Atom-doped photon engine: Extracting mechanical work from a quantum system via radiation pressure.

The possibility of efficiently converting heat into work at the microscale has triggered an intense research effort to understand quantum heat engines, driven by the hope of quantum superiority over classical counterparts. In this work, we introduce a model featuring an atom-doped optical quantum cavity propelling a classical piston through radiation pressure. The model, based on the Jaynes-Cummings Hamiltonian of quantum electrodynamics, demonstrates the generation of mechanical work through thermal energy injection. We establish the equivalence of the piston expansion work with Alicki's work definition, analytically for quasistatic transformations and numerically for finite-time protocols. We further employ the model to construct quantum Otto and Carnot engines, comparing their performance in terms of energetics, work output, efficiency, and power under various conditions. This model thus provides a platform to extract useful work from an open quantum system to generate net motion, and it sheds light on the quantum concepts of work and heat.

Single-Cell Recovery from Tumor Cell Xenotransplanted Zebrafish Embryos for the Study of Metastasis-Initiating Cells.

The study of metastasis-competent cells at the single-cell level represents an opportunity to decipher the molecular mechanisms associated with the metastatic cascade as well as to understand the functional and molecular heterogeneity of these cells. In this context, preclinical in vivo models of cancer metastasis are valuable tools to understand the behavior of cancer cells throughout the process. Here we describe a detailed protocol for the isolation and recovery of individual viable human metastatic cells from zebrafish embryos xenotransplanted with cancer cells for downstream molecular analysis. We cover the critical steps for the dissociation of the xenografted zebrafish embryos to generate a single-cell suspension, and the micromanipulation for their recovery as single cells.

Consensus document of the management of type 2 diabetes and heart failure: Consejo Interamericano de Falla Cardíaca e Hipertensión Pulmonar (CIFACAH) and Inter-American Society of Cardiology (IASC).

Heart failure (HF) syndrome is a global public health issue. On the other hand, type 2 diabetes is a risk factor associated with overweight/obesity and a sedentary lifestyle. This consensus aims to compile information available on the relationship between HF and type 2 diabetes and present, in a summarized and practical way, the management recommendations based on scientific evidence. The document includes the description of the epidemiology of HF and type 2 diabetes; pathophysiology of HF and type 2 diabetes; cardiovascular complications of type 2 diabetes; stages of HF; management of type 2 diabetes in patients with HF; and management of HF in patients with type 2 diabetes. Lastly, in the conclusions section, the growing trend of both events and the need to start preventive activities is presented, as well as the favorable role of antidiabetic drugs in the treatment of patients with HF.

El síndrome de insuficiencia cardíaca (IC) es un problema de salud pública global. Por su parte, la diabetes tipo 2 es un factor de riesgo asociado a sobrepeso/obesidad y sedentarismo. El presente consenso busca recopilar la información disponible sobre la relación entre la IC y la diabetes tipo 2, y presentar, de manera práctica y resumida, las recomendaciones de manejo basadas en la evidencia científica. El documento se estructura en la descripción de la epidemiología de la IC y la diabetes tipo 2; la fisiopatología de la IC y la diabetes tipo 2; las complicaciones cardiovasculares de la diabetes tipo 2; los estadios de la IC; el manejo de la diabetes tipo 2 en pacientes con IC; y el manejo de la IC en pacientes con diabetes tipo 2. Por último, en el apartado de conclusiones se presenta una clara tendencia creciente de ambos eventos y se señala la necesidad del inicio de actividades preventivas, así como también el papel favorable de los fármacos antidiabéticos en el tratamiento de los pacientes con IC.

Correction: Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment.

Correction for 'Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment' by Saínza Lores et al., Biomater. Sci., 2023, https://doi.org/10.1039/d2bm01456d.

Modelling metastasis in zebrafish unveils regulatory interactions of cancer-associated fibroblasts with circulating tumour cells.

The dynamic intercommunication between tumour cells and cells from the microenvironment, such as cancer-associated fibroblast (CAFs), is a key factor driving breast cancer (BC) metastasis. Clusters of circulating tumour cells (CTCs), known to bare a higher efficiency at establishing metastases, are found in the blood of BC patients, often accompanied by CAFs in heterotypic CTC-clusters. Previously we have shown the utility of CTC-clusters models and the zebrafish embryo as a model of metastasis to understand the biology of breast cancer CTC-clusters. In this work, we use the zebrafish embryo to study the interactions between CTCs in homotypic clusters and CTC-CAFs in heterotypic CTC-clusters to identify potential pro-metastatic traits derived from CTC-CAF communication. We found that upon dissemination CAFs seem to exert a pro-survival and pro-proliferative effect on the CTCs, but only when CTCs and CAFs remain joined as cell clusters. Our data indicate that the clustering of CTC and CAF allows the establishment of physical interactions that when maintained over time favour the selection of CTCs with a higher capacity to survive and proliferate upon dissemination. Importantly, this effect seems to be dependent on the survival of disseminated CAFs and was not observed in the presence of normal fibroblasts. Moreover, we show that CAFs can exert regulatory effects on the CTCs without being involved in promoting tumour cell invasion. Lastly, we show that the physical communication between BC cells and CAFs leads to the production of soluble factors involved in BC cell survival and proliferation. These findings suggest the existence of a CAF-regulatory effect on CTC survival and proliferation sustained by cell-to-cell contacts and highlight the need to understand the molecular mechanisms that mediate the interaction between the CTCs and CAFs in clusters enhancing the metastatic capacity of CTCs.

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment.

Gene therapy has long been proposed for cancer treatment. However, the use of therapeutic nucleic acids presents several limitations such as enzymatic degradation, rapid clearance, and poor cellular uptake and efficiency. In this work we propose the use of putrescine, a precursor for higher polyamine biosynthesis for the preparation of cationic nanosystems for cancer gene therapy. We have formulated and characterized putrescine-sphingomyelin nanosystems (PSN) and studied their endocytic pathway and intracellular trafficking in cancer cells. After loading a plasmid DNA (pDNA) encoding the apoptotic Fas Ligand (FasL), we proved their therapeutic activity by measuring the cell death rate after treatment of MDA-MB-231 cells. We have also used xenografted zebrafish embryos as a first in vivo approach to demonstrate the efficacy of the proposed PSN-pDNA formulation in a more complex model. Finally, intratumoral and intraperitoneal administration to mice-bearing MDA-MB-231 xenografts resulted in a significant decrease in tumour cell growth, highlighting the potential of the developed gene therapy nanoformulation for the treatment of triple negative breast cancer.

Magnetically propelled chained nanocomposites for biologically relevant media exploration.

Elongated nanostructures to be remotely and magnetically propelled in biologically relevant media, have gained attention as offering themselves as effective tools or carriers in theragnostics applications. However, the magnetic actuation associated remains challenging due to the lack of mechanical information in the media of interest, taking into account biophysical or biomedical purposes. In this study, we detail the magnetic actuation of magnetically propelled chained nanocomposites considering their dynamics, in which their velocity can be modulated in terms of the viscosity of the medium considered, given a magnetic field gradient. Simpler cases of distilled water, a water/glycerol mixture and a fluid made of cell extracts (imitating the cytosol of cells) of known viscosity are the basis experiments for the study of more complex media inside HeLa cells, murine NIH-3T3 fibroblasts and zebrafish larvae, offering the mechanical information required. The experimental results indicate that the magnetically propelled performance of the chained nanostructures can be precisely controlled in potentially changing scenarios, where drug and heat delivery, magnetic separation, or microfluidic technologies are demanded, using a magnetic field gradient and providing good estimations of the dynamical parameters involved.

Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer.

Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applications.

Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression.

Analyzing different tumor regions by next generation sequencing allows the assessment of intratumor genetic heterogeneity (ITGH), a phenomenon that has been studied widely in some tumor types but has been less well explored in endometrial carcinoma (EC). In this study, we sought to characterize the spatial and temporal heterogeneity of 9 different ECs using whole-exome sequencing, and by performing targeted sequencing validation of the 42 primary tumor regions and 30 metastatic samples analyzed. In addition, copy number alterations of serous carcinomas were assessed by comparative genomic hybridization arrays. From the somatic mutations, identified by whole-exome sequencing, 532 were validated by targeted sequencing. Based on these data, the phylogenetic tree reconstructed for each case allowed us to establish the tumors' evolution and correlate this to tumor progression, prognosis, and the presence of recurrent disease. Moreover, we studied the genetic landscape of an ambiguous EC and the molecular profile obtained was used to guide the selection of a potential personalized therapy for this patient, which was subsequently validated by preclinical testing in patient-derived xenograft models. Overall, our study reveals the impact of analyzing different tumor regions to decipher the ITGH in ECs, which could help make the best treatment decision.

Active interaction switching controls the dynamic heterogeneity of soft colloidal dispersions.

We employ Reactive Dynamical Density Functional Theory (R-DDFT) and Reactive Brownian Dynamics (R-BD) simulations to investigate the dynamics of a suspension of active soft Gaussian colloids with binary interaction switching, i.e., a one-component colloidal system in which every particle stochastically switches at predefined rates between two interaction states with different mobility. Using R-DDFT we extend a theory previously developed to access the dynamics of inhomogeneous liquids [Archer et al., Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2007, 75, 040501] to study the influence of the switching activity on the self and distinct part of the Van Hove function in bulk solution, and determine the corresponding mean squared displacement of the switching particles. Our results demonstrate that, even though the average diffusion coefficient is not affected by the switching activity, it significantly modifies the non-equilibrium dynamics and diffusion coefficients of the individual particles, leading to a crossover from short to long times, with a regime for intermediate times showing anomalous diffusion. In addition, the self-part of the van Hove function has a Gaussian form at short and long times, but becomes non-Gaussian at intermediates ones, having a crossover between short and large displacements. The corresponding self-intermediate scattering function shows the two-step relaxation patters typically observed in soft materials with heterogeneous dynamics such as glasses and gels. We also introduce a phenomenological Continuous Time Random Walk (CTRW) theory to understand the heterogeneous diffusion of this system. R-DDFT results are in excellent agreement with R-BD simulations and the analytical predictions of CTRW theory, thus confirming that R-DDFT constitutes a powerful method to investigate not only the structure and phase behavior, but also the dynamical properties of non-equilibrium active switching colloidal suspensions.

Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish.

BACKGROUND: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. METHODS: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. RESULTS: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. CONCLUSIONS: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.

COVID-19 Lockdown and Mental Health in a Sample Population in Spain: The Role of Self-Compassion.

Previous data support that mental health is affected during pandemic and lockdown situations. Yet, little is known about the positive factors that protect mental health during a lockdown. This study analyzed mental health status-particularly emotional problems-and the role of several sociodemographic and clinical variables; it also explored whether there is a positive relationship between self-compassion and better mental health status. A cross-sectional study was carried out in Spain with the participation of 917 fluent Spanish-speaking residents in a survey conducted approximately midway through the COVID-19 lockdown. The survey tested for anxiety, depression, and stress using the Depression Anxiety Stress Scale-21 (DASS-21), the Self-Compassion Scale (SCS) to measure self-compassion values, and the Perceived Vulnerability to Disease Questionnaire (PVDQ) to assess the degree of risk perceived by participants. Around 30% of the individuals surveyed (recruited by snowball sampling) showed clinically significant levels of anxiety, depression, and stress. The variables most frequently associated with anxiety, depression, and stress were low levels of self-compassion, age, gender, previous physical symptoms, a previous mental disorder, being a student, and perceived vulnerability to disease. We discuss the hypothetical protective role against anxiety, depression, and stress of certain skills such as self-compassion and the possibility that increasing self-compassion may be used to promote better mental health in similar situations.

Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs).

The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion of growth factors, cytokines and chemokines. During metastasis, circulating tumor cells (CTCs) are shed from the primary tumor to the bloodstream, where they can be detected as single cells or clusters. The current knowledge about the biology of CTC clusters positions them as key actors in metastasis formation. It also indicates that CTCs do not act alone and that they may be aided by stromal and immune cells, which seem to shape their metastatic potential. Among these cells, CAFs are found associated with CTCs in heterotypic CTC clusters, and their presence seems to increase their metastatic efficiency. In this review, we summarize the current knowledge on the role that CAFs play on metastasis and we discuss their implication on the biogenesis, metastasis-initiating capacity of CTC clusters, and clinical implications. Moreover, we speculate about possible therapeutic strategies aimed to limit the metastatic potential of CTC clusters involving the targeting of CAFs as well as their difficulties and limitations.

Sampling rare events across dynamical phase transitions.

Interacting particle systems with many degrees of freedom may undergo phase transitions to sustain atypical fluctuations of dynamical observables such as the current or the activity. In some cases, this leads to symmetry-broken space-time trajectories which enhance the probability of such events due to the emergence of ordered structures. Despite their conceptual and practical importance, these dynamical phase transitions (DPTs) at the trajectory level are difficult to characterize due to the low probability of their occurrence. However, during the last decade, advanced computational techniques have been developed to measure rare events in simulations of many-particle systems that allow the direct observation and characterization of these DPTs. Here we review the application of a particular rare-event simulation technique, based on cloning Monte Carlo methods, to characterize DPTs in paradigmatic stochastic lattice gases. In particular, we describe in detail some tricks and tips of the trade, paying special attention to the measurement of order parameters capturing the physics of the different DPTs, as well as to the finite-size effects (both in the system size and in the number of clones) that affect the measurements. Overall, we provide a consistent picture of the phenomenology associated with DPTs and their measurement.

A violation of universality in anomalous Fourier's law.

Since the discovery of long-time tails, it has been clear that Fourier's law in low dimensions is typically anomalous, with a size-dependent heat conductivity, though the nature of the anomaly remains puzzling. The conventional wisdom, supported by renormalization-group arguments and mode-coupling approximations within fluctuating hydrodynamics, is that the anomaly is universal in 1d momentum-conserving systems and belongs in the Lévy/Kardar-Parisi-Zhang universality class. Here we challenge this picture by using a novel scaling method to show unambiguously that universality breaks down in the paradigmatic 1d diatomic hard-point fluid. Hydrodynamic profiles for a broad set of gradients, densities and sizes all collapse onto an universal master curve, showing that (anomalous) Fourier's law holds even deep into the nonlinear regime. This allows to solve the macroscopic transport problem for this model, a solution which compares flawlessly with data and, interestingly, implies the existence of a bound on the heat current in terms of pressure. These results question the renormalization-group and mode-coupling universality predictions for anomalous Fourier's law in 1d, offering a new perspective on transport in low dimensions.

Statistics of the dissipated energy in driven diffusive systems.

Understanding the physics of non-equilibrium systems remains one of the major open questions in statistical physics. This problem can be partially handled by investigating macroscopic fluctuations of key magnitudes that characterise the non-equilibrium behaviour of the system of interest; their statistics, associated structures and microscopic origin. During the last years, some new general and powerful methods have appeared to delve into fluctuating behaviour that have drastically changed the way to address this problem in the realm of diffusive systems: macroscopic fluctuation theory (MFT) and a set of advanced computational techniques that make it possible to measure the probability of rare events. Notwithstanding, a satisfactory theory is still lacking in a particular case of intrinsically non-equilibrium systems, namely those in which energy is not conserved but dissipated continuously in the bulk of the system (e.g. granular media). In this work, we put forward the dissipated energy as a relevant quantity in this case and analyse in a pedagogical way its fluctuations, by making use of a suitable generalisation of macroscopic fluctuation theory to driven dissipative media.

Relaxation dynamics in a transient network fluid with competing gel and glass phases.

We use computer simulations to study the relaxation dynamics of a model for oil-in-water microemulsion droplets linked with telechelic polymers. This system exhibits both gel and glass phases and we show that the competition between these two arrest mechanisms can result in a complex, three-step decay of the time correlation functions, controlled by two different localization lengthscales. For certain combinations of the parameters, this competition gives rise to an anomalous logarithmic decay of the correlation functions and a subdiffusive particle motion, which can be understood as a simple crossover effect between the two relaxation processes. We establish a simple criterion for this logarithmic decay to be observed. We also find a further logarithmically slow relaxation related to the relaxation of floppy clusters of particles in a crowded environment, in agreement with recent findings in other models for dense chemical gels. Finally, we characterize how the competition of gel and glass arrest mechanisms affects the dynamical heterogeneities and show that for certain combination of parameters these heterogeneities can be unusually large. By measuring the four-point dynamical susceptibility, we probe the cooperativity of the motion and find that with increasing coupling this cooperativity shows a maximum before it decreases again, indicating the change in the nature of the relaxation dynamics. Our results suggest that compressing gels to large densities produces novel arrested phases that have a new and complex dynamics.

Scaling laws and bulk-boundary decoupling in heat flow.

When driven out of equilibrium by a temperature gradient, fluids respond by developing a nontrivial, inhomogeneous structure according to the governing macroscopic laws. Here we show that such structure obeys strikingly simple scaling laws arbitrarily far from equilibrium, provided that both macroscopic local equilibrium and Fourier's law hold. Extensive simulations of hard disk fluids confirm the scaling laws even under strong temperature gradients, implying that Fourier's law remains valid in this highly nonlinear regime, with putative corrections absorbed into a nonlinear conductivity functional. In addition, our results show that the scaling laws are robust in the presence of strong finite-size effects, hinting at a subtle bulk-boundary decoupling mechanism which enforces the macroscopic laws on the bulk of the finite-sized fluid. This allows one to measure the marginal anomaly of the heat conductivity predicted for hard disks.

Typical and rare fluctuations in nonlinear driven diffusive systems with dissipation.

We consider fluctuations of the dissipated energy in nonlinear driven diffusive systems subject to bulk dissipation and boundary driving. With this aim, we extend the recently introduced macroscopic fluctuation theory to nonlinear driven dissipative media, starting from the fluctuating hydrodynamic equations describing the system mesoscopic evolution. Interestingly, the action associated with a path in mesoscopic phase space, from which large-deviation functions for macroscopic observables can be derived, has the same simple form as in nondissipative systems. This is a consequence of the quasielasticity of microscopic dynamics, required in order to have a nontrivial competition between diffusion and dissipation at the mesoscale. Euler-Lagrange equations for the optimal density and current fields that sustain an arbitrary dissipation fluctuation are also derived. A perturbative solution thereof shows that the probability distribution of small fluctuations is always Gaussian, as expected from the central limit theorem. On the other hand, strong separation from the Gaussian behavior is observed for large fluctuations, with a distribution which shows no negative branch, thus violating the Gallavotti-Cohen fluctuation theorem, as expected from the irreversibility of the dynamics. The dissipation large-deviation function exhibits simple and general scaling forms for weakly and strongly dissipative systems, with large fluctuations favored in the former case but heavily suppressed in the latter. We apply our results to a general class of diffusive lattice models for which dissipation, nonlinear diffusion, and driving are the key ingredients. The theoretical predictions are compared to extensive numerical simulations of the microscopic models, and excellent agreement is found. Interestingly, the large-deviation function is in some cases nonconvex beyond some dissipation. These results show that a suitable generalization of macroscopic fluctuation theory is capable of describing in detail the fluctuating behavior of nonlinear driven dissipative media.

Nonlinear driven diffusive systems with dissipation: fluctuating hydrodynamics.

We consider a general class of nonlinear diffusive models with bulk dissipation and boundary driving and derive its hydrodynamic description in the large size limit. Both the average macroscopic behavior and the fluctuating properties of the hydrodynamic fields are obtained from the microscopic dynamics. This analysis yields a fluctuating balance equation for the local energy density at the mesoscopic level, characterized by two terms: (i) a diffusive term, with a current that fluctuates around its average behavior given by nonlinear Fourier's law, and (ii) a dissipation term which is a general function of the local energy density. The quasielasticity of microscopic dynamics, required in order to have a nontrivial competition between diffusion and dissipation in the macroscopic limit, implies a noiseless dissipation term in the balance equation, so dissipation fluctuations are enslaved to those of the density field. The microscopic complexity is thus condensed in just three transport coefficients-the diffusivity, the mobility, and a new dissipation coefficient-which are explicitly calculated within a local equilibrium approximation. Interestingly, the diffusivity and mobility coefficients obey an Einstein relation despite the fully nonequilibrium character of the problem. The general theory here presented is applied to a particular albeit broad family of systems, the simplest nonlinear dissipative variant of the so-called KMP model for heat transport. The theoretical predictions are compared to extensive numerical simulations, and an excellent agreement is found.