Institute of Fundamental Technological Research

Dobrzański J., Wojtacki K., Stupkiewicz S., Lamination-based efficient treatment of weak discontinuities for non-conforming finite element meshes, COMPUTERS AND STRUCTURES, ISSN: 0045-7949, DOI: 10.1016/j.compstruc.2023.107209, Vol.291, No.107209, pp.1-14, 2024

Abstract:
When modelling discontinuities (interfaces) using the finite element method, the standard approach is to use a conforming finite-element mesh in which the mesh matches the interfaces. However, this natural approach can prove cumbersome if the geometry is complex, in particular in 3D. In this work, we develop an efficient technique for a non-conforming finite-element treatment of weak discontinuities by using laminated microstructures. The approach is inspired by the so-called composite voxel technique that has been developed for FFT-based spectral solvers in computational homogenization. The idea behind the method is rather simple. Each finite element that is cut by an interface is treated as a simple laminate with the volume fraction of the phases and the lamination orientation determined in terms of the actual geometrical arrangement of the interface within the element. The approach is illustrated by several computational examples relevant to the micromechanics of heterogeneous materials. Elastic and elastic-plastic materials at small and finite strain are considered in the examples. The performance of the proposed method is compared to two alternative, simple methods showing that the new approach is in most cases superior to them while maintaining the simplicity.

Keywords:
Finite element method,Interface,Weak discontinuity,Laminate,Homogenization,Elasticity,Plasticity

Waszkiewicz R., Ranasinghe M., Fogg J., Catanese Jr. Daniel J., Ekiel-Jeżewska M.L., Lisicki M., Demeler B., Zechiedrich L., Szymczak P., DNA supercoiling-induced shapes alter minicircle hydrodynamic properties, Nucleic Acids Research, ISSN: 0305-1048, DOI: 10.1093/nar/gkad183, Vol.51, No.8, pp.4027-2042, 2023

Abstract:
DNA in cells is organized in negatively supercoiled loops. The resulting torsional and bending strain allows DNA to adopt a surprisingly wide variety of 3-D shapes. This interplay between negative supercoiling, looping, and shape influences how DNA is stored, replicated, transcribed, repaired, and likely every other aspect of DNA activity. To understand the consequences of negative supercoiling and curvature on the hydrodynamic properties of DNA, we submitted 336 bp and 672 bp DNA minicircles to analytical ultracentrifugation (AUC). We found that the diffusion coefficient, sedimentation coefficient, and the DNA hydrodynamic radius strongly depended on circularity, loop length, and degree of negative supercoiling. Because AUC cannot ascertain shape beyond degree of non-globularity, we applied linear elasticity theory to predict DNA shapes, and combined these with hydrodynamic calculations to interpret the AUC data, with reasonable agreement between theory and experiment. These complementary approaches, together with earlier electron cryotomography data, provide a framework for understanding and predicting the effects of supercoiling on the shape and hydrodynamic properties of DNA.

Rinoldi C., Ziai Y., Zargarian Seyed S., Nakielski P., Zembrzycki K., Haghighat Bayan Mohammad A., Zakrzewska A., Fiorelli R., Lanzi M., Kostrzewska-Księżyk A., Czajkowski R., Kublik E., Kaczmarek L., Pierini F., In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface, ACS Applied Materials and Interfaces, ISSN: 1944-8244, DOI: 10.1021/acsami.2c17025, Vol.15, No.5, pp.6283-6296, 2023

Abstract:
In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain–computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today’s major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

Keywords:
brain−machine interface,conductive hydrogels,nanostructured biomaterials,in vitro and in vivo biocompatibility,long-term neural recording

Kurniawan T., Sahebdivani M., Zaremba D., Błoński S., Garstecki P., van Steijn V., Korczyk P.M., Formation of droplets in microfluidic cross-junctions at small capillary numbers: Breakdown of the classical squeezing regime, Chemical Engineering Journal, ISSN: 1385-8947, DOI: 10.1016/j.cej.2023.145601, Vol.474, pp.14560-14560, 2023

Abstract:
Two decades of research on droplet formation in microchannels have led to the widely accepted view that droplets form through the squeezing mechanism when interfacial forces dominate over viscous forces. The initially surprising finding that the volume of the droplets is insensitive to the relative importance of these two forces is nowadays well understood from the constrained deformation of the droplet interface during formation. In this work, we show a lower limit of the squeezing mechanism for droplets produced in microfluidic cross-junctions. Below this limit, in the leaking regime, which was recently discovered for droplets produced in T-junctions, the volume of the produced droplets strongly depends on the relative importance of interfacial and viscous forces, as captured by the capillary number. We reveal a fundamental difference in the mechanisms at play in the leaking regime between T- and cross-junctions. In cross-junctions, the droplet neck elongates substantially, and unlike the case of the T-junction, the magnitude of this elongation depends strongly on the value of the capillary number. This elongation significantly affects the final droplet volume in a low capillary number regime. Generalizing the classical squeezing law by lifting the original assumptions and incorporating both identified mechanisms of leaking through gutters and neck elongation, we derive a model for droplet formation and show that it agrees with our experiments.

Keywords:
Microfluidics,Cross-junction,Flow-focusing device,Droplet formation,Two-phase flow,Scaling law,Squeezing regime

Jaruszewicz-Błońska J., Kosiuk I., Prus W.J., Lipniacki T., A plausible identifiable model of the canonical NF-κB signaling pathway, PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0286416, Vol.18, No.6, pp.e0286416-1-26, 2023

Abstract:
An overwhelming majority of mathematical models of regulatory pathways, including the intensively studied NF-κB pathway, remains non-identifiable, meaning that their parameters may not be determined by existing data. The existing NF-κB models that are capable of reproducing experimental data contain non-identifiable parameters, whereas simplified models with a smaller number of parameters exhibit dynamics that differs from that observed in experiments. Here, we reduced an existing model of the canonical NF-κB pathway by decreasing the number of equations from 15 to 6. The reduced model retains two negative feedback loops mediated by IκBα and A20, and in response to both tonic and pulsatile TNF stimulation exhibits dynamics that closely follow that of the original model. We carried out the sensitivity-based linear analysis and Monte Carlo-based analysis to demonstrate that the resulting model is both structurally and practically identifiable given measurements of 5 model variables from a simple TNF stimulation protocol. The reduced model is capable of reproducing different types of responses that are characteristic to regulatory motifs controlled by negative feedback loops: nearly-perfect adaptation as well as damped and sustained oscillations. It can serve as a building block of more comprehensive models of the immune response and cancer, where NF-κB plays a decisive role. Our approach, although may not be automatically generalized, suggests that models of other regulatory pathways can be transformed to identifiable, while retaining their dynamical features.

Demchenko Iraida N., Nikiforow K., Chernyshova M., Melikhov Y., Syryanyy Y., Korsunska N., Khomenkova L., Brodnikovskyi Y., Brodnikovskyi D., X-ray Photoelectron Spectroscopy Analysis of Scandia-Ceria-Stabilized Zirconia Composites with Different Transport Properties, Materials, ISSN: 1996-1944, DOI: 10.3390/ma16165504, Vol.16, No.16, pp.5504-1-12, 2023

Abstract:
This work aims to study a possible modification in the electronic structure of scandia-ceria-stabilized zirconia (10Sc1CeSZ) ceramics sintered at different temperatures. In addition to using X-ray diffraction (XRD), scanning electron microscopy (SEM) and impedance spectroscopy to investigate the structural and electrical properties, we employed X-ray photoelectron spectroscopy (XPS) to determine the chemical state information of the atoms involved, along with compositional analysis. As expected, a significant increase in grain ionic conductivity with the sintering temperature was present. This increase was accompanied by a decrease in the porosity of the samples, an increase in the grain size, and a transformation from the rhombohedral to the cubic phase. The phase transformation was detected not only using XRD, but also using XPS and, for this type of ceramic, XPS detected this transformation for the first time. In addition to the changes in the structural characteristics, the increase in the ionic conductivity was accompanied by a modification in the electronic structure of the ceramic surface. The XPS results showed that the surface of the ceramic sintered at the lower temperature of 1100 °C had a higher amount of Zr–OH bonds than the surface of the ceramic sintered at the higher temperature of 1400 °C. The existence of these Zr–OH bonds was confirmed using Fourier-transform infrared spectroscopy (FTIR). From this result, taken together with the difference between the oxygen/zirconium ratios in these ceramics, also identified using XPS, we conclude that there were fewer oxygen vacancies in the ceramic sintered at the lower temperature. It is argued that these two factors, together with the changes in the structural characteristics, have a direct influence on the conductive properties of the studied ceramics sintered at different temperatures.

Keywords:
XPS, zirconia, scandia-ceria-stabilized zirconia, ScCSZ, SOFC

Ziai Y., Zargarian Seyed S., Rinoldi C., Nakielski P., Sola A., Lanzi M., Truong Yen B., Pierini F., Conducting polymer-based nanostructured materials for brain–machine interfaces, WIREs Nanomedicine and Nanobiotechnology, ISSN: 1939-0041, DOI: 10.1002/wnan.1895, Vol.15, No.5, pp.e1895-1-33, 2023

Abstract:
As scientists discovered that raw neurological signals could translate into bioelectric information, brain–machine interfaces (BMI) for experimental and clinical studies have experienced massive growth. Developing suitable materials for bioelectronic devices to be used for real-time recording and data digitalizing has three important necessitates which should be covered. Biocompatibility, electrical conductivity, and having mechanical properties similar to soft brain tissue to decrease mechanical mismatch should be adopted for all materials. In this review, inorganic nanoparticles and intrinsically conducting polymers are discussed to impart electrical conductivity to systems, where soft materials such as hydrogels can offer reliable mechanical properties and a biocompatible substrate. Interpenetrating hydrogel networks offer more mechanical stability and provide a path for incorporating polymers with desired properties into one strong network. Promising fabrication methods, like electrospinning and additive manufacturing, allow scientists to customize designs for each application and reach the maximum potential for the system. In the near future, it is desired to fabricate biohybrid conducting polymer-based interfaces loaded with cells, giving the opportunity for simultaneous stimulation and regeneration. Developing multi-modal BMIs, Using artificial intelligence and machine learning to design advanced materials are among the future goals for this field.

Keywords:
3D printing,brain–machine interface,conductive hydrogels,electrospinning,neural recording

Grabowski F., Nałęcz‑Jawecki P., Lipniacki T., Predictive power of non-identifiable models, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/s41598-023-37939-8, Vol.13, No.1, pp.11143-1-12, 2023

Abstract:
Resolving practical non-identifiability of computational models typically requires either additional data or non-algorithmic model reduction, which frequently results in models containing parameters lacking direct interpretation. Here, instead of reducing models, we explore an alternative, Bayesian approach, and quantify the predictive power of non-identifiable models. We considered an example biochemical signalling cascade model as well as its mechanical analogue. For these models, we demonstrated that by measuring a single variable in response to a properly chosen stimulation protocol, the dimensionality of the parameter space is reduced, which allows for predicting the measured variable’s trajectory in response to different stimulation protocols even if all model parameters remain unidentified. Moreover, one can predict how such a trajectory will transform in the case of a multiplicative change of an arbitrary model parameter. Successive measurements of remaining variables further reduce the dimensionality of the parameter space and enable new predictions. We analysed potential pitfalls of the proposed approach that can arise when the investigated model is oversimplified, incorrect, or when the training protocol is inadequate. The main advantage of the suggested iterative approach is that the predictive power of the model can be assessed and practically utilised at each step.

Rybak D., Su Y., Li Y., Ding B., Lv X., Li Z., Yeh Y., Nakielski P., Rinoldi C., Pierini F., Dodda Jagan M., Evolution of nanostructured skin patches towards multifunctional wearable platforms for biomedical applications, NANOSCALE, ISSN: 2040-3364, DOI: 10.1039/D3NR00807J, Vol.15, No.18, pp.8044-8083, 2023

Abstract:
Recent advances in the field of skin patches have promoted the development of wearable and implantable bioelectronics for long-term, continuous healthcare management and targeted therapy. However, the design of electronic skin (e-skin) patches with stretchable components is still challenging and requires an in-depth understanding of the skin-attachable substrate layer, functional biomaterials and advanced self-powered electronics. In this comprehensive review, we present the evolution of skin patches from functional nanostructured materials to multi-functional and stimuli-responsive patches towards flexible substrates and emerging biomaterials for e-skin patches, including the material selection, structure design and promising applications. Stretchable sensors and self-powered e-skin patches are also discussed, ranging from electrical stimulation for clinical procedures to continuous health monitoring and integrated systems for comprehensive healthcare management. Moreover, an integrated energy harvester with bioelectronics enables the fabrication of self-powered electronic skin patches, which can effectively solve the energy supply and overcome the drawbacks induced by bulky battery-driven devices. However, to realize the full potential offered by these advancements, several challenges must be addressed for next-generation e-skin patches. Finally, future opportunities and positive outlooks are presented on the future directions of bioelectronics. It is believed that innovative material design, structure engineering, and in-depth study of fundamental principles can foster the rapid evolution of electronic skin patches, and eventually enable self-powered close-looped bioelectronic systems to benefit mankind.

Pruchniewski M., Sawosz E., Sosnowska-Ławnicka M., Ostrowska A., Łojkowski M., Koczoń P., Nakielski P., Kutwin M., Jaworski S., Strojny-Cieślak B., Nanostructured graphene oxide enriched with metallic nanoparticles as a biointerface to enhance cell adhesion through mechanosensory modifications, NANOSCALE, ISSN: 2040-3364, DOI: 10.1039/D3NR03581F, pp.1-21, 2023

Abstract:
Nanostructuring is a process involving surface manipulation at the nanometric level, which improves the mechanical and biological properties of biomaterials. Specifically, it affects the mechanotransductive perception of the microenvironment of cells. Mechanical force conversion into an electrical or chemical signal contributes to the induction of a specific cellular response. The relationship between the cells and growth surface induces a biointerface-modifying cytophysiology and consequently a therapeutic effect. In this study, we present the fabrication of graphene oxide (GO)-based nanofilms decorated with metallic nanoparticles (NPs) as potential coatings for biomaterials. Our investigation showed the effect of decorating GO with metallic NPs for the modification of the physicochemical properties of nanostructures in the form of nanoflakes and nanofilms. A comprehensive biocompatibility screening panel revealed no disturbance in the metabolic activity of human fibroblasts (HFFF2) and bone marrow stroma cells (HS-5) cultivated on the GO nanofilms decorated with gold and copper NPs, whereas a significant cytotoxic effect of the GO nanocomplex decorated with silver NPs was demonstrated. The GO nanofilm decorated with gold NPs beneficially managed early cell adhesion as a result of the transient upregulation of α1β5 integrin expression, acceleration of cellspreading, and formation of elongated filopodia. Additionally, the cells, sensing the substrate derived from the nanocomplex enriched with gold NPs, showed reduced elasticity and altered levels of vimentin expression. In the future, GO nanocomplexes decorated with gold NPs can be incorporated in the structure of architecturally designed biomimetic biomaterials as biocompatible nanostructuring agents with proadhesive properties.

Pruchniewski M., Sawosz E., Sosnowska-Ławnicka M., Ostrowska A., Łojkowski M., Koczoń P., Nakielski P., Kutwin M., Jaworski S., Strojny-Cieślak B., Nanostructured graphene oxide enriched with metallic nanoparticles as a biointerface to enhance cell adhesion through mechanosensory modifications, NANOSCALE, ISSN: 2040-3364, DOI: 10.1039/d3nr03581f, pp.1-21, 2023

Abstract:
Nanostructuring is a process involving surface manipulation at the nanometric level, which improves the mechanical and biological properties of biomaterials. Specifically, it affects the mechanotransductive perception of the microenvironment of cells. Mechanical force conversion into an electrical or chemical signal contributes to the induction of a specific cellular response. The relationship between the cells and growth surface induces a biointerface-modifying cytophysiology and consequently a therapeutic effect. In this study, we present the fabrication of graphene oxide (GO)-based nanofilms decorated with metallic nanoparticles (NPs) as potential coatings for biomaterials. Our investigation showed the effect of decorating GO with metallic NPs for the modification of the physicochemical properties of nanostructures in the form of nanoflakes and nanofilms. A comprehensive biocompatibility screening panel revealed no disturbance in the metabolic activity of human fibroblasts (HFFF2) and bone marrow stroma cells (HS-5) cultivated on the GO nanofilms decorated with gold and copper NPs, whereas a significant cytotoxic effect of the GO nanocomplex decorated with silver NPs was demonstrated. The GO nanofilm decorated with gold NPs beneficially managed early cell adhesion as a result of the transient upregulation of α1β5 integrin expression, acceleration of cellspreading, and formation of elongated filopodia. Additionally, the cells, sensing the substrate derived from the nanocomplex enriched with gold NPs, showed reduced elasticity and altered levels of vimentin expression. In the future, GO nanocomplexes decorated with gold NPs can be incorporated in the structure of architecturally designed biomimetic biomaterials as biocompatible nanostructuring agents with proadhesive properties.

Grabowski F., Kochańczyk M., Korwek Z., Czerkies M., Prus W., Lipniacki T., Antagonism between viral infection and innate immunity at the single-cell level, PLoS Pathogens, ISSN: 1553-7366, DOI: 10.1371/journal.ppat.1011597, Vol.19, No.9, pp. e1011597- e1011597, 2023

Abstract:
When infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is a lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection.

Zangoli M., Monti F., Zanelli A., Marinelli M., Flammini S., Spallacci N., Zakrzewska A., Lanzi M., Salatelli E., Pierini F., Di Maria F., Multifunctional Photoelectroactive Materials for Optoelectronic Applications Based on Thieno[3,4-b]pyrazines and Thieno[1,2,5]thiadiazoles, Chemistry - A European Journal, ISSN: 0947-6539, DOI: 10.1002/chem.202303590, pp.1-18, 2023

Abstract:
In this study, we introduce a novel family of symmetrical thiophene-based small molecules with a Donor–Acceptor–Donor structure. These compounds feature three different acceptor units: benzo[c][1,2,5]thiadiazole (Bz), thieno[3,4-b]pyrazine (Pz), and thieno[1,2,5]thiadiazole (Tz), coupled with electron donor units based on a carbazole-thiophene derivative. Using Density Functional Theory (DFT), we investigate how the molecular geometry and strength of the central acceptor unit impact the redox and spectroscopic properties. Notably, the incorporation of Pz and Tz moieties induces a significant redshift in the absorption and emission spectra, which extend into the near-infrared (NIR) region, simultaneously reducing their energy gaps (~1.4-1.6 eV). This shift is attributed to the increased coplanarity of the oligomeric inner core, both in the ground (S0) and excited (S1) states, due to the enhanced quinoidal character as supported by bond-length alternation (BLA) analysis. These structural changes promote better π-electron delocalization and facilitate photoinduced charge transfer processes in optoelectronic devices. Notably, we show that Pz- and Tz-containing molecules exhibit NIR electrochromic behavior and present ambivalent character in bulk heterojunction (BHJ) solar cells. Finally, theoretical calculations suggest that these molecules could serve as effective two-photon absorption (2PA) probes, further expanding their potential in optoelectronic applications.

Alachkar N., Norton D., Wolkensdorfer Z., Muldoon M., Paszek P., Variability of the innate immune response is globally constrained by transcriptional bursting, Frontiers in Molecular Biosciences, ISSN: 2296-889X, DOI: 10.3389/fmolb.2023.1176107, Vol.10, pp.1176107-1-16, 2023

Abstract:
Transcription of almost all mammalian genes occurs in stochastic bursts, however the fundamental control mechanisms that allow appropriate single-cell responses remain unresolved. Here we utilise single cell genomics data and stochastic models of transcription to perform global analysis of the toll-like receptor (TLR)-induced gene expression variability. Based on analysis of more than 2000 TLR-response genes across multiple experimental conditions we demonstrate that the single-cell, gene-by-gene expression variability can be empirically described by a linear function of the population mean. We show that response heterogeneity of individual genes can be characterised by the slope of the mean-variance line, which captures how cells respond to stimulus and provides insight into evolutionary differences between species. We further demonstrate that linear relationships theoretically determine the underlying transcriptional bursting kinetics, revealing different regulatory modes of TLR response heterogeneity. Stochastic modelling of temporal scRNA-seq count distributions demonstrates that increased response variability is associated with larger and more frequent transcriptional bursts, which emerge via increased complexity of transcriptional regulatory networks between genes and different species. Overall, we provide a methodology relying on inference of empirical mean-variance relationships from single cell data and new insights into control of innate immune response variability.

Downton P., Bagnall James S., England H., Spiller David G., Humphreys Neil E., Jackson Dean A., Paszek P., White Michael R.R., Adamson Antony D., Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression, Frontiers in Molecular Biosciences, ISSN: 2296-889X, DOI: 10.3389/fmolb.2023.1187187, Vol.10, pp.1187187-1-15, 2023

Abstract:
Cells respond to inflammatory stimuli such as cytokines by activation of the nuclear factor-κB (NF-κB) signalling pathway, resulting in oscillatory translocation of the transcription factor p65 between nucleus and cytoplasm in some cell types. We investigate the relationship between p65 and inhibitor-κB⍺ (IκBα) protein levels and dynamic properties of the system, and how this interaction impacts on the expression of key inflammatory genes. Using bacterial artificial chromosomes, we developed new cell models of IκB⍺-eGFP protein overexpression in a pseudo-native genomic context. We find that cells with high levels of the negative regulator IκBα remain responsive to inflammatory stimuli and maintain dynamics for both p65 and IκBα. In contrast, canonical target gene expression is dramatically reduced by overexpression of IκBα, but can be partially rescued by overexpression of p65. Treatment with leptomycin B to promote nuclear accumulation of IκB⍺ also suppresses canonical target gene expression, suggesting a mechanism in which nuclear IκB⍺ accumulation prevents productive p65 interaction with promoter binding sites. This causes reduced target promoter binding and gene transcription, which we validate by chromatin immunoprecipitation and in primary cells. Overall, we show how inflammatory gene transcription is modulated by the expression levels of both IκB⍺ and p65. This results in an anti-inflammatory effect on transcription, demonstrating a broad mechanism to modulate the strength of inflammatory response.

Keywords:
NF-κB, inflammation, IκB⍺, overexpression, gene expression, localisation

Wang Y., Melikhov Y., Meydan T., Dipole modelling of temperature-dependent magnetic flux leakage, NDT AND E INTERNATIONAL, ISSN: 0963-8695, DOI: 10.1016/j.ndteint.2022.102749, Vol.133, pp.102749-1-9, 2023

Abstract:
Due to the nonlinear coupling, assessing the direct effect of temperature on magnetic flux leakage (MFL) signal is a complicated task. If temperature induces inner stress, it makes the problem doubly difficult, so few models are available for predicting the MFL signal under this condition. To model the effect of temperature on MFL signal, the temperature-dependent magnetic dipole models are proposed. In the first case, where the direct thermal effect is involved only, the dipole model is improved via the modified temperature-dependent Jiles-Atherton (J-A) model. While in the second case, where the combined effects of temperature and thermal stress are considered, the magnetomechanical J-A parameters are further introduced into the dipole model. The thermal stress distribution around a cylindrical through-hole defect is solved by thermoelastic and solid mechanics theories. The magnetomechanical theory is employed to analyse the stress-dependent magnetisation distribution, the key parameter in the magnetic dipole model. The verified experiments are conducted on an M250-50A non-oriented grain (NO) silicon steel specimen with a cylindrical through-hole defect. And the MFL signals predicted by both proposed models agree with the experimental results. When the direct effect of temperature is involved only, the peak-to-peak amplitude of the MFL signal (MFLpp) presents approximately linear dependence on temperature in the range from −40 to 60 . In addition, when both temperature and thermal stress are considered, the MFLpp changes as a parabolic function of temperature, this being much more significant than the direct effect. The proposed models can act as effective tools to understand the temperature and thermal stress influences on MFL signals. They are also appropriate to solve the inverse problem of sizing the defects accurately when the temperature is involved.

Keywords:
Magnetic dipole model, Magnetic flux leakage, Temperature, J-A model, Thermal stress, Magnetomechanics

Wang M., Du J., Li M.S., Pierini F., Li X., Yu J., Ding B., In situ forming double-crosslinked hydrogels with highly dispersed short fibers for the treatment of irregular wounds, Biomaterials Science, ISSN: 2047-4849, DOI: 10.1039/D2BM01891H, Vol.11, No.7, pp.2383-2394, 2023

Abstract:
In situ forming injectable hydrogels hold great potential for the treatment of irregular wounds. However, their practical applications were hindered by long gelation time, poor mechanical performance, and a lack of a natural extracellular matrix structure. Herein, amino-modified electrospun poly(lactic-co-glycolic acid) (APLGA) short fibers with uniform distribution were introduced into gelatin methacrylate/oxidized dextran (GM/ODex) hydrogels. In comparison with the fiber aggregation structure in the PLGA fiber-incorporated hydrogels, the hydrogels with APLGA fibers possessed a uniform porous structure. The highly dispersed APLGA short fibers accelerated the sol–gel phase transition of the hydrogel due to the formation of dynamic Schiff-base bonds between the fibers and hydrogels. Furthermore, in combination with UV-assisted crosslinking, a rapid gelation time of 90 s was achieved for the double-crosslinked hydrogels. The addition of APLGA short fibers as fillers and the formation of the double-crosslinking network enhanced the mechanical performance of the hydrogels. Furthermore, the fiber–hydrogel composites exhibited favorable injectability, excellent biocompatibility, and improved cell infiltration. In vivo assessment indicated that the GM/ODex-APLGA hydrogels successfully filled the full-thickness defects and improved wound healing. This work demonstrates a promising solution for the treatment of irregular wounds.

Nałęcz-Jawecki P., Gagliardi Paolo A., Kochańczyk M.R., Dessauges C., Pertz O., Lipniacki T., The MAPK/ERK channel capacity exceeds 6 bit/hour, PLOS COMPUTATIONAL BIOLOGY, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1011155, Vol.19, No.5, pp.e1011155-1-21, 2023

Abstract:
Living cells utilize signaling pathways to sense, transduce, and process information. As the extracellular stimulation often has rich temporal characteristics which may govern dynamic cellular responses, it is important to quantify the rate of information flow through the signaling pathways. In this study, we used an epithelial cell line expressing a light-activatable FGF receptor and an ERK activity reporter to assess the ability of the MAPK/ERK pathway to transduce signal encoded in a sequence of pulses. By stimulating the cells with random light pulse trains, we demonstrated that the MAPK/ERK channel capacity is at least 6 bits per hour. The input reconstruction algorithm detects the light pulses with 1-min accuracy 5 min after their occurrence. The high information transmission rate may enable the pathway to coordinate multiple processes including cell movement and respond to rapidly varying stimuli such as chemoattracting gradients created by other cells.

Shashank H., Melikhov Y., Ekiel-Jeżewska M.L., Dynamics of ball chains and highly elastic fibres settling under gravity in a viscous fluid, SOFT MATTER, ISSN: 1744-683X, DOI: 10.1039/D3SM00255A, Vol.19, No.26, pp.4829-4846, 2023

Abstract:
We study experimentally the dynamics of one and two ball chains settling under gravity in a highly viscous silicon oil at a Reynolds number much smaller than unity. We record the motion and shape deformation using two cameras. We demonstrate that single ball chains in most cases do not tend to be planar and often rotate, not keeping the ends at the same horizontal level. Shorter ball chains usually form shapes resembling distorted U. Longer ones in the early stage of the evolution form a shape resembling distorted W, and later deform non-symmetrically and significantly out of a plane. The typical evolution of shapes observed in our experiments with single ball chains is reproduced in our numerical simulations of a single elastic filament. In the computations, the filament is modelled as a chain of beads. Consecutive beads are connected by springs. Additional springs link consecutive pairs of beads. Elastic forces are assumed to be much smaller than gravity. As a result, the fibre is very flexible. We assume that the fluid sticks to the surfaces of the beads. We perform multipole expansion of the Stokes equations, with a lubrication correction. This method is implemented in the precise HYDROMULTIPOLE numerical codes. In our experiments, two ball chains, initially one above the other, later move away or approach each other, for a larger or smaller initial distance, respectively.

Poblete S., Pantano S., Okazaki K., Liang Z., Kremer K., Poma Adolfo B., Editorial: Recent advances in computational modelling of biomolecular complexes, Frontiers in Chemistry, ISSN: 2296-2646, DOI: 10.3389/fchem.2023.1200409, Vol.11, pp.1200409-1-3, 2023

Keywords:
coarse-grained method, machine learning, multiscale approach, biopolymers, aggregation, GōMartini approach, Martini 3, nanomechanics

Titaux-Delgado G., Lopez-Giraldo Andrea E., Carrillo E., Cofas-Vargas Luis F., Carranza Luis E., Lopez-Vera E., García-Hernandez E., del Rio-Portilla F., Beta-KTx14.3, a scorpion toxin, blocks the human potassium channel KCNQ1, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, ISSN: 1570-9639, DOI: 10.1016/j.bbapap.2023.140906, Vol.1871, No.4, pp.140906-1-11, 2023

Abstract:
Potassium channels play a key role in regulating many physiological processes, thus, alterations in their proper functioning can lead to the development of several diseases. Hence, the search for compounds capable of regulating the activity of these channels constitutes an intense field of investigation. Potassium scorpion toxins are grouped into six subfamilies (α, β, γ, κ, δ, and λ). However, experimental structures and functional analyses of the long chain β-KTx subfamily are lacking. In this study, we recombinantly produced the toxins TcoKIK and beta-KTx14.3 present in the venom of Tityus costatus and Lychas mucronatus scorpions, respectively. The 3D structures of these β-KTx toxins were determined by nuclear magnetic resonance. In both toxins, the N-terminal region is unstructured, while the C-terminal possesses the classic CSα/β motif. TcoKIK did not show any clear activity against frog Shaker and human KCNQ1 potassium channels; however, beta-KTx14.3 was able to block the KCNQ1 channel. The toxin-channel interaction mode was investigated using molecular dynamics simulations. The results showed that this toxin could form a stable network of polar-to-polar and hydrophobic interactions with KCNQ1, involving key conserved residues in both molecular partners. The discovery and characterization of a toxin capable of inhibiting KCNQ1 pave the way for the future development of novel drugs for the treatment of human diseases caused by the malfunction of this potassium channel.
Statement of significance

Scorpion toxins have been shown to rarely block human KCNQ1 channels, which participate in the regulation of cardiac processes. In this study, we obtained recombinant beta-KTx14.3 and TcoKIK toxins and determined their 3D structures by nuclear magnetic resonance. Electrophysiological studies and molecular dynamics models were employed to examine the interactions between these two toxins and the human KCNQ1, which is the major driver channel of cardiac repolarization; beta-KTx14.3 was found to block effectively this channel. Our findings provide insights for the development of novel toxin-based drugs for the treatment of cardiac channelopathies involving KCNQ1-like channels.

Keywords:
β-KTx, Scorpion toxins, Cysteine-stabilized α/β motif, TcoKIK, Beta-KTx14.3, KCNQ1

Emadi A., Lipniacki T., Levchenko A., Abdi A., Single-Cell Measurements and Modeling and Computation of Decision-Making Errors in a Molecular Signaling System with Two Output Molecules, Biology, ISSN: 2079-7737, DOI: 10.3390/biology12121461, Vol.12, No.12, pp.1461-1-12, 2023

Abstract:
A cell constantly receives signals and takes different fates accordingly. Given the uncertainty rendered by signal transduction noise, a cell may incorrectly perceive these signals. It may mistakenly behave as if there is a signal, although there is none, or may miss the presence of a signal that actually exists. In this paper, we consider a signaling system with two outputs, and introduce and develop methods to model and compute key cell decision-making parameters based on the two outputs and in response to the input signal. In the considered system, the tumor necrosis factor (TNF) regulates the two transcription factors, the nuclear factor κB (NFκB) and the activating transcription factor-2 (ATF-2). These two system outputs are involved in important physiological functions such as cell death and survival, viral replication, and pathological conditions, such as autoimmune diseases and different types of cancer. Using the introduced methods, we compute and show what the decision thresholds are, based on the single-cell measured concentration levels of NFκB and ATF-2. We also define and compute the decision error probabilities, i.e., false alarm and miss probabilities, based on the concentration levels of the two outputs. By considering the joint response of the two outputs of the signaling system, one can learn more about complex cellular decision-making processes, the corresponding decision error rates, and their possible involvement in the development of some pathological conditions.

Keywords:
cell decision making, decision theory, molecular signaling systems, signal transduction noise, cellular decision error probabilities

Jain A., Ziai Y., Bochenek K., Manippady Sai R., Pierini F., Michalska M., Utilization of compressible hydrogels as electrolyte materials for supercapacitor applications, RSC Advances, ISSN: 2046-2069, DOI: 10.1039/d3ra00893b, Vol.13, pp.11503-11512, 2023

Abstract:
Utilization of CoO@Co3O4-x-Ag (x denotes 1, 3, and 5 wt% of Ag) nanocomposites as supercapacitor electrodes is the main aim of this study. A new low-temperature wet chemical approach is proposed to modify the commercial cobalt oxide material with silver nanoparticle (NP) balls of size 1–5 nm. The structure and morphology of the as-prepared nanocomposites were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and N2 adsorption–desorption measurements. Hydrogels known to be soft but stable structures were used here as perfect carriers for conductive nanoparticles such as carbons. Furthermore, hydrogels with a large amount of water in their network can give more flexibility to the system. Fabrication of an electrochemical cell can be achieved by combining these materials with a layer-by-layer structure. The performance characteristics of the cells were examined by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and galvanostatic charge discharge (GCD). Cobalt oxide modified with 5 wt% Ag gave the best supercapacitor results, and the cell offers a specific capacitance of ∼38 mF cm−2 in two-electrode configurations.

Peringath Anjana R., Haghighat Bayan Mohammad A., Beg M., Jain A., Pierini F., Gadegaard N., Hogg R., Manjakkal L., Chemical synthesis of polyaniline and polythiophene electrodes with excellent performance in supercapacitors, Journal of Energy Storage, ISSN: 2352-152X, DOI: 10.1016/j.est.2023.108811, Vol.73, No.Part A, pp.108811-1-9, 2023

Abstract:
The emergence of portable electronics in miniaturized and intelligent devices demands high-performance supercapacitors (SC) and batteries as power sources. For the fabrication of such energy storage devices, conducting polymers (CPs) have significant advantages due to their high theoretical capacitive performance and conductivity. In this work, we developed two CPs including polyaniline and polythiophene through a low-cost chemically synthesized approach and the film-by-spin coating method. The structural and morphological properties of the CPs are analyzed using Fourier-transform infrared spectroscopy (FTIR), contact angle measurement, and scanning electron microscopy (SEM). Based on these CPs, novel pristine polyaniline and polythiophene-based SCs (PASC and PTSC) are developed. The prepared CPs contribute to high electrochemical performances due to their high conductive nature of the electrode and conjugated polymer materials reaction. Hence both electrochemical double-layer formation and pseudocapacitance contributed to the energy-storing performances of the device. Electrochemical impedance spectroscopic analysis (0.1 Hz to 100 kHz) demonstrates faster ionic exchange and high capacitance of the PASC electrode as compared to PTSC in H3PO4 electrolyte. The PASC devices exhibit specific capacitance of 13.22 mF·cm−2 with energy and power densities of 1.175 μW·h·cm−2 and 4.99 μW·cm−2 at a current of 50 μA. Compared to PTSC (specific capacitance 3.30 mF·cm−2) the PASC shows four times higher specific capacitance due to its improved surface, structural and electrical properties. The electrochemical performance reveals the superior SC performance for this type of CP electrode.

Keywords:
Conductive polymers, Spin coating, Polyaniline, Polythiophene, Supercapacitor, Electrochemical performances

Zembrzycki K., Pawłowska S., Pierini F., Kowalewski T.A., Brownian Motion in Optical Tweezers, a Comparison between MD Simulations and Experimental Data in the Ballistic Regime, Polymers, ISSN: 2073-4360, DOI: 10.3390/polym15030787, Vol.15, No.3, pp.787-1-13, 2023

Abstract:
The four most popular water models in molecular dynamics were studied in large-scale simulations of Brownian motion of colloidal particles in optical tweezers and then compared with experimental measurements in the same time scale. We present the most direct comparison of col- loidal polystyrene particle diffusion in molecular dynamics simulations and experimental data on the same time scales in the ballistic regime. The four most popular water models, all of which take into account electrostatic interactions, are tested and compared based on yielded results and re- sources required. Three different conditions were simulated: a freely moving particle and one in a potential force field with two different strengths based on 1 pN/nm and 10 pN/nm. In all cases, the diameter of the colloidal particle was 50 nm. The acquired data were compared with experimental measurements performed using optical tweezers with position capture rates as high as 125 MHz. The experiments were performed in pure water on polystyrene particles with a 1 μm diameter in special microchannel cells.

Keywords:
Brownian motion,molecular dynamics,optical tweezers,ballistic regime

Shah S. A., Sohail M., Karperien M., Johnbosco C., Mahmood A., Kousar M., Chitosan and carboxymethyl cellulose-based 3D multifunctional bioactive hydrogels loaded with nano-curcumin for synergistic diabetic wound repair, International Journal of Biological Macromolecules, ISSN: 0141-8130, DOI: 10.1016/j.ijbiomac.2022.11.307, Vol.227, pp.1203-1220, 2023

Abstract:
Biopolymer-based thermoresponsive injectable hydrogels with multifunctional tunable characteristics containing anti-oxidative, biocompatibility, anti-infection, tissue regeneration, and/or anti-bacterial are of abundant interest to proficiently stimulate diabetic wound regeneration and are considered as a potential candidate for diversified biomedical application but the development of such hydrogels remains a challenge. In this study, the Chitosan-CMC-g-PF127 injectable hydrogels are developed using solvent casting. The Curcumin (Cur) Chitosan-CMC-g-PF127 injectable hydrogels possess viscoelastic behavior, good swelling properties, and a controlled release profile. The degree of substitution (% DS), thermal stability, morphological behavior, and crystalline characteristics of the developed injectable hydrogels is confirmed using nuclear magnetic resonance (1H NMR), thermogravimetric analysis, scanning electron microscopy (SEM), and x-ray diffraction analysis (XRD), respectively. The controlled release of cur-micelles from the hydrogel is evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC). Furthermore, compared to cur micelles the Cur-laden injectable hydrogel shows a significant increase in half-life (t1/2) up to 5.92 ± 0.7 h, mean residence time (MRT) was 15.75 ± 0.76 h, and area under the first moment curve (AUMC) is 3195.62 ± 547.99 μg/mL*(h)2 which reveals the controlled release behavior. Cytocompatibility analysis of Chitosan-CMC-g-PF127 hydrogels using 3T3-L1 fibroblasts cells and in vivo toxicity by subcutaneous injection followed by histological examination confirmed good biocompatibility of Cur-micelles loaded hydrogels. The histological results revealed the promising tissue regenerative ability and shows enhancement of fibroblasts, keratinocytes, and collagen deposition, which stimulates the epidermal junction. Interestingly, the Chitosan-CMC-g-PF127 injectable hydrogels ladened Cur exhibited a swift wound repair potential by up-surging the cell migration and proliferation at the site of injury and providing a sustained drug delivery platform for hydrophobic moieties.

Keywords:
Biomaterials,Injectable hydrogels,Wound healing,Chitosan,Carboxymethylcellulose

Kaźmierczak B.A., Sneyd J., Tsai J., Effect of Buffers with Multiple Binding Sites on Calcium Waves, BULLETIN OF MATHEMATICAL BIOLOGY, ISSN: 0092-8240, DOI: 10.1007/s11538-022-01109-0, Vol.85, No.1, pp.10-1-45, 2023

Abstract:
The existence and properties of intracellular waves of increased free cytoplasmic calcium concentration (calcium waves) are strongly affected by the binding and unbinding of calcium ions to a multitude of different buffers in the cell. These buffers can be mobile or immobile and, in general, have multiple binding sites that are not independent. Previous theoretical studies have focused on the case when each buffer molecule binds a single calcium ion. In this study, we analyze how calcium waves are affected by calcium buffers with two non-independent binding sites, and show that the interactions between the calcium binding sites can result in the emergence of new behaviors. In particular, for certain combinations of kinetic parameters, the profiles of buffer molecules with one calcium ion bound can be non-monotone.

Keywords:
Reaction-diffusion systems, Buffered calcium systems

Wang Y., Melikhov Y., Meydan T., Multifunctional induction coil sensor for evaluation of carbon content in carbon steel, IEEE TRANSACTIONS ON MAGNETICS, ISSN: 0018-9464, DOI: 10.1109/TMAG.2022.3217954, Vol.59, No.2, pp.6000305-1-5, 2023

Abstract:
Carbon steel has proven to be an important structural and functional material that plays an irreplaceable role in the worldwide economy. The influence of carbon on the mechanical and magnetic properties of the steel is well understood. Thus, the precise knowledge of the amount of carbon content in steel is crucial. Magnetic Barkhausen noise (MBN), magnetic hysteresis loop (MHL) and impedance measurements are reliable tools to assess carbon content. In this work, a multifunctional induction coil sensor used for MBN, MHL and impedance measurements is designed and optimised. A multifunctional measurement system using the optimised induction coil is employed to measure MBN, MHL and impedance signals. The parabolic dependence of the maximum value of MBN envelope on carbon content in steel is theoretically analysed and experimentally verified. Coercive field and remanence from MHL measurements as well as the maximum impedance value are found to be proportional to carbon content and their dependence is explained with analytical simulations.

Keywords:
Carbon content ,Impedance ,Magnetic Barkhausen Noise ,Magnetic Hysteresis Loop ,Multifunctional sensor

Sønstevold L., Czerkies M.K., Escobedo-Cousin E., Błoński S., Vereshchagina E., Application of Polymethylpentene, an Oxygen Permeable Thermoplastic, for Long-Term on-a-Chip Cell Culture and Organ-on-a-Chip Devices, Micromachines, ISSN: 2072-666X, DOI: 10.3390/mi14030532, Vol.14, No.3, pp.532-1-18, 2023

Abstract:
The applicability of a gas-permeable, thermoplastic material polymethylpentene (PMP) was investigated, experimentally and analytically, for organ-on-a-chip (OoC) and long-term on-a-chip cell cultivation applications. Using a sealed culture chamber device fitted with oxygen sensors, we tested and compared PMP to commonly used glass and polydimethylsiloxane (PDMS). We show that PMP and PDMS have comparable performance for oxygen supply during 4 days culture of epithelial (A549) cells with oxygen concentration stabilizing at 16%, compared with glass control where it decreases to 3%. For the first time, transmission light images of cells growing on PMP were obtained, demonstrating that the optical properties of PMP are suitable for non-fluorescent, live cell imaging. Following the combined transmission light imaging and calcein-AM staining, cell adherence, proliferation, morphology, and viability of A549 cells were shown to be similar on PMP and glass coated with poly-L-lysine. In contrast to PDMS, we demonstrate that a film of PMP as thin as 0.125 mm is compatible with high-resolution confocal microscopy due to its excellent optical properties and mechanical stiffness. PMP was also found to be fully compatible with device sterilization, cell fixation, cell permeabilization and fluorescent staining. We envision this material to extend the range of possible microfluidic applications beyond the current state-of-the-art, due to its beneficial physical properties and suitability for prototyping by different methods. The integrated device and measurement methodology demonstrated in this work are transferrable to other cell-based studies and life-sciences applications.

Keywords:
polymethylpentene (PMP), cell culture, oxygen control, microfluidic device, organ-on-a-chip

Bławzdziewicz J., Adamczyk Z., Ekiel-Jeżewska Maria L.L., Streaming Current for Surfaces Covered by Square and Hexagonal Monolayers of Spherical Particles, ACS Omega, ISSN: 2470-1343, DOI: 10.1021/acsomega.3c05603, pp.A-G, 2023

Abstract:
The interface and particle contributions to the streaming current of flat substrates covered with ordered square or hexagonal monolayers of spherical particles were theoretically evaluated for particle coverage up to close packing. The exact numerical results were approximated using fitting functions that contain exponential and linear terms to account for hydrodynamic screening and charge convection from the particle surfaces exposed to external flow. According to our calculations, the streaming currents for the ordered and random particle arrangements differ within a typical experimental error. Thus, streaming-current measurements, supplemented with our fitting functions, can be conveniently used to evaluate the particle coverage without detailed knowledge of the particle distribution. Our results for equal interface and particle ζ-potentials indicate that roughness can reduce the streaming current by more than 30%, even in the limit of the small size of spherical roughness asperities.

Shokri A., Melikhov Y., Syryanyy Y., Demchenko Iraida N., Point Defects in Silicon-Doped β-Ga2O3: Hybrid-DFT Calculations, ACS Omega, ISSN: 2470-1343, DOI: 10.1021/acsomega.3c05557, Vol.8, No.46, pp.43732-43738, 2023

Abstract:
In this work, hybrid density functional theory calculations are used to evaluate the structural and electronic properties and formation energies of Si-doped β-Ga2O3. Overall, eight interstitial (Sii) and two substitutional (SiGa) positions are considered. In general, our results indicate that the formation energy of such systems is significantly influenced by the charge state of the defect. It is confirmed that it is energetically more favorable for the substitution process to proceed under Ga-poor growth conditions than under Ga-rich growth conditions. Furthermore, it is confirmed that the formation of SiGaI with a tetrahedral coordination geometry is more favorable than the formation of SiGaII with an octahedral one. Out of all considered interstitial positions, due to the negative formation energy of the Si +3 charge state at i8 and i9 interstitial positions over the wide range of Fermi energy, this type of defect can be spontaneously stable. Finally, due to a local distortion caused by the presence of the interstitial atom as well as its charge state, these systems obtain a spin-polarized ground state with a noticeable magnetic moment.

Quadretti D., Marinelli M., Salatelli E., Pierini F., Zanelli A., Lanzi M., Effects of Water/Alcohol Soluble Cationic Polythiophenes as Cathode Interlayers for Eco-Friendly Solar Cells, Macromolecular Chemistry and Physics, ISSN: 1022-1352, DOI: 10.1002/macp.202200422, Vol.224, No.6, pp.2200422-1-14, 2023

Abstract:
Three new ionic polythiophene derivatives, soluble in polar solvents, are synthesized with good yields using simple, low-cost, and straightforward procedures. They are investigated as interfacial cationic conjugated
polyelectrolyte (CPE) layers for halogen-free bulk heterojunction polymeric solar cells, based on a water-soluble electron-donor polymer
(poly[3-(6-diethanolaminohexyl)thiophene]) and a water-soluble electron-acceptor fullerene derivative (malonodiserinolamide fullerene). The simple insertion of the CPE interlayer between the active layer and the aluminum cathode dramatically increases the power conversion efficiency of the final device up to nearly 5%, resulting from a decrease of the electrode work function, improved electron extraction, and optimization of the morphology of the layers. The obtained results demonstrate that the incorporation of CPE layer is a powerful and convenient methodology for the
development of highly efficient and eco-friendly processable polymeric solar cells.

Keywords:
conjugated polyelectrolyte,electron transport layers,polythiophene

Zakrzewska A., Zargarian S.S., Rinoldi C., Gradys A.D., Jarząbek D.M., Zanoni M., Gualandi C., Lanzi M., Pierini F., Electrospun Poly(vinyl alcohol)-Based Conductive Semi-interpenetrating Polymer Network Fibrous Hydrogel: A Toolbox for Optimal Cross-Linking, ACS Materials Au, ISSN: 2694-2461, DOI: 10.1021/acsmaterialsau.3c00025, Vol.3, No.5, pp.464-482, 2023

Abstract:
Cross-linking of poly(vinyl alcohol) (PVA) creates a three-dimensional network by bonding adjacent polymer chains. The cross-linked structure, upon immersion in water, turns into a hydrogel, which exhibits unique absorption properties due to the presence of hydrophilic groups within the PVA polymer chains and, simultaneously, ceases to be soluble in water. The properties of PVA can be adjusted by chemical modification or blending with other substances, such as polymers, e.g., conductive poly[3-(potassium-5-butanoate)thiophene-2,5-diyl] (P3KBT). In this work, PVA-based conductive semi-interpenetrating polymer networks (semi-IPNs) are successfully fabricated. The systems are obtained as a result of electrospinning of PVA/P3KBT precursor solutions with different polymer concentrations and then cross-linking using “green”, environmentally safe methods. One approach consists of thermal treatment (H), while the second approach combines stabilization with ethanol and heating (E). The comprehensive characterization allows to evaluate the correlation between the cross-linking methods and properties of nanofibrous hydrogels. While both methods are successful, the cross-linking density is higher in the thermally cross-linked samples, resulting in lower conductivity and swelling ratio compared to the E-treated samples. Moreover, the H-cross-linked systems have better mechanical properties─lower stiffness and greater tensile strength. All the tested systems are biocompatible, and interestingly, due to the presence of P3KBT, they show photoresponsivity to solar radiation generated by the simulator. The results indicate that both methods of PVA cross-linking are highly effective and can be applied to a specific system depending on the target, e.g., biomedical or electronic applications.

Keywords:
poly(vinyl alcohol),poly[3-(potassium-5-butanoate)thiophene-2.5-diyl],electrospun nanofibers,cross-linking,fibrous hydrogel,semi-IPN

Gregory Grace E., Jones Adam P., Haley Michael J., Hoyle C., Zeef Leo A. H., Lin I., Coope David J., King Andrew T., Evans D. G., Paszek P., Couper Kevin N., Brough D., Pathmanaban Omar N., The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma, Brain Communications, ISSN: 2632-1297, DOI: 10.1093/braincomms/fcad197, Vol.5, No.4, pp.1-15, 2023

Abstract:
Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

Keywords:
tumour microenvironment, vestibular schwannoma, tumour-associated macrophages, NF2, NF2-related schwannomatosis

Haghighat Bayan Mohammad A., Dias Yasmin J., Rinoldi C., Nakielski P., Rybak D., Truong Yen B., Yarin A., Pierini F., Near-infrared light activated core-shell electrospun nanofibers decorated with photoactive plasmonic nanoparticles for on-demand smart drug delivery applications, Journal of Polymer Science, ISSN: 2642-4169, DOI: 10.1002/pol.20220747, Vol.61, No.7, pp.521-533, 2023

Abstract:
Over the last few years, traditional drug delivery systems (DDSs) have been transformed into smart DDSs. Recent advancements in biomedical nanotech-nology resulted in introducing stimuli-responsiveness to drug vehicles. Nano-
platforms can enhance drug release efficacy while reducing the side effects of drugs by taking advantage of the responses to specific internal or external stim-uli. In this study, we developed an electrospun nanofibrous photo-responsive DDSs. The photo-responsivity of the platform enables on-demand elevated drug release. Furthermore, it can provide a sustained release profile and pre-vent burst release and high concentrations of drugs. A coaxial electrospinning setup paired with an electrospraying technique is used to fabricate core-shell PVA-PLGA nanofibers decorated with plasmonic nanoparticles. The fabricated
nanofibers have a hydrophilic PVA and Rhodamine-B (RhB) core, while the shell is hydrophobic PLGA decorated with gold nanorods (Au NRs). The presence of plasmonic nanoparticles enables the platform to twice the amount of drug release besides exhibiting a long-term release. Investigations into the photo-responsive release mechanism demonstrate the system's potential as a “smart” drug delivery platform.

Keywords:
electrospun core-shell nanofibers,NIR-light activation,on-demand drug release,plasmonic nanoparticles,stimuli-responsive nanomaterials