational abilities of living neurons. Biohybrid robotics has taken the popular and scientific media by storm with advances in the field, moving biohybrid robotics out of science fiction and into real science and engineering. So how did we get here, and where should the field of biohybrid robotics go next? In this perspective, we first provide the historical context of crucial subareas of biohybrid robotics by reviewing the past 10+ years of advances in microorganism-bots and sperm-bots, cyborgs, and tissue-based robots. We then present critical challenges facing the field and provide our perspectives on the vital future steps toward creating autonomous living machines.

Correction: Enzyme-powered micro- and nano-motors: key parameters for an application-oriented design.

[This corrects the article DOI: 10.1039/D2SC01806C.].

Enzyme-powered micro- and nano-motors: key parameters for an application-oriented design.

Nature has inspired the creation of artificial micro- and nanomotors that self-propel converting chemical energy into mechanical action. These tiny machines have appeared as promising biomedical tools for treatment and diagnosis and have also been used for environmental, antimicrobial or sensing applications. Among the possible catalytic engines, enzymes have emerged as an alternative to inorganic catalysts due to their biocompatibility and the variety and bioavailability of fuels. Although the field of enzyme-powered micro- and nano-motors has a trajectory of more than a decade, a comprehensive framework on how to rationally design, control and optimize their motion is still missing. With this purpose, herein we performed a thorough bibliographic study on the key parameters governing the propulsion of these enzyme-powered devices, namely the chassis shape, the material composition, the motor size, the enzyme type, the method used to incorporate enzymes, the distribution of the product released, the motion mechanism, the motion media and the technique used for motion detection. In conclusion, from the library of options that each parameter offers there needs to be a rational selection and intelligent design of enzymatic motors based on the specific application envisioned.