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Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease for which better therapies are urgently needed. Fibroblasts and macrophages are heterogeneous cell populations able to enhance metastasis, but the role of a macrophage-fibroblast crosstalk in regulating their pro-metastatic functions remains poorly understood. Here we deconvolve how macrophages regulate metastasis-associated fibroblast (MAF) heterogeneity in the liver. We identify three functionally distinct MAF populations, among which the generation of pro-metastatic and immunoregulatory myofibroblastic-MAFs (myMAFs) critically depends on macrophages. Mechanistically, myMAFs are induced through a STAT3-dependent mechanism driven by macrophage-derived progranulin and cancer cell-secreted leukaemia inhibitory factor (LIF). In a reciprocal manner, myMAF secreted osteopontin promotes an immunosuppressive macrophage phenotype resulting in the inhibition of cytotoxic T cell functions. Pharmacological blockade of STAT3 or myMAF-specific genetic depletion of STAT3 restores an anti-tumour immune response and reduces metastases. Our findings provide molecular insights into the complex macrophage–fibroblast interactions in tumours and reveal potential targets to inhibit PDAC liver metastasis.

Abstract Mercury (Hg) pollution in agricultural soils and its potential pathway to the human food chain can pose a serious health concern. Understanding the pathway of Hg in plants and how the speciation may change upon interaction with other elements used for biofortification can be critical to assess the real implications for the final plant-based product. In that respect, selenium (Se) biofortification of crops grown in Se-poor soil regions is becoming a common practice to overcome Se deficient diets. Therefore, it is important to assess the interplay between these two elements since Se may form complexes with Hg reducing its bioavailability and toxicity. In this work, the speciation of Hg in wheat plants grown hydroponically under the presence of Hg (HgCl2) and biofortified with Se (selenite, selenate, or a 1:1 mixture of both) has been investigated by X-ray absorption spectroscopy at the Hg L3-edge. The main Hg species found in wheat grains was the highly toxic methylmercury. It was found that the Se-biofortification of wheat did not prevent, in general, the Hg translocation to grains. Only the 1:1 mixture treatment seemed to have an effect in reducing the levels of Hg and the presence of methylmercury in grains.

Abstract Tumor growth is the result of the interplay of complex biological processes in huge numbers of individual cells living in changing environments. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or simple animal models with bounded-growth dynamics accurately. However, results for the growth of human cancers in patients are scarce. Our study mined a large dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up to find growth laws for untreated BMs and recurrent treated BMs. Untreated BMs showed high growth exponents, most likely related to the underlying evolutionary dynamics, with experimental tumors in mice resembling accurately the disease. Recurrent BMs growth exponents were smaller, most probably due to a reduction in tumor heterogeneity after treatment, which may limit the tumor evolutionary capabilities. In silico simulations using a stochastic discrete mesoscopic model with basic evolutionary dynamics led to results in line with the observed data.

Purpose: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. Materials and methods: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. Results: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808–0.861), SUVmean (r = 0.794–0.851) and TBR (r = 0.643–0.784), p

Summary: Organotypic brain cultures are short-term assays that phenotypically and functionally recapitulate brain metastatic cells in vivo. Here, we present a protocol to generate murine organotypic brain cultures for drug screening. We describe steps for sectioning of murine brains and plating of organotypic cultures. We then detail evaluation of the anti-metastatic effect of chemical compounds through bioluminescence imaging before and after drug treatment. Combined with downstream applications, this protocol allows comprehensive characterizations of both cancer cells and the tumor-associated microenvironment.For complete details on the use and execution of this protocol, please refer to Zhu et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Increasing levels of boron in water exceeding acceptable thresholds have triggered concerns regarding environmental pollution and adverse health effects. In response, significant efforts are being made to develop new adsorbents for the removal of boron from contaminated water. Among the various materials proposed, inorganic adsorbents have emerged as promising materials due to their chemical, thermal, and mechanical stability. This review aims to comprehensively examine recent advances made in the development of inorganic adsorbents for the efficient removal of boron from water. Firstly, the adsorption performance of the most used adsorbents, such as magnesium, iron, aluminum, and individual and mixed oxides, are summarized. Subsequently, diverse functionalization methods aimed at enhancing boron adsorption capacity and selectivity are carefully analyzed. Lastly, challenges and future perspectives in this field are highlighted to guide the development of innovative high-performance adsorbents and adsorption systems, ultimately leading to a reduction in boron pollution.

Abstract We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.

We consider interacting one-dimensional bosons in the universal low-energy regime. The interactions consist of a combination of attractive and repulsive parts that can stabilize quantum gases, droplets, and liquids. In particular, we study the role of effective three-body repulsion, in systems with weak attractive pairwise interactions. Its low-energy description is often argued to be equivalent to a model including only two-body interactions with nonzero range. Here, we show that, at zero temperature, the equations of state in both theories agree quantitatively at low densities for overall repulsion, in the gas phase. However, this agreement is absent in the attractive regime, where universality only occurs in the long-distance properties of quantum droplets. We develop analytical tools to investigate the properties of the theory and obtain astounding agreement with exact numerical calculations using the density-matrix renormalization group.

Uncovering the complexity of the microenvironment that emerges in brain disorders is key to identify potential vulnerabilities that might help challenging diseases affecting this organ. Recently, genomic and proteomic analyses, especially at the single cell level, have reported previously unrecognized diversity within brain cell types. The complexity of the brain microenvironment increases during disease partly due to the immune infiltration from the periphery that contributes to redefine the brain connectome by establishing a new crosstalk with resident brain cell types. Within the rewired brain ecosystem, glial cell subpopulations are emerging hubs modulating the dialogue between the Immune System and the Central Nervous System with important consequences in the progression of brain tumors and other disorders. Single cell technologies are crucial not only to define and track the origin of disease-associated cell types, but also to identify their molecular similarities and differences that might be linked to specific brain injuries. These altered molecular patterns derived from reprogramming the healthy brain into an injured organ, might provide a new generation of therapeutic targets to challenge highly prevalent and lethal brain disorders that remain incurable with unprecedented specificity and limited toxicities. In this perspective, we present the most relevant clinical and pre-clinical work regarding the characterization of the heterogeneity within different components of the microenvironment in the healthy and injured brain with a special interest on single cell analysis. Finally, we discuss how understanding the diversity of the brain microenvironment could be exploited for translational purposes, particularly in primary and secondary tumors affecting the brain.

A periodically driven system may show a novel type of topologically protected edge modes that has no static analogue. Here, Mukherjeeet al. report the observation of such anomalous chiral edge modes in an ultrafast-laser-inscribed slowly-driven photonic lattice.

Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3) as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.

The neuro-immune axis has emerged as a key aspect to understand the normal function of the Central Nervous System (CNS) as well as the pathophysiology of many brain disorders. As such, it may represent a promising source for novel therapeutic targets. Glial cells, and in particular the extensively studied microglia, play important roles in brain disorders. Astrocytes, in their reactive state, have been shown to positively and negatively modulate the progression of multiple CNS disorders. These seemingly opposing effects, might stem from their underlying heterogeneity, an aspect that has recently come to light. In this article we will discuss the link between reactive astrocytes and the neuro-immune axis with a perspective on their potential importance in brain tumors. Based on the gained knowledge from studies in other CNS disorders, reactive astrocytes are undoubtfully emerging as a key component of the neuro-immune axis, with ability to modulate both the innate and adaptive branches of the immune system. Lastly, we will discuss how we can exploit our improved understanding of the basic biology of astrocytes to further enhance the efficacy of emerging immune-based therapies in primary brain tumors and brain metastasis.

Brain metastasis, the secondary growth of malignant cells within the central nervous system (CNS), exceeds the incidence of primary brain tumors (i.e., gliomas) by tenfold and are seemingly on the rise owing to the emergence of novel targeted therapies that are more effective in controlling extracranial disease relatively to intracranial lesions. Despite the fact that metastasis to the brain poses a unmet clinical problem, with afflicted patients carrying significant morbidity and a fatal prognosis, our knowledge as to how metastatic cells manage to adapt to the tissue environment of the CNS remains limited. Answering this question could pave the way for novel and more specific therapeutic modalities in brain metastasis by targeting the specific makeup of the brain metastatic niche. In regard to this, astrocytes have emerged as the major host cell type that cancer cells encounter and interact with during brain metastasis formation. Similarly to other CNS disorders, astrocytes become reactive and respond to the presence of cancer cells by changing their phenotype and significantly influencing the outcome of disseminated cancer cells within the CNS. Here, we summarize the current knowledge on the contribution of reactive astrocytes in brain metastasis by focusing on the signaling pathways and types of interactions that play a crucial part in the communication with cancer cells and how these could be translated into innovative therapies.

Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.

This paper aims to synthesize hybrid materials with high pollutant-uptake capacity and low costbased based on Luffa cylindrica (L.C) and different percentage of Zn2+ in the presence and absence of alternating current (AC). Physico-chemical, morphological and structural characterizations of the hybrid materials were performed by Boehm method, point zero charge (pHpzc), infrared characterizations (IR), scanning electron microscopy (SEM), energy−dispersive spectroscopyand and X-ray photoelectron spectroscopy. The efficiency of the designed hybrid materials was optimized based on their performance in water depollution. Methylene blue (MB) and industrial textile wastewater were the investigated pollutants models. IR characterizations confirmed the fixation of Zn2+ onto the L.C by the creation of Zn-OH, Zn-O and Zn-O-C bonds. Boehm titration showed that the fixation of Zn2+ onto L.C is accompanied by an increase of the basic functions of its surface and subsequently an increase in the pHpzc. SEM results confirmed the fixation of Zn2+ onto the L.C coupling AC with biosorption showed an increase in the adsorbed amount of MB and speed when adding the 4% of Zn2+ compared to the pure L.C the Qm shifted from 3.22 to 9.84 and 8.81 mg/g, respectively, for hybrid materials synthesized under AC, in absence of AC and pure L.C.

Fenton and Fenton-like processes, both in homogeneous and heterogeneous phases, have been applied to an aqueous solution containing the dye AR 14 in order to study the mineralization and toxicity of the solutions generated after color elimination. The mineralization of AR 14 occurred slower than the decolorization. The Microtox analysis of the treated solutions showed low toxicity intrinsic to the chemicals used in the process rather than the degradation products obtained after the treatment of the dye solution. The dye degradation for the Fenton oxidation process was initially faster than for the Fenton-like process but after a short time, the four processes showed similar degradation yields. All processes have shown good results being the heterogeneous process the most convenient since the pH adjustment is not necessary, the catalyst is recovered and reused and the generation of contaminated sludge is avoided.

The mechanisms through which cancer cells lock in altered transcriptional programs in support of metastasis remain largely unknown. Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we identified RNA binding motif protein 47 (RBM47) as a suppressor of breast cancer progression and metastasis. RBM47 inhibited breast cancer re-initiation and growth in experimental models. Transcriptome-wide HITS-CLIP analysis revealed widespread RBM47 binding to mRNAs, most prominently in introns and 3′UTRs. RBM47 altered splicing and abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1, inhibit tumor progression downstream of RBM47. Our work identifies RBM47 as an RNA-binding protein that can suppress breast cancer progression and demonstrates how the inactivation of a broadly targeted RNA chaperone enables selection of a pro-metastatic state.

We study the dynamics of a vortex in a quasi two-dimensional Bose gas consisting of light-matter coupled atoms forming two-component pseudo spins. The gas is subject to a density dependent gauge potential, hence governed by an interacting gauge theory, which stems from a collisionally induced detuning between the incident laser frequency and the atomic energy levels. This provides a back-action between the synthetic gauge potential and the matter field. A Lagrangian approach is used to derive an expression for the force acting on a vortex in such a gas. We discuss the similarities between this force and the one predicted by Iordanskii, Lifshitz and Pitaevskii when scattering between a superfluid vortex and the thermal component is taken into account.

It is surprising to note the lack of information usually given by manufacturers about their sprinklers, making it very difficult to correctly select a sprinkler and its working conditions when designing a sprinkler irrigation system or improving an existing one, using only the discharged volume and radius of throwing for every pressure-nozzle combination. This paper shows the results of two studies made principally on three individual sprinklers: one measuring the single-leg distribution curves and the other measuring the complete water distribution model of a sprinkler in windy conditions. Our purpose is therefore to establish a set of general rules valid for selecting a sprinkler. These rules must take into consideration the optimum working conditions that will maximize the possible uniformity of water distribution.

This study compares analytical figures of merit such as sensitivity, background, % 140Ce16O+/140Ce+, 40Ar16O+, time dependent and matrix induced interference effects for solutions containing up to 500 mg L−1Na for a conventional sampler cone designated as the High Performance Interface (HPI) with that obtained with a so-called Xi cone. HPI counts were higher than those observed using the Xi cone by factors of about 10 at low mass, the difference decreasing with increasing mass, and at high mass they were approximately equal to those observed with the Xi cone. As a consequence of low sensitivity when using the Xi interface, there is potential for determining high concentrations of low mass elements. The 4-times lower 40Ar16O+signals and up to two times lower % 140Ce16O+of the Xi cone are important analytical figures of merit for minimizing polyatomic ion interferences.% 140Ce16O+/140Ce+varied considerably with depth of sampling and were much higher in the HPI cone than in the Xi cone at large depths of sampling. Na-induced variations were mass dependent and larger in the Xi cone than in the HPI cone, amounting to about 25 and 60%, respectively. Long-term variations for 250 min amounted to about 10 and 25%, respectively. It is concluded that the HPI cone when coupled to a robust ICP (power > 1.3 kW, nebulizer gas flow rate < 0.85 L min−1) is more suited for routine analysis of environmental samples. However, in cases where oxide ion interferences must be reduced and high concentrations of low mass analytes are to be determined, the Xi cone has advantages. [ABSTRACT FROM AUTHOR]

Abstract  Nowadays there is a great concern about new adsorbent materials for either the removal or fixation of arsenic species because of their high toxicity and the health problems associated with such species. In this paper the kinetics of absorption of As(V) on Fe(III)-loaded sponge have been studied and the results are compared with those of other natural and synthetic adsorbents. Arsenate was adsorbed very rapidly by Fe(III)-loaded sponge with saturation being reached in less than ten minutes. Arsenate was also adsorbed by Fe(III)-loaded Lewatit-TP-207 and non-loaded Purolite A100S ion-exchange resins but the times required to reach total saturation of the adsorbent were more than 100 minutes. The experimental data followed first-order kinetics. The extraordinarily superior kinetics are postulated to be related to the open-celled internal structure of the sponge material. The effect of flow rate on the dynamic removal of As(V) was studied in a fixed-bed column reactor for Fe(III)-loaded sponge and Fe(III)-loaded resin. The adsorption of As(V) on fixed-bed columns of adsorbent also indicated better kinetic properties for the sponge. Column studies showed a good correlation between the experimental data and the calculated breakthrough curves obtained by the Wolborska and Clark models. Application of the Wolborska model to the data at low C/C 0 ratios enabled the determination of the kinetic coefficient of mass transfer for the sponge and resin materials at the different flow rates used and gave a good prediction of the 5% breakthrough times. Furthermore, the breakthrough curves were well described by the Clark model at the ratios of concentration of effluent to influent up to 0.5 for the sponge and 0.3 for the Fe(III)-loaded resin. Above these levels, a large deviation occurred for the resin adsorption. Thus, the sponge was found to be kinetically effective and favored for As(V) adsorption from solution over the conventional adsorbents used and for most of the adsorbents reported in the bibliography. [ABSTRACT FROM AUTHOR]

We consider quantum scattering of particles in media exhibiting strong dispersion degeneracy. In particular, we study flat-banded lattices and linearly dispersed energy bands. The former constitute a prime example of single-particle frustration while the latter show degeneracy at the few- and many-particle level. We investigate both impurity and two-body scattering and show that, quite generally, scattering does not occur, which we relate to the fact that transition matrices vanish on the energy shell. We prove that scattering is instead replaced by projections onto band-projected eigenstates of the interaction potential. We then use the general results to obtain localized flat band states that are eigenstates of impurity potentials with vanishing eigenvalues in one-dimensional flat bands and study the particular case of a sawtooth lattice. We also uncover the relation between certain solutions of one-dimensional systems that have been categorized as ‘strange’, and the scattering states in linearly dispersed continuum systems. [ABSTRACT FROM AUTHOR]

We consider a two-dimensional weakly interacting ultracold Bose gas whose constituents are two-level atoms. We study the effects of a synthetic density-dependent gauge field that arises from laser–matter coupling in the adiabatic limit with a laser configuration such that the single-particle zeroth-order vector potential corresponds to a constant synthetic magnetic field. We find a new exotic type of current nonlinearity in the Gross–Pitaevskii equation which affects the dynamics of the order parameter of the condensate. We investigate the rotational properties of this system in the Thomas–Fermi limit, focusing in particular on the physical conditions that make the existence of a quantized vortex in the system energetically favourable with respect to the non-rotating solution. We point out that two different physical interpretations can be given to this new nonlinearity: firstly it can be seen as a local modification of the mean field coupling constant, whose value depends on the angular momentum of the condensate. Secondly, it can be interpreted as a density modulated angular velocity given to the cloud. Looking at the problem from both of these viewpoints, we show that the effect of the new nonlinearity is to induce a rotation to the condensate, where the transition from non-rotating to rotating states depends on the density of the cloud. [ABSTRACT FROM AUTHOR]