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The pretransitional behavior of dodecylcyanobiphenyl (12CB) (isotropic-smectic-A-solid mesomorphism) with d=50nmBaTiO3 nanoparticles (NPs) linked to the cubic phase was monitored via temperature studies of dielectric constant. Tests were carried out in the isotropic, liquid crystal mesomorphic, and solid phases. For each phase transition the same value of the critical exponent α~0.5 was obtained, including nanocolloids. All phase transitions show the weakly discontinuous nature. The temperature metric of the discontinuity ΔT notably decreases when adding nanoparticles. The addition of nanoparticles first decreases the dielectric constant by approximately 50% in comparison with pure 12CB, but already for a concentration ~x=0.4% NP an increase over 50% takes place. It is notable that for the latter concentration unique hallmarks of the pretransitional effect emerge also for the solid-mesophase transition. All these indicate the important impact of nanoparticles on multimolecular mesoscale fluctuations. [ABSTRACT FROM AUTHOR]

Olivine-like NaFePO 4 glasses and nanocomposites are promising materials for cathodes in sodium batteries. Our previous studies focused on the preparation of NaFePO 4 glass, transforming it into a nanocomposite using high-pressure-high-temperature treatment, and comparing both materials' structural, thermal, and DC electric conductivity. This work focuses on specific features of AC electric conductivity, containing messages on the dynamics of translational processes. Conductivity spectra measured at various temperatures are scaled by apparent DC conductivity and plotted against frequency scaled by DC conductivity and temperature in a so-called master curve representation. Both glass and nanocomposite conductivity spectra are used to test the (effective) exponent using Jonscher's scaling law. In both materials, the values of exponent range from 0.3 to 0.9, with different relation to temperature. It corresponds to the electronic conduction mechanism change from low-temperature Mott's variable range hopping (between Fe 2+ /Fe 3+ centers) to phonon-assisted hopping, which was suggested by previous DC measurements. Following the pressure treatment, AC conductivity activation energies were reduced from EAC≈0.40 eV for glass to EAC≈0.18 eV for nanocomposite and are lower than their DC counterpart, following a typical empirical relation with the value of the exponent. While pressure treatment leads to a 2-3-orders-of-magnitude rise in the AC and apparent DC conductivity due to the reduced distance between the hopping centers, a nonmonotonic relation of AC power exponent and temperature is observed. It occurs due to the disturbance of polaron interactions with Na + mobile ions.

The dynamic heterogeneities occurring just before the transition to the glassy phase have been named as the cause of amorphization in supercooled systems. Numerous studies conducted so far have confirmed this hypothesis, and based on it, a widely accepted solution to the puzzle of glass transition has been developed. This report focuses on verifying the existence of a strong pretransitional anomaly near the glass transition Tg. For this purpose, supercooled liquid-crystalline systems with a strong rod-like structure were selected. Based on the obtained experimental data, we demonstrate in this article that the previously postulated dynamic heterogeneities exhibit a critical characteristic, meaning a strong pretransitional anomaly can be observed with the described critical exponent α=0.5. Due to this property, it can be concluded that these heterogeneities are critical fluctuations, and consequently, the transition to the glassy state can be described based on the theory of critical phenomena. To measure the pretransitional anomaly near Tg in supercooled liquid-crystalline systems, broadband dielectric spectroscopy (BDS) and nonlinear dielectric effect (NDE) methods were applied. The exponent α provides insight into the nature and intensity of critical fluctuations in the system. A value of α=0.5 suggests that the fluctuations become increasingly intense as the system approaches the critical point, contributing to the divergence in specific heat. Understanding the role of critical fluctuations in the glass transition is crucial for innovating and improving a wide range of materials for energy storage, materials design, biomedical applications, food preservation, and environmental sustainability. These advancements can lead to materials with superior properties, optimized manufacturing processes, and applications that meet the demands of modern technology and sustainability challenges.

This model discussion focuses on links between the unique properties of relaxor ceramics and the basics of Critical Phenomena Physics and Glass Transition Physics. It indicates the significance of uniaxiality for the appearance of mean-field type features near the paraelectric-to-ferroelectric phase transition. Pretransitional fluctuations, that are increasing up to the size of a grain and leading to inter-grain, random, local electric fields are responsible for relaxor ceramics characteristics. Their impact yields the pseudospinodal behavior associated with "weakly discontinuous" local phase transitions. The emerging model redefines the meaning of the Burns temperature and polar nanoregions (PNRs). It offers a coherent explanation of "dielectric constant" changes with the "diffused maximum" near the paraelectric-to-ferroelectric transition, the sensitivity to moderate electric fields (tunability), and the "glassy" dynamics. These considerations are challenged by the experimental results of complex dielectric permittivity studies in a Ba 0.65 Sr0. 35 TiO 3 relaxor ceramic, covering ca. 250 K, from the paraelectric to the "deep" ferroelectric phase. The distortion-sensitive and derivative-based analysis in the paraelectric phase and the surrounding paraelectric-to-ferroelectric transition reveal a preference for the exponential scaling pattern for ε ( T ) changes. This may suggest that Griffith-phase behavior is associated with mean-field criticality disturbed by random local impacts. The preference for the universalistic "critical & activated" evolution of the primary relaxation time is shown for dynamics. The discussion is supplemented by a coupled energy loss analysis. The electric field-related tunability studies lead to scaling relationships describing their temperature changes.

One critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays. The tumor cell lines were grouped into three subsets by their canonical E-selectin ligand status (sialyl-Lewis A and X +/+, -/+, -/-) and their adhesiveness was compared after enzymatic, pharmacologic, chemical treatment or antibody blockade of the tumor cells or endothelial cells, respectively. Tumor cells were also screened regarding their glycosyltransferase expression profile. We found that although E-selectin and terminal α2,3-sialic acid largely determined firm adhesion, adhesive events did not exclusively depend on the presence of sialyl-Lewis A and/or sialyl-Lewis X. Nevertheless, two of the three sialyl-Lewis A/X-/- tumor cells additionally or fully depended on vascular cell adhesion molecule-1 for firm adhesion. The significance of O-GalNAc- and N-glycans for adhesion varied remarkably among the tumor cells. The sialyl-Lewis A/X+/+ subset showed glycoprotein-independent adhesion, suggesting a role of glycolipids as well. All sialyl-Lewis A/X-/- tumor cells lacked FUT3 and FUT7 expression as opposed to sialyl-Lewis A/X+/+ or -/+ cell lines. In summary, the glycans on tumor cells mediating endothelial adhesion are not as much restricted to sialyl-Lewis A /X as previously assumed. The present study specifically suggests α2,3-linked sialic acid, O-GalNAc glycans, glycosphingolipids, and FUT3/FUT7 products as promising targets for future studies., (© The Author(s) 2023. Published by Oxford University Press.)

The properties of composites of mesogens and two-dimensional (2D) materials are of great interest due to their practical applications in flexible displays, optoelectronics, microelectronics, and novel nanodevices. The properties of such composites are very complex and strongly depend on the interactions between the host material and the mesogen filling. We have performed molecular dynamics simulations for 4-cyano-4^{'}-pentylbiphenyl embedded between graphene and hexagonal 2D boron nitride layers. The structural and dynamical properties of such systems were investigated in terms of the order parameters, density profiles, mean square displacement, and autocorrelation function of the single-molecule dipole moment. Our simulations have shown that the mesogenic molecules form highly stable ordered layered structures and that their dynamics are strongly related to the structural properties. We have investigated not only the effects of the polarization of the host material, but also the effects of the spatial repetition of such composites by using two models of mesogens embedded in 2D layers: the direct sheet and the structure formed by multiplying a single unit of the composite in the direction perpendicular to the substrate surface.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis., Competing Interests: Declaration of interests S.K. declares honoraria from GSK, BMS, Novartis, and TCR2, Inc.; license fees from TCR2, Inc. and Carina Biotech; and research support from TCR2, Inc., Plectonic GmbH, Tabby Therapeutics, and Arcus Biosciences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

A new nanocomposite material was prepared by high pressure processing of starting glass of nominal composition NaFePO4. Thermal, structural, electrical and dielectric properties of the prepared samples were studied by differential thermal analysis (DTA), X-ray diffraction (XRD) and broadband dielectric spectroscopy (BDS). It was demonstrated that high-pressure-high-temperature treatment (HPHT) led to an increase in the electrical conductivity of the initial glasses by two orders of magnitude. It was also shown that the observed effect was stronger than for the lithium analogue of this material studied by us earlier. The observed enhancement of conductivity was explained by Mott's theory of electron hopping, which is more frequent in samples after pressure treatment. The final composite consisted of nanocrystalline NASICON (sodium (Na) Super Ionic CONductor) and alluaudite phases, which are electrochemically active in potential cathode materials for Na batteries. Average dimensions of crystallites estimated from XRD studies were between 40 and 90 nm, depending on the phase. Some new aspects of local dielectric relaxations in studied materials were also discussed. It was shown that a combination of high pressures and BDS method is a powerful method to study relaxation processes and molecular movements in solids. It was also pointed out that high-pressure cathode materials may exhibit higher volumetric capacities compared with commercially used cathodes with carbon additions.

Merkel cell polyomavirus is the causative agent for most Merkel cell carcinomas (MCCs). This highly aggressive skin cancer shows rapid progression, with metastasis being a significant challenge for patient therapy. Virus-positive MCCs show low mutation rates, and tumor cell proliferation is dependent on viral oncoproteins small T antigen (sT) and large T antigen. Although the role of sT and large T antigen in early events of tumorigenesis has been extensively studied, their role in tumor progression has been scarcely addressed. In this study, we investigate the possible mechanisms of how Merkel cell polyomavirus oncoproteins, particularly sTs, contribute to metastasis. We show that sT specifically affects selectin ligand binding and processing by altering the presentation of multiple MCC surface molecules, thereby influencing initial metastasis events and tumor cell immune recognition. Furthermore, we show that sT regulates the surface antigen CD47, which inhibits phagocytosis by macrophages. By applying either sT short hairpin RNAs, CD47-targeted small interfering RNAs, or a therapeutic anti-CD47 antibody, we show that immune recognition of MCC cells can be restored. Thus, CD47 is a promising therapeutic target on MCC cells. Blocking the CD47‒SIRPα interaction effectively promotes phagocytosis of MCC cells and might be a promising combinatorial immunotherapy approach together with PD-1/PD-L1 axis in MCC treatment., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We consider history-dependent behavior in domain-type configurations in orientational order that are formed in configurations reached via continuous symmetry-breaking phase transitions. In equilibrium, these systems exhibit in absence of impurities a spatially homogeneous order. We focus on cases where domains are formed via (i) Kibble-Zurek mechanism in fast enough quenches or by (ii) Kibble mechanism in strongly supercooled phases. In both cases, domains could be arrested due to pinned topological defects that are formed at domain walls. In systems exhibiting polar or quadrupolar order, point and line defects (disclinations) dominate, respectively. In particular, the disclinations could form complex entangled structures and are more efficient in stabilizing domains. Domain patterns formed by fast quenches could be arrested by impurities imposing a strong enough random-field type disorder, as suggested by the Imry-Ma theorem. On the other hand, domains formed in supercooled systems could be also formed if large enough energy barriers arresting domains are established due to large enough systems' stiffness. The resulting effective interactions in established domain-type patterns could be described by random matrices. The resulting eigenvectors reveal expected structural excitations formed in such structures. The most important role is commonly played by the random matrix largest eigenvector. Qualitatively different behavior is expected if this eigenvector exhibits a localized or extended character. In the former case, one expects a gradual, non-critical-type transition into a glass-type structure. However, in the latter case, a critical-like phase behavior could be observed., (© 2022. The Author(s).)

LiFePO 4 is an important base material for generation of new batteries. One of the important developments is its use in the form of a solid glass, which allows an increase in the electrical conductivity after the high-pressure process. Such a treatment allows full control of the vitrification and nanocrystallization processes as well. This report shows the basic reference for the pressure dependence of the glass transition temperature. The unique behavior has been proven with a maximum of T g ( P ) already at moderate pressures. The protocol for depicting the resulting evolution is as follows: it enables a reliable extrapolation beyond the experimental domain. The importance of the presented results for the general topic of glass transition physics is also remarkable due to the scant evidence of the existence of systems with clearly inverted vitrification under compression.

Heparan sulfate (HS), a highly negatively charged glycosaminoglycan, is ubiquitously present in all tissues and also exposed on the surface of mammalian cells. A plethora of molecules such as growth factors, cytokines or coagulation factors bear HS binding sites. Accordingly, HS controls the communication of cells with their environment and therefore numerous physiological and pathophysiological processes such as cell adhesion, migration, and cancer cell metastasis. In the present work, we found that HS exposed by blood circulating melanoma cells recruited considerable amounts of plasmatic von Willebrand factor (vWF) to the cellular surface. Analyses assisted by super-resolution microscopy indicated that HS and vWF formed a tight molecular complex. Enzymatic removal of HS or genetic engineering of the HS biosynthesis showed that a reduced length of the HS chains or complete lack of HS was associated with significantly reduced vWF encapsulation. In microfluidic experiments, mimicking a tumor-activated vascular system, we found that vWF-HS complexes prevented vascular adhesion. In line with this, single molecular force spectroscopy suggested that the vWF-HS complex promoted the repulsion of circulating cancer cells from the blood vessel wall to counteract metastasis. Experiments in wild type and vWF knockout mice confirmed that the HS-vWF complex at the melanoma cell surface attenuated hematogenous metastasis, whereas melanoma cells lacking HS evade the anti-metastatic recognition by vWF. Analysis of tissue samples obtained from melanoma patients validated that metastatic melanoma cells produce less HS. Transcriptome data further suggest that attenuated expression of HS-related genes correlate with metastases and reduced patients' survival. In conclusion, we showed that HS-mediated binding of plasmatic vWF to the cellular surface can reduce the hematogenous spread of melanoma. Cancer cells with low HS levels evade vWF recognition and are thus prone to form metastases. Therefore, therapeutic expansion of the cancer cell exposed HS may prevent tumor progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Results of broadband dielectric spectroscopy studies in liquid crystalline octyloxycyanobiphenyl (8OCB) and its colloids with BaTiO 3 nanoparticles (paraelectric, diameter d = 50 nm) are presented. Studies were carried out in isotropic liquid, nematic, smectic A and solid crystalline phases. They are supported by derivative-based and distortion-sensitive analyses, revealing a set of universal scaling patterns for temperature evolution of static and dynamic dielectric properties. All these yielded evidence for a pretransitional fluctuation impact on the dielectric constant, primary relaxation time, loss curve maximum and translational-orientational decoupling associated with anomalous values of the fractional Debye-Stokes-Einstein (DSE) exponent 0.2 < S < 2.2. The evidence for critical like changes in a distribution of relaxation times is shown. For mesophases, a tiny addition of nanoparticles causes permanent orientation of LC molecules, leading even to a 16% increase of the dielectric constant above a maximal value in pure 8OCB. A split of two regions, dominated by pre-isotropic and pre-smectic fluctuations, is evidenced. Model explanations for detected phenomena, particularly in the isotropic liquid phase, are presented. New evidence for a premelting effect in the solid phase is also shown.

Extravasation of circulating tumor cells (CTCs) is critical for metastasis and is initiated by adhesive interactions between glycoligands on CTCs and E-selectin on endothelia. Here, we show that the clinically approved proteasome inhibitor bortezomib (BZM; Velcade) counteracts the cytokine-dependent induction of E-selectin in the lung mediated by the primary tumor, thereby impairing endothelial adhesion and thus spontaneous lung metastasis in vivo. However, the efficacy of BZM crucially depends on the tumor cells' E-selectin ligands, which determine distinct adhesion patterns. The canonical ligands sialyl-Lewis A (sLeA) and sLeX mediate particularly high-affinity E-selectin binding so that the incomplete E-selectin-reducing effect of BZM is not sufficient to disrupt adhesion or metastasis. In contrast, tumor cells lacking sLeA/X nevertheless bind E-selectin, but with low affinity, so that adhesion and lung metastasis are significantly diminished. Such low-affinity E-selectin ligands apparently consist of sialylated MGAT5 products on CD44. BZM no longer has anti-metastatic activity after CD44 knockdown in sLeA/X-negative tumor cells or E-selectin knockout in mice. sLeA/X can be determined by immunohistochemistry in cancer samples, which might aid patient stratification. These data suggest that BZM might act as a drug for inhibiting extravasation and thus distant metastasis formation in malignancies expressing low-affinity E-selectin ligands., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

We show that on cooling towards glass transition configurational entropy exhibits more significant changes than predicted by classic relation. A universal formula according to Kauzmann temperature [Formula: see text] is given: [Formula: see text], where [Formula: see text]. The exponent [Formula: see text] is hypothetically linked to dominated local symmetry. Such a behaviour is coupled to previtreous evolution of heat capacity [Formula: see text] associated with finite temperature singularity. These lead to generalised VFT relation, for which the basic equation is retrieved. For many glass-formers, basic VFT equation may have only an effective meaning. A universal-like reliability of the Stickel operator analysis for detecting dynamic crossover phenomenon is also questioned. Notably, distortions-sensitive and derivative-based analysis focused on previtreous changes of configurational entropy and heat capacity for glycerol, ethanol and liquid crystal is applied., (© 2022. The Author(s).)

The outcome of prostate cancer (PCa) patients is highly variable and depends on whether or not distant metastases occur. Multiple chromosomal deletions have been linked to early tumor marker PSA recurrence (biochemical relapse, BCR) after radical prostatectomy (RP), but their potential role for distant metastasis formation is largely unknown. Here, we specifically analyzed whether deletion of the tumor suppressor CHD1 (5q21) influences the post-surgical risk of distant metastasis and whether CHD1 loss directly contributes to metastasis formation in vivo. By considering >6800 patients we found that the CHD1 deletion negatively influences metastasis-free survival in R0 patients (HR: 2.32; 95% CI: 1.61, 3.33; p < 0.001) independent of preoperative PSA, pT stage, pN status, Gleason Score, and BCR. Moreover, CHD1 deletion predicts shortened BCR-free survival in pT2 patients and cancer-specific survival in all patients. In vivo, CHD1 loss increases spontaneous pulmonary metastasis formation in two distinct PCa models coupled with a higher number of multicellular colonies as compared to single-cell metastases. Transcriptome analyses revealed down-regulation of the PCa-specific metastasis suppressor and TGFβ signaling regulator PMEPA1 after CHD1 depletion in both tested PCa models. CHD1 loss increases the risk of postoperative metastasis in R0-resected PCa patients and promotes spontaneous metastasis formation in vivo., (© 2021. The Author(s).)

This article presents evidence for the long-range previtreous changes of two static properties: the dielectric constant ( ε ) and its strong electric field related counterpart, the nonlinear dielectric effect (NDE). Important evidence is provided for the functional characterizations of ε ( T ) temperature changes by the 'Mossotti Catastrophe' formula, as well as for the NDE vs. T evolution by the relations resembling those developed for critical liquids. The analysis of the dynamic properties, based on the activation energy index, excluded the Vogel-Fulcher-Tammann (VFT) relation as a validated tool for portraying the evolution of the primary relaxation time. This result questions the commonly applied 'Stickel operator' routine as the most reliable tool for determining the dynamic crossover temperature. In particular, the strong electric field radically affects the distribution of the relaxation times, the form of the evolution of the primary relaxation time, and the fragility. The results obtained in this paper support the concept of a possible semi-continuous phase transition hidden below T g . The studies were carried out in supercooled squalene, a material with an extremely low electric conductivity, a strongly elongated molecule, and which is vitally important for biology and medicine related issues.

Mammalian platelets, devoid of nuclei, are the smallest cells in the blood stream. They are essential for hemostasis, but also transmit cell signals that are necessary for regenerative and generative processes such as inflammation, immunity and tissue repair. In particular, in malignancies they are also associated with cell proliferation, angiogenesis, and epithelial-mesenchymal transition. Platelets promote metastasis and resistance to anti-tumor treatment. However, fundamental principles of the interaction between them and target cells within tumors are complex and still quite obscure. When injected into animals or circulating in the blood of cancer patients, cancer cells ligate platelets in a timely manner closely related to platelet activation either by direct contact or by cell-derived substances or microvesicles. In this context, a large number of different surface molecules and transduction mechanisms have been identified, although the results are sometimes species-specific and not always valid to humans. In this mini-review, we briefly summarize the current knowledge on the role of the direct and indirect platelet-tumor interaction for single steps of the metastatic cascade and specifically focus on the functional role of P-selectin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fabricius, Starzonek and Lange.)

We report on strong pretransitional effects across the isotropic liquid-plastic crystal melting temperature in linear and nonlinear dielectric response. Studies were carried out for cyclooctanol (C 8 H 16 O) in the unprecedented range of temperatures 120 K < T < 345 K. Such pretransitional effects have not yet been reported in any plastic crystals. Results include the discovery of the experimental manifestation of the Mossotti Catastrophe behavior, so far considered only as a hypothetical paradox. The model interpretations of experimental findings are proposed. We compare the observed pretransitional behavior with the one observed in octyloxycyanobiphenyl (8OCB), typical liquid crystal (LC), displaying a reversed sequence of phase transitions in orientational and translational degrees of order on varying temperature. Furthermore, in its nematic phase, we demonstrate first-ever observed temperature-driven crossover between regions dominated by isotropic liquid and smectic A pretransitional fluctuations. We propose a pioneering minimal model describing plastic crystal phase behavior where we mimic derivation of classical Landau-de Gennes-Ginzburg modeling of Isotropic-Nematic-Smectic A LC phase behavior.

The report shows the strong impact of fullerene C 60 nanoparticles on phase transitions and complex dynamics of rod-like liquid crystal dodecylcyanobiphenyl (12CB), within the limit of small concentrations. Studies were carried out using broadband dielectric spectroscopy (BDS) via the analysis of temperature dependences of the dielectric constant, the maximum of the primary loss curve, and relaxation times. They revealed a strong impact of nanoparticles, leading to a ~20% change of dielectric constant even at x = 0.05% of C 60 fullerene. The application of the derivative-based and distortion-sensitive analysis showed that pretransitional effects dominate in the isotropic liquid phase up to 65 K above the clearing temperature and in the whole Smectic A mesophase. The impact of nanoparticles on the pretransitional anomaly appearance is notable for the smectic-solid phase transition. The fragility-based analysis of relaxation times revealed the universal pattern of its temperature changes, associated with scaling via the "mixed" ("activated" and "critical") relation. Phase behavior and dynamics of tested systems are discussed within the extended Landau-de Gennes-Ginzburg mesoscopic approach.

Background: Distant metastasis formation is the major clinical problem in prostate cancer (PCa) and the underlying mechanisms remain poorly understood. Our aim was to identify novel molecules that functionally contribute to human PCa systemic dissemination based on unbiased approaches., Methods: We compared mRNA, microRNA (miR) and protein expression levels in established human PCa xenograft tumours with high (PC-3), moderate (VCaP) or weak (DU-145) spontaneous micrometastatic potential. By focussing on those mRNAs, miRs and proteins that were differentially regulated among the xenograft groups and known to interact with each other we constructed dissemination-related mRNA/miR and protein/miR networks. Next, we clinically and functionally validated our findings., Results: Besides known determinants of PCa progression and/or metastasis, our interaction networks include several novel candidates. We observed a clear role of epithelial-to-mesenchymal transition (EMT) pathways for PCa dissemination, which was additionally confirmed by an independent human PCa model (ARCAP-E/-M). Two converging nodes, CD46 (decreasing with metastatic potential) and DDX21 (increasing with metastatic potential), were used to test the clinical relevance of the networks. Intriguingly, both network nodes consistently added prognostic information for patients with PCa whereas CD46 loss predicted poor outcome independent of established parameters. Accordingly, depletion of CD46 in weakly metastatic PCa cells induced EMT-like properties in vitro and spontaneous micrometastasis formation in vivo., Conclusions: The clinical and functional relevance of the dissemination-related interaction networks shown here could be successfully validated by proof-of-principle experiments. Therefore, we suggest a direct pro-metastatic, clinically relevant role for the multiple novel candidates included in this study; these should be further exploited by future studies., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Endothelial E- and P-selectins promote metastasis formation by interacting with sialyl-Lewis X and A (sLeX/sLeA) on circulating tumor cells. This interaction precedes extravasation and can take place under dynamic and static conditions. Metastasis formation is often studied in xenograft models. However, it is unclear whether species differences exist in the ligand specificity of human (h) vs. murine (m) selectins and whether different ligands are functional under dynamic vs. static conditions. We systematically compared the h vs. m E- and P-selectin (ESel/PSel) binding of a range of human tumor cells under dynamic vs. static conditions. The tumor cells were categorized by their sLeA/X status (sLeA+/sLeX+, sLeA-/sLeX+ and sLeA-/sLeX-). The general biological nature of the tumor-selectin interaction was analyzed by applying several tumor cell treatments (anti-sLeA/X blockade, neuraminidase, pronase and inhibition of O/N-glycosylation). We observed remarkable differences in the static vs. dynamic interaction of tumor cells with h vs. m ESel/PSel depending on their sLeA/X status. The tumor cell treatments mostly affected either static or dynamic as well as either h- or m-selectin interaction. mESel showed a higher diversity of potential ligands than hESel. Inhibition of O-GalNAc-glycosylation also affected glycosphingolipid synthesis. Summarized, different ligands on human tumor cells are functional under static vs. dynamic conditions and for the interaction with human vs. murine ESel/PSel. Non-canonical selectin ligands lacking the sLeA/X glycan epitopes exist on human tumor cells. These findings have important implications for the current development of glycomimetic, antimetastatic drugs and encourage the development of immunodeficient mice with humanized selectins., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of the study was to investigate the effect of high-pressure processing (HPP) and thermal processing (TP) on the bioaccessibility of vitamin C and anthocyanins as well as changes in the antioxidant capacity (AC) using ABTS+• and DPPH• tests on blackcurrant ( Ribes nigrum L.) puree during the steps in the digestive process. The puree was subjected to HPP at 200, 400, and 600 MPa for 5 min (room temperature) or TP at 85 °C for 10 min. The controls were untreated puree (P) and fruit crushed in a mortar (M). All the samples were digested in a static in vitro digestion model, including the mouth, stomach, and small intestine, and subjected to dialysis. The vitamin C, anthocyanin, and antioxidant capacity were monitored at each step of the digestion process. The potential bioaccessibility of the antioxidants studied was calculated in relation to the undigested sample. TP and HPP enabled a high content of vitamin C, anthocyanins, and AC to be maintained. After simulated digestion in the small intestine, a significant decrease was observed in the vitamin C and anthocyanins (approximately 98%) content. However, a high stability (approximately 70%) of both compounds was noted at the gastric stage. HPP and TP significantly affected the potential bioaccessibility of vitamin C and anthocyanins, although the bioaccessibility of both compounds in the samples treated using HPP was higher than when using TP. Moreover, the potential bioaccessibility of vitamin C after HPP treatment (400 and 600 MPa) was higher than the bioaccessibility calculated for the M and P control samples. TP and HPP treatment negatively affected anthocyanin bioaccessibility after dialysis. The most favorable pressure was 400 MPa, as it allowed maintaining the best antioxidant activity after digestion.

The majority of cancer-related deaths are due to hematogenous metastases, and the bone marrow (BM) represents one of the most frequent metastatic sites. To study BM metastasis formation in vivo, the most efficient approach is based on intracardiac injection of human tumor cells into immunodeficient mice. However, such a procedure circumvents the early steps of the metastatic cascade. Here we describe the development of xenograft mouse models (balb/c rag2 and severe combined immunodeficient (SCID)), in which BM metastases are spontaneously derived from subcutaneous (s.c.) primary tumors (PTs). As verified by histology, the described methodology including ex vivo bioluminescence imaging (BLI) even enabled the detection of micrometastases in the BM. Furthermore, we established sublines from xenograft primary tumors (PTs) and corresponding BM (BM) metastases using LAN-1 neuroblastoma xenografts as a first example. In vitro "metastasis" assays (viability, proliferation, transmigration, invasion, colony formation) partially indicated pro-metastatic features of the LAN-1-BM compared to the LAN-1-PT subline. Unexpectedly, after s.c. re-injection into mice, LAN-1-BM xenografts developed spontaneous BM metastases less frequently than LAN-1-PT xenografts. This study provides a novel methodologic approach for modelling the spontaneous metastatic cascade of human BM metastasis formation in mice. Moreover, our data indicate that putative bone-metastatic features get rapidly lost upon routine cell culture.-/- and severe combined immunodeficient (SCID)), in which BM metastases are spontaneously derived from subcutaneous (s.c.) primary tumors (PTs). As verified by histology, the described methodology including ex vivo bioluminescence imaging (BLI) even enabled the detection of micrometastases in the BM. Furthermore, we established sublines from xenograft primary tumors (PTs) and corresponding BM (BM) metastases using LAN-1 neuroblastoma xenografts as a first example. In vitro "metastasis" assays (viability, proliferation, transmigration, invasion, colony formation) partially indicated pro-metastatic features of the LAN-1-BM compared to the LAN-1-PT subline. Unexpectedly, after s.c. re-injection into mice, LAN-1-BM xenografts developed spontaneous BM metastases less frequently than LAN-1-PT xenografts. This study provides a novel methodologic approach for modelling the spontaneous metastatic cascade of human BM metastasis formation in mice. Moreover, our data indicate that putative bone-metastatic features get rapidly lost upon routine cell culture., Competing Interests: All authors declare that they have no financial or personal conflicts of interest related to this study.

We investigated the impact of high pressure and high-temperature annealing on lithium-vanadium-iron-phosphate (LiFe 0.75 V 0.10 PO 4 ) glass materials, proposed for the use in cathodes for high-performance batteries. The treatment was carried out below the glass transition temperature (T g ≈ 483 °C) at P = 1 GPa pressure, in an argon atmosphere. It led to the multifold electrical conductivity increase. Broadband dielectric spectroscopy (BDS) measurements before and after the process revealed the strong DC-conductivity increase across the whole studied frequency range by two orders of magnitude. The phenomenon is explained using Mott's theory of polaron hopping in disordered solids containing transition metal oxides. The pressure evolution of the glass transition temperature and the crystallisation temperature above T g is shown.

This report presents the results of high-pressure and broadband dielectric spectroscopy studies in polyvinylidene difluoride (PVDF) and barium strontium titanate (BST) microparticles composites (BST/PVDF). It shows that the Arrhenius behaviour for the temperature-related dynamics under atmospheric pressure is coupled to Super-Arrhenius/Super-Barus isothermal pressure changes of the primary relaxation time. Following these results, an explanation of the unique behaviour of the BST/PVDF composite is proposed. Subsequently, it is shown that when approaching the GPa domain the negative electric capacitance phenomenon occurs.

Results of broad-band dielectric spectroscopy studies in liquid crystal (pentylcyanobiphenyl, 5CB)-based nanocolloids are presented. They reveal the strong impact of BaTiO&#95;{3} nanoparticles on dynamics and uniaxial ordering. Studies were carried out in an extreme range of temperatures (∼150 K), including the supercooled nematic phase. For the latter, the unique "pretransitional" effect for dielectric constant on approaching solid state is reported. The distortion-sensitive analysis revealed super-Arrhenius dynamics but associated with critical-like behavior. In the isotropic phase, translational-orientational decoupling, unusual for the high temperature dynamic domain, was detected. It can be directly link to heterogeneities-prenematic fluctuations. The model linking the classical Landau-de Gennes approach with Imry-Ma arguments has been developed to discuss experimental results.

We studied properties of monolayer films of n-cyanobiphenyl (with n=5,...,8) series of mesogens anchored on the surface of single walled boron nitride nanotube. In order to assess the impact of substrate polarization on the ordering effects we compare translational and reorientational dynamics of the films with the characteristics of analogous carbon and silicon carbide nanotube based systems. We observed significant increase of the ordering degree accompanied by increased thermal stability. This ordering is less selective than those induced by the silicon carbide nanotube, which were previously reported. The antiparallel orientation of the nearest neighboring mesogens is predominant, while the system does not exhibit any long-range spatial correlations which indicates that the size of the domains is constrained to this region. These features might be of potential importance in the design of novel optoelectronic devices.

The previtreous dynamics in the glass-forming monomer, glycerol monoacrylate (GMA), was tested using the broadband dielectric spectroscopy (BDS). The measurements revealed a clear dynamic crossover at the temperature [Formula: see text] K and the time scale [Formula: see text] ns for the primary (structural) relaxation time and no hallmarks for the crossover for the DC electric conductivity [Formula: see text]. This result was revealed via the derivative-based and distortions-sensitive analysis [Formula: see text] vs. [Formula: see text] , where [Formula: see text] stands for the apparent activation energy. Subsequent tests of the fractional Debye-Stokes-Einsten relation [Formula: see text] showed that the crossover is associated with [Formula: see text] [Formula: see text] (for [Formula: see text]. The crossover coexists with the emergence of the secondary beta relaxation, which smoothly develops deeply into the solid amorphous phase below the glass temperature [Formula: see text].

The pretransitional behavior of dodecylcyanobiphenyl (12CB) (isotropic-smectic-A-solid mesomorphism) with d=50nmBaTiO(3) nanoparticles (NPs) linked to the cubic phase was monitored via temperature studies of dielectric constant. Tests were carried out in the isotropic, liquid crystal mesomorphic, and solid phases. For each phase transition the same value of the critical exponent α∼0.5 was obtained, including nanocolloids. All phase transitions show the weakly discontinuous nature. The temperature metric of the discontinuity ΔT notably decreases when adding nanoparticles. The addition of nanoparticles first decreases the dielectric constant by approximately 50% in comparison with pure 12CB, but already for a concentration ∼x=0.4% NP an increase over 50% takes place. It is notable that for the latter concentration unique hallmarks of the pretransitional effect emerge also for the solid-mesophase transition. All these indicate the important impact of nanoparticles on multimolecular mesoscale fluctuations.

One of the major features of glass forming ultraviscous liquids is the decoupling between translational and orientational dynamics. This paper presents studies of this phenomenon in glycerol, an accepted molecular glass former, concentrating on the impact of two exogenic factors: high pressures (P) up to the extreme 1.5 GPa and silver (Ag) nanoparticles (NPs). The analysis is focused on the fractional Debye-Stokes-Einstein (FDSE) relationship: σ(T,P)(τ(T,P))(S) = const, linking DC electric conductivity (σ) and primary (alpha, structural) relaxation time (τα). In glycerol and its nanocolloid (glycerol + Ag NPs) at atmospheric pressure only negligible decoupling (S ∼ 1) was detected. However, in the compressed nanocolloid, a well-defined transformation (at P = 1.2 GPa) from S ∼ 1 to the very strongly decoupled dynamics (S ∼ 0.5) occurred. For comparison, in pressurized 'pure' glycerol the stretched shift from S ∼ 1 to S ∼ 0.7 took place. This paper also presents the general discussion of FDSE behavior in ultraviscous liquids, including the new link between the FDSE exponent, fragility and the apparent activation enthalpy and volume.

The concept of 'fragility' constitutes a central point of the glass transition science serving as the 'universal' metric linking previtreous dynamics of qualitatively distinct systems. Finding the fundamental meaning of fragility is the 'condicio sine qua' for reaching the long expected conceptual breakthrough in this domain. This report shows that fragility is determined by the ratio between two fundamental process energies, viz. the activation enthalpy and activation energy. The reasoning, avoiding any underlying physical model, is supported by the experimental evidence ranging from low molecular weight liquids and polymers to plastic crystals and liquid crystals. All these lead to the new general scaling plot for dynamics of arbitrary glass former. The limited adequacy of broadly used so far semi-empirical relationships between fragility and the activation energy is shown. Results presented remain valid for an arbitrary complex system and collective phenomena if their dynamics is described by the general super-Arrhenius relation.

Results of broadband dielectric spectroscopy (BDS) in Saccharomyces cerevisiae (baker's yeast), in situ as the function of pressure are presented. They show a clear evidence of a threshold to the new pattern of the pressure evolution of the static dielectric permittivity and DC electric conductivity already for P t  ≈ 200 MPa at T  = 5 o C and P t  ≈ 300 MPa at T  = 25 o C . BDS monitoring versus pressure tests up to P  = 400 MPa revealed particularly notable changes of properties after 30 minutes of compressing. Finally, the correlation between the amount of the spectrophotometric maximum absorbance and the DC electric conductivity was found. All these indicate significance of BDS as the tool for testing of pressure properties of cells assemblies, model foods etc., in situ under high pressures.